(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2018/064163 Al 05 April 2018 (05.04.2018) W !P O PCT

(51) International Patent Classification: KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, C07F 7/08 (2006.01) MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (21) International Application Number: SC, SD, SE, SG, SK, SL, SM, ST, SV, SY,TH, TJ, TM, TN, PCT/US2017/053714 TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (22) International Filing Date: (84) Designated States (unless otherwise indicated, for every 27 September 2017 (27.09.2017) kind of regional protection available): ARIPO (BW, GH, (25) Filing Language: English GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, (26) Publication Langi English TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, (30) Priority Data: EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, 62/400,195 27 September 2016 (27.09.2016) US MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, 62/442,091 04 January 2017 (04.01.2017) US TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). (71) Applicant: UNIVERSITY OF DELAWARE [US/US]; 1 Innovation Way, Delaware Technology Park, Building 1, Published: Suite 500, Newark, DE 1971 1 (US). — with international search report (Art. 21(3)) (72) Inventors: WATSON, Donald; 108 W. Mill Station Drive, — before the expiration of the time limit for amending the Newark, DE 1971 1 (US). CINDERELLA, Andrew; 307 claims and to be republished in the event of receipt of Park Circle, Elkton, MD 21921 (US). VULOVIC, Bojan; amendments (Rule 48.2(h)) Smrdan 24, Vlaska, 11406 (RS). (74) Agent: DONNELLY, Rex, A. et al; RatnerPrestia, 2200 Renaissance Blvd., Suite 350, King of Prussia, PA 19406 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP,

(54) Title: METHOD FOR PREPARING SILAHYDROCARBONS (57) Abstract: The present disclosure is directed to a process for preparing silahy- drocarbons of formula (I), the process comprising the step of reacting a compound of formula (II), with a compound of formula (III), as well as to silahydrocarbons R2 prepared by such a process, and to compositions and articles of manufacture com prising such silahydrocarbons. -Si- - R3 (I)

R4

R MX (II)

R2

X" Si (Hi)

R4 METHOD FOR PREPARING SILAHYDROCARBONS

RELATED APPLICATIONS

[1] This application claims priority t o U.S. Provisional Patent Application Serial Nos. 62/400,195, filed September 27, 2016, and 62/442,091, filed January 4, 2017, both of which are hereby incorporated by reference herein in their entireties.

GOVERNMENT LICENSE RIGHTS

[2] This invention was made with government support under Grant No. 1254360, awarded by the National Science Foundation (NSF). The government has certain rights in the invention.

FIELD OF THE INVENTION

[3] The present disclosure relates generally to processes for preparing silahydrocarbons. The present disclosure is also directed to silahydrocarbons prepared by such processes, as well as to compositions and articles of manufacture comprising such silahydrocarbons.

BACKGROUND OF THE INVENTION

[4] Silahydrocarbons are broadly useful materials and have a multitude of applications in basic science, medicine, and industry, including in materials, pharmaceuticals, and agrochemicals, as well as organic synthesis. The subtle steric, electronic, and spectroscopic differences between carbon and silicon are ideal for studies in bioisosterism. Small silicon-containing molecules are used as additives in rubber manufacturing (such as automobile tires), and silahydrocarbons are used as cryogenic fluids and as lubricants in aerospace applications due to drastically altered phase properties compared to their carbon analogues. Thus, methods to install a silicon atom with various substitution patterns in a rapid manner can have significant impact across a range of disciplines.

[5] Syntheses of silahydrocarbons have been reported for over a century. Historically, hydrosilylation has been a workhorse reaction for the synthesis of n - alkylsilanes. However, hydrosilylation often encounters issues of isomerization and regioselectivity with 1,2-disubstituted olefins. Arguably, the most attractive method for preparing alkyl silanes is the alkylation of widely available silyl electrophiles with equally abundant organometallic nucleophiles. Unfortunately, these reactions suffer from low yields, long reaction times, and significant side reactions. Alkylations with primary and aryl nucleophiles are known. However, the addition of secondary organometallic reagents to silyl electrophiles is rarely effective. In fact, over the past seventy years only five isolated examples with secondary nucleophiles have been reported in the chemical literature. This is due to lack of reactivity or competitive reductive processes with these more sterically demanding and electron-rich nucleophiles. Prior catalytic methods, which have proven effective with primary and aryl nucleophiles, are ineffective in coupling secondary alkyl groups.

[6] In an effort to circumvent this poor reactivity, developments have been made in the cross-coupling of silyl nucleophiles and carbon electrophiles. While these are highly valuable transformations that allow access to secondary alkyl silanes, they rely on nucleophilic silicon reagents, the umpolung reactivity of naturally electropositive silicon. Since silyl electrophiles are the main feedstock of silicon reagents, developing a general method of alkyl silane synthesis from these abundant and cheap starting materials is highly appealing.

[7] Furthermore, the development of cross-coupling conditions that allow for the use of silyl chlorides would be a significant advance, as silyl chlorides are not only much less air and moisture sensitive, they are much more abundant and functional group tolerant than silyl iodides. Whereas silyl iodides typically require multiple steps to access, chlorosilanes are the product of the Muller-Rochow "Direct" Process, which is widely practiced on commodity scale. Thus, the ability to directly engage monochlorosilanes in cross-coupling is important for the ability to modify feedstock chemicals of critical importance to the silane industry,

[8] Despite this appeal, the high bond strength of the Si-CI bond (113 kcal/mol) has severely hampered the development of transition metal methods involving its activation. Reports of productive chlorosilane activation have been limited to the weaker Si-CI bonds of polychloro- or hydrochlorosilanes. However, those reactions have not been exploited in synthetic applications. In addition, three reports of monochlorosilane activation using iridium (I) complexes have also been described, but the resultant silyliridium chlorides are unstable to /3-hydride elimination.

[9] Finally, several metal-catalyzed arylations of monochlorosilanes have been reported. However, these reactions are believed to proceed via nucleophile activation, and not via activation of the Si-CI bond. Moreover, none of those conditions exhibited any advantage in the case of alkyl Grignard reagents. [10] Thus, there exists a continuing need for improved processes for synthesizing silahydrocarbons, particularly with regard to coupling secondary alkyl groups and the ability to leverage the advantages of silyl chlorides.

EMBODIMENTS OF THE INVENTION

[11] This need is met by the process of the present invention.

[12] Thus, one embodiment of the present invention is a process for preparing a compound of formula (I):

R2

R -Si- R3

R 4 (I)

comprising the step of reacting a compound of formula (II):

R1— MX

wherein M is Zn or Mg; R s an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heterocycloalkyl, heterocycloalkenyl, heterocycloalkynyl, aryl, or heteroaryl group, each of which is optionally substituted with one or more substituents, wherein at least one of the one or more substituents is optionally a moiety of formula -M'X', wherein M' is Zn or Mg and X' is CI, Br, or I ; and X is CI, Br, or I, or, when R1 is an alkyl group, X is optionally an alkyl group identical to that of R1; with a compound of formula (III):

R2

X"- Si- R3

R4 (III)

2 wherein X" is CI, Br, I , -OS(0) 2alkyl, -OS(0) 2perfluoroalkyl, or -OS(0) 2aryl; and R , R3, and R4 are, independently, selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heterocycloalkyl, heterocycloalkenyl, heterocycloalkynyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heterocycloalkyl, heterocycloalkenyl, heterocycloalkynyl, aryl, heteroaryl group is optionally substituted with one or more substituents, CI, Br, I,

-OS(0)2alkyl, -OS(0)2perfluoroalkyl, and -OS(0) 2aryl groups, wherein at least one of the one or more substituents is optionally a moiety of formula -SiR R X"', wherei n R5 and R6 are each, independently, selected from the grou p consisting of alkyl, alkenyl , alkynyl, cycloal kyl, cycloal kenyl, cycloal kynyl, heterocycloalkyl, heterocycloal kenyl, heterocycloalkynyl, aryl, heteroa ryl, each of which is optionally substituted with one or more substituents, and X'" is CI, Br, I , -OS (0 )2al kyl, -OS (0 )2perfluoroa lkyl, or - OS(0 )2a ryl ; and wherei n R2, R3, and/or R4, when taken together, optiona lly defi ne an optional ly substituted ring system ; in the presence of a catalyst com prisi ng a Grou p 8, 9, or 10 transition metal, a ligand, a solvent, and, optiona lly, an add itive; wherei n R2, R3, and/or R4 are optionally covalently linked to R1; and R1, R2, R3, and R4 of the com pou nd of formu la (I) are as defi ned above.

[13] I n certa in embod iments of the above process, R1 is sterically hindered . I n certai n embod iments of the above process, R1 is selected from the grou p consisting of pri mary, secondary and tertia ry alkyl grou ps, primary, secondary and tertiary alkenyl grou ps, and primary, secondary and tertiary alkynyl groups, each of which is optionally substituted . I n certain embod iments of the above process, one or more of R1, R2, R3, and R4 is substituted with a least one silyl grou p.

[14] I n certai n embodiments of the above process, R2 is selected from the grou p consisting of CI, Br, I , -OS (0 )2alkyl grou ps, -OS (0 )2perfluoroalkyl grou ps, and - OS(0 )2a ryl grou ps. I n certain embod iments of the above process, R3 is selected from the grou p consisti ng of CI, Br, I , -OS (0 )2al kyl grou ps, -OS (0 )2perfluoroal kyl grou ps, and -OS (0 )2a ryl grou ps. I n certa in embod iments of the above process, R4 is selected from the grou p consisting of CI, Br, I , -OS (0 )2al kyl groups, -OS (0 )2perfl uoroalkyl grou ps, and -OS (0 )2a ryl grou ps. I n certa in em bod iments, X" and R2 are both C I. I n certain embodiments, X", R2, and R3 are all CI.

[15] I n certai n embodiments of the above process, the Grou p 8, 9, or 10 tra nsition metal is selected from the grou p consisting of Pd, Ni, Co, Rh, and Ir. I n certain embod iments of the above process, the catalyst com prises Pd and is selected from the grou p consisti ng of Pd (OAc)2, Pd Br2, Pdl 2, Pd (dba) 2, Pd (dba) 3, [allylPdCI] 2,

Pd2d ba3»CHCl3, [(3,5 -C H3(t-Bu)2) 3P]2Pdl2, [(3,5 -C6H 3(t-Bu) 2)3P]2PdCl2,

(COD) Pd (CH 2TMS) 2, (COD) PdCI 2, ( PPh3)2PdCI 2, ( PPh 3)4Pd, and (MeCN )2PdCI 2. I n certain embod iments of the above process, the catalyst comprises Ni and is selected from the grou p consisting of Ni halide salts, Ni halide solvent complexes, and Ni(COD)2 .

[16] I n certain embodiments of the above process, the ligand is selected from the grou p consisti ng of phosphi ne ligands, arsi ne ligands, nitrogen-contai ning ligands, and N- heterocyclic carbene ligands. I n certain embodiments of the above process, the ligand is selected from the group consisti ng of PPh3, (3, 5-t-BuC6H3)2P(tBu ), Ph2P(tBu ),

PhP(t-Bu) 2, (3, 5-C6H3( - Bu)2)3P, (4-MeO-C H4)3P, (t- Bu )3P, (t- Bu ) PCy, (t- Bu )PCy2,

Cpy3P, Cy2PMe, Cy2PEt, Cy3P, (o-tol) 3P, (furyl )3P, (4-F-C H )3P, (4-CF 3-C6H 4)3P, BIPH EP, Na pthPhos, XantPhos, dppf, dppe, dppb, dpppe, dcpe, dcpp, dcpb, SPhos, XPhos, DavePhos, John Phos, BrettPhos, QPhos, AmgenPhos, RockPhos, RuPhos, VPhos, tBuXPhos, tBuBrettPhos, TrixiePhos, AZPhos, CPhos, (3, 5- - BuC6H3)2P( iPr), (3, 5- -

BuC6H3)2P( Et), (3, 5-t-BuC 6H3) 2P(Me), (3,5-/-PrC 6 H 3)2P(i:Bu), (3, 5-/-PrC 6 H 3)2P(iPr), (3, 5-

/-PrC 6 H 3)2P( Et), (3, 5-/-PrC 6 H 3)2P(Me), (3, 5- - Bu-4-MeO-C 6H2)2P(tBu ), (3,5-f-Bu-4-MeO-

C6H 2)3 , BINAP, SIPr, IPr, IMes, ISMes, and derivatives thereof.

[17] I n certa in embodiments of the above process, the solvent is selected from the group consisti ng of dioxane, toluene, 1,2-d ich loroethane, acetonitrile, dibutyl ether, diethyl ether, hexane, tetrahyd rofuran, and mixtures thereof.

[18] In certa in embod iments of the above process, additive is present during the reaction and is selected from the group consisting of trial kylami nes and iodide sa lts. I n certai n embodiments, the add itive is triethylami ne or TMEDA. I n certai n embod iments, the additive is Lil, Nal, KI, or ammoniu m iodide salts.

[19] I n certain embod iments of the above process, and X of the compou nd of formu la (II) are Zn and Br or I , respectively, X" of the compou nd of formu la (III) is I, the catalyst is [ (3,5-C6H3(i -Bu)2)3P]2Pdl2, the add itive is triethylamine, and the solvent is dioxane. I n certain embod iments, and X of the compou nd of formu la (II) are Mg and Br or I , respectively, X" of the compou nd of formu la (III) is CI, the catalyst is

[ (3,5-C 6 H 3(t-Bu)2)3P]2Pdl2, and the solvent is Et 20 .

[20] Another embodi ment of the present invention is a compou nd of formu la (I) :

R2

R — Si R3

R4 wherei n R , R2, R3, and R4 are each, independently, an alkyl, alkenyl, alkynyl, cycloal kyl, cycloalkenyl, cycloal kynyl, heterocycloalkyl, heterocycloalkenyl, heterocycloalkynyl, aryl , or heteroaryl group, each of which is optionally substituted with one or more substituents; wherein R2, R3, and/or R , when taken together, optionally define an optionally substituted ring system; and R2, R3, and/or R4 are optionally covalently linked to R1.

[21] In certain embodiments of the above compound, R1 is sterically hindered. I n certain embodiments of the above compound, R1 is selected from the group consisting of secondary and tertiary alkyl groups, secondary and tertiary alkenyl groups, and secondary and tertiary alkynyl groups, each of which is optionally substituted. In certain embodiments of the above compound, one or more of R1, R2, R3, and R4 is substituted with a least one silyl group.

[22] In certain embodiments, the above compound is selected from the group consisting of compounds of formulae (2), (3), (7)-(9), (13), (16)-(23), (25)-(27), and (30)-(47):

(46), and [23] Another embodiment of the present invention is a composition comprising at least one of the above compounds of formula (I). In certain embodiments, the composition is selected from the group consisting of aerospace materials, pharmaceuticals, agrochemicals, rubber materials, lubricants, hydraulic fluids, damping fluids, diffusion pump fluids, cryogenic fluids, waterproofing agents, hydrophobing agents, heat transfer media, anti-stick coatings, and fuel additives.

DETAILED DESCRIPTION OF THE INVENTION

[24] In one aspect of the present invention, the present disclosure provides for a process for preparing a compound of formula (I):

Si- R3

4 R (I).

[25] The process comprises the step of reacting a compound of formula (II):

R1— MX I with a compound of formula (III):

R2

X" - S - R3

R4 (III)

[26] In the compounds of formula (II), M is Zn or Mg and R1 is an alkyl, alkenyl, alkynyl, cycloalkyi, cycloalkenyl, cycloalkynyl, heterocycloalkyi, heterocycloalkenyi, heterocycloalkynyl, aryl, or heteroaryl group, each of which is optionally substituted with one or more substituents. At least one of these one or more substituents may optionally be a moiety of formula -M'X', wherein M' is Zn or Mg and X' is CI, Br, or I . Variable X of the compounds of formula (II) is CI, Br, or I, or, when R1 is an alkyl group, X is optionally an alkyl group identical to that of R1. In certain embodiments, R1 is a sterically hindered group, such as a primary, secondary, or tertiary alkyl, alkenyi, or alkynyl group, each of which is optionally substituted.

[27] I n the compounds of formula (III), X" is CI, Br, I, -OS(0)zalkyl, -OS(0)2perfluoroalkyl, or -OS(0)2aryl. Examples of -OS(0)2alkyl, -OS(0)2perfluoroalkyl, and -OS(0)2aryl groups include, but are not limited to, methanesulfonate, trifluoromethanesulfonate, and toluenesulfonate groups, respectively. R2, R3, and R4 of the compounds of formula (III) are, independently, selected from the group consisting of alkyl, alkenyi, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heterocycloalkyi, heterocycloalkenyl, heterocycloalkynyl, aryl, heteroaryl, wherein each alkyl, alkenyi, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heterocycloalkyi, heterocycloalkenyl, heterocycloalkynyl, aryl, heteroaryl group is optionally substituted with one or more substituents, as well as from CI, Br, I, -OS(0)2alkyl, -OS(0)2perfluoroalkyl, and -OS(0)2aryl groups. In certain embodiments, R2, R3, and/or R4, when taken together, optionally define an optionally substituted ring system. Furthermore, R2, R3, and/or R4 are optionally covalently linked to R of the compound of formula (II).

[28] I n certain embodiments, at least one of the one or more optional substituents on R2, R3, and R4 of the compounds of formula (III) may be a moiety of formula -SiR 5R X"'. R5 and R are each, independently, selected from the group consisting of alkyl, alkenyi, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heterocycloalkyi, heterocycloalkenyl, heterocycloalkynyl, aryl, heteroaryl, each of which, in turn, is optionally substituted with one or more substituents. X'" is CI, Br, I, -OS(0)2alkyl, -OS(0)2perfluoroalkyl, or -OS(0)2aryl.

[29] I n certain embodiments, in addition to X", R2 and/or R3 and/or R4 of the compound of formula (III) is selected from the group consisting of CI, Br, I, -OS(0)2alkyl groups, -OS(0)2perfluoroalkyl groups, and -OS(0)2aryl groups. Examples of such compounds of formula (III) include, but are not limited to, dimethyldichlorosilane ( .e, Me2SiCl2) and trichlorophenylsilane {i.e., PhSiCb). These polychlorosilanes can be monoalkylated with alkyl zinc halides, as shown in the following reaction schemes: (OEt)

51% (NMR) 29% isolated

then EtOH, Et3N

no double alkylation observed

The respective ethoxy-substituted products result from post-reaction workup with ethanol to yield a stable adduct.

[30] The compounds of formula (II) and (III) are reacted in the presence of a catalyst comprising a Group 8, 9, or 10 transition metal, a ligand, a solvent, and, optionally, an additive.

[31] Any suitable catalyst comprising a Group 8, 9, or 10 transition metal (e.g., Fe, Ru, Os, Co, Rh, Ir, Ni, Pd, and Pt) may be used in the processes of the present invention. I n certain embodiments, the catalyst comprises a Group 8, 9, or 10 transition metal selected from the group consisting of Pd, Ni, Co, Rh, and Ir. I n embodiments where the catalyst comprises Pd, examples of such catalysts include, but are not limited to, Pd(OAc) 2, PdBr2, Pdh, Pd(dba) 2, Pd(dba) 3, [allylPdCI] 2,

Pd 2dba 3»CHCI 3, [(3,5-C H3(t-Bu) 2)3P] 2PdI , [(3,5-C 6H3(t-Bu) 2)3P] 2PdCI2,

(COD)Pd(CH 2TMS) 2, (COD)PdCI 2, (PPh3)2PdCI2, (PPh3) Pd, and (MeCN) 2PdCI 2. I n embodiments, where the catalyst comprises Ni, examples of such catalysts include, but are not limited to, Ni halide salts, Ni solvent complexes, and Ni(COD) .

[32] Any suitable ligand may be used in the processes of the present invention. Examples of classes of such ligands include, but are not limited to, phosphine iigands, arsine ligands, nitrogen-containing ligands, and N-heterocyclic carbene (NHC) ligands. An example of an NHC ligand that may be used in the processes of the present invention includes, but is not limited to, a ligand having the following structure: For example, this particular ligand can be used to alkylate Me2PhSiCI with cyclohexylmagnesium bromide, as shown in the following reaction scheme

2 mo %

Me,PhSiCI 78%

Examples of other particular ligands that may be used, include, but are not limited to,

PPh )2P(tBu), Ph )3P, 3, (3,5-t-BuC 6H3 2P(tBu), PhP(f-Bu) 2, (3,5-C 6 H 3(t-Bu) 2 (4-MeO-

C6H )3P, (t-Bu) 3P, (t-Bu) 2PCy, (t-Bu)PCy 2, Cpy3P, Cy2PMe, Cy2PEt, Cy3P, (o-tol) 3P, -C (furyl) 3P, (4-F-C H )3P, (4-CF3 H4 )3P, BIPHEP, NapthPhos, XantPhos, dppf, dppe, dppb, dpppe, dcpe, dcpp, dcpb, SPhos, XPhos, DavePhos, JohnPhos, BrettPhos, QPhos, AmgenPhos, RockPhos, RuPhos, VPhos, tBuXPhos, tBuBrettPhos, TrixiePhos, AZPhos,

CPhos, (3,5-t-BuC H3)2P(iPr), (3,5-t-BuC 6H3)2P(Et), (3,5-t-BuC 6H3)2P(Me), (3,5-/- PrC P(i-Bu), )2P(iPr), )2P(Et), )2P(Me), H3)2 (3,5-/-PrC6H 3 (3,5-/-PrC 6 H 3 (3,5-/-PrC 6 H 3 (3,5-t-

Bu-4-MeO-C H2)2P(ffiu), (3,5-t-Bu-4-MeO-C H2 )3P, BINAP, SIPr, IPr, IMes, ISMes, and derivatives thereof. In certain embodiments, the ligand can be a XantPhos derivative having the following structure:

[33] Any suitable solvent may be used in the processes of the present invention. Examples of such solvents include, but are not limited to, dioxane, toluene, 1,2- dichloroethane, acetonitrile, dibutyl ether, diethyl ether, hexane, tetrahyd rofuran, and mixtu res thereof.

[34] Add itives that facilitate the processes of the present invention may be present during the reaction . Examples of such add itives include, but are not limited to, trialkylamines, such as triethylamine, TMEDA, and iodide salts, such as Lil, Nal, KI, or ammonium iod ide salts.

[35] The processes according the present invention can be performed at any suitable temperatu re. Exam ples of suita ble temperatu res include, but are not limited to, temperatu res in the range of from -78 °C to 100 °C. In certai n embodi ments, the reaction temperatu re is room or ambient temperatu re, i.e., approxi mately 20 to 25 °C. In certain other embodi ments, the reaction temperatu re is 50 °C.

[36] In another aspect of the present invention, the present disclosu re provides for compou nds of formu la (I) :

R2

R Si R3

4 (I) wherein R , R2, R3, and R4 are as defined above. Substituents R2, R3, and/or R4, when taken together, optionally defi ne an optionally substituted ring system and are optionally covalently linked to R . In certain embodiments, R1 is a sterically hindered group, such as an optiona lly substituted seconda ry and tertiary alkyl, alkenyl, or alkynyl group. I n certai n embod iments, one or more of grou ps R1, R2, R3, and R4 is substituted with a least one silyl group.

[37] I n another aspect of the present invention, the present disclosu re provides for com positions and articles comprisi ng at least one compou nd of formu la (I) . Examples of such compositions and articles include, but are not limited to, aerospace materials, pharmaceuticals, agrochemica ls, rubber materia ls, lubricants, hyd raulic fluids, dampi ng fluids, diffusion pump flu ids, cryogenic fluids, waterproofi ng agents, hydrophobi ng agents, heat tra nsfer media, anti-stick coati ngs and fuel additives.

[38] The followi ng examples are included to demonstrate preferred embodiments. It should be appreciated by those of ski ll in the art that the tech niques disclosed in the examples which follow represent techniques discovered by the inventor to function well in the practice of the products, compositions, and methods described herein, and thus can be considered to constitute preferred modes for its practice. However, those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments which are disclosed and still obtain a like or similar result without departing from the spirit and scope of the disclosure.

EXAMPLES

[39] General Experimental Details

[40] Dioxane, trimethylamine, toluene, dibutyl ether ( BU2O), diethyl ether ( Et20), methyl te -buty ether (MTBE), triethylamine, dichloromethane (DCM), acetonitrile (MeCN), and tetrahydrofuran (THF), were dried on alumina according to published

procedures. Cyclopentylmethyl ether (CPME) was dried over CaH2, distilled under N2, and stored in a Straus flask.

[41] The following Grignard reagents were purchased from commercial suppliers and titrated with iodine before use: phenylmagnesium bromide [3M] in Et20 (Aldrich), /70-tolylmagnesium bromide [2M] in Et20 (Aldrich), 2-mesitylmagnesium bromide [1M] in Et20 (Aldrich), cyclopentylmagnesium bromide [2M] in Et 0 (Acros), and 2- methyl-2-phenylpropylmagnesium chloride [0.5M] in Et 20 (Acros).

[42] Instrumentation and Chromatography

[43] 400 MHz 101 MHz 1 C, and 376 MHz 1 F spectra were obtained on a 400 MHz FT-NMR spectrometer equipped with a Bruker CryoPlatform. 600 MHz H, 151 MHz 13 C, 119 MHz 2 Si, and 243 MHz 1P spectra were obtained on a 600 MHz FT-NMR spectrometer equipped with a Bruker SMART probe. All samples were analyzed in the indicated deutero-solvent and were recorded at ambient temperatures. All chemical shifts are reported in ppm. H NMR spectra were calibrated using the residual protio- signal in deutero-solvents as a standard. 1 C NMR spectra were calibrated using the deutero-solvent as a standard. Product 2 Si spectra were calibrated using a hexamethyldisiloxane capillary standard at 7.32ppm. R spectra were recorded on a Nicolet Magma-IR 560 FT-IR spectrometer as thin films on KBr plates. High resolution MS data was obtained on a Waters GCT Premier spectrometer using chemical ionization (CI), electron ionization (EI), or liquid injection field desorption ionization (LIFDI). Vacuum controller refers to J-Kem Digital Vacuum Regulator Model 200. Unless otherwise noted, column chromatography was performed either by hand or by use of Isolera 4 Biotage unit with 40- 63 µ silica gel, and the eluent reported in parentheses. Analytical thin-layer chromatography (TLC) was performed on silica gel

(60 F254 Merck) pre-coated glass plates and visualized by UV or by staining with iodine, KMn04, or eerie ammonium molybdate (CAM).

[44] Synthesis of Liqand "DrewPhos"

[45] An oven-dried 500 m _ round bottom flask equipped with a magnetic stir bar and rubber septum was attached to a double manifold and cooled under vacuum. The flask was backfilled with N2, the rubber septum was removed, l-bromo-3,5-di-te/t- butylbenzene (32.4 g, 120 mmol, 3.01 equiv.) was added, and the septum replaced.

The flask was then purged with N 2 for 15 minutes. THF (240 ml_, [0.5 M]) was added and the flask was cool to -78 °C in a dry ice/acetone bath. While stirring, nBuLi (48.2 mL, 120 mmol, 3 equiv., [2.49 M] in hexanes) was added dropwise via syringe pump over 30 minutes. PCI3 (3.5 mL, 40 mmol, 1 equiv.) was added dropwise via syringe pump over 15 minutes. After the addition was complete, the flask was warmed to 0 °C in an ice/water bath and stirred for 4 hours. The flask was allowed to warm to RT, the septum was removed and the reaction was quenched by adding brine (100 mL). The reaction was poured into a separatory funnel and the product was extracted 2X with

Et20 (100 mL). The organic layer was dried over MgS04, filtered through a glass frit, and the solvent removed in vacuo. The product was purified by recrystallization from hot EtOH (200 mL), cooled under ambient conditions, then placed in a -20 °C freezer overnight. Collection of the solid via filtration and washing with EtOH resulted in white crystals (10.6 g, 44% yield): H NMR (600 MHz, CDCb) δ 7.38 (t, J = 1.8 Hz, 3H), 7.12 (dd, J = 8.5, 1.8 Hz, 6H), 1.22 (s, 54H); 3 C NMR (151 MHz, CDCb) δ 150.6 (d, J = 6.7 Hz), 137.3 (d, J = 9.4 Hz), 128.1 (d, J = 19.3 Hz), 122.4 , 35.0 , 31.5; 1P NMR (243 MHz, CDCb) δ -3.59; FTIR (cm 1) : 2963, 1589, 1577, 1362, 1249, 1130, 875, 710; mp P] + = 145-147 °C; HRMS (LIFDI) m/z, calculated for [C42H 3 : 598.4667; found: 598.4688.

[46] Synthesis of Catalyst (DrewPhos)2Pdl2 [47] A 50 mL round bottom flask equipped with a magnetic stirbar was charged with palladium(II) iodide (1.08 g, 3 mmol, 1.0 equiv.) and DrewPhos (3.59 g, 6 mmol, 2.0 equiv.). The flask was sealed with a rubber septum and purged 10 min with Toluene (24 mL) was added via syringe and the reaction was stirred for 24 hours at 85 °C. The reaction was cooled to RT, transferred to a 250 mL round bottom flask and the solvent evaporated in vacuo. The resulting solid was recrystallized from hot 3 :1 ethanoktoluene (100 mL), cooled under ambient conditions, then placed in a -20

°CVfreezer overnight. Collection of the solid via filtration resulted in a stable, red solid

(3.52 g, 75% yield). A second crop of product was obtained by subsequent recrystallization with same solvent system resulted in red crystals (900 mg, 19%). Total 4.42 g, 95%: H NMR (600 MHz, CDC ) δ 7.60 - 7.54 (m, 12H), 7.29 (s, 6H), 1.21 (s, 108H); 3C NMR (151 MHz, CDCb) δ 149.2 (t, J = 5.1 Hz), 134.5 (t, J = 24.9 Hz), 129.9 (t, J = 6.2 Hz), 123.2, 35.1, 31.6; 3 1P NMR (243 MHz, CDCb) δ 18.90 ; FTIR (cm 1) : 2953, 1589, 1384, 1247, 1087, 702, 584; mp = >250 °C. HRMS (LIFDI) m/z, + calculated for [C 4H P2PdI] :1429.7414; found: 1429.7373.

[48] Synthesis of Alkyl Zinc Halides

[49] General Procedure

[50] An oven dried Schlenk flask equipped with a magnetic stirbar and rubber septum was attached to a double manifold and cooled under vacuum. The flask was

backfilled with N2, the septum removed, and zinc dust (2 equiv.) added. The septum was replaced; the flask was attached t o a double manifold and evacuated. Under vacuum, the zinc was heated for 5 minutes with a heat gun then allowed to cool to RT

under vacuum. The flask was backfilled with N 2 then dioxane [2 M], trimethylsilyl chloride (0.03 equiv), and alkyl bromide ( 1 equiv) were added. The flask was then stirred in an oil bath at 100 °C for the indicated time. Conversion of starting haiide was

monitored via GC by quenching reaction aliquots with saturated NH4C I solution and extracting with Et20 . Once all starting haiide was consumed, the excess zinc was allowed to settle while the flask cooled. The mixture was filtered via cannula to a Schlenk tube. If insoluble particles persist, filtration through a 0.2 µιτι PTFE syringe filter was employed. Solutions were then titrated according to the literature procedure by Knochel.

[51] Synthesis of Cyclohexylzinc Iodide

[52] According to the general procedure, a 25 mL Schlenk flask was charged with zinc dust (3.92 g, 60 mmol), dioxane (15 mL), trimethylsilyl chloride (115 L, 98 mg, 0.9 mmol), and cyclohexyl iodide (3.88 mL, 6.3 g, 30 mmol). The flask was heated t o 100 °C for 12 hours. Filtration and titration resulted in a [0.97 M] solution of cyclohexylzinc iodide in dioxane.

[53] Synthesis of Isopropylzinc Iodide

[54] According to the general procedure, a 25 mL Schlenk flask was charged with zinc dust (3.92 g, 60 mmol), dioxane (15 mL), trimethylsilyl chloride (115 pL, 98 mg, 0.9 mmol), and isopropyl iodide (3.0 mL, 5.1 g, 30 mmol). The flask was heated to 100 °C for 20 hours. Filtration and titration resulted in a [1.56 ] solution of isopropylzinc iodide in dioxane.

[55] Synthesis of Isopropylzinc Bromide

Me nBr

Me

[56] According to the general procedure, a 25 mL Schlenk flask was charged with zinc dust (3.92 g, 60 mmol), dioxane (15 mL), trimethylsilyl chloride (120 pL, 102 mg, 0.9 mmol), and isopropyl bromide (2.9 mL, 3.8 g, 3 1 mmol). The flask was heated t o 100 ° C for 20 hours. Filtration and titration resulted in a [1.81 ] solution of isopropylzinc bromide.

[57] Synthesis of Isobutylzinc Iodide [58] According to the general procedure, a 25 mL Schlenk flask was charged with zinc dust (3.92 g, 60 mmol), dioxane (15 mL), trimethylsilyl chloride (115 pL, 98 mg, 0.9 mmol), and isobutyl iodide (3.6 mL, 5.8 g, 30 mmol). The flask was heated to 100 °C for 17 hours. Filtration and titration resulted in a [1.59 M] solution of isobutylzinc iodide in dioxane.

[59] Synthesis of Isobutylzinc Bromide

Me ^^ZnBr Me'

[60] According to the general procedure, a 25 mL Schlenk flask was charged with zinc dust (3.92 g, 60 mmol), dioxane (15 mL), trimethylsilyl chloride (115 pL, 98 mg, 0.9 mmol), and isobutyl bromide (3.3 mL, 4.2 g, 30 mmol). The flask was heated to 100 °C for 17 hours. Filtration and titration resulted in a [1.40 M] solution of isobutylzinc bromide in dioxane.

[61] Synthesis of n-Propylzinc Iodide

[62] According to the general procedure, a 25 mL Schlenk flask was charged with zinc dust (1.52 g, 23 mmol), dioxane (6 mL), trimethylsilyl chloride (50 L, 45 mg, 0.4 mmol), and n-propyl iodide (1.5 mL, 2.61 g, 15 mmol). The flask was heated to 100 °C for 20 hours. Filtration and titration resulted in a [2.25 ] solution of n-propylzinc iodide in dioxane.

[63] Synthesis of Cyclopentylzinc Bromide

[64] According to the general procedure, a 25 mL Schlenk flask was charged with zinc dust (2.6 g, 40 mmol), dioxane (10 mL), trimethylsilyl chloride (80 pL, 66 mg 0.6 mmol), and cyclopentyl bromide (2.2 mL, 20 mmol). The flask was heated to 100 °C for 18 hours. Filtration and titration resulted in a [0.89 M] solution of cyclopentylzinc bromide.

[65] Synthesis of n-Butylzinc Bromide

[66] According to the general procedure, a 25 mL Schlenk flask was charged with zinc dust (3.92 g, 60 mmol), dioxane (15 mL), trimethylsilyl chloride (115 pL, 98 mg, 0.9 mmol), and n-butyl bromide (3.3 mL, 4.2 g, 30 mmol). The flask was heated to 100 °C for 17 hours. Filtration and titration resulted in a [1.51 ] solution of n- butylzinc bromide in dioxane.

[67] Synthesis of Pentan-3-ylzinc Bromide

[68] According to the general procedure, a 25 mL Schlenk flask was charged with zinc dust (2.6 g, 40 mmol), dioxane (10 mL), trimethylsilyl chloride (80 pL, 66 mg 60 mo ), and 3-bromopentane (2.5 mL,3.0 g, 20 mmol). The flask was heated to 100 °C for 4 hours. Filtration and titration resulted in a [1.35 ] solution of pentan-3-ylzinc bromide.

[69] Synthesis of 1-Octylethylzinc Bromide

[70] According to the general procedure, a 25 mL Schlenk flask was charged with zinc dust (2.1 g, 32 mmol), dioxane (8 mL), trimethylsilyl chloride (60 pL, 52 mg, 0.5 mmol), and 2-bromodecane (3.4 mL, 16 mmol). The flask was heated to 100 °C for 2 hours. Filtration and titration resulted in a [1.00 ] solution of 1-octylethylzinc bromide.

[71] Synthesis of (4-Methylpentan-2-yl)zinc Bromide [72] According to the general procedure, a 25 mL Schlenk flask was charged with zinc dust (1.83 g, 28 mmol), dioxane (7 mL), trimethylsilyl chloride (50 L, 43 mg, 0.4 mmol), and 2-bromo-4-methylpentane (2.29 g, 14 mmol). The flask was heated to 100 °C for 2 hours. Filtration and titration resulted in a [0.91 ] solution of (4- methylpentan-2-yl)ztnc bromide in dioxane.

[73] Synthesis of (lS,4#)-Bicyclo[2.2.1 |heptan-2-ylzinc Bromide

[74] According to the general procedure, a 25 mL Schlenk flask was charged with zinc dust (2.6 g, 40 mmol), dioxane (10 mL), trimethylsilyl chloride (80 pL, 65 mg, 0.6 mmol), and 2-exo-bromonorbornane (2.6 mL, 3.5 g, 20 mmol). The flask was heated to 100 °C for 3 hours. Filtration and titration resulted in a [1.23 M] solution of (1S,4/?)- bicyclo[2.2.1]heptan-2-ylzinc bromide.

[75] Synthesis of a-Methylbenzylzinc Bromide

[76] A 50 mL Schlenk flask equipped with a stirbar and rubber septum attached to a double manifold (with cold trap) was charged with titrated, [0.38 M] a- methylbenzylzinc bromide (Aldrich) in THF (25 mL, 9.5 mmol) and dioxane (8 mL). Solvent was removed in vacuo (26 °C/0.3 mm Hg) until total volume was reduced to approximately 2-3 mL (solution became viscous). Dioxane (12 mL) was added and solvents were removed again in vacuo (26 °C/0.2 mm Hg) until total volume was reduced to approximately 2-3 mL (viscous solution). Dioxane (8 mL) was added to afford a total volume of approximately 10 mL. Filtration via cannula to a Schlenk bomb and titration resulted in a [0.82 ] solution of a-methylbenzylzinc bromide in dioxane. The solvent exchange setup diagram is depicted in Figure 2.

[77] Synthesis of (4-Phenylbutan-2-yl)zinc Bromide [78] According to the general procedu re, a 10 mL Sch lenk flask was charged with

zinc dust (1.3 g, 20 mmol), dioxane (5 mL), tri methylsilyl chloride (40 pL, 33 mg 0.3 mmol), and 2-bromo-4- phenyl butane (2.1 g, 10 mmol) . The flask was heated to 100 °C for 2 hours. Filtration and titration resulted in a [ 1.32 M] solution of (4-phenylbutan- 2-yl )zinc brom ide.

[79] Synthesis of (4-f4- (Ethoxycarbonyl) phenyl )butan-2yl)zinc Bromide

[80] According to the general procedu re, a 10 mL Schlenk flask was cha rged with zinc dust ( 1.3 g, 20 mmol) , dioxane (6 mL) , trimethylsilyl chloride (100 L, 86 mg, 0.8 mmol ), and ethyl 4-( 3- bromobutyl)benzoate (2.85 g, 10 mmol) . The flask was heated to 100 °C for 2 hours. Filtration and titration resulted in a [ 1.09 M] solution of (4- (4- (ethoxycarbonyl )phenyl) butan-2yl)zinc bromide in dioxane.

[81] Synthesis of (4-(4- Methoxyphenyl )buta n-2yl )zinc Bromide

[82] Accord ing to the general procedu re, a 10 mL Sch len k flask was charged with zinc dust (1.3 g, 20 mmol), dioxane (5 mL), tri methylsilyl chloride (40 pL, 33 mg, 0.3 mmol), and l-(3- bromobutyl)-4- methoxybenzene (2.4 g, 10 mmol) . The flask was heated to 100 °C for 2 hou rs. Filtration and titration resu lted in a [ 1.26 M] solution of (4- (4- methoxyphenyl)butan- 2yl)zinc bromide.

[83] Synthesis of (4- (4-Chlorophenyl)butan-2-yl )zi nc Bromide [84] According to the general procedure, a 10 mL Schlenk flask was charged with zinc dust (1.3 g, 20 mmol), dioxane (5 mL), trimethylsilyl chloride (40 L, 33 mg, 0.3 mmol), and l-(3-bromobutyl)-4- chlorobenzene (2.5 g, 10 mmol). The flask was heated to 100 °C for 2 hours. Filtration and titration resulted in a [1.25 M] solution of (4-(4- chlorophenyl)butan-2-yl)zinc bromide.

[85] Synthesis of (4-(4-(Trifluoromethyl)phenyl)butan-2yl)zinc Bromide

[86] According to the general procedure, a 10 mL Schlenk flask was charged with zinc dust (1.3 g, 20 mmol), dioxane (5 mL), trimethylsilyl chloride (40 µ , 33 mg, 0.3 mmol), and l-(3- bromobutyl)-4-(trifluoromethyl)benzene (2.82 g, 10 mmol). The flask was heated to 100 °C for 2 hours. Filtration and titration resulted in a [1.14 ] solution of (4-(4-(trifluoromethyl)phenyl)butan-2yl)zinc bromide in dioxane.

[87] Synthesis of (3-Methylbutan-2-yl)zinc Iodide

[88] According to a modified procedure, a 10 mL Schlenk flask was charged with zinc dust (294 mg, 4.5 mmol), dioxane ( 1 mL), trimethylsilyl chloride (20 µ , 17 mg, 0.1 mmol), and 2-iodo-3-methylbutane (446 mg, 2.3 mmol) was added dissolved in dry dioxane (1.1 mL). The flask was heated to 50 °C for 1 hour. Filtration and titration resulted in a [1.05 ] solution of (3-methylbutan-2-yl)zinc iodide.

[89] Synthesis of (3,3-Dimethylbutan-2-yl)zinc Iodide [90] According to a modified procedure, a 10 mL Schlenk flask was charged with zinc dust (0.8 g, 12 mmol), dioxane (5 mL), trimethylsilyl chloride (50 µ ., 43 mg, 0.4 mmol), and 3-iodo-2,2-dimethylbutane (1.31 g, 6 mmol). The flask was heated to 50 °C for 2 hours. Filtration and titration resulted in a [0.54 M] solution of (3,3- dimethylbutan-2-yl)zinc iodide in dioxane.

[9 1 Synthesis of Alkylmaqnesium Halides

[92] General Procedure

[93] An oven dried round bottom flask equipped with a magnetic stirbar and rubber septum was attached to a double manifold and cooled under vacuum. The flask was

backfilled with N2, the septum removed, magnesium turnings (1.5 equiv.) and a single chip of I (~20-30 mg) were added. The septum was replaced; the flask was attached to a double manifold and purged with N 2 for 10 min. The flask was held under positive

N 2 then Et20 [ 3 ] was added. The solution was stirred until clarity was reached

(disappearance of brown I 2 color). An initial amount of alkyl halide (~200-400 µ Ι ) was added to start the reaction as evidenced by a minor exotherm. If reaction does not initiate, gentle warming (for example with a heating mantle) may be necessary. Once initiated, the alkyl halide was added dropwise so as to keep the mixture warm, but below full reflux. If desired, a reflux condenser may be used as well. After full addition of the alkyl halide, the flask was allowed to stir at RT for an additional 1-4 hours. The excess magnesium was allowed to settle and the mixture was filtered via cannula to a Schlenk tube. If insoluble particles persist, filtration through a 0.2 m PTFE syringe filter was employed. Solutions were then titrated according to the literature procedure by Knochel. Titration concentrations used in the isolation runs in Section 5 may differ from those reported here. The procedures listed below reflect titrations from specific experimental runs.

[94] Synthesis of Isopropylmaqnesium Iodide [95] According to the general procedure, magnesium turnings (1.1 mg, 45 mmol, 1.5 equiv.), diethyl ether (10 mL), 2 chip, and isopropyl iodide (3.0 mL, 5.1 g, 30 mmol, 1 equiv.) were combined under nitrogen and stirred for 2 hours at RT. Filtration and titration resulted in a [1.84 M] solution of isopropylmagnesium iodide.

[96] Synthesis of Isopropylmagnesium Bromide

Me^^MgBr

Me

[97] According to the general procedure, magnesium turnings (1.1 mg, 45 mmol, 1.5 equiv.), diethyl ether (10 mL), chip, and isopropyl bromide (2.8 mL, 3.69 g, 30 mmol, 1 equiv.) were combined under nitrogen and stirred for 2 hours at RT. Filtration and titration resulted in a [2.23 ] solution of isopropylmagnesium bromide.

[98] Synthesis of Isopropylmagnesium Chloride

Me-^MgCI

Me

[99] According to the general procedure, magnesium turnings (1.1 mg, 45 mmol, 1.5 equiv.), diethyl ether (10 mL), no iodine, and isopropyl chloride (2.7 mL, 2.36 g, 30 mmol) were combined under nitrogen and stirred for 4 hours at RT. Filtration and titration resulted in a [2.65 M] solution of isopropylmagnesium chloride.

[100] Synthesis of n-Butylmagnesium Bromide

[101] According to the general procedure, magnesium turnings (730 mg, 30 mmol), diethyl ether (7 mL), no iodine, and a solution of n-butyl bromide (2.7 mL, 3.4 g, 25 mmol) in diethyl ether (5 mL) were combined under nitrogen and stirred for 4 hours at RT. Filtration and titration resulted in a [1.93 ] solution of n-butylmagnesium bromide.

[102] Synthesis of 3-Pentyl magnesium Bromide

MgBr [103] According to the general procedure, magnesium turnings (300 mg, 12 mmol), diethyl ether (3 mL), I 2 chip, and solution of 3-bromopentane (1.2 mL, 1.5 g, 10 mmol) in diethyl ether (2 mL) were combined under nitrogen and stirred for 4 hours at RT. Filtration and titration resulted in a [0.67 M] solution of 3- pentylmagnesium bromide.

[104] Synthesis of (15,4fl)-Bicyclo[2.2.1]heptan-2-ylmagnesium Bromide

J According to the general procedure, magnesium turnings (730 mg, 30 mmol,

1.5 equiv.), diethyl ether (6.7 mL), I 2 chip, and (lS,4/?)-2-bromobicyclo[2.2.1]heptane (2.6 mL, 3.5 g, 20 mmol, 1 equiv.) were combined under nitrogen and stirred 3 hour at RT. Filtration and titration resulted in a [1.21 M] solution of (lS,4fl)- bicyclo[2.2.1]heptan-2-ylmagnesium bromide in an exo:endo ratio of 41:59, as determined by NMR.

[106] Synthesis of Neopentylmaqnesium Bromide

[107] According to the general procedure, magnesium turnings (730 mg, 30 mmol), diethyl ether (7 mL), I 2 chip, and solution of neopentyl bromide (3 mL, 3.6 g, 24 mmol) in diethyl ether (5 mL). Filtration and titration resulted in a [0.95 ] solution of neopentylmagnesium bromide.

[108] Synthesis of (4-Phenylbutan-2-yl)maqnesium Bromide

[109] According to the general procedure, magnesium turnings (1.1 g, 45 mmol, 1.5 equiv.), I 2 chip, Et20 (10 mL), and (3-bromobutyl)benzene (6.4 g, 30 mmol, 1 equiv.) were combined under nitrogen and stirred for 1 hour at RT. Filtration and iodometric titration resulted in a [1.34 M] solution of (4- phenylbutan-2-yl)magnesium bromide. [110] Synthesis of (4-(4-Chlorophenyl)butan-2- yQmagnesium Bromide (GR9)

[111] According to the general procedure, magnesium turnings (292 mg, 12 mmol, 1.2 equiv.), chip, Et20 (3.3 mL), and l-(3-bromobutyl)-4-chlorobenzene (2.48 g, 10 mmol, 1 equiv.) were combined under nitrogen and stirred for 2 hours at RT. Filtration and iodometric titration resulted in a [0.85 M] solution of (4-(4-chlorophenyl)butan-2- yl)magnesium bromide.

[112] Synthesis of (4-(4-Methoxyphenyl)butan-2-yl)magnesium Bromide

[113] According to the general procedure, magnesium turnings (292 mg, 12 mmol, 1.2 equiv.), chip, Et20 (3.3 mL), and l-(3- bromobutyl)-4-methoxybenzene (2.43 g, 10 mmol, 1 equiv.) were combined under nitrogen and stirred for 2 hours at RT. Filtration and iodometric titration resulted in a [0.85 ] solution of (4-(4- methoxyphenyl)butan-2-yl)magnesium bromide.

[114] Synthesis of (l-Phenylethyl)maqnesium Bromide)

[115] According to a modified version of the general procedure, magnesium turnings (1.1 g, 45 mmol, 1.5 equiv.), diethyl ether (10 mL), and chip were added. Once clarity of the solution was reached, the flask was cooled to 0 °C in an ice/water bath. Stirring at 0 °C, (l-bromoethyl)benzene (5.6 g, 4.1 mL, 30 mmol, 1 equiv.) was added dropwise via syringe pump over ~ 1 hour. After addition, the flask was allowed to stir at RT ~ 3 h. Filtration and titration resulted in a [0.55 ] solution of (1- phenylethyl)magnesium bromide. [116] Synthesis of Silahydrocarbons

[117] General Procedure A

[118] Reactions were run at [0.5 M] overall concentration based on the sum of all liquid reagents. THF quenches were performed for certain substrates due to inseparable disiloxane formed upon aqueous workup. This quench generates the more easily separated (4-iodobutoxy)silane through silyl iodide induced ring opening of THF.

[119] An oven dried 10 m L Schienk flask equipped with a magnetic stirbar and rubber septum was attached to a double manifold and cooled under vacuum. The flask was backfilled with the rubber septum was removed, and (DrewPhos)2Pdl2 (0.01 equiv.) was added. The septum was replaced and the flask purged with 2 for 10 minutes. Dioxane, triethylamine ( 1 equiv.), silyl iodide (2 equiv.), and alkylzinc bromide ( 1 equiv.) were added via syringe. The flask was then stirred at RT for the indicated time. The reaction was quenched as indicated, diluted with Et20 (20 mL) or EtOAc (20 mL) then washed 2 times with brine (20 mL). The organic layer was dried over gSC , filtered, and the solvent removed in vacuo. The crude material was purified via silica gel flash chromatography in the indicated solvent.

[120] General Procedure B: Room Temperature Coupling

[121] An oven dried 10 m L Schienk flask equipped with a magnetic stirbar and rubber septum was attached to a double manifold and cooled under vacuum. The flask was backfilled with N2, the rubber septum was removed, and (DrewPhos)2Pdb (0.01 equiv.) was added. The septum was replaced and the flask purged with N 2 for 10 minutes. Et20, silyl chloride (1.2 equiv.), and alkylmagnesium halide ( 1 equiv.) were added sequentially via syringe. The solution was then stirred at RT for 24 h. A vent needle was added and the reaction was quenched with EtOAc (3 mL) then H2O (3 mL) via syringe. The mixture was washed 2 times with brine (20 mL) and extracted using

EtOAc or Et20. The combined organic layer was dried over g S C 4, filtered, and the solvent removed in vacuo. The crude material was purified via silica gel flash chromatography in the indicated solvent.

[122] General Procedure C: 50 °C Coupling

[123] An oven dried 10 m L Schienk flask equipped with a magnetic stirbar and rubber septum was attached to a double manifold and cooled under vacuum. The flask was backfilled with N2, the rubber septum was removed, and (DrewPhos)2Pdl2 (0.01 equiv.) was added. The septum was replaced and the flask purged with N 2 for 10 minutes. BU2O, silyl chloride (2 equiv.), and alkylmagnesium halide ( 1 equiv.) were added sequentially via syringe. The solution was then stirred in an oil bathour at 50 °C for 24 h . The flask was cooled to RT, a vent needle was added and the reaction was quenched with EtOAc (3 mL) then H2O (3 mL) via syringe. The mixture was washed 2 times with brine (20 mL) and extracted using EtOAc or Et20. The combined organic layer was dried over MgS0 , filtered, and the solvent removed in vacuo. The crude material was purified via silica gel flash chromatography in the indicated solvent.

[124] General Procedure D: Coupling Using Solid Silyl Chlorides

[125] An oven dried 10 m L Schlenk flask equipped with a magnetic stirbar and rubber septum was attached to a double manifold and cooled under vacuum. The flask was backfilled with N2, the rubber septum was removed, (DrewPhos)2Pdl2 (0.01 equiv.) and silyl chloride (2 equiv.) were added. The septum was replaced and the flask purged with N 2 for 10 minutes. BU2O and alkylmagnesium halide ( 1 equiv.) were added sequentially via syringe. The solution was then stirred in an oil bathour at the indicated temperature for 24 h . The flask was cooled to RT, a vent needle was added and the reaction was quenched with EtOAc (3 mL) then H2O (3 mL) via syringe. The mixture was washed 2 times with brine (20 mL) and extracted using EtOAc or Et.20. The combined organic layer was dried over MgS0 4, filtered, and the solvent removed in vacuo. The crude material was purified via silica gel flash chromatography in the indicated solvent.

[126] Example 1 - Synthesis of Compound (1)

[127] According to general procedure A, (DrewPhos)2Pdl2 (16 mg, 10 pmol), dioxane (820 L), triethylamine (140 pL, 1 mmol), dimethylphenylsilyl iodide (360 pL, 2 mmol), and [1.56 ] isopropylzinc iodide (640 pL, 1 mmol) were combined under l and stirred at RT for 1 h . The reaction was quenched with wet EtOAc (0.5 mL) and brine (3 mL) via syringe then worked up according t o general procedure B and purified via silica gel flash chromatography (hexanes) to afford compound (1) as a clear volatile oil (165.1 mg, 93%): H NMR (400 MHz, CDCb) δ 7.59 - 7.45 (m, 2H), 7.44 - 7.31 (m, 3H), 1.02 - 0 .92 (m, 7H), 0 .25 (s, 6H) ; 1 C NMR (101 MHz, CDC ) δ 138 .7, 134. 1, 128.9, 127.7, 17. 7, 13.9, -5.2; 2 Si NMR ( 119 MHz, CDCb) δ -0.40 ; FTIR (cm 1) : 2955, 2864, 1463, 1427, 1248, 1112, 882, 831, 812, 770, 733, 699 . HRMS (CI) m/z, + calcu lated for [C Hi8S i] : 178 .1178; found : 178. 1179 .

[128] According to general proced ure A, (DrewPhos)2Pdl2 (16 mg, 10 pmol ), dioxane

(940 pL), triethyla mine (140 pL, 1 mmol) , dimethyl phenylsi lyl iodide (360 L, 2 mmol ), and [ 1.79 M] isopropylzi nc brom ide (560 l_, 1 mmol) were combi ned under N 2 and stirred at RT for 4 h. The reaction was quenched with wet EtOAc (0. 5 mL) and bri ne (3 mL) via syringe then worked up accord ing to genera l procedu re B and purified via silica gel flash chromatog raphy (hexanes) to afford com pou nd (1) as a clear volatile oil (160. 5 mg, 90%) . NMR spectra matched previous isolation : H NMR (400 MHz, CDCb) δ 7.57 - 7.45 (m, 2H) , 7.40 - 7 .32 (m, 3H), 1.07 - 0.86 (m, 7H), 0 .25 (s, 6 H); 1 C NMR (10 1 MHz, CDCb) δ 138 .7, 134. 1, 128.9, 127.7, 17.7, 13.9, -5.2.

[129] A two dram via l with stirbar (open t o air) was charged with (DrewPhos)2Pdl2 ( 16 mg, 10 pmol), dioxane (910 pL), triethylami ne ( 140 pL, 1 mmol) and dimethyl phenylsilyl iodide (360 pL, 2 mmol ) . The vial was sealed with a Teflon lined cap. Whi le sti rri ng, the cap was removed, [ 1.70 M] solution isopropylzinc iod ide (590 pL, 1 mmol) was added via syringe, and the cap was replaced . Sti rring at RT was conti nued for 1 h. The reaction was quenched by removing the cap and add ing wet EtOAc (0.5 mL) and bri ne (3 mL) via syringe and then worked up according to general procedu re B and purified via silica gel flash chromatog raphy (hexanes) to afford com pound (1) as a clea r volatile oil (156 .1 mg, 88%) . NMR spectra matched previous isolations : H NMR (400 MHz, CDCb) δ 7 .52-7 .49 (m, 2H), 7.36-7 .35 (m, 3H), 0.99- 0.94 (m, 7H), 0.25 (s, 6 H); 3C NMR (10 1 MHz, CDCb) δ 138. 6, 133.9, 128. 7, 127. 6, 17 .6, 13.8, -5.3.

[130] According t o general procedure A, (DrewPhos)2Pdl2 (390 mg, 0.25 mmol), dioxa ne (21 mL), triethylami ne (3.5 mL, 25 mmol), dimethyl phenylsilyl iodide (9 mL, 50 mmol ), and [ 1.52 M] isopropylzi nc bromide ( 16 .5 mL, 25 mmol ) were com bined under N 2 and sti rred at RT for 4 h. The reaction was quenched with THF (10 mL) , sti rred for 15 in then worked up according to general procedu re B and purified via silica gel flash chromatog raphy (hexanes) t o afford compou nd (1) as a clear volatile oil

(4. 35 g, 98%) . NMR spectra matched previous isolation : H NMR (400 MHz, CDCb) δ 7.53 - 7.49 (m, 2H), 7.37 - 7.33 (m, 3H), 0 .97 - 0.94 (m, 7H), 0 .25 (s, 6 H); C NMR (10 1 MHz, CDCb) δ 138.8, 134. 1, 128. 9, 127.7, 17 .7, 13.9, -5.2. [13 1] Accord ing t o general procedu re B, ( DrewPhos)2Pdl2 ( 16 mg, 10 pmol ), Et20

( 1.36 mL), d imethylphenylsilyl chloride (200 µ Ι , 1.2 m mol ), and [2. 29 M] isopropylmag nesiu m bromide (440 pL, 1.0 mmol ) were combi ned under H and sti rred at RT for 1 h. After worku p, the crude product was purified via silica gel flash chromatogra phy (hexanes) t o afford com pou nd ( 1) as a clear oil ( 178 mg , 99%) : H NMR (600 MHz, CDCb) δ 7 .55 - 7 .50 (m, 2H), 7 .39 - 7 .33 ( m , 3H), 1.0 1 - 0 .94 (m, 7H), 0 .26 (s, 6H) . 13 C NMR ( 15 1 MHz, CDCb) δ 138. 8, 134. 1, 128.9, 127 .8, 17. 7, 13.9, - 5 .2 . 2 Si NMR ( 119 MHz, CDCb) δ 0 .4 .

[132] Example 2 - Synthesis of Compou nd ( 2 )

(2)

[133] Accord ing t o genera l procedu re A, ( DrewPhos )2Pd ( 16 mg, 10 pmol), dioxane ( 1.00 mL) , triethylamine ( 140 L, 1 mmol ), d imethylphenylsilyl iod ide (360 pL, 2 mmol), and [2. 25 M] n-propylzinc iodide (440 pL, 1 mmol) were combined u nder 2 and stirred at RT for 1 h . The reaction was q uenched with wet EtOAc (0. 5 mL) and bri ne ( 3 mL) via syri nge then worked up accord ing t o genera l procedure B and purified via silica gel flash chromatogra phy (hexa nes) t o afford com pou nd (2) as a clear very volatile oil ( 169. 5 mg, 96%) : H NMR (400 MHz, CDCb) δ 7 .56 - 7 .49 ( m , 2H), 7 .39 - 7.3 1 ( m , 3H), 1.42 - 1.3 1 (m, 2H), 0 .96 (t, J 7 .2 Hz, 3H), 0 .79 - 0 .72 ( m , 2H) , 0 .26 (s, 6 H) ; 1 C NMR ( 10 1 MHz, CDCb) δ 139 .9, 133 .7, 128. 9, 127 .8, 18. 5 1, 18 .48, 17 .6, - 2.8 ; 2 Si NMR ( 119 MHz, CDCb) δ - 3 .37 ; FTIR (cm 1) : 2955, 2868, 1427, 1248, 1114,

+ 1065, 997, 882, 834, 767, 727, 699. HRMS (CI) m/z, ca lcu lated for [CioH i 5Si] : 163 .0943 ; fou nd : 163 .0941 .

[134] Example 3 - Synthesis of Compou nd (3)

[135] Accord ing t o general procedure A, ( DrewPhos )2Pdl2 ( 16 mg, 10 pmol ) , dioxane (900 pL) , triethylamine ( 140 pL, 1 mmol), dimethylphenylsilyl iodide (360 pL, 2 mmol), and [ 1.59 M] isobutylzinc iod ide (640 pL, 1 m mol) were com bined under N and sti rred at RT for 1 h. The reaction was quenched with wet EtOAc (0. 5 m L) and bri ne (3 mL) via syringe then worked up according t o general procedure B and purified via silica gel flash chromatog raphy (hexa nes) to afford compou nd (3) as a clear volatile oil ( 187 .0 mg, 95%) . NMR spectra matched previous isolation : H N R (400 MHz, CDCh) δ 7.58 - 7.44 ( , 2H), 7.43 - 7 .31 (m, 3H) , 1.77 (dh, J = 13.3, 6.6 Hz, 1H), 0 .90 (d, J = 6.6

Hz, 6H), 0.77 (d, J = 6.9 Hz, 2 H), 0.29 (s, 6H) ; 13C NMR ( 10 1 MHz, CDCh) δ 140.4, 133.7, 128.8, 127.8, 26.50, 26.48, 25. 1, - 1.9.

[136] Accord ing t o general procedu re A, (DrewPhos)2Pdl2 (16 mg, 10 mo ), dioxane

(800 µ Ι_) , triethylami ne (140 µ Ι , 1 mmol ), dimethylphenylsilyl iodide (360 µΙ , 2 mmol ), and [ 1.34 M] isobutylzinc bromide (750 µΙ , 1 mmol ) were combi ned under l and sti rred at RT for 4 h. The reaction was quenched with wet EtOAc (0.5 mL) and bri ne (3 mL) via syri nge then worked up accord ing to general proced ure B and purified via silica gel flash chromatog raphy (hexanes) t o afford compou nd 3 as a clear volati le oil ( 183 .3 mg, 95%) : H NMR (400 MHz, CDCh) δ 7.55 - 7.50 (m, 2 H), 7 .38 - 7.32 (m, 3H), 1.77

(dh, J = 13.3, 6.7 Hz, 1H), 0 .91 (d, J = 6.6 Hz, 6H), 0.78 (d, J = 6.9 Hz, 2H), 0.29 (s, 6H); 13 C NMR ( 101 MHz, CDCh) δ 140 .3, 133.7, 128.8, 127.8, 26. 50, 26.48, 25.1, - 1.9 ; 2 Si NMR ( 119 MHz, CDCh) δ -4. 17; FTIR (cm 1) 2953, 2893, 236 1, 2338, 1248, + 1112, 838, 812, 790, 698 . HRMS (CI) m/z, calcu lated for [Ci Hi9S i] : 19 1.1256; fou nd : 19 1.1253 .

[137] Example 4 - Synthesis of Com pound (4)

[138] Accordi ng to general procedure A, (DrewPhos)2Pdl2 (16 mg, 10 mol), dioxane

(440 \ ) , triethylami ne ( 140 µ , 1 mmol), dimethylphenylsi lyl iodide (360 L, 2 mmol), and [0. 97 M] cyclohexylzinc iodide ( 1.00 mL, 0 .97 mmol) were combined under N 2 and sti rred at RT for 1 h The reaction was quenched with wet EtOAc (0. 5 mL) and bri ne (3 mL) via syri nge then worked up accordi ng t o general proced ure B and purified via silica gel flash chromatog raphy (hexanes) to afford compound (4) as a clear oil (205 .6 mg, 97%) : H NMR (400 MHz, CDCh) δ 7.52 - 7.47 (m, 2H), 7.40 - 7.32 (m, 3 H), 1.75 - 1.61 (m, 5H), 1.27 - 1.02 (m, 5H), 0 .84 - 0 .73 (m, 1H), 0.24 (s, 6H) ; 13 C NMR ( 101 MHz, CDCh) δ 138.8, 134. 1, 128.8, 127. 7, 28. 2, 27.5, 27.0, 25.9, -5. 1; 2 Si NMR ( 119 MHz, CDCh) δ -2. 20; FTIR (cm 1) : 2919, 2846, 1446, 1427, 1247, 1112, 850, 834, + 818, 770, 699. HRMS (CI) m/z, calcu lated for [Ci4H22Si ] : 218. 149 1; fou nd : 218. 1486 .

[139] Exam ple 5 - Synthesis of Compou nd (5) Me SiMe2Ph (5)

According to general procedure A, (DrewPhos)2Pdl2 (16 mg, 10 pmol), dioxane (900 pL), triethylamine (140 pL, 1 mmol), dimethylphenylsilyl iodide (360 pL, 2 mmol), and [1.60 ] ri-butylzinc bromide (630 pL, 1 mmol) were combined under 2 and stirred at T for 4 h. The reaction was quenched with wet EtOAc (0.5 mL) and brine (3 mL) via syringe then worked up according to general procedure B and purified via silica gel flash chromatography (hexanes) to afford compound (5) as a clear oil (175.1 mg, 91%): H NMR (400 MHz, CDC ) δ 7.55 - 7.49 (m, 2H), 7.39 - 7.33 (m, 3H), 1.37 - 1.26 (m, 4H), 0.87 (t, J 6.9 Hz, 3H), 0.80 - 0.73 (m, 2H), 0.26 (s, 6H); 13C NMR (101 MHz, CDCb) δ 139.9, 133.7, 128.9, 127.8, 26.7, 26.2, 15.6, 13.9, -2.9; 2 Si NMR (119 MHz, CDCb) δ -3.08; FTIR (cm 1) : 2956, 2922, 2872, 1427, 1248, 1113, 887, 837, 779, 727, 699. HRMS (CI) m/z, calculated for [C H Si] + : 177.1100; found: 177.1102.

According to general procedure B, (DrewPhos)2Pdl2 (16 mg, 10 mo ), Et20 (1.32 mL), dimethylphenylsilyl chloride (200 pL, 1.2 mmol), and [2.1 M] n - butylmagnesium bromide (480 pL, 1.0 mmol) were combined under N 2 and stirred at RT for 1 h . After workup, the crude product was purified via silica gel flash chromatography (hexanes) to afford compound (3) as a clear oil (192 mg, 99%): H NMR (600 MHz, CDCb) δ 7.55 - 7.48 (m, 2H), 7.39 - 7.32 (m, 3H), 1.37 - 1.26 (m, 4H), 0.87 (t, J = 6.9 Hz, 3H), 0.78 - 0.73 (m, 2H), 0.26 (s, 6H). 1 C NMR (151 MHz, CDCb) δ 139.9, 133.7, 128.9, 127.8, 26.7, 26.2, 15.6, 13.9, -2.9. 2 Si NMR (119 MHz, CDCb) δ -3.1.

[142] Example 6 - Synthesis of Compound (6)

[143] According to general procedure A, (DrewPhos)2Pdb 16 mg, 10 pmol), dioxane (380 pL), triethylamine (140 L, 1 mmol), dimethylphenylsilyl iodide (360 pL, 2 mmol), and [0.89 M] cyclopentylzinc bromide (1.1 mL, 1 mmol) were combined under N 2 and stirred at RT for 4 h . The reaction was quenched with wet Et20 (3 mL) and H2O (3 mL) via syringe then worked up according to general procedure B and purified via silica gel flash chromatography (hexanes) to afford compound (6) as a clear oil (197 mg, 97%): H NMR (600 MHz, CDC ) δ 7 .55 - 7.50 ( , 2H), 7.36 - 7.33 (m, 3H), 1.80 - 1.73 (m, 2H), 1.59 - 1.46 ( , 4H), 1.36 - 1.25 (m, 2H), 1.11 (tt, J = 8.4 Hz, 1H), 0 .25 (s, 6H); 1 C NMR (151 MHz, CDCb) δ 139.4, 133 .9, 128. 7, 127.6, 28.2, 27.0, 25.5, -4. 5; 2 Si NMR ( 119 MHz, CDCb) δ -2.01 ; FTIR (cm 1) : 3068, 2950, 2862, 1427, 1248, 1114, + 827, 8 11, 699, 4 15. HRMS (CI) m/z, calcu lated for [Ci 3H2oSi] : 204. 1334; found : 204. 1337 .

[ 144] Accord ing to general procedure B, (DrewPhos)2Pdl2 ( 16 mg, 10 mol), diethyl

ether ( 1.24 m L), dimethyl phenylsilyl chloride (200 µΙ_, 1.2 mmol ), and [ 1.77 M]

cyclopentyl magnesiu m bromide (0. 56 mL, 1.0 mmol ) were combined under N2 and sti rred at RT for 24 h. After worku p, crude prod uct was purified via silica gel flash chromatog raphy (hexanes) to afford compound (6) as a clear oil (200 mg, 99%) : NMR (600 MHz, CDCb) δ 7.56 - 7.52 (m, 2H), 7.40 - 7.32 (m, 3H), 1.83 - 1.72 (m, 2H), 1.58 - 1.49 ( , 4H), 1.39 - 1.27 (m, 2H), 1.13 (tt, J = 10.8, 8.2 Hz, 1H), 0 .26 (s, 6H) . 13C NMR (151 MHz, CDCb) δ 139.5, 134. 0, 128 .8, 127. 8, 28.4, 27.2, 25.6, - 4 .3. 2 Si NMR ( 119 MHz, CDCb) δ -2. 0.

[ 145] Exam ple 7 - Synthesis of Com pound (7)

(7)

µιτιοΙ [ 146] Accord ing to general procedure A, (DrewPhos)2PdI2 (16 mg, 10 ), dioxane (760 µ ), triethylami ne (140 µ , 1 mmol ), dimethyl phenylsilyl iodide (360 µ , 2 mmol),

and [ 1.35 M] pentan-3-ylzi nc bromide (740 µ Ι_, 1 mmol) were combined under 2 and

sti rred at RT for 4 h. The reaction was quenched with wet Et2 (3 mL) and H2O (3 mL) via syri nge and worked up accord ing to general proced ure B and purified via silica gel flash chromatography (hexanes) to afford com pou nd 7 as a clear oil ( 192 mg, 93%) : NMR (600 MHz, CDCb) δ 7.53 - 7.49 (m, 2 H), 7.36 - 7.32 (m, 3H), 1.57 - 1.47 (m, 2H), 1.36 (dp, J = 14 .7, 7.4 Hz, 2 H), 0 .87 (t, J = 7.4 Hz, 6 H), 0 .74 - 0.68 (m, 1H), 0 .28 (s, 6H) ; 13C NMR ( 151 MHz, CDCb) δ 139. 7, 133.8, 128.6, 127 .6, 28.9, 21.7, 13.7, -3.6; 2 Si NMR (119 MHz, CDCb) δ - 1.04; FTIR θ , 2959, 287 1, 1427, 0, RMS calcu + 149 1248, 1029, 831, 81 700, 47 1. H (CI) m/z, lated for [Ci 3H 2Si] : 206. 1; fou nd : 206 .1495.

[ 147] Example 8 - Synthesis of Compound (8) Bu SiMe2Ph

Me

[148] Accord ing t o genera l procedure A, ( DrewPhos )2Pdl2 ( 16 mg, 10 µιηοΙ ), dioxane (500 pL), triethylami ne ( 140 L, 1 m mol ), dimethylphenylsilyl iodide ( 360 pL, 2 mmol), and [ 1.00 M] 1-octylethylzinc bromide ( 1 mL, 1 mmol ) were combi ned under l and sti rred at RT for 4 h. The reaction was quenched with dry THF (405 pL, 5 eq uiv, 5 mmol ) via syringe and allowed to stir 15 minutes at RT then worked up according to general procedu re B and purified via sil ica gel flash chromatog raphy ( hexanes) t o afford compound (8) as a clear oil (26 1 mg , 94%) : H NMR (600 MHz, CDCb) δ 7 .5 1 - 7 .48 ( m , 2H) , 7 .36 - 7 .3 1 (m, 3H) , 1.49 - 1.36 ( m , 2H), 1.33 - 1.20 ( m , 9 H), 1.19 -

1.13 (m, 2H), 1.13 - 1.06 ( m , 1H), 0.92 (d, J 7 .2 Hz, 3H), 0 .88 (t, J = 7 .1 Hz, 3H), 0.86 - 0.80 ( , 1H) , 0 .24 (d, J = 2 .6 Hz, 6 H) ; 3 C NMR ( 15 1 MHz, CDCb) δ 139. 1, 134. 1, 128.8, 127. 7, 32 .1, 3 1.7, 29 .8, 29 .7, 29 .5, 28 .7, 22. 8, 19. 2, 14. 3, 14. 2, -4. 7 ; 2 Si NMR ( 119 MHz, CDCb) δ -0. 17 ; FTIR (cm 1) : 3069, 2955, 2924, 2853, 1466, 1427,

+ 1248, 1112, 832, 8 13, 770, 733, 700 . HRMS (CI) m/z, calculated for [Ci H3iSi] : 275 .2 19 5 ; fou nd : 275 .2206.

[149] Example 9 - Synthesis of Compou nd (9)

[150] According t o general proced ure A, (DrewPhos )2Pdl2 ( 16 mg, 10 m ol), dioxa ne (400 pL) , triethylamine ( 140 pL, 1 mmol), dimethylphenylsilyl iodide (360 pL, 2 mmol), and [0.9 1 M] (4-methyl pentan-2-yl )zinc bromide in d ioxa ne ( 1.10 mL, 1 mmol) were combi ned under 2 and sti rred at RT for 15 h. The reaction was quenched with wet EtOAc (0. 5 mL) and bri ne ( 3 mL) via syri nge and worked up accordi ng to general procedure B and purified via silica gel flash chromatog raphy ( hexanes) t o afford compou nd (9) as a clea r volatile oil ( 170 .1 mg, 77% ) : H NMR (600 MHz, CDCb) δ 7 .52 - 7 .49 ( m , 2 H), 7 .37 - 7 .33 ( m , 3H), 1.67 (ttd, J = 13 .2, 6 .6, 4.4 Hz, 1H), 1.16 (ddd, J

= 13 .4, 9 .7, 3 .6 Hz, 1H), 1.09 (ddd, J = 13 .5, 10.8, 4.4 Hz, 1H), 1.00 - 0 .94 (m, 1H),

0.90 (d, J = 7 .0 Hz, 3 H), 0.86 (d, J = 6 .6 Hz, 3H), 0 .79 (d, J = 6 .5 Hz, 3H), 0 .25 (s, 3H), 0 .24 (s, 3H) ; 1 C NMR ( 15 1 MHz, CDCb) δ 138 .9, 134. 1, 128.8, 127. 7, 40.9, 25. 5, 24. 1, 2 1.1, 16. 5, 14.0, -4. 8, -4.9; 2 Si NMR ( 119 MHz, CDCb) δ 0 .16; FTIR (cm 1) : 2954, 2900, 2867, 1248, 1112, 830, 767, 733, 699 . HRMS (CI) m/z, calculated for + [Ci 3H2iSi] : 205.1413; found: 205.1419.

[151] Example 10 - Synthesis of Compounds (10-exo) and (10-endo)

(10-exo) 1 o-en o)

[152] According to general procedure A, (DrewPhos)2Pdl2 (16 mg, 10 mo ), dioxane (690 µ Ι_), triethylamine (140 L, 1 mmol), dimethylphenylsilyl iodide (360 L, 2 mmol), and [1.23 ] (lS,4#)-bicyclo[2.2.1]heptan-2ylzinc bromide (810 pL, 1 mmol) were combined under l and stirred at RT for 4 h . The reaction was quenched with wet Et.20

(3 mL) and H2O (3 mL) via syringe and worked up according to general procedure B and purified via silica gel flash chromatography (hexanes) to afford compounds (10- exo) and (10-endo) as an inseparable mixture of exo:endo (80:20) diastereomers as a clear oil (230 mg, 99%). Useful diagnostic peaks for each compound are listed: (10- exo): H M R (600 MHz, CDCI3) δ 2.21 (dd, J = 3.7, 2.0 Hz, 2H), 1.06 - 1.05 (m, 2H), 0.84 - 0.78 (m, 1H), 0.24 (s, 3H), 0.22 (s, 3H); 13 C NMR (151 MHz, CDC ) δ 139.6, 134.1, 128.8, 127.8, 38.1, 37.9, 37.1, 34.5, 32.9, 29.1, 28.8, - 3.9, -3.9; 2 Si NMR (119 MHz, CDCb) δ -3.23. (10-endo): H NMR (600 MHz, CDCI3) δ 2.33 - 2.25 (m, 2H), 1.78 - 1.69 (m, 1H), 1.03 - 0.98 (m, 1H), 0.31 (s, 3H), 0.29 (s, 3H); 13C NMR (151 MHz, CDCb) δ 140.4, 133.9, 128.7, 127.8, 41.9, 39.8, 37.3, 32.0, 30.0, 28.6, 27.6, - 2.7, -2.9; Si NMR (119 MHz, CDCb) δ -2.81.

[153] According to general procedure B, (DrewPhos)2Pdl2 16 mg, 10 mo ), Et 0 (970 pL), dimethylphenylsilyl chloride (200 pL, 1.2 mmol), and [1.21 M] (1S,4/?)-

bicyclo[2.2.1]heptan-2-ylmagnesium bromide (830 µ Ι , 1.0 mmol) were combined

under N 2 and stirred at RT for 24 h. After workup, crude product was purified via silica gel flash chromatography (hexanes) t o afford compounds (10-exo) and (10-enoO) as an inseparable mixture of exo:endo (73:27) diastereomers as a clear oil (150 mg,

65%). Useful diagnostic peaks for each compound are listed :[¾](10-exo): NMR (600

MHz, CDCb) δ 2.22 - 2.20 (m, 2H), 1.06 - 1.05 (m, 2H), 0.83 - 0.79 (m, 1H), 0.24 (s, 3H), 0.22 (s, 3H), 13 C NMR (151 MHz, CDCb) δ 139.5, 134.0, 128.8, 127.8, 38.1, 37.9, 37. 1, 34.5, 32.9, 29.0, 28.7, -3.9, -3.9, Si NMR (119 MHz, CDCb) δ -3.20. (10- endo): NMR (600 MHz, CDCb) δ 2.31 (s, 1H), 2.27 (t, J = 4.3 Hz, 1H), 1.77 - 1.70 (m, 1H), 1.02 (tdd, J = 11.0, 4.9, 2.0 Hz, 1H), 0.31 (s, 3H), 0.28 (s, 3H), 13C NMR (151 MHz, CDCb) δ 140.4, 133.9, 128.7, 127.8, 41.9, 39.7, 37.3, 32.0, 30.0, 28.5, 27.6, -2.7, -3.0, 2 Si NMR (119 MHz, CDCb) δ -2.78. [154] Example 11 - Synthesis of Compound (11)

[155] Accordi ng to genera l procedure A, (DrewPhos) 2PdI2 ( 16 mg, 10 ol), dioxane (260 pL), triethyla mine (140 pL, 1 mmol ), dimethylphenylsiiyi iodide (360 pL, 2 mmol) , and [ 0.80 ] a-methyl benzylzi nc bromide in dioxane (1.25 mL, 1 mmol) were

com bined under N2 and stirred at RT for 16 h. The reaction was quenched with THF (0.4 mL), sti rred for 15 in, and then wet EtOAc (0. 5 mL) and brine (3 mL) were added via syri nge and worked up accord ing to general procedure B and purified via sil ica gel flash chromatography (hexanes) t o afford 233 mg of mixtu re : compou nd (11), DL-2, 3- diphenylbutane, /r?eso-2,3-d iphenyl butane, and (PhMe2Si )20 in a relative ratio

78 :8 :5 :9 . This mixture was purified by reverse phase chromatography on Biotage

instrument using SNAP Ultra C18 120 g colu mn (50 :50 MeCN :H20 to 80 :20 MeCN :H20 linear gradient) to obta in compou nd (11) as a colorless oil ( 171.1 mg, 71%) : H N R (600 MHz, CDCb) δ 7.43 - 7.29 ( , 5H), 7.20 (t, J = 7.7 Hz, 2H), 7.09 (t, J = 7.3 Hz, 1H), 6.95 (d, J = 7.3 Hz, 2H), 2 .39 (q, J = 7.5 Hz, 1H), 1.35 (d, J = 7.5 Hz, 3H), 0 .25 (s, 3 H), 0.21 (s, 3H) ; 1 C NMR ( 151 MHz, CDCb) δ 145 .4, 137.8, 134. 3, 129 .1, 128. 1, 127.7, 127.5, 124. 6, 29 .7, 15.3, -4. 2, -5. 3; 2 Si NMR (119 MHz, CDCb) δ - 1.06; FTIR (cm 1) : 3023, 2957, 2870, 1495, 1450, 1427, 1248, 1112, 833, 8 17, 775, 735, 699. + HRMS (CI) m/z, calculated for [Ci 6H2oSi] : 240. 1334; fou nd : 240. 1345 .

[156] According to general procedu re B, (DrewPhos) PdI2 16 mg, 10 mol ), Et 20 ( 100 pL), dimethyl phenylsi iyi chloride (200 pL, 1.2 mmol) , and [0. 55 M] (1-

phenylethyl) magnesi um bromide ( 1.8 mL, 1.0 mmol) were com bined under N2 and sti rred at RT for 24 h. After worku p, crude prod uct was purified via silica gel flash chromatog raphy (hexanes) then by reverse phase chromatog raphy on C18 modifed sil ica (gradient from acetonitri le :water = 50 :50 to acetonitrile :water = 75 :25) to afford com pou nd ( 11) as a clea r oil ( 129 mg, 54%) : NMR (600 MHz, CDCb) δ 7.40 - 7.30 (m, 5H), 7.19 (t, J = 7.6 Hz, 2 H), 7.08 (t, J = 7.3 Hz, 1H), 6.94 (d, J = 7.2 Hz, 2H), 2.38 (q, J = 7 .5 Hz, 1H), 1.33 (d, J = 7.5 Hz, 3H), 0 .24 (s, 3H), 0 .19 (s, 3H), 1 C NMR ( 151 MHz, CDCb) δ 145 .2, 137.5, 134. 1, 129. 0, 127.9, 127 .5, 127. 3, 124.4, 29 .5, 15.1, -4.4, -5.5, 2 Si NMR (119 MHz, CDCb) δ - 1.03.

[157] Example 12 - Synthesis of Compou nd (12) [158] Accord ing t o general procedure A, (DrewPhos)2Pdh ( 16 mg, 10 pmol), dioxane (745 pL), triethyiamine ( 140 L, 1 mmol ), dimethylphenylsi lyl iodide (360 L, 2 mmol ), and [ 1.32 M] (4- phenylbutan-2-yl)zinc bromide (760 pL, 1 m mol) were combi ned under N and sti rred at RT for 4 h. The reaction was quenched with dry T HF (405 pL, 5 equ iv, 5 mmol) via syri nge and allowed t o stir 15 minutes at RT then worked up according to general procedu re B and purified via silica gel flash chromatog raphy (hexanes) t o afford com pound ( 12) as a clear oil (267 mg, 99%) : H N R (600 MHz, δ CD2 CI2) 7.49 - 7 .46 (m , 2H), 7 .36 - 7.30 (m, 3H), 7 .24 (t, J = 7.6 Hz, 2H), 7 .14 (t,

J = 7.4 Hz, 1H), 7 .11 (d, J = 7 .4 Hz, 2H), 2 .76 (ddd, J = 14. 6, 10.4, 4 .9 Hz, 1H), 2 .46 (ddd, J = 13.5, 10. 1, 6 .7 Hz, 1H), 1.79 (dddd, J = 13.7, 10 .3, 6 .6, 3.5 Hz, 1H), 1.44 -

1.36 (m, 1H), 1.02 (d, J = 7.3 Hz, 3H), 0 .92 (dd p, J = 11.2, 7 .3, 3.7 Hz, 1H), 0 .26 (s, 3H), 0 .25 (s, 3H) ; 3C NMR ( 151 MHz, CDC ) δ 143 .0, 138 .6, 134. 1, 128. 9, 128 .6, 128 .4, 127.8, 125.7, 35.0, 33.9, 19.0, 14 .1, -4 .6, -4.8 ; 2 Si NMR ( 119 MHz, CDC ) δ - 0 .08 ; FTIR (cm 1) : 3067, 3025, 2953, 2864, 1454, 1427, 1248, 1112, 833, 8 12, 772, + 699. HRMS (CI) m/z, ca lcu lated for [Ci H22Si] : 253 .14 13 ; fou nd : 253 .1403 .

[159] According t o genera l procedure B, (DrewPhos)2Pdl2 ( 16 mg, 10 pmol) , diethyl ether ( 1.1 m L), dimethyl phenylsilyl chloride (200 pL, 1.2 mmol ), and [ 1.34 M] (4-

phenyl buta n-2-yl )mag nesium bromide (750 pL, 1.0 mmol ) were combi ned under 2 and sti rred at RT for 24 h. After worku p, crude product was purified via silica gel flash chromatog raphy (hexanes grad ient t o hexa nes :dichloromethane = 95 :5) to afford compound ( 12) as a clear oil (264 mg, 98%) : H NMR (600 MHz, CD2CI2) δ 7.50 - 7 .47 (m, 2H), 7.37 - 7 .3 1 ( , 3H), 7 .24 (t, J = 7 .5 Hz, 2H), 7 .17 - 7.13 (m , 1H), 7.11 (d, J

= 7 .5 Hz, 2H), 2 .76 (ddd, J = 14 .0, 10.4, 4.9 Hz, 1H), 2.46 (ddd, J = 13.6, 10. 1, 6 .7 Hz, 1H), 1.79 (dddd , J = 13.7, 10. 3, 6 .7, 3.6 Hz, 1H), 1.41 (dtd, J = 13.6, 10 .3, 4.9 Hz, 1H), 1.02 (d, J = 7.2 Hz, 3H), 0.96 - 0 .89 ( m , 1H), 0 .26 (s, 3H), 0.25 (s, 3H), 13 C NMR ( 151 MHz, CDCb) δ 143. 0, 138. 7, 134. 1, 128. 9, 128 .6, 128.4, 127.8, 125.7, 35.0, 33.9, 19. 0, 14. 1, -4. 6, -4.8, 2 Si NMR ( 119 MHz, CDCb) δ -0.05 .

[160] Example 13 - Synthesis of Compound ( 13) [161] According to general procedu re A, (DrewPhos)2Pdl2 ( 16 mg, 10 mol), dioxa ne

(580 µΙ_), triethylamine ( 140 L, 1 mmol) , dimethyl phenylsilyl iodide (360 µΙ , 2 mmol ),

and [ 1.09 M] 4- (4-(ethoxyca rbonyl )phenyl) butan-2yl )zi nc bromide (920 µ Ι_, 1 mmol )

were combi ned under 2 and stirred at RT for 4 h. The reaction was quenched with wet EtOAc (0. 5 mL) and brine (3 ml_) via syri nge and worked up accord ing to general procedure B and purified via silica gel flash chromatog raphy (hexanes :dichlorometha ne = 90 :10 gradient to hexanes :dich loromethane = 80 :20) and product dried (50 °C/0. 1 mmHg) for 43 h t o afford compou nd ( 13) as a clear oil (276 .1 mg, 8 1% ) : H NMR (600 MHz, CDCb) δ 7.94 (d, J = 8.2 Hz, 2H) , 7.49 - 7.43 (m, 2 H), 7.39 - 7.30 (m, 3H) , 7.16 (d, J = 8.2 Hz, 2H), 4 .37 (q, J = 7.1 Hz, 2H), 2.80 (ddd, J = 14. 3, 9.9, 4.9 Hz, 1H), 2.52 (ddd , J = 13.6, 9.7, 7.0 Hz, 1H), 1.80 (dddd, J = 13.5, 10 .2, 7.0, 3.5 Hz, 1H), 1.48 - 1.39 ( , 1H) , 1.39 (t, J = 7.1 Hz, 3H), 1.02 (d, J = 7.2 Hz, 3H), 0.89 (dtq, J = 14.9, 7.6, 3.4 Hz, 1H), 0.26 (s, 3H), 0 .25 (s, 3H) ; 3C NMR ( 10 1 MHz, CDCI3) δ 166.8, 148.4, 138.4, 134. 0, 129. 7, 129. 0, 128. 5, 128. 0, 127.8, 60.9, 34. 9, 33. 5, 18.8, 14 .5, 14 .0, -4 .6, - 5.0; 2 Si NMR ( 119 MHz, CDCI3) δ -0.04 ; FTIR (cm 1) : 2954, 2864, 236 1, 2340, 1427, 1718, 16 10, 1275, 1248, 1107, 1021, 833, 701. HRMS (CI) m/z, + calculated for [C2 iH290 2Si] : 34 1.1937 ; found : 34 1.1926.

[162] Example 14 - Synthesis of Com pound ( 14)

Accord ing to general procedu re A, (DrewPhos)2Pdl2 ( 16 mg, 10 mol), dioxane

(710 l_), triethylami ne ( 140 µ 1_, 1 mmol), dimethylphenylsilyl iodide (360 µ Ι_, 2 mmol), and [ 1.26 M] (4- (4-methoxyphenyl) buta n-2yl )zi nc bromide (795 pL, 1 mmol ) were

combined under N 2 and sti rred at RT for 4 h. The reaction was quenched with wet Et20 (3 mL) and H2O (3 mL) via syri nge and worked up accordi ng to general procedu re B and purified via silica gel flash chromatog raphy (hexanes :DCM = 85:15;) to afford compou nd ( 14) as a clear oil (257 mg, 86%) : H NMR (600 MHz, CDCb) δ 7.50 - 7.44 (m, 2H), 7.38 - 7.30 (m, 3H), 7.03 (d, J = 8.5 Hz, 2H), 6.8 1 (d, J = 8.6 Hz, 2H), 3.79 (s, 3H), 2.71 (ddd, J = 14.4, 10.2, 4.8 Hz, 1H), 2.41 (ddd, J = 13.7, 9.9, 6.9 Hz, 1H), 1.82 - 1.73 (m, 1H), 1.42 - 1.34 (m, 1H), 1.01 (d, J = 7.3 Hz, 3H), 0.94 - 0.85 (m, 1H), 0.25 (s, 3H), 0.24 (s, 3H); 13 C NMR (151 MHz, CDCb) δ 157.8, 138.7, 135.1, 134.1, 129.4, 128.9, 127.8, 113.9, 55.4, 34.08, 34.07, 18.9, 14.1, -4.6, -4.8; 2 Si NMR (119 MHz, CDCb) δ -0.08; FTIR (cm 1) : 3068, 2998, 2952, 2864, 1612, 1512, 1246, 1177, 1113, 1038, 816, 771, 735, 702. HRMS (CI) m/z, calculated for + [Ci9H 260Si ] : 298.1753; found: 298.1741.

[ 164] According to procedure B, (DrewPhos)2Pdl2 (16 mg, 10 mol), diethyl ether

(620 L), dimethylphenylsilyl chloride (200 µ , 1.2 mmol), and [0.85 M] (4-(4- methoxyphenyl)butan-2-yl)magnesium bromide (1.18 mL, 1.0 mmol) were combined under l and stirred at RT for 24 h. After workup, crude product was purified via silica gel flash chromatography (hexanes gradient to hexanes:dichloromethane = 90: 10) t o afford compound (14) as a clear oil (283 mg, 95%): H NMR (600 MHz, CD2CI2) δ 7.50 - 7.46 (m, 2H), 7.36 - 7.31 (m, 3H), 7.02 (d, J = 8.6 Hz, 2H), 6.78 (d, J = 8.6 Hz, 2H), 3.75 (s, 3H), 2.70 (ddd, J = 14.5, 10.2, 4.9 Hz, 1H), 2.40 (ddd, J = 13.6, 10.0, 6.8 Hz, 1H), 1.74 (dddd, J = 13.6, 10.2, 6.8, 3.5 Hz, 1H), 1.40 - 1.33 ( , 1H), 1.00 (d, J = 7.3 Hz, 3H), 0.90 (dqd, J = 11.0, 7.6, 7.2, 3.5 Hz, 1H), 0.25 (s, 3H), 0.24 (s, 3H), 1 C NMR (151 MHz, CD2CI2) δ 158.3, 139.2, 135.5, 134.5, 129.8, 129.3, 128.1, 114.1, 55.7, 34.6, 34.4, 19.3, 14.3, - 4.5, -4.7, 2 Si NMR (119 MHz, CDCb) δ -0.17.

[ 165] Example 15 - Synthesis of Compound (15)

[ 166] According to general procedure A, (DrewPhos)2Pdl2 (16 mg, 10 mo ), dioxane (700 pL), triethylamine (140 pL, 1 mmol), dimethylphenylsilyl iodide (360 pL, 2 mmol), and [1.25 M] (4-(4-chlorophenyl)butan-2-yl)zinc bromide (800 L, 1 mmol) were combined under N 2 and stirred at RT for 4 h . The reaction was quenched with dry THF (405 pL, 5 equiv, 5 mmol) via syringe and allowed to stir 15 minutes at RT then worked up according to general procedure B and purified via silica gel flash chromatography (hexanes) to afford compound (15) as a clear oil (285 mg, 94%): H NMR (600 MHz, CDCb) δ 7.46 (dd, J = 7.3, 1.9 Hz, 2H), 7.34 (q, J = 5.6 Hz, 3H), 7.21 (d, J = 8.3 Hz, 2H), 7.02 (d, J = 8.3 Hz, 2H), 2.71 (ddd, J = 14.3, 10.0, 4.9 Hz, 1H), 2.43 (ddd, J = 13.7, 9.7, 7.0 Hz, 1H), 1.76 (dddd, J = 13.5, 10.2, 7.0, 3.5 Hz, 1H), 1.42 - 1.34 (m, 1H), 1.01 (d, J = 7.3 Hz, 3H), 0.87 (dqd, J 10 .9, 7.3, 3.5 Hz, 1H), 0 .25 (s, 3H), 0 .24 (s, 3H); 1 C N R ( 151 MHz, CDCb) δ 141 .4, 138. 5, 134. 1, 131.4, 129. 9, 129 .0, 128 .5, 127.8, 34. 3, 33.8, 18.9, 14. 1, -4. 6, -4. 9; 2 Si NMR (119 MHz, CDCb) δ -0. 05; FTIR ( η Οδδ , 2953, 2864, 1492, 1427, 1248, 1111, 1092, 1015, + 831, 8 12, 701, 522, 472. HRMS (CI) m/z, calculated for [Ci 8H22SiCI] 301.1179; found : 301 .1166 .

[167] Accord ing to genera l procedure B, (DrewPhos)2Pdb ( 16 mg, 10 µιτιοΙ ), diethyl ether (0. 52 ml_) , dimethylphenylsilyl chloride (200 µ Ι_, 1.2 mmol) , and [0.79 M] 4-(4-

(chloro)phenyl )butan-2-yl)mag nesium bromide (1.28 m L, 1.0 mmol) were combi ned under I and sti rred at RT for 24 h. After worku p, crude product was purified via silica gel flash chromatog raphy (hexanes) then by reverse phase chromatog raphy on C18 mod ified silica (gradient from acetonitrile :water = 50 :50 to acetonitri le :water 100 :0) to afford compou nd (15) as a clea r oil (272 mg, 89%) : H NMR (600 MHz, CDCb) δ 7.52 - 7.43 (m, 2H), 7.40 - 7.32 (m, 3H), 7.22 (d, J = 8.4 Hz, 2H), 7.03 (d, J = 8.3 Hz, 2H), 2.76 - 2.69 (m, 1H), 2.44 (ddd, J = 13.7, 9.7, 7.0 Hz, 1H), 1.77 (dddd , J = 13.5, 10 .2, 7.0, 3.5 Hz, 1H) , 1.40 (dtd, J = 13.9, 10 .1, 4.9 Hz, 1H), 1.02 (d, J 7.3 Hz, 3H), 0 .94 - 0 .83 (m, 1H), 0.27 (s, 3H), 0.26 (s, 3H) . 13C NMR ( 151 MHz, CDCb) δ 141 .4, 138.6, 134. 1, 131.5, 129. 9, 129. 0, 128.5, 127.8, 34. 3, 33.8, 18 .9, 14. 1, -4. 6, -4.9 . 2 Si NMR ( 119 MHz, CDCb) δ -0.05.

[ 168] Example 16 - Synthesis of Compound (16)

[ 169] Accordi ng to general proced ure A, (DrewPhos)2Pdl2 ( 16 mg, 10 mo ), dioxane

(640 L), triethylamine ( 140 µ Ι_, 1 mmol), dimethyl phenylsilyl iodide (360 pL, 2 mmol), and [ 1.14 M] (4- (4-(trifluoromethyl )phenyl )butan-2yl)zi nc bromide (880 L, 1 mmol) were combi ned under 2 and sti rred at RT for 8 h. The reaction was quenched with THF

(405 pL, 5 equ iv, 5 mmol ) via syringe and allowed to stir 15 minutes at RT then worked up accord ing to general procedure B and purified via silica gel flash chromatography (hexanes :ethyl acetate = 99 : 1) and product dried (45 °C/0. 1 mmHg) for 7 h to afford compou nd ( 16) as a clear oil (276. 1 mg, 8 1%) : H NMR (400 MHz, CDCb) δ 7.50 (d, J = 8.0 Hz, 2 H), 7.48 - 7.44 ( , 2H), 7.39 - 7.31 (m, 3H), 7.19 (d, J = 8.0 Hz, 2H), 2.80 (ddd, J = 14 .4, 10 .1, 5.0 Hz, 1H) , 2.51 (ddd, J = 13.6, 9 .8, 6.9 Hz, 1H) , 1.79 (dddd, J = 13.6, 10. 2, 6.9, 3.5 Hz, 1H), 1.47 - 1.36 (m, 1H), 1.02 (d, J = 7.2 Hz, 3H), 0.89 (ddp, J = 11.4, 7.6, 3.8 Hz, 1H), 0 .26 (s, 3H), 0 .25 (s, 3H) ; 13C NMR ( 101 MHz, CDC ) δ 147 .0, 138.4, 134. 0, 129. 0, 128 .8, 128. 0 (q, J = 32.2 Hz), 127.8, 125.3 (q, J = 3.8 Hz), 124. 5 (q, J = 27 1.9 Hz), 34f. 8, 33.6, 18. 9, 14. 1, -4. 6, - 5.0; 1 F NMR (376 MHz, CDCb) δ -62. 22; 2 Si NMR ( 119 MHz, CDCb) δ -0. 03; FTIR (cm 1) : 2954, 2866, 2361 , 1618, 1427, 1326, 1249, 1163, 1124, 1068, 10 18, 814, + 701 . HRMS (CI) m/z, ca lcu lated for [Ci8H 2oF3Si] : 321.1286 ; found : 321.127 1.

[ 170] Example 17 - Synthesis of Compou nd (17

[ 17 1] According to general procedu re A, (DrewPhos)2Pdl2 (16 mg, 10 mol), dioxane

(780 pL) , triethylami ne ( 140 µΙ , 1 mmol ), tri methylsi lyl iod ide (290 l , 2 mmol), and

[ 1.25 M] (4- (4-chlorophenyl) butan-2-yl)zinc bromide (800 µΙ , 1 mmol ) were combi ned under N2 and stirred at RT for 4 h. The reaction was quenched with wet Εί 0 (3 mL) and H2O (3 m L) via syri nge then worked up accord ing to general procedu re B and purified via silica gel flash chromatog raphy (hexanes) to afford compou nd ( 17) as a clear oil (232 mg, 96%) : NMR (600 MHz, CDCb) δ 7.25 - 7.22 ( , 2H), 7.13 - 7.08 (m, 2 H), 2 .76 (ddd, J = 14 .4, 10 .1, 4.8 Hz, 1H) , 2.47 (ddd, J = 13 .8, 10.1, 6.7 Hz, 1H ), 1.74 (dddd , J = 13.8, 10.4, 6.7, 3.6 Hz, 1H), 1.38 (dtd, J = 13.5, 10 .2, 4 .8 Hz, 1H), 0 .99 (d, J = 7.3 Hz, 3H), 0.65 - 0.56 (m, 1H), -0. 04 (d, J = 1.7 Hz, 9H) ; 13C NMR (151 MHz, CDCb) δ 14 1.6, 131.4, 129.9, 128. 5, 34. 5, 34. 0, 19.4, 14. 0, -3.1; 2 Si NMR (119 MHz, CDCb) δ 4 .55; FTIR (cm 1) : 2953, 2865, 1492, 1248, 1093, 1016, 856, 834, + 747, 521. HRMS (CI) m/z, calcu lated for [Ci 3H2oSiCI] : 239. 1023 ; fou nd : 239. 1026.

[ 172] Example 18 - Synthesis of Compou nd (18)

[ 173] According to genera l procedu re A, (DrewPhos)2Pdl2 16 mg, 10 mol), dioxane

(650 µ Ι_), triethylamine ( 140 µ Ι , 1 mmol), benzyldimethylsilyl iodide (41 0 µ Ι , 2 mmol), and [ 1.25 M] (4-(4-chlorophenyl )butan-2-yl)zi nc bromide (800 µ , 1 mmol ) were combi ned under 2 and sti rred at RT for 4 h. The reaction was diluted with dry THF

(405 µ Ι_, 5 equ iv, 5 mmol) via syri nge and allowed to sti r 15 minutes at RT then worked up according to general proced ure B and purified via silica gel flash chromatog raphy (hexa nes) to afford compou nd ( 18) as a clear oil (313 mg, 99%) : N R (600 MHz, CDC ) δ 7.24 (d, J = 8 .3 Hz, 2H), 7.19 (t, J = 7 .6 Hz, 2H), 7.09 (d, J = 8 .3 Hz, 2H), 7.06 (t, J = 7.6 Hz, 1H), 6.95 (d, J = 7.5 Hz, 2H), 2.77 (ddd, J = 14. 3, 10. 1, 4 .8 Hz, 1H), 2.45 (ddd, J = 13.6, 9.8, 7.0 Hz, 1H), 2.08 (s, 2H) , 1.74 (dddd, J = 13.4, 10.0, 6 .9, 3.2 Hz, 1H), 1.43 - 1.35 (m, 1H), 1.01 (d, J = 7.4 Hz, 3H), 0.69 (dqd, J 10. 7, 7.3, 3.2 Hz, 1H), -0. 08 (s, 6H) ; C NMR ( 151 MHz, CDCb) δ 14 1.2, 140. 2, 131.3, 129 .7 , 128.4, 128.1, 123.9, 34. 1, 33.7, 23.9, 17 .8, 13.7, -5.2, -5.3; Si NMR (119 MHz, CDCb) δ 5.24 ; FTIR (cm 1) : 308 1, 3024, 2952, 2864, 1600, 1492, 1452, + 1248, 1093, 10 15, 830, 699. HRMS (CI) m/z, calcu lated for [C 9H26SiCI] : 317.1492 ; found : 317 .1490.

[174] Example 19 - Synthesis of Compound ( 19)

[175] Accordi ng to general procedu re A, (DrewPhos)2Pdh 16 mg, 10 mol ), dioxane

(610 L), triethylami ne (140 µΙ , 1 mmol ), methyldiphenylsilyl iod ide (450 µ Ι_, 2 mmol) ,

and [ 1.25 M] (4-(4-chlorophenyl )butan-2-yl )zinc bromide (800 µ Ι_, 1 mmol) were

combined under N 2 and sti rred at RT for 4 h. The reaction was quenched with dry THF

(405 µ Ι , 5 equ iv, 5 mmol) via syri nge and allowed to stir 15 minutes at RT then worked up according to general procedu re B and purified via silica gel flash chromatog raphy (hexanes) t o afford compou nd (19) as a clear oil (29 1 mg, 80%) : H NMR (600 MHz, CDCb) δ 7.49 - 7.45 (m, 4 H), 7.4 1 - 7 .30 (m, 6 H), 7.22 (d, J = 8 .3 Hz, 2H), 7.01 (d, J = 8.2 Hz, 2H), 2.75 (ddd, J = 13.9, 9.4, 4.8 Hz, 1H), 2.47 (dt, J = 13.7, 8.4 Hz, 1H), 1.9 1 - 1.79 (m, 1H), 1.49 - 1.40 (m, 1H), 1.35 - 1.23 (m, 1H), 1.08 (d, J = 7.3 Hz, 3H) , 0 .52 (s, 3H) ; 13 C NMR (151 MHz, CDCb) δ 14 1.0, 136.4, 136 .2, 134. 8, 134. 8, 13 1.3, 129. 8, 129. 1, 129. 1, 128. 3, 127.8, 127 .8, 34. 0, 33.6, 17 .0, 14. 1, -6.4 ; 2 Si NMR (119 MHz, CDCb) δ -4.70 ; FTIR (cm 1) : 3068, 2952, 2864, 149 1, 1427, 1252, 1111, 1015, 788, 737, 700, 490, 477. HRMS (CI) m/z, calcu lated + for [C23H24SiCI] : 363 .1336; fou nd : 363 .1320.

[176] Exa mple 20 - Synthesis of Compou nd (20) [177] According t o general procedu re A, (DrewPhos)2Pdl2 ( 16 mg, 10 pmol), dioxane

(700 pL) , triethylami ne ( 140 L, 1 mmol ), triethylsi lyl iod ide (360 l_, 2 mmol ), and [ 1.25 M] (4-(4-ch lorophenyl)butan-2-yl)zinc bromide (800 pL, 1 mmol ) were combi ned under l and stirred at RT for 4 h. The reaction was quenched with wet E 20 (3 m L) and H2O (3 mL) via syri nge then worked up accord ing t o general proced ure B and purified via silica gel flash chromatog raphy (hexanes) t o afford compound (20) as a clear oil (85 mg, 30%) : H N R (600 MHz, CDC ) δ 7 .24 (d, J 8.3 Hz, 2H), 7 .10 (d, J = 8 .3 Hz, 2H), 2.79 (ddd, J = 14. 3, 10 .2, 4.8 Hz, 1H), 2.45 (ddd, J = 13.6, 9.9, 6 .9 Hz, 1H), 1.75 (dddd, J = 13.4, 10 .0, 6 .9, 3 .1 Hz, 1H), 1.46 - 1.38 (m, 1H), 1.02 (d, J = 7 .4 Hz, 3H), 0 .92 (t, J = 7.9 Hz, 9H) , 0 .82 - 0 .74 (m, 1H), 0 .53 (q, J = 7.9 Hz, 6H) ; 1 C NMR ( 151 MHz, CDCb) δ 14 1.6, 131.4, 129 .9, 128. 5, 34.6, 34 .2, 16 .5, 14. 2, 7.8, 2 .3; 2 Si NMR ( 119 MHz, CDCb) δ 8 .20; FTIR (cm 1) : 2952, 2909, 874, 1492, 1456, + 1239, 1093, 10 16, 834, 806, 732, 52 1. HRMS (CI) m/z, ca lcu lated for [Ci 4H22SiCI] : 253 .1179 ; fou nd : 253 .1177.

[ 178] Exam ple 2 1 - Synthesis of Compou nd (2 1)

[179] Accord ing t o general proced ure A, (DrewPhos)2Pdl2 ( 16 mg, 10 pmol) , dioxane (500 l_), triethylami ne ( 140 pL, 1 mmol), dimethylphenylsilyl iodide (360 pL, 2 mmol), and [ 1.05 M] (3-methyl butan-2-yl)zinc iodide in dioxane ( 1.00 mL, 1.05 mmol) were combi ned under N 2 and sti rred at RT for 4 h . The reaction was quenched with wet EtOAc (0 .5 m L) and bri ne (3 m L) via syri nge then worked up accord ing to genera l procedure B and purified via silica gel flash chromatog raphy (hexa nes) to afford compound (21) as a clea r volatile oil ( 17 5.1 mg, 81%) : H NMR (600 MHz, CDCb) δ 7.54 - 7 .51 (m, 2H), 7 .37 - 7.33 (m, 3H), 1.87 (heptd, J = 6.8, 3.4 Hz, 1H), 0.94 - 0 .89 (m, 7 H), 0 .8 1 (d, J = 6 .9 Hz, 3H), 0 .30 (s, 3H), 0 .29 (s, 3H) ; 1 C NMR ( 151 MHz, CDCb) δ 139 .9, 134 .0, 128.7, 127.8, 29.0, 26.8, 23.2, 19 .9, 9 .7, - 3.2, - 3.3; 2 Si NMR ( 119 MHz, CDCb) δ -0.85 ; FTIR (cm 1) : 2955, 287 1, 1465, 1427, 1248, 1111, 834, H 2 + 8 17, 768, 733, 700 . HRMS (CI) m/z, calculated for [Ci 2Si] : 206. 1491 ; fou nd : 206. 1482 .

[180] Example 22 - Synthesis of Compounds (22) and (23)

[181] Accord ing to general procedure A, (DrewPhos)2Pdl2 (16 mg, 10 mol ), dioxane

(60 µ Ι_) , triethylamine (140 µ Ι , 1 mmol ), dimethyl phenylsi lyl iodide (360 µ , 2 mmol ), and [0. 54 ] (3,3- dimethylbutan-2-yl)zi nc iod ide ( 1.85 mL, 1 mmol) were com bined

under 2 and sti rred at RT for 8 h. The reaction was quenched with wet EtOAc (0. 5 mL) and brine (3 mL) via syri nge then worked up according to general proced ure B and purified via silica gel flash chromatog raphy (hexanes) t o afford an inseparable mixtu re of isomers (22) :(23) (62 :38) as a clear oil ( 123.0 mg, 56%) : Useful diag nostic pea ks for each compound are listed . (22) : H NMR (400 MHz, CDC ) δ 7.56 - 7.50 (m, 2H), 7.38 - 7.31 (m, 3H), 0 .98 - 0 .92 (m, 4H), 0 .89 (s, 9H), 0.36 (s, 3H), 0.32 (s, 3H) ; 13C NMR (10 1 MHz, CDCI3) δ 141 .2, 134.0, 128. 6, 127 .7, 33. 7, 32. 3, 30. 3, 11.9, -0.5, - 2 .0; 2 Si NMR ( 119 MHz, CDCb) δ -2.06. HRMS (CI) m/z, calculated for [C H iSi] + : 13 2 205 .14 13; found : 205. 1407. (23) : H NMR (400 MHz, CDCb) δ 7.55 - 7.50 (m, 2H), 7.38 - 7.31 (m, 3H), 1.22 - 1.15 (m, 2H), 0.85 (s, 9 H), 0.72 - 0 .65 (m, 2H), 0 .25 (s, 6H) ; 13 C NMR (10 1 MHz, CDCb) δ 139.8, 133.7, 128.9, 127.8, 37.9, 31.2, 28,9, 9.8, - 3.0 ; 2 Si NMR ( 119 MHz, CDCb) δ -2.21. HRMS (CI) m/z, calcu lated for [C H iSi] + : 13 2 205 .141 3; fou nd : 205 .1406. (22) +(23) : FTIR (cm 1) : 2955, 29 11, 1466, 1427, 1363, 1249, 1112, 834, 8 15, 700 .

[182] Example 23 - Synthesis of Compou nd (24)

[183] Accordi ng to general procedu re B, (DrewPhos)2Pdl2 ( 16 mg, 10 mo ), Et20 (0. 3 mL) , dimethylphenylsilyl chloride (200 µ , 1.2 mmol) , and [0 .67 M] 3-

pentylmagnesium bromide ( 1.50 mL, 1.0 mmol) were combi ned under N 2 and sti rred at RT for 24 h. After worku p, the crude product was purified via silica gel flash chromatog raphy (hexanes) t o afford compou nd (24) as a clear oil (203 mg , 99%) : H NMR (600 MHz, C DC ) δ 7 .55 - 7 .50 ( m , 2H), 7 .38 - 7 .34 (m, 3H), 1.54 (dqd, J =

14. 7, 7 .5, 5.3 Hz, 2H), 1.38 (d p, J = 14. 7, 7 .4 Hz, 2H), 0 .88 (t, J = 7 .4 Hz, 6H) , 0 .72 (tt, J = 7 .5, 5 .1 Hz, 1H), 0 .29 (s, 6 H) . 3 C NMR ( 15 1 MHz, CDCb) δ 139 .8, 134.0, 128 .8, 127 .8, 29. 04, 2 1.9, 13.8, - 3 .4. 2 Si NMR ( 119 MHz, CDCb) δ 1.0 .

[184] Example 24 - Synthesis of Compound ( 25)

[185] Accordi ng t o general procedu re B, ( DrewPhos)2Pdb ( 16 mg, 10 pr ol), d iethyl ether (0. 76 mL) , d imethyl phenylsilyl chloride (200 pL, 1.2 mmol ), and [0. 96 M] (tri methylsi lyl) methyl mag nesiu m chloride ( 1.04 mL, 1.0 mmol ) were combi ned under

N 2 and sti rred at RT for 24 h. After workup, crude product was purified via silica gel flash chromatog raphy ( hexanes) t o afford com pou nd (25) as a clear oil ( 122 mg, 55%) : JH NMR (600 MHz, CDCb) δ 7 .59 - 7 .48 (m, 2H), 7 .38 - 7 .33 ( m , 3H), 0 .3 1 (s, 6H), 0.02 (s, 2H), -0. 0 1 (s, 9H) . 13C NMR ( 15 1 MHz CDCb) δ 14 1.5, 133.4, 128 .86, 127 .8, 3.4, 1.4, 0 .0 . 2 Si NMR ( 119 MHz, CDCb) δ 0 .5, -4. 2 . FTIR (cm 1) : 2953, 2897, 1426, 1250, 1113, 105 1, 836, 698. HRMS (CI) m/z, calcu lated for [CnHi9Si ]+ [M- + CH3] : 207 .1025 ; found : 207. 1027.

[186] Exa m ple 2 5 - Synthesis of Compou nd (26)

[187] Accord ing t o general procedu re B, ( DrewPhos)2Pdl2 ( 16 mg, 10 prnol), Et 2 (750 L) , d imethyl phenylsilyl chloride (200 pL, 1.2 m mol) , and [0. 9 5 M] neopentylmag nesiu m bromide ( 1.05 mL, 1.0 mmol) were combi ned under N and sti rred at RT for 24 h. After worku p, crude prod uct was purified via silica gel flash chromatography ( hexa nes) t o afford compou nd (26) as a clear oil (205 mg , 99%) : H NMR (400 MHz, CDCb) δ 7 .55 - 7 .52 ( m , 2H), 7 .42 - 7 .29 ( , 3H), 0 .9 5 (s, 11H), 0 .35 (s, 6H) . 1 C NMR ( 10 1 MHz, CDCb) δ 141 .0, 133 .6, 128 .7, 127 .8, 33 .2, 33 .2, 3 1.3, -0.4. 2 Si NMR ( 119 MHz, CDCb) δ - 5.7 . FTIR (cm 1) : 2954, 2893, 2869, 1465,

+ + 1427, 1363, 1249, 1113, 832, 707 . HRMS (CI) m/z, calcu lated for [Ci 3H22Si] [ M] : 206.1491; found: 206.1501.

[188] Example 26 - Synthesis of Compound (27)

[189] According to general procedure B, (DrewPhos)2Pdl2 (16 mg, 10 pmol), Et20 (50 pL), dimethylphenylsilyl chloride (200 L, 1.2 mmol), and [0.40 M] 2-methyl-2- phenylpropylmagnesium chloride (2.50 mL, 1.0 mmol) were combined under 2 and stirred at RT for 24 h. After workup, crude product was purified via silica gel flash chromatography (hexanes) to afford compound (27) as a clear oil (136.2 mg, 51%): H NMR (600 MHz, CDC ) δ 7.42 - 7.37 (m, 2H), 7.33 - 7.32 (m, 2H), 7.30 - 7.27 (m, 3H), 7.27 - 7.22 (m, 2H), 7.15 - 7.13 (m, 1H), 1.37 (s, 2H), 1.32 (s, 6H), 0.01 (s, 6H). C NMR (151 MHz, CDCb) δ 151.1, 140.8, 133.6, 128.7, 128.1, 127.8, 125.7, 125.6, 37.5, 34.2, 32.6, -1.2. 2 Si NMR (119 MHz, CDCb) δ -5.7. FTIR (cm 1) : 2959, 2360, 2339, 1652, 1558, 1456, 1110, 826. 668. HRMS (CI) m/z, calculated for + + Ci7H 2iSi [M-CH3] : 253.1413; found: 253.1417.

[190] Example 27 - Synthesis of Compound (28)

[191] According to general procedure B, (DrewPhos)2Pdb (16 mg, 10 pmol), Et20 (1.40 mL), dimethylphenylsilyl chloride (200 pL, 1.2 mmol), and [2.62 M] phenylmagnesium bromide (400 pL, 1.0 mmol) were combined under N 2 and stirred at RT for 24 h. After workup, crude product was purified via silica gel flash chromatography (hexanes) then by reverse phase chromatography on C18 modifed silica (gradient from acetonitrile:water = 50:50 to acetonitrile:water = 100:0) to afford compound (28) as a clear oil (215 mg, 97%): H NMR (600 MHz, CDCb) δ 7.61 - 7.50 (m, 4H), 7.40 - 7.35 (m, 6H), 0.59 (s, 6H). 13 C NMR (151 MHz, CDCb) δ 138.4, 134.4, 129.2, 128.0, -2.2. 2 Si NMR (119 MHz, CDCb) δ -8.1.

[192] Example 28 - Synthesis of Compound (29) [193] According to general procedure B, (DrewPhos)2Pdh (16 mg, 10 mo ), Et20 (1.3 mL), dimethylphenylsilyl chloride (200 L, 1.2 mmol), and [2.0 M] ortho- tolylmagnesium bromide (0.500 mL, 1.0 mmol) were combined under and stirred at RT for 24 h. After workup, crude product was purified via silica gel flash chromatography (hexanes) t o afford compound (29) as a clear oil (210 mg, 93%): H NMR (600 MHz, CD2CI2) δ 7.51 - 7.47 (m, 3H), 7.38 - 7.31 (m, 3H), 7.29 (td, J = 7.5, 1.3 Hz, 1H), 7.18 (t, J = 7.4 Hz, 1H), 7.14 (d, J 7.6 Hz, 1H), 2.25 (s, 3H), 0.58 (s, 6H), 13C NMR (151 MHz, CD2CI2) δ 144.7, 139.7, 136.8, 135.9, 134.6, 130.4, 130.1, 129.5, 128.4, 125.5, 23.5, -1.0, 2 Si NMR (119 MHz, CDC ) δ -8.1, FTIR (cm 1) : 3067, 3050, 3003, 2956, 1589, 1428, 1250, 1130, 1112, 817, 775, 701, 642, 474. HRMS + + (CI) m/z, calculated for Ci 4Hi 5Si [M] : 211.0943; found: 211.0952.

[194] Example 29 - Synthesis of Compound (30)

[195] According to general procedure B, (DrewPhos)2Pdb (16 mg, 10 mo ), E.20 (720 L), dimethylphenylsilyl chloride (200 pL, 1.2 mmol), and [0.93 M] 2-

mesitylmagnesium bromide (1.08 mL, 1,0 mmol) were combined under 2 and stirred at RT for 24 h . After workup, crude product was purified via silica gel flash chromatography (hexanes) to afford compound (30) as a clear oil (250 mg, 98%): H NMR (400 MHz, CDCb) δ 7.52 - 7.44 (m, 2H), 7.35 - 7.29 (m, 3H), 6.84 (s, 2H), 2.30 (s, 6H), 2.29 (s, 3H), 0.63 (s, 6H). 13C NMR (101 MHz, CDCb) δ 145.2, 141.7, 139.2, 133.5, 130.8, 129.3, 128.7, 128.0, 25.1, 21.1, 3.2. 2 Si NMR (119 MHz, CDCb) δ -9.0. FTIR (cm 1) : 2954, 1605, 1450, 1427, 1250, 1105, 816, 701, 667. HRMS (CI) m/z, calculated for Ci H22Si + [M] + : 254.1491; found: 254.1495.

[196] Example 30 - Synthesis of Compound (31) [197] According to procedure B, (DrewPhos)2Pdl2 (16 mg, 10 prnol), Et20 (1.04 mL), trimethylsilyl chloride (150 µ Ι , 1.2 mmol), and [1.43 M] (4-phenylbutan-2- yl)magnesium bromide (700 µί., 1.0 mmol) were combined under l and stirred at RT for 24 h. After workup, crude product was purified via silica gel flash chromatography (hexanes) to afford compound (31) as a clear oil (154 mg, 75%): NMR (600 MHz, CDC ) δ 7.29 (t, J = 7.6 Hz, 2H), 7.21 - 7.16 (m, 3H), 2.81 (ddd, J = 14.8, 10.6, 4.9 Hz, 1H), 2.51 (ddd, J = 13.5, 10.3, 6.6 Hz, 1H), 1.79 (dddd, J = 13.9, 10.3, 6.5, 3.7 Hz, 1H), 1.49 - 1.33 (m, 1H), 1.01 (d, J = 7.4 Hz, 3H), 0.65 (dqd, J = 10.9, 7.4, 3.7 Hz, 1H), -0.03 (s, 9H), 13 C NMR (151 MHz, CDCb) δ 143.3, 128.6, 128.4, 125.7, 35.2, 34.1, 19.6, 14.0, -3.1, 29Si NMR (119 MHz, CDCb) δ 4.53, FTIR (cm 1) : 3027, 2953, 2865, 1604, 1496, 1454, 1248, 856, 834, 745, 698. HRMS (CI) m/z, calculated for [Ci H2iSi] + : 205.1413; found: 205.1418.

[198] Example 31 - Synthesis of Compound (32)

[199] According to procedure B, (DrewPhos)2Pdh (16 mg, 10 mo ), Et20 (950 µ Ι ) , phenethyldimethylsilyl chloride (240 µ , 1.2 mmol), and [1.23 M] (4-phenylbutan-2- yl)magnesium bromide (810 µ Ι_, 1.0 mmol) were combined under N 2 and stirred at RT for 24 h . After workup, crude product was purified via silica gel flash chromatography (hexanes) then by reverse phase chromatography on C18 modifed silica (gradient from acetonitrile:water = 75:25 to acetonitrile:water = 95:0) to afford compound (32) as a clear oil (280 mg, 94%): H NMR (600 MHz, CD2CI2) δ 7.29 - 7.23 (m, 4H), 7.22 - 7.12 (m, 6H), 2.82 (ddd, J = 14.3, 10.5, 4.8 Hz, 1H), 2.59 (dd, J = 11.4, 6.1 Hz, 2H), 2.50 (ddd, J = 13.6, 10.1, 6.7 Hz, 1H), 1.84 - 1.76 (m, 1H), 1.47 - 1.39 (m, 1H), 1.04 (d, J = 7.4 Hz, 3H), 0.90 - 0.85 (m, 2H), 0.78 - 0.70 (m, 1H), -0.01 (s, 6H), C NMR (151 MHz, CDCI3) δ 145.5, 143.1, 128.6, 128.4, 127.9, 125.8, 125.7, 35.2, 34.1, 30.2, 18.5, 1.6.1, 14.0, -4.98, -5.00, 2 Si NMR (119 MHz, CDCb) δ 5.5. HRMS (CI) m/z, + calculated for [Ci 9H25Si] : 281.1726; found: 281.1716.

[200] Example 32 - Synthesis of Compound (33)

[201] According to procedure B, (DrewPhos)2PdI 2 (16 mg, 10 pmol), Et20 (930 L), (3,3-dimethylbutyl)dimethylsilyl chloride (250 l , 1.2 mmol), and [1.23 ] (4- phenylbutan-2-yl)magnesium bromide (810 µ Ι_, 1.0 mmol) were combined under and stirred at RT for 24 h . After workup, crude product was purified via silica gel flash chromatography (hexanes) then by reverse phase chromatography on C18 modified silica (gradient from acetonitrile:water = 75:25 to acetonitrile:water = 100:0) to afford compound (33) as a clear oil (255 mg, 92%): H NMR (600 MHz, CDCb) δ 7.28 (t, J = 7.6 Hz, 2H), 7.21 - 7.16 (m, 3H), 2.82 (ddd, J 14.1, 10.4, 4.8 Hz, 1H), 2.50 (ddd, J = 13.5, 10.1, 6.7 Hz, 1H), 1.78 (dddd, J = 13.7, 10.3, 6.7, 3.5 Hz, 1H), 1.46 - 1.37 (m, 1H), 1.11 (ddd, J = 12.7, 5.8, 2.1 Hz, 2H), 1.01 (d, J = 7.4 Hz, 3H), 0.84 (s, 9H), 0.74 - 0.66 (m, 1H), 0.45 - 0.40 (m, 2H), -0.07 (s, 3H), -0.07 (s, 3H), 13 C NMR (151 MHz, CDCb) δ 143.2, 128.6, 128.4, 125.7, 38.0, 35.2, 34.1, 31.2, 29.0, 18.4, 14.1, 7.8, -5.1, 2 Si NMR (119 MHz, CDCb) δ 6.14, FTIR (cm 1) : 3027, 2952, 2913, 2865, 1604, 1466, 1454, 1363, 1248, 1159, 886, 835, 745, 698. HRMS (CI) m/z, calculated + for [Ci 7H29Si] : 261.2039; found: 261.2038.

[202] Example 33 - Synthesis of Compound (34)

[203] According to procedure B, (DrewPhos)2Pdh (16 mg, 10 pmol), Et20 (1.23 i L), (3,3,3-trifluoropropyl)dimethylsilyl chloride (210 pL, 1.2 mmol), and [1.78 M] (4- phenylbutan-2-yl)magnesium bromide (560 L, 1.0 mmol) were combined under N2 and stirred at RT for 24 h . After workup, crude product was purified via silica gel flash chromatog raphy (hexanes) to afford compou nd (34) as a clear oil (234 mg, 81% ) : H NMR (600 MHz, CDC ) δ 7.29 (t, J = 7.6 Hz, 2H), 7.21 - 7.15 (m, 3H), 2.83 (ddd, J = 14 .2, 10.1, 4.8 Hz, 1H), 2 .51 (ddd , J = 13.6, 9.8, 6.9 Hz, 1H), 2.03 - 1.89 (m, 2H), 1.77 (dddd, J = 13.6, 10. 2, 6.9, 3.3 Hz, 1H) , 1.49 - 1.39 (m, 1H), 1.03 (d, J = 7.4 Hz, 3H), 0.78 - 0 .66 (m, 3H) , -0.0 1 (s, 3H), -0.01 (s, 3H), 13 C NMR ( 151 MHz, CDCb) δ 142 .7, 128. 5, 128 .5, 127.80 (q, J = 276. 7 Hz) 125.9, 34. 9, 33.8, 28.95 (q, J = 29.8 Hz), 18. 0, 13.8, 5.5, -5.3, -5.4, 1 F NMR (565 MHz, C CDCb) δ 68 .78, 2 Si NMR (119 MHz, CDCb) δ 6.11, FTIR (cm 1) : 3028, 2953, 2867, 1604, 1497, 1364, 1264, 1212, + 1125, 1067, 900, 844, 699. HRMS (CI) m/z, calculated for [Ci H 4 F 3Si] : 289. 1599; fou nd : 289. 1587.

[204] Example 34 - Synthesis of Compou nd (35)

[205] Accord ing to procedu re B, (DrewPhos)2Pdl2 ( 16 mg, 10 mol ), t20 ( 1.1 mL), chloromethyldi methylsilyl chloride ( 160 L, 1.2 mmol), and [ 1.34 M] (4- phenylbutan-2- yl)mag nesiu m brom ide (750 l_, 1.0 mmol ) were combi ned under N 2 and stirred at RT for 24 h. After worku p, crude product was purified via silica gel flash chromatog raphy

(hexa nes) to afford compou nd (35) as a clear oil ( 154 mg, 64%) : H NMR (600 MHz, CDCb) δ 7 .29 (t, J = 7.7 Hz, 2H), 7.21 - 7.16 (m, 3H), 2.8 1 (s, 3 H), 2.52 (ddd, J = 13.5, 10 .3, 6.5 Hz, 1H), 1.80 (dddd, J = 13.9, 10 .3, 6 .5, 3.6 Hz, 1H), 1.51 - 1.42 (m, 1H), 1.05 (d, J = 7.4 Hz, 3H), 0.90 (dqd, J = 11.1, 7.3, 3.6 Hz, 1H), 0 .10 (s, 3H), 0.09 (s, 3H), 13C NMR ( 151 MHz, CDCb) δ 142 .7, 128. 5, 128. 5, 125.9, 35. 0, 33.8, 29 .5, 17 .6, 13.9, -6. 0, -6.1, 2 Si NMR (119 MHz, CDCb) δ 6.21, FTIR (cm 1) : 3027, 2954, 2927, 2865, 1604, 1496, 1454, 1251, 842, 746, 699. HRMS (CI) m/z, calcu lated for + [Ci 3H22CISi] : 24 1.1179 ; fou nd : 241 .1182 .

[206] Example 35 - Synthesis of Com pound (36) C

[207] According to procedure B, (DrewPhos) 2PdI2 (16 mg, 10 mo ), Et 0 (970 L), 4- chlorobutyidimethylsilyl chloride (220 µ Ι_, 1.2 mmol), and [1.23 ] (4-phenylbutan-2-

µ Ι , yl)magnesium bromide (810 1.0 mmol) were combined under N2 and stirred at RT for 24 h . After workup, crude product was purified via silica gel flash chromatography (hexanes) to afford compound (36) as a clear oil (247 mg, 87%) : H NMR (600 MHz, CDCb) δ 7.28 (dd, J = 8.3, 6.9 Hz, 2H), 7.21 - 7.14 (m, 3H), 3.53 (t, J = 6.6 Hz, 2H), 2.81 (ddd, J = 13.6, 10.3, 4.8 Hz, 1H), 2.50 (ddd, J 13.5, 10.1, 6.7 Hz, 1H), 1.82 - 1.73 (m, 3H), 1.46 - 1.36 (m, 3H), 1.01 (d, J = 7.4 Hz, 3H), 0.69 (dqd, J = 10.8, 7.3, 3.5 Hz, 1H), 0.55 - 0.48 (m, 2H), -0.05 (s, 3H), -0.05 (s, 3H), 3 C NMR (151 MHz, CDCb) δ 143.1, 128.6, 128.4, 125.7, 44.9, 36.4, 35.1, 34.1, 21.4, 18.5, 14.0, 13.1, - 4.98, -5.01, 2 Si NMR (119 MHz, CDCb) δ 5.45, FTIR (cm 1) : 3026, 2952, 2931, 2864, + 1603, 1496, 1454, 1248, 834, 747, 699. HRMS (CI) m/z, calculated for [Ci6H 28CISi] : 283.1649; found: 283.1658.

[208] Example 36 - Synthesis of Compound (37)

[209] According to procedure B, (DrewPhos) 2Pd (16 mg, 10 pmol), Et 20 (810 pL), 4- bromobutyldimethylsilyl chloride (220 pL, 1.2 mmol), and [1.34 M] (4-phenylbutan-2- µ Ι yl)magnesium bromide (750 , 1.0 mmol) were combined under N2 and stirred at RT for 24 h. After workup, crude product was purified via silica gel flash chromatography (hexanes) then reverse phase chromatography on C18 modified silica (gradient from acetonitle:water = 70:30 to acetonitrile:water = 100:0) to afford compound (37) as a clear oil (302 mg, 92%) : H NMR (600 MHz, CDCb) δ 7.28 (t, J = 7.6 Hz, 2H), 7.18 (d, J = 6.4 Hz, 3H), 3.41 (t, J = 6.8 Hz, 2H), 2.82 (ddd, J = 14.7, 10.4, 4.8 Hz, 1H), 2.49 (ddd, J = 13.5, 10.1, 6.7 Hz, 1H), 1.85 (p, J 6.9 Hz, 2H), 1.77 (dddd, J = 13.7, 10.2, 6.7, 3.4 Hz, 1H), 1.41 (dddd, J = 14.7, 10.3, 6.8, 3.5 Hz, 3H), 1.01 (d, J = 7.3 Hz, 3H), 0.69 (dqd, J = 10. 8, 7.4, 3.4 Hz, 1H), 0.53 - 0.47 (m, 2H), -0.05 (s, 6 H), 1 C NMR (151 MHz, CDC ) δ 143. 1, 128 .6, 128.4, 125.7, 36. 6, 35.1, 34. 1, 33.8, 22.6, 18 .4, 14. 0, 12 .9, -4.98, -5.01, 2 Si NMR (119 MHz, CDC ) δ 5.42, FTIR (cm 1) : 3026, 29 51, 2930, 2864, 1603, 1496, 1454, 1248, 835, 748, 699 . HRMS (CI) m/z, calculated + for [Ci 5H24BrSi ] : 311.083 1; fou nd : 311.0842.

[210] Example 37 - Synthesis of Compou nd (38)

[211] Accord ing to procedu re B, (DrewPhos) 2PdI2 (16 mg, 10 mol ), Et 20 (950 L), 5- hexenyld imethylsi lyl chloride (240 pL, 1.2 mmol), and [ 1.23 M] (4-phenyl butan-2- yl) mag nesiu m brom ide (8 10 l , 1.0 mmol ) were combi ned under N2 and stirred at RT for 24 h. After worku p, crude product was purified via silica gel flash chromatog raphy (hexanes) then reverse phase chromatography on C18 modified silica (gradient from acetonitle :water = 70 :30 to acetonitrile :water = 100 :0) t o afford com pound (38) as a clea r oil (25 1 mg, 9 1%) : H NMR (600 MHz, CDCb) δ 7.31 - 7.26 (m, 2H), 7.20 - 7.15 (m, 3 H), 5.80 (ddt, J = 16.9, 10.2, 6.7 Hz, 1H), 4.99 (dq, J = 17.1, 1.5 Hz, 1H), 4 .95 - 4.9 1 ( , 1H), 2.84 - 2.77 (m, 1H), 2.49 (ddd, J = 13.5, 10.2, 6 .6 Hz, 1H), 2.04 (q, J = 7 .0 Hz, 2H), 1.77 (dddd, J = 13.7, 10 .2, 6.6, 3.5 Hz, 1H), 1.45 - 1.35 (m, 3H), 1.31 - 1.24 (m, 2H), 1.00 (d, J = 7.4 Hz, 3H), 0.68 (dqd, J = 10. 8, 7.4, 3.5 Hz, 1H), 0.53 - 0.47 (m, 2H) , -0.07 (s, 3H), -0.07 (s, 3H), 13C NMR ( 151 MHz, CDCb) δ 143 .2, 139. 3, 128.6, 128.4, 125.7, 114. 3, 35.2, 34. 1, 33.6, 33.1, 23.6, 18.6, 14. 1, 13.7, -4. 9, 2 Si NMR (119 MHz, CDCb) δ 5.31. FTIR (cm 1) : 3063, 3027, 2923, 2854, 164 1, 1604,

1496, 1454, 1248, 909, 834, 746, 698 . HRMS (CI) m/z, calcu lated for [C H 7Si ] + : 1 2 259. 1882 ; fou nd : 259. 1882.

[212] Example 38 - Synthesis of Compou nd (39) [213] According to procedure B, (DrewPhos )2Pdl2 (16 mg, 10 µπποΙ ), Et20 (1.0 mL),

pentafluorophenyldimethylsilyl chloride (230 µ Ι_, 1.2 mmol), and [1.34 ] (4-

phenylbutan-2-yl)magnesium bromide (750 µ Ι_, 1.0 mmol) were combined under l and stirred at RT for 24 h . After workup, crude product was purified via silica gel flash chromatography (hexanes) to afford compound (39) as a clear oil (227 mg, 63%): H NMR (600 MHz, CD2CI2) δ 7.25 (t, J = 7.6 Hz, 2H), 7.15 (t, J = 7.4 Hz, 1H), 7.12 (d, J = 7.2 Hz, 2H), 2.80 (ddd, J = 14.6, 10.3, 4.9 Hz, 1H), 2.49 (ddd, J = 13.5, 10.0, 6.7 Hz, 1H), 1.76 (dddd, J = 13.7, 10.2, 6.7, 3.4 Hz, 1H), 1.45 (dddd, J = 16.9, 12.2, 8.5, 3.5 Hz, 1H), 1.09 (dp, J = 12.3, 4.7, 4.1 Hz, 1H), 1.04 (d, J = 6.9 Hz, 3H), 0.39 (s, 3H), 0.38 (s, 3H), 13 C NMR (151 MHz, CDC ) δ 149.2 (dddt, J = 241.4, 17.4, 8.7, 4.0 Hz), 142.5, 142.0 (dtt, J = 254.3, 12.9, 5.7 Hz), 138.3 - 136.2 (m), 128.5, 125.9, 110.0 - 109.3 (m), 34.9, 33.6, 19.0, 13.8, -3.34 (dt, J = 14.4, 3.7 Hz), 1 F NMR (565 MHz, CD2CI2) δ -126.48 - - 126.61 (m), -152.97 (t, J 19.8 Hz), -162.37 (td, J = 22.6, 8.6 Hz), 2 Si NMR (119 MHz, CDCb) δ 4.07, FTIR (cm 1) : 3028, 2955, 2868, 1642, 1517, 1457, 1374, 1283, 1256, 1086, 969, 841, 802, 747, 699. HRMS (CI) m/z, + calculated for [Ci 7Hi F5Si] : 343.0941; found: 343.0945.

[214] Example 39 - Synthesis of Compound (40)

[215] According to procedure B, (DrewPhos)2Pdb (16 mg, 10 µηηοΙ ), Et20 (1.3 mL), 4- btphenyldimethylsilyl chloride (300 mg, 1.2 mmol), and [1.43 M] (4-phenylbutan-2- yl)magnesium bromide (700 L, 1.0 mmol) were combined under N 2 and stirred at RT for 24 h. After workup, crude product was purified via silica gel flash chromatography (hexanes) then reverse phase chromatography on C18 modified silica (gradient from acetonitle: water = 80:20 to acetonitrile: water = 90: 10) to afford compound (40) as a clear oil (287 mg, 83%): H NMR (600 MHz, CD2CI2) δ 7.64 - 7.61 (m, 2H), 7.61 - 7.55 ( , 4H), 7.45 (t, J = 7.6 Hz, 2H), 7.36 (t, J = 7.3 Hz, 1H), 7.25 (t, J = 7.5 Hz, 2H), 7.14 (t, J = 6.3 Hz, 3H), 2.84 - 2.76 (m, 1H), 2.53 - 2.44 (m, 1H), 1.87 - 1.78 (m, 1H), 1.48 - 1.39 (m, 1H), 1.06 (t, J 5.9 Hz, 3H), 1.00 - 0.92 (m, 1H), 0.31 - 0.27 (m, 6H), 13C NMR (151 MHz, CDCI3) δ 143.0, 141.7, 141.3, 137.4, 134.6, 128.9, 128.6, 128.4, 127.5, 127.3, 126.5, 125.7, 35.0, 33.9, 19.0, 14.2, -4.5, -4.7, 2 Si NMR (119 MHz, CDCb) δ -0.04, FTIR (cm 1) : 3062, 3025, 2952, 2863, 1597, 1496, 1485, 1454, 1384, 1250, 1115, 1007, 826, 811, 756, 697. HRMS (CI) m/z, calculated for [C H25Si] + : 329.1726; found: 329.1731.

[216] Example 40 - Synthesis of Compound (41)

[217] According to procedure B, (DrewPhos)2Pdl2 (16 mg, 10 mol), Et.20 (1.0 mL), 3- phenoxydimethylsilyl chloride (285 µ Ι_, 1.2 mmol), and [1.43 M] (4-phenylbutan-2- yl)magnesium bromide (700 µ Ι , 1.0 mmol) were combined under N 2 and stirred at RT for 24 h . After workup, crude product was purified via silica gel flash chromatography (hexanes) then reverse phase chromatography on C18 modified silica (gradient from acetonitle:water = 80:20 to acetonitrile:water = 90: 10) to afford compound (41) as a clear oil (314 mg, 87%): JH NMR (600 MHz, CD2CI2) δ 7.32 (q, J = 7.5 Hz, 3H), 7.26 - 7.22 (m, 3H), 7.18 - 7.13 (m, 2H), 7.11 (d, J = 7.1 Hz, 2H), 7.09 (t, J = 7.4 Hz, 1H), 7.00 - 6.95 (m, 3H), 2.76 (ddd, J = 14.9, 10.4, 4.9 Hz, 1H), 2.46 (ddd, J = 13.5, 10.2, 6.6 Hz, 1H), 1.78 (dddd, J = 13.8, 10.3, 6.6, 3.6 Hz, 1H), 1.40 (dtd, J = 13.6, 10.2, 4.9 Hz, 1H), 1.02 (d, J = 7.3 Hz, 3H), 0.96 - 0.87 (m, 1H), 0.25 (s, 3H), 0.24 (s, 3H), 1 C NMR (151 MHz, CD2CI2) δ 158.2, 157.0, 143.5, 141.7, 130.3, 129.7, 129.6, 128.9, 128.8, 126.1, 125.1, 123.5, 120.0, 118.9, 35.4, 34.4, 19.4, 14.3, -4.5, -4.8, 2 Si NMR (119 MHz, CDCb) δ 0.34, FTIR (cm 1) : 3061, 3026, 2952, 2864, 1566, 1489, 1476,

+ 1401, 1226, 1110, 812, 771, 697. HRMS (CI) m/z, calculated for [C2 3H 5SiO] : 345.1675; found: 345.1685. [218] Example 4 1 - Synthesis of Com pou nd (42)

[219] Accord ing to proced ure C, (DrewPhos)2Pdb (16 mg, 10 pmol), BU2O (910 pL), triethylsi lyl chloride (340 pL, 2 mmol), and [ 1.34 ] (4- phenyl butan-2-yl )magnesiu m

bromide (750 pL, 1.0 mmol ) were combi ned under N2 and sti rred at RT for 24 h. After worku p, crude product was purified via sil ica gel flash chromatog raphy (hexa nes) to afford com pou nd (42) as a clear oil (249 mg, 99%) : Η N R (600 MHz, CDCI3) δ 7.28 (t, J = 7.6 Hz, 2H) , 7.20 - 7 .15 (m, 3H), 2 .84 (ddd, J = 14. 1, 10 .5, 4.8 Hz, 1H), 2.48 (ddd, J = 13.5, 10 .2, 6.7 Hz, 1H), 1.80 (dddd, J = 13.6, 10.0, 6.6, 3.1 Hz, 1H), 1.50 - 1.41 ( , 1H), 1.04 (d, J = 7.4 Hz, 3H), 0.93 (t, J = 8 .0 Hz, 9H), 0.8 1 (dqd , J = 10. 6, 7.4, 3.3 Hz, 1H), 0.54 (q, J = 8 .0 Hz, 6H), 1 C NMR ( 151 MHz, CDCI3) δ 143 .2, 128 .6, 128.4, 125.7, 35.3, 34. 3, 16.7, 14. 3, 7.8, 2.3, 2 Si NMR (119 MHz, CDC ) δ 8 .21, FTIR (cm 1) : 3027, 2952, 2909, 2874, 1604, 1496, 1454, 141 6, 1238, 10 16, 730, 698 . + HRMS (CI) m/z, calculated for [Ci 6H27Si] : 247 .1882; found : 247 .1884.

[ 220] Example 42 - Synthesis of Compou nd (43)

[221] Accord ing to proced ure C, (DrewPhos)2Pdb 16 mg, 10 mol), BU2O (880 pL), cyclohexyldimethylsilyl chloride (370 µ Ι , 2 mmol) , and [ 1.34 M] (4-phenylbutan-2- yl) mag nesium bromide (750 pL, 1.0 mmol ) were combined under N2 and sti rred at RT for 24 h. After workup, crude product was purified via silica gel flash chromatog raphy (hexanes) to afford com pound (43) as a clea r oil (210 mg, 90%) : H NMR (600 MHz, CDCb) δ 7.28 (t, J = 7.6 Hz, 2H), 7.20 - 7.15 (m, 3H), 2.82 (ddd, J = 14. 3, 10 .5, 4 .8 Hz, 1H), 2.48 (ddd, J = 13.5, 10 .2, 6 .7 Hz, 1H), 1.78 (dddd, J = 13.6, 10 .1, 6.6, 3.2 Hz, 1H), 1.74 - 1.67 (m, 3H), 1.61 (dd, J = 26.0, 13.0 Hz, 2H), 1.46 - 1.36 (m, 1H), 1.24 - 1.15 ( , 3H), 1.13 - 1.03 ( , 2H), 1.01 (d, J = 7.4 Hz, 3H), 0 .74 (dqd, J = 10.7, 7 .4, 3.3 Hz, 1H), 0 .68 (tt, J = 12.7, 3 .0 Hz, 1H), -0 .11 (s, 3H), -0 .12 (s, 3H), 1 C NMR ( 15 1 MHz, CDC ) δ 143 .3, 128 .6, 128 .4, 125.7, 35.2, 34. 2, 28. 37, 28 .36, 27.9, 27.8, 27.2, 24. 3, 17 .2, 14. 2, -6 .9, 2 Si NMR ( 119 MHz, CDCb) δ 5.66, FTIR (cm 1) : 3026, 29 19, 2847, 1604, 1496, 1446, 1246, 1099, 996, 888, 833, 799, 767, 698. + HRMS (CI) m/z, ca lculated for [Ci 8H29Si] : 273 .2039 ; fou nd : 273 .203 1.

[222] Exam ple 4 3 - Synthesis of Compou nd (44)

[223] Accord ing to proced ure C, (DrewPhos)2Pdl2 ( 16 mg, 10 ol), BU2O (950 µ Ι_),

isopropyld imethylsi lyl chloride (310 µ _, 2 m mol), and [ 1.34 M] (4~phenyl butan-2- yl)mag nesium bromide (750 L, 1.0 mmol ) were combined under I and sti rred at RT for 24 h. After workup, crude product was purified via silica gel flash chromatog raphy (hexanes) to afford compound (44) as a clear oil (210 mg , 90%) : H NMR (600 MHz,

CDCb) δ 7.28 (t, J = 7.6 Hz, 2H), 7 .20 - 7 .15 (m, 3H), 2.83 (ddd, J = 14. 8, 10 .6, 4 .8 Hz, 1H), 2.49 (ddd, J = 13.5, 10.3, 6.6 Hz, 1H), 1.78 (dddd, J = 13.7, 10.1, 6.6, 3.2 Hz, 1H), 1.4 1 (ddt, J = 14. 0, 10.5, 5.3 Hz, 1H), 1.02 (d, J = 7 .4 Hz, 3H), 0.95 - 0 .90 (m, 6H), 0 .88 - 0 .8 1 (m, 1H), 0.76 (dqd, J = 10 .7, 7 .4, 3.3 Hz, 1H), -0 .10 (s, 3H), - 0 .11 (s, 3H), 1 C NMR ( 151 MHz, CDCb) δ 143. 2, 128. 6, 128 .4, 125.7, 35.2, 34. 3, 18. 0, 17.9, 17 .5, 14. 2, 12.1, -7. 20, -7.23, FTIR (cm 1) : 3027, 2953, 2864, 1604, 1496, + 1454, 1249, 997, 883, 832, 808, 765, 697 . HRMS (CI) m/z, calculated for [Ci H23Si] : 219. 1569; fou nd : 2 19. 1559.

[224] Example 44 - Synthesis of Compou nd (45)

µ τ ο Ι µ Ι [225] Accordi ng to procedu re C, (DrewPhos) 2Pdl2 ( 16 mg, 10 ), Bu20 (850 _), diphenyl methylsi lyl chloride (41 0 µ , 2 mmol), and [ 1.34 M] (4-phenylbutan-2- yl) magnesium bromide (750 µ , 1.0 mmol ) were combined under N and stirred at RT for 24 h. After workup, crude prod uct was purified via silica gel flash chromatog raphy (hexanes) to afford com pou nd (45) as a clear oil (315 mg, 95%) : H NMR (600 MHz,

CD2CI2) δ 7 .50 - 7 .47 (m, 4 H), 7.39 - 7.31 (m, 6H), 7.24 (t, J 7 .5 Hz, 2H), 7 .16 (t, J = 7 .4 Hz, 1H) , 7 .10 (d, J = 7.1 Hz, 2H), 2 .80 (ddd, J = 14. 1, 9 .9, 4.8 Hz, 1H), 2.50 (ddd, J = 13.5, 9 .5, 7.2 Hz, 1H) , 1.91 - 1.82 ( m, 1H), 1.51 - 1.43 (m, 1H), 1.41 - 1.33 (m, 1H), 1.09 (d, J = 7.3 Hz, 3H), 0.53 (s, 3H), 13C NMR ( 151 MHz, CD2CI2) δ 143 .4, 137.4, 137 .2, 135.40, 135.37, 129 .7, 129 .6, 129. 1, 128.8, 128. 37, 128 .35, 2 δ 1 126. 2, 35.4, 34. 5, 17.8, 14. 5, -6. 2, Si NMR ( 119 MHz, CDCi3) -4. 7, FTIR (cm ) : 3068, 2953, 2856, 1603, 1495, 1427, 125 1, 1110, 788, 737, 698, 476. HRMS (CI) + m/z, calcu lated for [C22H 23Si] : 3 15.1569 ; found : 315.1579.

[226] Example 4 5 - Synthesis of Compound (46)

[227] Accord ing to procedu re D, (DrewPhos)2Pdl2 ( 16 mg, 10 mol), BU2O ( 1.25 m L), triphenylsilyl chloride ( 590 mg, 2 mmol), and [ 1.34 M] (4- phenylbutan-2- yl) mag nesiu m bromide (750 µ Ι_, 1.0 mmol ) were combined under N and sti rred at 50 °C for 24 h. After worku p, crude product was purified via silica gel flash chromatog raphy (hexanes :DCM 100 :0 t o hexa nes :DCM 90 : 10) t o afford compound (46) as a viscous clear oil (267 mg, 68%) : NMR (600 MHz, CD2CI2) δ 7.50 (dd, J = 8.0, 1.4 Hz, 6H) , 7 .42 - 7 .37 (m, 3H), 7 .37 - 7 .31 (m, 6H) , 7 .26 (t, J = 7 .5 Hz, 2H) ,

7.17 (t, J = 7.4 Hz, 1H), 7.12 (d, J = 7 .0 Hz, 2H), 2.86 (ddd, J = 13.8, 9.3, 4 .7 Hz, 1H), 2.57 (dt, J = 13.5, 8.3 Hz, 1H), 2 .09 - 2 .02 (m, 1H), 1.75 - 1.68 (m, 1H), 1.52 -

1.44 (m, 1H), 1.2 1 (d, J = 7.3 Hz, 3H), 13 C NMR ( 151 MHz, CDCI3) δ 143 .2, 136 .5, 135.2, 129 .9, 129 .2, 128.8, 128 .4, 126. 3, 35.3, 34. 7, 16 .7, 14.8, 2 Si NMR ( 119 MHz, CD2CI2) δ -8 .7 , FTIR (cm 1) : 3067, 3024, 2935 , 2856, 1602, 1495, 1428, 1189, 1108, + 998, 741 , 698, 575, 510 . HRMS (CI) m/z, calcu lated for [C22H 23Si] : 3 15.1569 ; fou nd : 315.1578.

[228] Exa mple 4 6 - Synthesis of Compou nd (47) [229] According to procedure D, (DrewPhos)2Pdl2 (16 mg, 10 µηηοΙ ), BU2O (1.25 mL), tert-butyldimethylsilyl chloride (300 mg, 2 mmol), and [1.34 M] (4-phenylbutan-2-

yl)magnesium bromide (750 L, 1.0 mmol) were combined under I and stirred at 100 °C for 24 h . After workup, crude product was purified via silica gel flash chromatography (hexanes) to afford compound (47) as a clear oil (74 mg, 30%): NMR (600 MHz, CD2CI2) δ 7.26 (t, J = 7.6 Hz, 2H), 7.20 - 7.14 ( , 3H), 2.83 (ddd, J = 13.7, 10.5, 4.8 Hz, 1H), 2.48 (ddd, J 13.4, 10.2, 6.6 Hz, 1H), 1.85 (dddd, J = 13.5, 10.2, 6.6, 2.9 Hz, 1H), 1.48 - 1.39 (m, 1H), 1.07 (d, J = 7.4 Hz, 3H), 0.89 (s, 9H), 0.85 (ddq, J 15.0, 7.5, 4.5, 3.6 Hz, 1H), -0.070 (s, 3H), -0.075 (s, 3H), 3C NMR (151 MHz, CDC ) δ 143.2, 128.6, 128.4, 125.7, 35.2, 35.0, 27.6, 17.6, 17.4, 15.2, - 7.0, 2 Si NMR (119 MHz, CDCb) δ 9.7, FTIR (cm 1) : 3027, 2928, 2856, 1604, 1470, + 1250, 828, 765, 697. HRMS (CI) m/z, calculated for [Ci H25Si3 : 233.1726; found: 233.1722.

[230] All-Chloride Experiments

[231] Synthesis of (DrewPhos)2Pdl2

[232] A 100 mL round bottom flask equipped with a magnetic stirbar was charged with bis(acetonitrile)dichloropalladium(II) (259 mg, 1 mmol, 1.0 equiv.) and DrewPhos (1.2 g, 2 mmol, 2.0 equiv.). The flask was sealed with a rubber septum and purged 10

min with N2. CH2CI2 (20 mL) was added via syringe and the solution was stirred for 6 hours at RT. The solvent was then removed in vacuo. EtOAc (15 mL) was added and the flask sat overnight at RT. The solid was collected via vacuum filtration and rinsing with EtOH resulted in a stable, yellow solid (905 mg, 66% yield): H NMR (600 MHz, CDC ) δ 7.52 - 7.48 (m, 12H), 7.38 (s, 6H), 1.19 (s, 108H); 1 C NMR (151 MHz,

CDCI3) δ 149.69 (t, J = 5.0 Hz), 130.41 (t, J = 23.9 Hz), 129.87 (t, J = 6.4 Hz), 123.83 , 35.01 , 31.54, 3 1P NMR (243 MHz, CDCb) δ 26.82; FTIR (cm 1) : 2963, 2903, 2868, 1590, 1477, 1421, 1363, 1266, 1249, 1138, 731, 705, 586; mp = >250 °C. HRMS + (LIFDI) m/z, calculated for [C84H 26P2PdCI 2 ] : 1372.7747; fou nd : 1372.7599.

[233] Synthesis of Isopropylmagnesium Chloride

Me^MgCI

Me

[234] An oven-dried 25 mL round-bottom flask equipped with a magnetic stirbar and rubber septum was attached to a double manifold and cooled under vacuum. The flask was backfilled with N2, the septum removed, magnesium turnings (1.1 g, 45 mmol, 1.5 equiv.) were added. The septum was replaced; the flask was attached to a double

manifold and purged with N 2 for 10 min. The flask was held under positive N 2 then Et20 (10 mL, [3 M]) was added. An initial amount of alkyl halide (~200-400 pL) was added and the reaction to start the reaction as evidenced by a minor exotherm. If reaction does not initiate, gentle warming (for example with a heating mantle) may be necessary. Once initiated, the flask was placed in a RT water bath and the remaining alkyl halide (2.74 mL, 2.36 g, 30 mmol, 1 equiv., total addition amount) was added dropwise over ~30 min. After full addition of the alkyl halide, the mixture was allowed to stir at RT for an additional 4 h . The excess magnesium was allowed to settle and the mixture was filtered via cannula to a Schlenk tube. Titration resulted in a [2.65 M] solution of isopropylmagnesium chloride. I n this preparation, I 2 was not used to activate the magnesium turnings.

[235] All-Chloride Process According to the Present Invention

[236] I n a nitrogen filled glovebox, a 1-dram vial equipped with a magnetic stirbar was charged with (DrewPhos)2PdCl2 (3.4 mg, 2.5 pmol, 0.01 equiv.), Et20 (350 pL) or

BU2O (350 pL), and dimethylphenylsilyl chloride (50 L, 51 mg, 300 mol, 1.2 equiv.). Vial was then sealed with a septum cap and removed from the glovebox. Isopropylmagnesium chloride [2.65 M] (94 pL, 250 pmol, 1 equiv.) was then added via syringe and the vial was then stirred at the indicated temperature for 24 h . The

reaction was quenched with Et20 ( 1 mL) then H2O (0.5 mL) via syringe. n-Nonane (32 mg, 45 pL, 0.25 mmol, 1 equiv.) and 1,3,5-trimethoxybenzene (TMB) (14 mg, 0.25 mmol, 0.33 equiv.) were added as GC internal standards. Brine ( 1 mL) and Et20 ( 1 mL) were then added and the vials sha ken . An aliquot was then filtered through a MgS04 and silica plug . The solution was directly analyzed by GC.

[ 237] Table 1: All-Chloride Cond itions

MgC| 1 mol % (DrewPhos) 2 PdCI2 e S M Ph J + Me2 PhSiCI ► Me solvent, X °C, 24 h Me 1 Entry Solvent Temp Additive Yield (%) 1 Et20 rt 6 2 Bu20 50 °C 70 3 Et20 rt 0.25 equiv TMEDA 52 Yields determined by GC. All reactions gave >99: 1 B :L selectivity by GC.

[ 238] All reactions in the fol lowi ng parag raphs were performed at 0.25 mmol in a nitrogen-fi lled glovebox with a [0. 5 M] overal l concentration based on the sum of all liqu id reagents.

[239] Exami nation of Stoich iometry

[ 240] I n a nitrogen filled glovebox, a 1-d ram vial equ ipped with a magnetic sti rbar was cha rged with (DrewPhos)2Pdl2 (4 mg, 2.5 µ ιτιοΙ , 0 .0 1 equiv. ), Er.20 (330 pL), and dimethylphenylsilyl chloride (52 pL, 53 mg, 313 pmol, 1.25 equ iv. , or 46 µ Ι , 47 mg,

275 pmol, 1.1 equ iv. , or 4 2 l_, 43 mg, 250 pmol, 1 equiv. ) . Vial was then sealed with a septu m cap and removed from the glovebox. Isopropyl magnesiu m bromide [2.13 M]

(117 µ Ι_, 250 pmol, 1 equiv. , or 129 pL, 275 L, 1.1 equiv. , or 147 L, 313 µ ηηοΙ , 1.25 equ iv. ) was then added via syringe and the vial was then sti rred at RT for the indicated t ime. The reaction was quenched with Et 0 ( 1 m L) then H2O (0. 5 m L) via syringe , n -

Nona ne (32 mg, 45 pL, 0.25 mmol, 1 equiv. ) and 1,3,5-tri methoxybenzene (TM B) ( 14 mg, 0 .25 mmol, 0 .33 equiv. ) were added as GC internal standards. Bri ne ( 1 mL) and Et 0 ( 1 mL) were then added and the vials shaken . An aliquot was then filtered through a MgS04 and Silica plug . The solution was directly analyzed by GC.

[ 241 ] Table 2 : Effect of Stoichiometry 1 mol % (DrewPhos) 2Pdl2 Me^MgBr X equiv Me,PhS,CI Me^SiMe Ph

Me Et20 , rt, X h Me 1 Entry g:Si 4 h (%)a 8 h (%)a 24 h (%)a 1 1:1.25 99 99 99 2 1:1.1 78 96 99 3 1:1 73 90 97 4 1.1:1 74 88 93 5 1.25: 1 7 1 86 93 Yields determined by GC. All reactions gave >99:1 B:L selectivity by GC.

[242] Examination of Ethereal Solvents

[243] I n a nitrogen filled glovebox, a 1-dram vial equipped with a magnetic stirbar was charged with (DrewPhos^Pdb (4 mg, 2.5 µιτιοΙ , 0.01 equiv.), MTBE or CPME (280

µ Ι_), and triethylsilyl chloride (84 µ Ι , 75 mg, 500 µ ι ο Ι, 2 equiv.) or iso-

propyldimethylsilyl chloride (78 µ , 68 mg, 500 µιτιοΙ , 2 equiv.). Vial was then sealed with a septum cap and removed from the glovebox. (4-phenylbutan- 2-yl)magnesium

bromide [1.78 M] (140 µ Ι , 250 µηηοΙ , 1 equiv.) was then added via syringe and the vial was then stirred at 50 ° C for the indicated time. The reaction was quenched with Et20

( 1 mL) then H2O (0.5 mL) via syringe. n-Nonane (32 mg, 45 µ Ι , 0.25 mmol, 1 equiv.) and 1,3,5- trimethoxybenzene (TMB) (14 mg, 0.25 mmol, 0.33 equiv.) were added as GC and NMR internal standards. Brine ( 1 mL) and Et.20 ( 1 mL) were then added and the vials shaken. An aliquot was then filtered through a MgS0 and Silica plug. The solution was directly analyzed by GC then concentrated in vacuo and analyzed by NMR.

[244] Table 3 : Examination of Ethereal Solvents 1 mol % DrewPhos Pdl

Et3Si = 28

'PrMe 2Si = 30

Entry [Si] MTBE CPME 1 Et3Si 99 99 2 'PrMe2Si 97 90 Yields determined by NMR. All reactions gave >99:1 B:L selectivity by GC.

[245] Examination of Silyl Electrophiles

[246] The use of other silyl electrophiles other than silyl iodides was also examined. Previous studies have shown that the addition of iodide additives can be beneficial with use of silyl chlorides, bromides, and triflates, so the reaction was also examined with Na additive. The results show minimal reactivity with Me3SiBr in the absence of Nal,

and modest reactivity with. For silyl chlorides and triflates, negligible reactivity was observed with or without Nal.

[247] In a nitrogen filled glovebox, a 1-dram vial equipped with a magnetic stirbar was charged with (DrewPhos)2Pdl2 (0.01 equiv.), dioxane, triethylamine ( 1 equiv.), and trimethylsilyl halide (2 equiv.). Vial was then sealed with a septum cap and removed from GB. (4-phenylbutan-2-yl)zinc bromide ( 1 equiv.) was added via syringe and the flask was then stirred at RT for 4 h . The reaction was quenched with Et20 ( 1 mL) then

H2O (0.5 mL) via syringe. Nonane (32 mg, 45 µΙ , 0.25 mmol, 1 equiv.) and 1,3,5- trimethoxybenzene (TMB) (14 mg, 0.25 mmol, 0.33 equiv.) were added as GC and NMR internal standards respectively. Brine ( 1 mL) and Et20 ( 1 mL) were then added

and the vials shaken. An aliquot was then filtered through a MgS04 and Silica plug. The solution was directly analyzed by GC. The solvent was removed in vacuo then analyzed by NMR.

[248] Table 4 : Examination of Silyl Electrophiles 1 mol % DrewPhos Pdl

a Entry Me3SiX 0 equiv Nal 3 equiv Nal 1 Me3Sil 98% 99% 2 Me3SiBr 26% 6 1% 3 Me3SiCI 1% 11% 4 Me3SiOTf 2% 5% "Yields obtained by H NMR with TMB as an internal standard.

[249] Examination of Dibutyl Zinc Reactivity

[250] The use of dialkylzinc reagents in the coupling reaction was also examined. As can be seen in Table 5, with Bu2 n only trace background reaction is observed, which is comparable to the background reaction with BuZnBr. Under palladium-catalyzed conditions, quantitative alkylation resulted. Et 3 does not effect this reaction. It is notable that only 0.5 equiv of Bu Zn is required in this reaction, both alkyl groups transfer to the product.

[251] I n a nitrogen filled glovebox, a 1-dram vial equipped with a magnetic stirbar was charged with (DrewPhos)2Pdl2 (0.01 equiv.), dioxane, triethylamine ( 1 equiv.), and dimethylphenylsilyl iodide (2 equiv.), and dibutylzinc (0.5 equiv.). Vial was then sealed with a septum cap, removed from GB, and stirred at RT for 4 h . The reaction was quenched with Et20 ( 1 mL) then H2O (0.5 mL) via syringe. Nonane (32 mg, 45 L, 0.25 mmol, 1 equiv.) and 1,3,5-trimethoxybenzene (TMB) (14 mg, 0.25 mmol, 0.33 equiv.) were added as GC and NMR internal standards respectively. Brine ( 1 mL) and Et20 ( 1 mL) were then added and the vials shaken. An aliquot was then filtered through a MgS04 and Silica plug. The solution was directly analyzed by GC. The solvent was removed in vacuo then analyzed by NMR.

[252] Table 5: Reactivity of Dibutylzinc X mo % (DrewPhos) 2Pdl 2 X equiv Et3N 2PhSil dioxane, rt, 4 h

a Entry % Pd 1 equiv Et3N 0 equiv Et3N 1 1 99% 99% 2 0 7% 7% aYields obtained by H NMR with TMB as an internal standard.

[253] Isolation of the palladium catalyzed reaction in the presence of triethylamine via flash chromatography (hexanes) afforded 5 as a clear oil (42 mg, 88%): H NMR (400 MHz, CDC ) δ 7.54 - 7.50 (m, 2H), 7.37 - 7.34 (m, 3H), 1.36 - 1.26 (m, 4H), 0.88 (t,

13 δ J = 6.9 Hz, 3H), 0.79 - 0.73 (m, 2H), 0.26 (s, 6H); C NMR (101 MHz, CDCI 3 ) 139.9, 133.7, 128.9, 127.8, 26.7, 26.3, 15.6, 13.9, -2.9.

[254] Examination of Alkene Additives

[255] Alkenes appear t o interfere with the reaction, as is reflected in the study shown in Table 6 . This appears to be a function of alkene substitution, as the effect is most notable with lower substituted alkenes.

[256] I n a nitrogen filled glovebox, a 1-dram vial equipped with a magnetic stirbar was charged with (DrewPhos)2Pdh (0.01 equiv), dioxane, triethylamine ( 1 equiv), alkene ( 1 equiv) and trimethylsilyl halide (2 equiv). Vial was then sealed with a septum cap and removed from GB. Isopropylzinc bromide ( 1 equiv) was added via syringe and the flask was then stirred at RT for 4 h . The reaction was quenched with Et.20 ( 1 mL) then H2O (0.5 mL) via syringe. Nonane (32 mg, 45 L, 0.25 mmol, 1 equiv) and 1,3,5- trimethoxybenzene (TMB) (14 mg, 0.25 mmol, 0.33 equiv) were added as GC and NMR internal standards respectively. Brine ( 1 mL) and Et20 ( 1 mL) were then added and the vials shaken. An aliquot was then filtered through a MgS0 and Silica plug. The solution was directly analyzed by GC. The solvent was removed in vacuo then analyzed by NMR.

[257] Table 6 : Impact of Alkene Additives 1 mol % (DrewPhos) 2Pdl 2

Me Z equiv Et3N M s i e Ph ► + Et\^SiMe Ph

Me 2 equiv Me2PhSil Me 1 equiv alkene 2 dioxane, rt, 4 h

Entry Alkene 1+2 (%)a 1:2 1 None 98 >99:1 2 4-octene 55 98:2 3 -m ethy| - 99 >99:1 cyclohexene 4 (+)-limonene 75 >99:1 Yields obtained by 1H N R with TMB as an internal standard. Ratio determined by GC. CLAIMS

A process for preparing a compound of formula (I):

R Si-

4 R (I) comprising the step of reacting a compound of formula (II):

MX (ID

wherein

M is Zn or Mg;

R1 is an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heterocycloalkyl, heterocycloalkenyl, heterocycloalkynyl, aryl, or heteroaryl group, each of which is optionally substituted with one or more substituents, wherein at least one of the one or more substituents is optionally a moiety of formula -M'X', wherein M' is Zn or Mg and X' is CI, Br, or I ; and

is CI, Br, or I, or, when R1 is an alkyl group, X is optionally an alkyl group identical to that of R1; with a compound of formula (III):

R2

X"- Si-

R4 (III)

wherein

X" is CI, Br, I, -OS(0) 2alkyl, -OS(0) 2perfluoroa

R2, R3, and R4 are, independently, selected from the grou p consisting of alkyl , alkenyl , alkynyl, cycloal kyl , cycloal kenyl, cycloalkynyl, heterocycloal kyl, heterocycloa lkenyl , heterocycloal kynyl, aryl, heteroa ryl, wherei n each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloa lkynyl, heterocycloal kyl, heterocycloal kenyl, heterocycloa lkynyl, aryl, heteroa ryl grou p is optionally substituted with one or more substituents, CI, Br, I , -OS(0)2alkyl groups, - OS(0)2perfluoroalkyl grou ps, and -OS(0)2aryl groups, wherein at least one of the one or more substituents is optionally a moiety of formula -SiR R6X"', wherein R5 and R6 are each, independently, selected from the grou p consisti ng of alkyl, alkenyl, alkynyl, cycloa lkyl, cycloal kenyl, cycloalkynyl, heterocycloal kyl, heterocycloal kenyl, heterocycloal kynyl, aryl, heteroa ryl, each of which is optionally substituted with one or more substituents, and X'" is CI, Br, I, -OS(0)2alkyl, - OS(0)2perfluoroalkyl, or -OS(0)2aryl; and

wherei n R2, R3, and/or R4, when taken together, optiona lly define an optionally substituted ring system ;

in the presence of a cata lyst com prising a Grou p 8, 9, or 10 transition metal, a ligand, a solvent, and, optionally, an add itive;

wherei n R2, R3, and/or R4 are optionally covalently linked to R1; and

R1, R2, R3, and R4 of the compou nd of formula (I) are as defi ned above.

2. The process of clai m 1, wherein R1 is sterical ly hindered .

3. The process of claims 1 and 2, wherein R1 is selected from the grou p consisting of pri mary, seconda ry, and tertiary alkyl grou ps, primary, secondary and tertiary alkenyl grou ps, and pri mary, seconda ry and tertiary alkynyl grou ps, each of which is optionally substituted .

4 . The process of clai ms 1-3, wherei n one or more of R1, R2, R3, and R4 is substituted with a least one silyl grou p. 5. The process of claims 1-4, wherein R2 is selected from the group consisting of CI, Br, I , -OS(0)2alkyl groups, -OS(0)2perfluoroalkyl groups, and -OS(0)2aryl groups.

6 . The process of claim 5, wherein X" and R2 are both CI.

7 . The process of claims 1-6, wherein R3 is selected from the group consisting of CI, Br, I , -OS(0)2alkyl groups, -OS(0)2perfluoroalkyl groups, and -OS(0)2aryl groups.

8 . The process of claims 1-7, wherein X", R2, and R3 are all CI.

9. The process of claims 1-8, wherein R4 is selected from the group consisting of CI, Br, I , -OS(0)2alkyl groups, -OS(0)2perfluoroalkyl groups, and -OS(0)2aryl groups.

10. The process of claims 1-9, wherein the Group 8, 9, or 10 transition metal is selected from the group consisting of Pd, Ni, Co, Rh, and Ir.

11. The process of claims 1-10, wherein the catalyst comprises Pd and is selected from the group consisting of Pd(OAc)2, PdBr2, Pdb, Pd(dba)2, Pd(dba)3,

[allylPdCI] , Pd dba3«CHCI 3, [(3,5-C 6H3(f-Bu)2)3P]2Pdl2, [(3,5-C 6H3( -

Bu) 2)3P]2PdCI 2, (COD)Pd(CH 2TMS) 2, (COD)PdCI 2, (PPh 3)2PdCI 2, (PPh 3) Pd,

(MeCN) PdCI 2, and (IPr) 2PdCI 2.

12. The process of claims 1-11, wherein the catalyst comprises Ni and is selected from the group consisting of Ni halides, Ni halide solvent complexes, and

Ni(COD) 2.

13. The process of claims 1-12, wherein the ligand is selected from the group consisting of phosphine ligands, arsine ligands, nitrogen-containing ligands, and N-heterocyclic carbene ligands.

14. The process of claim 1-13, wherein the ligand is selected from the group

consisting of PPh3, (3,5-t-BuC6H 3)2P(tBu), Ph2P(ffiu), PhP(t-Bu) 2, (3,5-C H3( -

Bu) 2)3P, (4-MeO-C H4)3P, (t-Bu) 3P, (t-Bu) 2PCy, (t-Bu)PCy 2, Cpy3P, Cy2PMe,

Cy2PEt, Cy3P, (o-tol) 3P, (furyl) 3P, (4-F-CeH4) 3P, (4-CF 3 -C6H4 )3P, BIPHEP, NapthPhos, XantPhos, dppf, dppe, dppb, dpppe, dcpe, dcpp, dcpb, SPhos, XPhos, DavePhos, JohnPhos, BrettPhos, QPhos, AmgenPhos, RockPhos, RuPhos, VPhos, tBuXPhos, tBuBrettPhos, TrixiePhos, AZPhos, CPhos, (3,5-t- BuC H3)2P(iPr), (3,5-t-BuC6H 3 )2P (Et), (3,5-t-BuC H3)2P(Me), (3,5-/-

PrC6H3)2P(tBu), (3,5-/-PrC 6H3) P(iPr), (3,5-/-PrC6H 3)2P(Et), (3,5-/-PrC 6H3)2P(Me),

(3,5-t-Bu-4-MeO-C 6H2)2P(tBu), (3,5-t-Bu-4-MeO-C 6H2 )3P, BINAP, SIPr, IPr, IMes, ISMes, and derivatives thereof.

15. The process of claims 1-14, wherein the solvent is selected from the group consisting of dioxane, toluene, 1,2-dichloroethane, acetonitrile, dibutyl ether, diethyl ether, hexane, tetrahydrofuran, and mixtures thereof.

16. The process of claims 1-15, wherein additive is present during the reaction and is selected from the group consisting of trialkylamines and iodide salts.

17. The process of claims 1-16, wherein the additive is triethylamine or TMEDA.

18. The process of claims 1-17, wherein the additive is Lil, Nal, KI, or ammonium iodide.

19. The process of claims 1-18, wherein M and X of the compound of formula (II) are Zn and Br or I , respectively, X" of the compound of formula (III) is I, the

catalyst is [(3,5-C6H 3(i--Bu)2) 3P]2Pdl2, the additive is triethylamine, and the solvent is dioxane.

20. The process of claims 1-19, wherein M and X of the compound of formula (II) are Mg and Br or I , respectively, X" of the compound of formula (III) is CI, the

catalyst is [(3,5-C H 3(t-Bu)2) 3P]2Pdl2, and the solvent is Et 20 .

21. A compound of formula (I):

R2

R Si R3

R4

wherein

R1, R2, R3, and R4

are each, independently, an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heterocycloalkyl, heterocycloalkenyl, heterocycloalkynyl, aryl, or heteroaryl group, each of which is optionally substituted with one or more substituents; wherein

R2, R3, and/or R4, when taken together, optionally define an optionally substituted ring system; and R2, R3, and/or R4 are optionally covalently linked to R1.

22. The compound of claim 21, wherein R1 is sterically hindered.

23. The compound of claims 2 1 and 22, wherein R1 is selected from the group consisting of secondary and tertiary alkyl groups, secondary and tertiary alkenyl groups, and secondary and tertiary alkynyl groups, each of which is optionally substituted.

24. The compound of claims 21-23, wherein one or more of R1, R2, R3, and R4 is substituted with a least one silyl group.

25. The compound of claim 21, wherein the compound is selected from the group consisting of compounds of formulae (2), (3), (7)-(9), (13), (16)-(23), (25)- (27), and (30)-(47):

Me ,SiMe2Ph SiMe Ph Me' 2 (2), (3), (34), and 26. A composition comprising at least one compound of claims 21-25.

27. The composition of claim 26, wherein the composition is selected from the group consisting of aerospace materials, pharmaceuticals, agrochemicals, rubber materials, lubricants, hydraulic fluids, damping fluids, diffusion pump fluids, cryogenic fluids, waterproofing agents, hydrophobing agents, heat transfer media, anti-stick coatings, and fuel additives. INTERNATIONAL SEARCH REPORT International application No.

PCT/US 17/53714

Box No. II Observations where certain claims were found unsearchable (Continuation of item 2 of first sheet)

This international search report has not been established in respect of certain claims under Article 1 (2)(a) for the following reasons:

1. Claims Nos.: because they relate to subject matter not required to be searched by this Authority, namely:

□ Claims Nos.: because they relate to parts of the international application that do not comply with the prescribed requirements to such an extent that no meaningful international search can be carried out, specifically:

3. Claims Nos.: 3-20, 23-24 and 26-27 because they are dependent claims and are not drafted in accordance with the second and third sentences of Rule 6.4(a).

Box No. Ill Observations where unity of invention is lacking (Continuation of item 3 of first sheet)

This International Searching Authority found multiple inventions in this international application, as follows:

1 I I As all required additional search fees were timely paid by the applicant, this international search report covers all searchable claims.

2. 1 I As all searchable claims could be searched without effort justifying additional fees, this Authority did not invite payment of additional fees.

3. □ As only some of the required additional search fees were timely paid by the applicant, this international search report covers only those claims for which fees were paid, specifically claims Nos.:

No required additional search fees were timely paid by the applicant. Consequently, this international search report is restricted to the invention first mentioned in the claims; it is covered by claims Nos.:

The additional search fees were accompanied by the applicant's protest and, where applicable, the payment of a protest fee. The additional search fees were accompanied by the applicant's protest but the applicable protest fee was not paid within the time limit specified in the invitation. No protest accompanied the payment of additional search fees.

Form PCT/ISA/210 (continuation of first sheet (2)) (January 201 5) INTERNATIONAL SEARCH REPORT International application No.

PCT/US 17/53714

A , CLASSIFICATION O F SUBJECT MATTER IPC(8) - C07F 7/08 (201 7.01 ) CPC - C07F 7/0805; C07F 7/0809; C07F 7/0827

According to International Patent Classification (IPC) or to both national classification and IPC

B . FIELDS SEARCHED

Minimum documentation searched (classification system followed by classification symbols)

See Search History Document

Documentation searched other than minimum documentation to the extent that such documents are included in the fields searched See Search History Document

Electronic data base consulted during the international search (name of data base and, where practicable, search terms used) See Search History Document

C . DOCUMENTS CONSIDERED T O B E RELEVANT

Category* Citation of document, with indication, where appropriate, of the relevant passages Relevant to claim No.

Pubchem 12835841 deposited on 08 February 2007 (08.02.2007) pp. 1-10. pg 3 2 1; 22; 25

PILLOT et al. 'Synthese Originale et Pratique de L'Artemisia Cetone', Tetrahedron Letters, 1; 2 1976, pp. 1871-1872. pg 1871, para 6 and reaction

KING et al. Ά General Synthesis of Terminal and Internal Arylalkynes by the Palladium- 1; 2 Catalyzed Reaction of Alkynylzinc Reagents with aryl Halides', Journal of Organic Chemistry, 1978, Vol. 43, pp. 358-360. pg 358, Col 2 , reaction 1; pg 359, Table 1; pg 359, Col 1, para 4

NEGISHI et al. 'Stereo- and Regioselective Routes of Allylic Shanes', Tetrahedron Letters, 1982, Vol. 23, pp. 27-30. ENTIRE DOCUMENT 1; 2 ; 21; 22; 25

US 4,593,1 12 A (TAKAMIZAWA et al.) 03 June 1986 (03.06.1986) ENTIRE DOCUMENT 1; 2 ; 2 1; 22; 25

US 5,151 ,538 A (HAYASHI et al.) 29 September 1992 (29.09.1992) ENTIRE DOCUMENT 1; 2 ; 2 1; 22; 25

I Further documents are listed in the continuation of Box C . | | See patent family annex.

Special categories of cited documents: "T later document published after the international filing date or priority document defining the general state of the art which is not considered date and not in conflict with the application but cited to understand to be of particular relevance the principle or theory underlying the invention earlier application or patent but published on or after the international "X" document of particular relevance; the claimed invention cannot be filing date considered novel or cannot be considered to involve an inventive document which may throw doubts on priority claim(s) or which is step when the document is taken alone cited to establish the publication date of another citation or other "Y" document of particular relevance; the claimed invention cannot be special reason (as specified) considered to involve an inventive step when the document is document referring to an oral disclosure, use, exhibition or other combined with one or more other such documents, such combination means being obvious to a person skilled in the art document published prior to the international filing date but later than "&" document member of the same patent family the priority date claimed Date of the actual completion of the international search Date of mailing of the international search report 02 January 2018 2 7 FEB 2018

Name and mailing address of the ISA/US Authorized officer: Mail Stop PCT, Attn: ISA/US, Commissioner for Patents Lee W . Young P.O. Box 1450, Alexandria, Virginia 22313-1450 Facsimile No. 571-273-8300

Form PCT/ISA/210 (second sheet) (January 2015)