2006 VOLUME 6 NUMBER 10

Asymmetric Synthesis quinoxP* ligands

Carreira Dolefin ligands

vaulted biaryl ligands and binol derivatives

oxazolidinethione and thiazolidinethione auxiliaries

gleason chiral auxiliary

shi epoxidation diketal catalyst

shvo’s catalyst

(7R,10S)-(+)-1-Aza-10-isopropyl-8-oxa-4-thiabicyclo(5,3,0)-2-decanone chiral lactam auxiliary capable of forming chiral quaternary centers

sigma-aldrich.com 

Introduction Vol. 6 No. 10 Asymmetric synthesis remains a challenge to synthetic chemists as the demand for enantiomerically pure compounds continues to increase. Many scientists working in Aldrich Chemical Co., Inc. chemical synthesis and drug discovery are striving to find new methods for asymmetric Sigma-Aldrich Corporation synthesis that would lead to the development of new and exciting chiral auxiliaries. In 6000 N. Teutonia Ave. addition, asymmetric catalysis is exploding, as new methods for obtaining enantiomerically Milwaukee, WI 53209, USA pure compounds has fueled a rapidly growing field in chemical synthesis. This edition of ChemFiles describes the applications of new chiral ligands and auxiliaries for use in asymmetric synthesis. Sigma-Aldrich is proud to carry over 5,000 chiral products To Place Orders for the successful construction of complex asymmetric architectures. In most cases, the Telephone 800-325-3010 (USA) cutting-edge methodologies illustrated herein exhibit exceptional levels of stereoselectivity. FAX 800-325-5052 (USA)

Introduction For a complete listing of products related to asymmetric synthesis, please visit us at sigma-aldrich.com/asymmetric. Customer & Technical Services At Sigma-Aldrich™, we are committed to being your preferred supplier for all of your research needs. If you are unable to find a product for your research in asymmetric Customer Inquiries 800-325-3010 synthesis, we welcome your input. “Please Bother Us” with your suggestions and contact Technical Service 800-231-8327 your local Sigma-Aldrich office. SAFC™ 800-244-1173 Custom Synthesis 800-244-1173 Flavors & Fragrances 800-227-4563 International 414-438-3850 Coming Soon! 24-Hour Emergency 414-438-3850 Web Site sigma-aldrich.com The NEW 2007–2008 Email [email protected] Aldrich Handbook of Fine Chemicals

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All prices are subject to change without notice. About Our Cover ChemFiles is a publication of Aldrich Chemical The cover graphic depicts the structure of the Gleason Chiral Auxiliary, (7R,10S)-(+)-1-aza- Co., Inc. Aldrich is a member of the Sigma-Aldrich 10-isopropyl-8-oxa-4-thiabicyclo[5.3.0]-2-decanone. This chiral lactam auxiliary has been Group. © 2006 Sigma-Aldrich Co. successfully employed in the stereocontrolled synthesis of all carbon quaternary centers. The unique methodology developed by Gleason allows for the creation of either antipode of the product using a single isomer of the auxiliary. sigma-aldrich.com  QuinoxP* Ligands

O rder: 1.800.325.3010 T e c h n i c a l S ervice: 1.800.231.8327 2 R ) ) ) S S S 8 2 ) ) ) ) ) ,2 ,2 ,2 ) 100 mg 500 mg O OH S S S S Table 2 Table Table 1 Table R R R R R R -Bu t Me 3

Scheme 2 Scheme 3 Scheme 1 P P R * Ph 96.3 ( 99.9 ( 99.6 ( 99.7 ( 99.2 ( 99.9 ( Me NHAc -Bu 95.6 (1 97.6 (1 93.8 (1 t N N 1 ee (%) (config) 1 1 97%, 99% ee R ee (%) (config) R R a h Me 3 , rt 2 H H H H H 2 R -Bu Me -Bu 90 88 90 Me t t O, 1 Cl CO 2 2 P P P P h Yield (%) Yield -Bu Me t

Me Me -Bu -Bu P P t t 3 N N N N Zn, CH H 2 6 (3 mol %) Me 2 (1 mol %) -Bu 2 t 4 ] R N N 2 ) 4 ]BF Me 2 2 2 2 . H 2 H H H 15 R Ph 2 m CO , KOH, dioxane/H Time (h) 2 % (3 atm), MeOH, 6 2 H % 4-AcO-3-MeOC [Rh(nbd) [RhCl(C 3 mol (cod) (5 mol %), 2 QuinoxP* 2 Et PhB(OH) R 5 mol Me Me -butylmethylphosphino)quinoxaline PdCl Me Me 1 2 2 2 R Ph G G Me Me tert R O 1 CO CO 3 F H H R R 1-adamantyl www.safcglobal.co 2 O NHAc P 2 1 N R 28 a )-2,3-Bis( 2 3 4 5 6 1 2 3 1 H S , Entry 1 1 Entry 18 Isolated yield. The reaction The was completed within 1 h. S R R a a ( C 334.38 FW: 676411-100M 676411-500M

2

8 500 mg 100 mg ). The 4,5 -Bu 2 Me t

P P It is Me -Bu 3 t N N (cod) and 2 at 244-1173 1-800- (USA), or visit Scheme ™ 3 -Bu-BisP* ligands, -unsaturated carbonyl b For instance, known tert , 1 )- a contact SAFC S,S 3 ). This alkylative ring-opening 2 Ready to scale up? For competitive quotes on larger quantities or custom synthesis, -configuration amine with >96% ). These experiments were carried S 6 ). The reactivity profile of these innovative, † Table Table -chiral ligands for industrially useful , P Scheme 1 Table 1 Table -butylmethylphosphino)quinoxaline tert G G Scheme 3 High yields of the addition products were obtained -chiral phosphine ligands offer good to excellent 3 P 2 P 2 N 28 )-2,3-Bis( H R , 18 R metal-catalyzed transformations. the ring-opened products and selectivities that rival the highest reported for this transformation. These results, when combined with the outstanding methodologies presented above, indicate that QuinoxP* is broadly useful for a variety of asymmetric diethylzinc ( methodology benefits from simply premixing PdCl QuinoxP* for 2 hours at room temperature, leading to a highly active catalyst. This catalyst system excellent affords yields of BINAP as the chiral ligand. Imamoto and co-workers Additionally, have succeeded in developing a Pd-catalyzed C–C bond-forming reaction, which displays high enantioselectivities with both dimethyl- and substrates. by running the reactions between 40 and 50 ºC ( exceptional enantiocontrol exerted by this Rh(I)-catalyzed system is evident in the robust performance when compared to the use of enantioselectivity ( Imamoto and co-workers have also exploited the high activity of the QuinoxP* ligand in rhodium-catalyzed enantioselective 1,4-additions of arylboronic acids to 99.9%. Dramatic stereochemical reversal, consistent with the results observed with the related ( was obtained when 1-acetylamino-1-adamantylethene was hydrogenated to the afford amine derivatives ( out at room temperature in methanol under low of pressures hydrogen (3 atm). All hydrogenation reactions were complete in 6 hours and with enantiomeric excesses ranging from 96 to enantiomerically pure transformations such as asymmetric hydrogenation. Impressively, a diverse array of prochiral amino acid and amine substrates were hydrogenated with great efficiency to yield highly enantiopure phosphorus center on standing at ambient temperature in air for more than 9 months. Imamoto has also gone to great lengths to develop in synthetic transformations ranging from metal-catalyzed asymmetric 1,4-additions of arylboronic acids to enantioselective alkylative ring opening to asymmetric hydrogenations. worth noting that QuinoxP* is not oxidized at the stereogenic for the market. research chiral ligands is covered below and highlights the impressive breadth of valuable transformations mediated by QuinoxP*. These powerfully efficient ligands exhibit high levels of enantiocontrol chemistry. Imamoto and co-workers chemistry. have addressed this deficiency through the development of QuinoxP*, which is based on an electron-withdrawing quinoxaline architecture. Sigma-Aldrich is pleased to offer both enantiomers of QuinoxP* classes of enantiocontrol in Ru- and Rh-catalyzed hydrogenation reactions. The one limitation associated with these ligands is their sensitivity which has to impeded air, widespread applicability in bench-top QuinoxP* QuinoxP* Ligands optically Various active phosphine ligands incorporating a chiral center at phosphorus display exceptional enantiosectivities in metal-catalyzed asymmetric synthesis. 676403-100M 676403-500M C 334.38 FW: ( Carreira DOLEFIN Ligands 

sigma-aldrich.com 672254-100M [ FW: 310.47 C (2’-methylpropyl)bicyclo[2.]octa-,5-diene (1 656763-1 656763-100M [ FW: 388.93 C m enantioselectivity in the conjugate addition (89–93% ee). (89–93% addition conjugate the in enantioselectivity ( ee 93% and yield 90% in 1,4-adduct the provided cinnamaldehyde to 4-fluorophenylboronicacid of addition The groups. aryl the of natureelectronic the of independent route general a offers However,aromatics. Rh(I)- the electron-poor with well work not Unfortunately,does method this derivatives. acrolein 3-substituted to nucleophiles aromatic of addition amine-catalyzed an researchersvia other by achieved been recently has 3,3-diarylpropanals chiral of preparation The ee). (89–94% enantioselectivity high consistently with and yields excellent to good preparedin werepropanoates ( and acid phenylboronicfrom donor.manner,and this ( acceptor In the aryl the switching by simply achieved be can product a of enantiomers both to access ligand, the of enantiomer single a Rh(I)- the of presence the in 3-(4-methoxyphenyl)-3-phenylpropanoate report, one In preparation. its for methods limited rather with challenge, a been had motif this of synthesis stereoselective Heretofore,the groups. aryl two the between differentiationlittle is there when even centers, stereogenic diarylmethine of preparations selective facilitates ligand new This to acids arylboronic of 1,4-addition the in enantioselectivity improved substantially exhibited which ( 1 ligand recently,Morethe developed has Carreira acids. boronic of reactions addition conjugate Rh(I)-catalyzed carbonates allylic of resolution kinetic Ir(I)-catalyzed in ( from derived [2.2.2]bicyclooctadienes chiral employing been has groupCarreira the years, past the For Carreira DOLEFINLigands 862499-50-1 12081-16-2 Scheme 4 Scheme 8 22 -Dichlorotetraethylene dirhodium(I) -Dichlorotetraethylene S H H ,4 16 30 Cl 1 S O complex in excellent yield and selectivity.and fromyield Furthermore, excellent in complex ,8 2 Rh S G Scheme 5 Scheme )-5-Benzyl-8-methoxy-1,8-dimethyl-2- 2 ). Similarly, other 3,3-diaryl- and 3-aryl-3-heteroaryl- Similarly,and ). 3,3-diaryl- other ] ] G G tert -butyl cinnamate was converted to ( to converted was cinnamate -butyl ). Again, other substrates maintained high maintained substrates other Again, ). 10 tert 1 -catalyzed conjugate addition conjugate ­-catalyzed -butyl 4-methoxycinnamate -butyl 5-3010 (USA), or visit or (USA), 1-800-325-3010 call a ORDER: Contact your local Sigma-Aldrich office (see back cover), back (see office Sigma-Aldrich local your Contact TO ORDER: , b -unsaturated carbonyls. -unsaturated

R )-isomer was preparedwas )-isomer R )- or ( or )- H H 2 2 C C

CH CH S Figure 1 Figure Rh H )-carvone 2 2 3 7 H S CO and Cl Cl 3 )- C Rh H tert H 12 2 C 2 C CH 100 mg 100 mg -butyl CH 8 ), 8 8 CH 11 3

2 9

2

1 g sigma-aldrich.com/chemicalsynthesi 275891-1 275891-250M [ FW: 285.51 C Dichloro(1,5-cyclooctadiene)palladium(II) 669490-100M FW: 310.47 C (2’-methylpropyl)bicyclo[2.]octa-,5-diene (1 X 12107-56-1 1 8 22 R H H ,4 12 30 Cl R O ,8 2 Pd R G O )-5-Benzyl-8-methoxy-1,8-dimethyl-2- O ] O H t -B G G u + + F X 2 B(OH) B(OH) H s 3 . 2 H CO 2 3 C MeOH/H 1 [Rh( 3.3 mol% MeOH/ 0.5 eqKOH 1.5 mol [Rh( C CH 3.3 mol% 0.5 eqKOH 2 1.5 mol 50 H 2 C 4 O (10:1) ) 3 °C 2 2 % H 50 Cl H 1 2 2 4 O (10:1) ] ) 2 °C 2 % Cl 1 2 ] X X 2 1 1 =H, =OMe, H X 1 3 C

X 2 =OMe85%,93%ee X CH OCH 2 =H95%,91%ee Pd X 3 Scheme 5 Scheme 4 Scheme 2 3 Figure 1 Figure Cl Cl F O 100 mg 250 mg 8 O t -B O u 1 g H

Vaulted Biaryl Ligands

 and BINOL Derivatives

O rder: 1.800.325.3010 T e c h n i c a l S ervice: 1.800.231.8327 2 ∆ 2 , NO 2 H 2 NO Cl Et 4 2

H 2 80% Table 4 Table Table 3 Table 2 CO N O O HCCO 377 20 96 95 94 2 − a 3 H N Scheme 7 Scheme 8 Scheme 6 60% OH Cl 1,2-C ee (%) N C 22 CHPh N 91 CH 3 NH BIRT H Ph ee (%) C C O 2 2 (>99% ee recryst.) 3 CHO HC 78 °C EtO EtO CH 2 − 96 (99% ee recryst.) Br , Cl 2 H Cl 2 , MeOH 4 78 °C; 17:1 − >50:1 >50:1 >50:1 catalyst X = (EDA) 3 , CH cis:trans O, 3 2 2 O N 78 °C to rt 97% (NMR), 97.7% ee (GC) 97% (NMR), 97.7% 2) NaBH − 1) 4 19:1 30:1 X = 4-Br B(OPh) >50:1

/ O cis:trans Et Et 3 61 85 77 87 2 2 74% 2 NaBH 2 2 EtO CH Ligand CO CO LDA, DME/Et then MeI, MeOH, 0 °C Yield (%) Yield 80 °C CHPh CHPh N CHPh N + − 72 77 80 N 86% . catalyst (10 mol %) m (xs) 3 Yield (%) Yield , ca. 3 3 X 48 20 2 0.5 X Cl CH 2 Br Time (h) toluene, 0 to 22 °C 2 B(OPh) / CHO 26 26 21 NO H H H X )-VAPOL catalyst (1:1) )-VAPOL catalyst 4-Br Time (h) H S Ligand

H, MeOH, rt X =

2 2 Pd black AlCl/( OH 2 HCO (0.5 mol %), CH NH Et CHPh )-BINOL www.safcglobal.co )-VAPOL )-BINOL, )-BINOL, O )-VANOL )-VAPOL, )-VAPOL, )-VAPOL, N )-VANOL, )-VANOL, )-chloramphenicol Ligand, Ligand, Ligand, Ligand, R 2 mol % 1 mol % Et S R S Loading S S S 10 mol % 10 mol % ( 2 ( − ( ( ( ( ( ( HC HO + 2 CO 2 EDA Cl NH 1 2 3 1 2 3 4 N 2 Product is the enantiomer of aziridine shown. Entry Entry Ph D-phenylalanine ethyl ester, 80% O a OH ). The O Figure Figure 2 P O O Table 3 Table at 244-1173 1-800- (USA), or visit , ™ )-VAPOL Hydrogenphosphate Ph Ph S ( AlCl and was VAPOL 2 Scheme 7 OH OH contact SAFC , the cycloaddition of acrolein )-VAPOL S -symmetric diol ligands have ( 2 C Ph Ph Ready to scale up? For competitive quotes on larger quantities or custom synthesis, Scheme 6 OH OH Additionally, the phosphoric acid Additionally, derivative The aziridination reaction exhibits excellent isomer, and high enantiomeric isomer, excesses 13 15 ). Both and gave VANOL VAPOL higher yields . cis ). 3 )-VANOL 2 S ( Ph Ph Table 4 Table As shown in , Figure Figure 14 OH OH isomer in very Analogous high reactions optical purity. exo )-BINOL S ( Scheme 8 reaction, reaction, followed by a nucleophilic ring opening of the aziridine with dichloroacetic acid and subsequent acyl group migration ( and stereoselectivities than the BINOL-derived catalyst. hydantoin target in excellent overall yield. The highly expeditious synthesis of the antibacterial agent (–)-chloramphenicol utilized the asymmetric aziridination undergo a variety of reactions, including: deprotection, reductive ring opening, and alkylation reactions ( asymmetric synthesis of leukointegrin antagonist LFA-1 BIRT-377 utilized an aziridination/alkylation methodology to provide the presence presence of arylborate catalysts from prepared vaulted aryl ligands and B(OPh) selectivities for the are obtained. The resultant benzyhydryl-protected aziridines group group has developed a robust catalytic asymmetric aziridination reaction providing optically active aziridines in high yields and selectivities. The reaction relies on the addition of commercially available ethyl diazoacetate (EDA) to benzhydryl imines in the because they allow for convenient access to amines, amino alcohols, diamines, and other useful nitrogen-containing molecules. Most contemporary methods of chiral aziridine preparation have relied on the the chiral Wulff pool. Recently, the with the BINOL-derived catalyst provided the cycloadduct in high yield, but in very low enantiomeric excess (13–41%). Aziridines are important building blocks in organic synthesis shown to be an effective catalyst for the asymmetric Diels-Alder reactions. with cyclopentadiene in the presence of the VAPOL-derived catalyst gave high conversions and excellent stereoselectivities for catalyst. In many of the examples illustrated herein, the vaulted biaryls give both higher yields and higher inductions than the same reactions using a BINOL ligand. early Very on, a catalyst generated from Et 2,2’-binaphthol (VANOL) 2,2’-binaphthol have (VANOL) proven to be excellent ligands in imine catalytic aldol, asymmetric and Diels-Alder, aziridination reactions ( of was VAPOL shown to be effective as a chiral Brønsted acid with the BINOL platform, other attracted considerable attention. Among these are the vaulted biaryl ligands developed by and Wulff co-workers (Michigan State University). Both vaulted and 3,3’-biphenanthrol (VAPOL) vaulted classes of ligands in asymmetric synthesis, and are utilized in a broad array of reaction ene, classes including: Diels-Alder, carbonyl addition and reductions, Michael additions, as well as many others. While tremendous success has been obtained Vaulted Biaryl Ligands and BINOL and BINOL Biaryl Ligands Vaulted Derivatives BINOL and its derivatives are some of the mostly widely used Vaulted Biaryl Ligands

and BINOL Derivatives 

sigma-aldrich.com 675156-250M [ FW: 428.52 C ( 676098-250M [ FW: 438.52 C ( ketones bearing similar alkyl groups is pronounced. is groups alkyl similar bearing ketones prochiraltoward selectivity facial catalyst the and ketones, methyl ( amines aryl functionalized as well as motifs, substitution ketone ( yields good in amines secondary giving amination, reductive underwent ketones alkyl and aryl both (HEH), ester Hantzsch ethyl and derivative acid phosphoric this of presence the In in depicted derivative acid phosphoric BINOL silylated the on relying reaction, amination reductive organocatalytic enantioselective direct first the reportedrecently co-workers and MacMillan imines. bench-stable preformed, of use requirethe methods these amines, chiral corresponding the to ketimines of reduction enantioselective the for developed been have protocols of variety a Although compounds. stable shelf- are aminals protectedresultant the and reaction, amidation imine the in active are imines aryl and sulfonamides of variety A obtained. was ee) (<5% induction asymmetric of level dismal a but (95%), yield excellent an gave catalyst acid Brønsted derived BINOL- a with reaction identical The enantiopurities. impressive resultant ( imines aryl Boc-activated to sulfonamides of addition the in catalyst acid Brønsted chiral useful a be to VAPOLhydrogenphosphatedemonstrated co-workers and Antilla catalyst. BINOL-derived analogous the over induction of levels higher substantially exhibit ( yield excellent in and induction asymmetric Zr-VAPOLhigh with proceeds catalysts Zr-VANOLeither of presenceor the in imines aryl to acetals chiral of synthesis the for method important an providing catalysts, biaryl-derived vaulted by catalyzed also arereactions aldol imine Asymmetric Ph 147702-14-5 147702-13-4 Figure 4 Figure 11 Scheme S R 32 32 HO )-VANOL,97% )-VANOL,97% Figure 3 Figure H H N 22 22 O O 2 2 N,N ). Additionally, the reaction is chemoselective towards chemoselective Additionally,is ). reaction the . 18 ). The reaction conditions are tolerant of a variety a of tolerant are conditions reaction The ). + ] ] -aminal products were prepared in high yields with yields high preparedin wereproducts -aminal G G Me

Scheme 9 Scheme O b -amino esters. The addition of silyl ketene silyl of addition The esters. -amino OTMS 16 , Table5 Ligand/Zr(O (2.2:1), (2mol%) toluene, 40°C 5-3010 (USA), or visit or (USA), 1-800-325-3010 call ORDER: Contact your local Sigma-Aldrich office (see back cover), back (see office Sigma-Aldrich local your Contact TO ORDER: ). Significantly,). catalysts both i -Pr) Scheme 10 Scheme 4 catalyst Ph Ph Ph Ph Ph 100%, 86%ee ). 17 NH Scheme 9 Scheme The OH OH OH OH 2 250 mg 250 mg O 8 8 OM e sigma-aldrich.com/chemicalsynthesi 675210-250M [ FW: 538.63 C ( 675334-250M [ FW: 538.63 C ( F 147702-16-7 147702-15-6 R S Entry 40 40 )-VAPOL,97% )-VAPOL,97% H 3 2 1 H H 2 81%, 95%ee R =alkyl,aryl 90%, 93%ee R HN N 26 26 N O O O HN CH ( ( ( 2 2 S S R Boc Ligand + CH )-VAPOL )-VAPOL )-BINOL 3 CH + X 3 3 TsNH N Ts ] ] G G OCH 2 Loading (mol %) (via cyclicimine

3 82%, 97%ee ( R 20 20 75%, 85%ee ( 2 S )-phosphoric acidcatalyst(10mol%) )-VAPOL Hydrogenphosphate(5mol%) O N H HN

5 ÅMS,40 Solvent EtO O CH Toluene Toluene CH ) H 3 2 3 2 Cl C C s Et OCH . 2 H Et O − H N 3 2 Temp H 50 °C, O, rt,1 O O SiPh SiPh (°C) 3 H 40 25 25 C 85%, 96%ee 72%, 91%ee P ( CH CO O HN 3 3 ) HN 5 OH

C h 3 2 6 Time (h) CH Et CH H (HEH) 6 3 3 15 6 4 OCH OCH Ph Ph Ph Ph 3 H 3 Yield (%) 3 C 71%, 83%ee 100 100 94 92%, 91%ee HN HN R 95%, 94%ee Scheme 11 Scheme 10 Scheme HN CH CH OH OH OH OH HN Figure 4 Figure 3 Figure 3 CH 3 Table5 250 mg 250 mg ee (%) 8 8 * N(H)Ts Boc 3 86 89 28 O OCH X 3 Vaulted Biaryl Ligands

 and BINOL Derivatives

O rder: 1.800.325.3010 T e c h n i c a l S ervice: 1.800.231.8327

3 3 3 3 CF CF CF CF 8 8 100 mg 100 mg 3 3 3 3 OH O P CF CF CF CF OH OH O O



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CPR . m [email protected] G G ] ]  Discovery

P www.safcglobal.co 2 4 O O Let High Throughput Back Operation! in Your 12 12 F F or contact us at at us contact or 18 17 m H H )-3,3’-Bis(3,5-trifluoromethyl)phenyl)-1,1’- )-3,3’-Bis(3,5-bis(trifluoromethyl)phenyl)-1,1’- 36 36 R R 756491-54-0 791616-62-1 ( bi-2-naphthol, 95% C 710.51 FW: [ 674591-100M ( binaphthyl-2,2’-diyl hydrogenphosphate, 95% C 772.47 FW: [ 674605-100M

discoverycpr.co 3 3 8 8 8 OH OH 3 3 100 mg 250 mg 100 mg O O Order fill amounts from 1 mg to 25 g Web-based quoting and ordering P P • • SiPh SiPh OH OH SiPh SiPh O O O O

today at at today CPR at 244-1173 1-800- (USA), or visit ™ Ph Ph to submit inquiries or to sign up for an internet ordering account. ordering internet an for up sign to or inquiries submit to Discovery contact SAFC

Ready to scale up? For competitive quotes on larger quantities or custom synthesis, Learn more about about more Learn gives you the ability to place a single order and receive preweighed, application-ready compounds that allow high-value scientific CPR G G G ] ] ] 2 Widest selection of reagents available No minimum number of components to purchase 2 • • PSi Si P want, submit your order, and receive the fastest delivery possible. delivery the fastest and receive your order, submit want, Fast, custom delivery of single and large series of preweighed compounds and reagents. resources to resources rather focus than on the discovery, tedious process of reagent management and preparation. The use of custom weighed compounds can save you time and money and reduce chemical waste. per vial (mg or and mmol) required and the quantities for the application, set, the type of compound required vials us with your desired provide Simply you to 24 the Then within select compounds you hours. usually compounds party any third including and information price availability we will provide Sigma-Aldrich proudly offers a turn-key solution designed to save you time, reduce waste, and enhance productivity. Discovery Is Weighing and Prepping Reagents Reagents Prepping and Weighing Is Lab? Your in a Bottleneck Creating 4 2 4 O O O 41 42 25 H H H 2,2’-diyl )-3,3’-Bis(triphenylsilyl)-1,1’-binaphthyl- 2-naphthol, )-3,3’-Bis(triphenylsilyl)-1,1’-bi- 96% )-VAPOL hydrogenphosphate )-VAPOL 56 56 40 R R R 791616-55-2 111822-69-6 871130-18-6 674745-100M FW: 865.07 FW: [ ( hydrogenphosphate C [ 674737-100M ( C 803.1 FW: 675512-250M ( C 600.6 FW: [ Oxazolidinethione and Thiazolidinethione

Auxiliaries 

sigma-aldrich.com was obtained preferentially when 2 equivalents of base were base of equivalents 2 preferentiallywhen obtained was the while sparteine, of equivalent 1 using when ratio diastereomeric high in obtained was product aldol ( diastereoselectivities excellent the of enolates auxiliaries. chiral efficient and selective highly be to proven have oxazolidinones, Evans well-known the of variants structural thiazolidinethiones, and oxazolidinethiones Chiral formation. bond C–C asymmetric for methods important most the of one be to considered is auxiliaries chiral by mediated reaction aldol asymmetric The Thiazolidinethione Auxiliaries Oxazolidinethione and diastereomeric ratio of >98:2. of ratio diastereomeric a gave and (87%) yield excellent in proceeded step stereoinducing N (4 of enolate chlorotitanium the and aldehyde TIPS-protected the from starting steps 10 of total a in diastereoselectively constructed was fragment ring pyran The regulation. cycle cell on effects as well as properties cytotoxic and neuro- with ascidian marine the from isolated molecules bioactive of class new a of member a A, Bistramide of synthesis total enantioselective convergent a in DeBaillie and Crimmins by applied successfully was Recently,auxiliary thiazolidinethione the imidazole N,O with treatment by accomplished be can Weinrebamides the to transamination while esters, corresponding the to hydride. diisobutylaluminum with cleavage reductive by auxiliary chiral the and aldehydes corresponding their to reduceddirectly and thiazolidinethiones the analogs, oxazolidinone the to contrast In ( conditions reaction the either to access giving sequence aldol iterative an in methodology this of utility the demonstrated Crimmins accomplished. be also can diastereoselectivity high with sequences aldol Iterative pathway.mechanistic the in states transition nonchelated and chelated between switching of result a be to proposed is additions aldol the in selectivity facial in change The effect. this to used and oxazolidinethiones ( auxiliary chiral same the with “Evans- either bearing products condensation aldol synthesize selectively to possible is it conditions, reactionappropriate the choosing by that, detail in shown has Crimmins experiments, of series a In transformation. particular this in diastereoselectivities poor achieve to able only employed. S -propionyl-4-benzylthiazolidine-2-thione ( -propionyl-4-benzylthiazolidine-2-thione S 70%, dr>99:1 N -dimethylhydroxylamine hydrochloride in the presence of presence the in hydrochloride-dimethylhydroxylamine syn O - syn OH 23 22 Alcoholysis using methanol and imidazole leads imidazole and methanol using Alcoholysis syn t -Bu 20 or organoaluminum compounds ( compounds organoaluminum or - However, the corresponding oxazolidinones areHowever, oxazolidinones corresponding the syn aldol syn 2) RCHO 2 1) 1 adduct or adduct 21 N eq eq ” or “non-Evans- or ” -acylated auxiliaries with aldehydes results in results aldehydes with auxiliaries -acylated . (-)-sparteine . TiCl Scheme 14 Scheme 4 N N 19 -propionyl thiazolidinethiones can be can thiazolidinethiones -propionyl -acyl oxazolidinethiones can be can oxazolidinethiones -acyl syn The acetate aldol reaction of titanium of reaction aldol acetate The - 25 S anti Scheme 13 Scheme Scheme 12 Scheme S ). N - syn O syn 5-3010 (USA), or visit or (USA), 1-800-325-3010 call ORDER: Contact your local Sigma-Aldrich office (see back cover), back (see office Sigma-Aldrich local your Contact TO ORDER: ” stereochemistry starting stereochemistry ” adduct depending on the on depending adduct 2) RCHO 1 1) 1 eq eq )! Both )! anti ). Interestingly,). the Scheme 16 Scheme . (-)-sparteine . TiCl Lissoclinum bistratum Lissoclinum Scheme 15 Scheme N aldol product aldol 4 -acyl anti N -propionyl aldol S ). This ). Scheme 12 Scheme S 70%, dr>99:1 ). N 24 O S syn 22 )- OH t -Bu

sigma-aldrich.com/chemicalsynthesi X X=O, S O H S S S S N O Bn H S S S S S O N N N N O R R O O O O CH CH CH TIP OTBMDS 3 OH OH OH OMOM O H 3 3 CH S 3 C RCHO S CH 3 + OPM OBn N Bn 3 O S B OSEM O S H N Bn 3 C O O O 2.5 eq(-)-sparteine 1.0 eqTiCl 1.0 eq(-)-sparteine 2.0 eqTiCl + O CH (CH S S CH 2 CH H Cl O CH N N 3 pyran fragment Bn Bn Bn 3 2 ) 3 L H O 2 , 12h,-20°Ctort imidazole imidazole ONHCH Bistramide

O x O O s i AlN(CH 3 CH R Bn -Bu M . CH THF H N O 4 4 CH 3 (-)-sparteine TiCl H 2 OH O AlH O N 3 2 X Cl 3 3 4 N OH ⋅ )OCH , NMP, HCl O H 2 X 4 steps , -78°,6 O CH CH CH A S R Ti O O 3 3 S 3 H 3 Cl Cl N H O H Cl O O O 3 h C N H S S 3 OH O CO H H N H N 3 Bn Bn H C CH 3 S CO 3 H O CH N O O 83%, 98:2dr 77%, 98:2dr CO S 3 O O CH CH CH 3 N O CH CH N Bn O 87%, >98:2dr OTBMDS OH OH O O O 3 3 3 77% 77% 79% 3 3 95% CH OMOM OH CH CH CH CH CH X X OH 3 OH non-Evans- OH 3 OTBMDS OTBMDS CH 3 S S 3 3 3 Evans- OBn OPMB CH CH N N 3 Scheme 16 Scheme 15 Scheme Scheme 14 Scheme 13 Scheme Bn Bn CH CH O O 3 3 OSEM OTIP syn CH CH 3 3 OH OH syn S

3 3 R R 

(S)-4-Isopropyl-1,3-thiazolidine-2-thione 8 (S)-4-Isopropyl-1,3-oxazolidine-2-thione 8 S C6H11NS2 S C6H11NOS FW: 161.29 S NH FW: 145.22 O NH [76186-04-4] [104499-08-3]

39933-500MG-F 500 mg 04987-1G-F 1 g 39933-2.5G-F 2.5 g 04987-5G-F 5 g

(R)-4-Isopropyl-1,3-thiazolidine-2-thione 8 (R)-4-Isopropyl-1,3-oxazolidine-2-thione 8 C H NS S 6 11 2 C6H11NOS S FW: 161.29 S NH FW: 145.22 O NH [110199-16-1]

05329-500MG 500 mg 08914-1G-F 1 g 05329-2.5G 2.5 g (S)-4-Phenyl-1,3-oxazolidin-2-thione 8 (S)-4-Phenyl-1,3-thiazolidine-2-thione 8 C9H9NOS S C9H9NS2 S FW: 179.24 FW: 195.3 O NH S NH [190970-57-1]

[185137-29-5] Auxiliaries Thiazolidinethione and Oxazolidinethione

08913-1G-F 1 g 39911-1G-F 1 g 08913-5G-F 5 g 39911-5G-F 5 g

(R)-4-Phenyl-1,3-oxazolidine-2-thione 8 (R)-4-Phenyl-1,3-thiazolidine-2-thione 8 C9H9NOS S C H NS S 9 9 2 FW: 179.24 FW: 195.3 O NH S NH [171877-37-5] [110199-18-3]

00762-1G-F 1 g 05802-1G-F 1 g 00762-5G-F 5 g 05802-5G-F 5 g

(S)-4-Benzyl-1,3-thiazolidine-2-thione 8 (S)-4-Benzyl-1,3-oxazolidine-2-thione 8 S C H NOS S C10H11NS2 10 11 FW: 193.27 O NH FW: 209.33 S NH O

[171877-39-7] [145588-94-9] 0 1 0 3 . 5 2 3 . 0 0 8 . 1 : r e d r

06357-1G-F 1 g 08416-1G-F 1 g 06357-5G-F 5 g 08416-5G-F 5 g

(R)-4-Benzyl-1,3-thiazolidine-2-thione 8 (R)-4-Benzyl-1,3-oxazolidine-2-thione 8 S S C10H11NS2 C10H11NOS FW: 209.33 S NH FW: 193.27 O NH [110199-17-2] [190970-58-2]

42787-1G-F 1 g 00749-1G-F 1 g 42787-5G-F 5 g 00749-5G-F 5 g T l a c i n h c e

Want to try a series of auxiliaries on a small scale to find the best one for your chemistry? S 7 2 3 8 . 1 3 2 . 0 0 8 . 1 : e c i v r e Consider a custom-packaged kit from DiscoveryCPR. A complete R or S set of these auxiliaries at 1 mmol, or less, packaged in the vial of your choice. Contact us at [email protected] for pricing and lead-time. DiscoveryCPR

Ready to scale up? For competitive quotes on larger quantities or custom synthesis, contact SAFC™ at 1-800-244-1173 (USA), or visit www.safcglobal.com. 10

Gleason Chiral Auxiliary A B The stereocontrolled synthesis of all-carbon quaternary centers is Sequence Yield (%) dr (%) Sequence Yield (%) dr (%) a formidable challenge in asymmetric synthesis. Alkylation of an enolate is a fundamental reaction that may be used towards this 1. LDA / EtI 95 99:1 1. LDA / MeI 90 99:1 task. While progress has been made using catalytic asymmetric 2. LDA / MeI 90 99:1 2. LDA / EtI 86 99:1 methods in allylation and arylation, the majority of direct alkylation methods continue to require the use of chiral auxiliaries. 3. Li-NH3 / PrI 88 99:1 3. Li-NH3 / PrI 91 99:1

Professor James Gleason of McGill University has developed an 4. H2SO4 79 n/a 4. H2SO4 82 n/a elegant method for preparing quaternary carbons using a chiral thioglycolate lactam auxiliary (Figure 5).26 Table 6 The lactam can be alkylated three times; twice using basic O enolization and once using reductive enolization, to give O Cl a-quaternary carboxylic acid derivatives (Scheme 17). Each HO HO HO alkylation step occurs in excellent yield and with a high degree of Me Et Et Me Pr Et diastereoselectivity. Cleavage of the auxiliary via acidic or reductive conditions furnishes the corresponding carboxylic acid or primary Figure 6 alcohol, respectively. Furthermore, from a single chiral auxiliary, access to both antipodes can be achieved simply by altering the order of Vanadium-Catalyzed Asymmetric enolate alkylation. For instance, both enantiomers of 2-ethyl-2- Oxidation methylpentanoic acid were synthesized in good overall yield and in excellent optical purity (Scheme 18, Table 6). Importantly, this Anson and co-workers have reported example illustrates that the third reductive alkylation step proceeds that the 3,5-diiodo Schiff base 1 in

diastereoselectively for both (Z)- or (E)-disubstituted enolates. combination with VO(acac)2 gives Gleason and co-workers have demonstrated that synthetically I excellent results in the catalytic N useful groups such as: allyl, functionalized alkyl, and benzyl groups asymmetric sulfoxidation of alkyl OH 1 can be introduced at the quaternary center while maintaining OH aryl sulfides. Recently, Jackson and good yields and stereocontrol (Figure 6). Sigma-Aldrich is pleased I co-workers have demonstrated to offer this versatile auxiliary for your research purposes. its use in the kinetic resolution 1 of alkyl aryl sulfoxides with high enantioelectivities.2 O

N O- O S 1.5 mol % 1 S+ H S 1.0 mol % VO(acac) CH Figure 5 CH3 2 3 1.2 eq H2O2

Gleason Chiral Auxiliary O O O 2 CH Cl , 0 °C a) LDA, LiCl, 1 a) LDA, LiCl, R a) Li−NH3, 2 2 81%, 90% ee R 1 N THF, 0 °C N THF, 0 °C N R THF, −78 °C S S S O b) R1-X O b) R2-X O H H H - O- O 1.5 mol % (R)-1 + S+ O S 1.0 mol % VO(acac) CH3 2 CH3 5 M H2SO4 R3 HO dioxane, ∆ 1 2 0.6 eq H2O2 OLi O R R H3C H3C 1 3 R 3 R CHCl3, 0 °C N b) R -X N 41%, 98% ee O R2 O R1 R2 or

SLi SR3 Li H2NBH3 R3 HO 8 THF, ∆ R1 R2 (S)-2-[(1-Hydroxy-3,3-dimethylbutan-2-ylimino) methyl]-4,6-diiodophenol, 97% Scheme 17 C13H17I2NO2 FW: 473.09 [477339-39-2] O O O Pr A N B Pr HO HO 677558-100MG 100 mg O S Et Me Me Et H 677558-500MG 500 mg

Scheme 18 Vanadyl acetylacetonate, 98%

C10H14O5V FW: 265.16 (7R,10S)-(+)-1-Aza-10-isopropyl-8-oxa-4- 8 [3153-26-2] thiabicyclo[5.3.0]-2-decanone, 97% C H NO S 10 17 2 O 550787-10G 10 g FW: 215.31 N 550787-50G 50 g O S H References: (1) Pelotier, B. et al. Synlett 2002, 1055. (2) (R)-isomer used. Drago, C. et al. Angew. Chem. Int. Ed. 2005, 44, 7221. 667587-1G 1 g

TO ORDER: Contact your local Sigma-Aldrich office (see back cover), sigma-aldrich.com call 1-800-325-3010 (USA), or visit sigma-aldrich.com/chemicalsynthesis. Shi Epoxidation

11 Diketal Catalyst

O rder: 1.800.325.3010 T e c h n i c a l S ervice: 1.800.231.8327 27 H 13 C O Scheme 21 Scheme 20 Bu O 2 t- :H OH O 2 90% 27 O O H dr = 12:1 CH 2 13 OH C C 3 OH , Oxone H OH 2 CN:(MeO) 2 OH 3 analogue 2 H NH 2 Cl

CH D O 2 O C 2 O O 3 H H , 2 H O O 1-deoxy-5-hydroxysphingosine C O (+)-Aurilol . H m O CN:EtOH:CH 3 30 mol % B O CH H OH OH 27 83% O H A 13 dr = >15:1 H C H O Bu O O t- Br H H O O www.safcglobal.co OSEM OSEM HO HO C 3 H sigma-aldrich.com/chemnews Got ChemNews? 5 g 3 Monthly Chemistry E-Newsletter 3 CH 33 CH O Figure Figure 7 O 3 O and Scheme 19 cells. O 3 27 CH O O O at 244-1173 1-800- (USA), or visit C ™ 3 C 3 H H 93%, 92% ee 3 (+)-Aurilol has been 32 3 alkenes with good to CH ). CH h cis 2 O 21 O 2 contact SAFC O This organocatalyst is able H O , 29 O 2 2 ). 2,3-hexodiulo-2,6- -D-erythro- b Ready to scale up? For competitive quotes on larger quantities or custom synthesis, O Scheme CN , 0 °C, 12 3 O C 15 mol % 3 CH These 2-amino-3,5-diols are 1-deoxy- C Figure Figure 7 3 H 31 H 3 ). Shi has also developed a very efficient method CH 20 alkenes and certain 28 30 -fructose ( trans -isopropylidene- ). d ] O Scheme G 6 O 18 H 12 based on Scheme 19 18422-53-2 total synthesis of (+)-aurilol ( shown to exhibit significant cytotoxicity against HeLa S anticancer agents. The Shi epoxidation has also appeared in various total syntheses. In one example, Morimoto and coworkers have used Shi’s methodology to achieve the cis conformation of the D ring in the coworkers recently reported a robust and selective synthesis of 2-amino-3,5-diols that employs the Shi epoxidation in a key step ( 5-hydroxysphingosine analogues, which show promise as ( Other groups have found methodology use in of pursuit Shi’s of various unique moieties. For example, McDonald and excellent yields Shi and has selectivities. achieved More recently, excellent results using hydrogen peroxide as an oxidant instead of Oxone, which allows a significant reduction in the amount of additional salts introduced and solvent used in the reaction Jacobsen-Katsuki. for asymmetric epoxidation, using ketone-derived organocatalyst 2 to epoxidize Shi Epoxidation Diketal Catalyst Diketal Shi Epoxidation Catalytic asymmetric epoxidation of alkenes has been the focus of many efforts research over the past two decades, the best known methods probably being those developed by Sharpless 520160-5 C 258.27 FW: [ 1,2:4,5-Di- pyranose, 98% 12

Shvo’s Catalyst Ph OH Ph OH O OH In catalytic asymmetric synthesis enzyme-mediated kinetic 4 + + 4 + 1 H Ph Ph 1 2 1 R2 R 2 Ru R R R resolution is an important area. Lipases are particularly successful R OC H H in kinetic resolutions and hence are manufactured on commercial OC scale. However, conventional kinetic resolution has a maximum Scheme 24 theoretical yield of 50%. Dynamic kinetic resolution (DKR) circumvents this limitation by epimerizing the slow-reacting CALB OH OAc enantiomer concurrently with the kinetic resolution. In this way, 3 eq. p-Cl-C6H4OAc one enantiomer of the epimerized substrate is converted faster R CH3 2 mol % 3 R CH3 to the product (e.g. by transesterification) by the enzyme, and toluene 78-92% yield (0.25 M) the yield can theoretically be increased to 100% using DKR >99% ee (Scheme 22).34 Diruthenium complex 3, first reported by Shvo,35 has found Scheme 25 numerous applications as a versatile catalyst in organic synthesis, including the reduction of aldehydes and ketones to alcohols, OAc bimolecular disproportionation reaction of aldehydes to esters, CH3 isomerization of allylic alcohols and oxidation of alcohols.36 Under thermal conditions, the Shvo catalyst dissociates into the catalytically active 16-electron species 4 and 18-electron complex 80%, >99% ee OAc 5 (Scheme 23). OAc Bäckvall has successfully used Shvo’s complex as an efficient R CO2R' epimerization catalyst in several enzyme mediated DKRs.37 In the first step of the proposed epimerization mechanism of secondary 60-80%, 30-98% ee 77%, >99% ee OH alcohols, one of the oxygens on 4 abstracts a proton (removing the need of an external base as cocatalyst) and the ruthenium R1 R2 metal acts as a hydride acceptor, subsequently leading to ketone OAc OAc formation. The ketone generated is then reduced in reverse O CH fashion, resulting in an overall epimerization of the corresponding 3 CH3 alcohol (Scheme 24). 79%, >99% ee 88%, >99% ee The nature of acyl donor is critical to take into account for successful chemoenzymatic DKR, and Bäckvall and co-workers OAc

have discovered certain aryl esters are efficient acyl donors in the CH3 DKR of several alcohols. An efficient protocol using immobilized 90%, >97% ee Candida antarctica lipase B (CALB) is shown in Scheme 25. Based on the use of CALB in combination with Shvo’s ruthenium catalyst Scheme 26 and p-chlorophenyl acetate as acyl donor, a number of secondary alcohols were successfully transesterified and obtained in good Entrya Starting Material Product Yield (%) Selectivity to high yields and excellent enantioselectivities (Scheme 26). In OH OH OAc OAc >99% ee

Shvo’s Catalyst Shvo’s the case of the DKR of the racemic a-hydroxy esters, immobilized 1 90 H3C CH3 H3C CH3 (R,R):meso 38:62 Pseudomonas cepacia lipase (PS-C) in cyclohexane was used. OH OH OAc OAc The chemoenzymatic DKR was also applied to symmetrical diols, N N >99% ee 2 H3C CH3 H3C CH3 78 hydroxy esters, azido alcohols, hydroxy nitriles, halo alcohols and (R,R):meso >99:1 hydroxy phosphonates (Table 7). Similarly, using a slightly higher amount of Shvo’s catalyst, various b-hydroxy esters were obtained OH Bn OH OAc Bn OAc >96% ee 3 N N 64 in a tandem aldol-deracemization-transesterification reaction H3C CH3 H3C CH3 (R,R):meso 89:11 sequence in good yields and enantioselectivities (Scheme 27). OH OAc 4 N N 71–87 85–99% ee R 3 R 3

OH kfast OAc OH OAc 5 CN CN 72–98 36–99% ee R1 R2 R1 R2 R R

OH OAc 6 Cl Cl 74–98 87–95% ee R R krac

OH O OAc O P P 7 R (OR') R (OR') 69–86 >99% ee OH OAc n 2 n 2 kslow 1 2 1 2 a R R R R Typical reaction conditions: CALB, 4 mol % 3, 3 eq. p-Cl-C6H4OAc in toluene. Scheme 22 Table 7

H Ph O O Ph Ph Ph O- OH PS-C Ph Ph Ph + Ph O OLi OH O OAc O Ph Ph 6 mol % 3 Ru Ru Ph + Ph Ph Ph + Ph H Ph Ru Ru OC OC R H OEt R OEt 3 eq. p-Cl-C6H4OAc R OEt OC CO OC CO H OC OC cyclohexane up to 82%, up to 99% ee Shvo's catalyst (3) 4 5

Scheme 23 Scheme 27

TO ORDER: Contact your local Sigma-Aldrich office (see back cover), sigma-aldrich.com call 1-800-325-3010 (USA), or visit sigma-aldrich.com/chemicalsynthesis. 13

1-Hydroxytetraphenyl-cyclopentadienyl 8 Lipase immobilized from Candida antarctica (tetraphenyl-2,4-cyclopentadien-1-one)-m- hydrotetracarbonyldiruthenium(II) 73940-1G 1 g C H O Ru H 62 42 6 2 Ph O O Ph 73940-5G 5 g FW: 1085.13 Ph Ph Ph Ph [104439-77-2] Ru Ru Ph H Ph Lipase, immobilized in Sol-Gel-AK on pumice from Candida OC CO OC CO antarctica 668281-100MG 100 mg 668281-500MG 500 mg 89137-1G-F 1 g 89137-5G-F 5 g Lipase A, Candida antarctica, CLEA 8 Amano Lipase PS from Pseudomonas cepacia 12117-1G 1 g 12117-5G 5 g 534641-10G 10 g 534641-50G 50 g Lipase B, Candida antarctica, recombinant from Aspergillus oryzae Lipase from Pseudomonas cepacia [9001-62-1] [9001-62-1] 62288-50MG-F 50 mg 62309-100MG 100 mg 62288-250MG-F 250 mg 62309-500MG 500 mg

Lipase, immobilized in Sol-Gel-AK from Pseudomonas cepacia Lipase, Candida antarctica, CLEA 62279-1G 1 g 16698-100MG-F 100 mg 62279-5G 5 g 16698-500MG-F 500 mg Lipase, immobilized on ceramic particle from Pseudomonas Lipase from Candida antarctica cepacia [9001-62-1] 62299-100MG-F 100 mg 17261-1G 1 g

62299-500MG-F 500 mg 17261-5G 5 g Shvo’sCatalyst

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Ready to scale up? For competitive quotes on larger quantities or custom synthesis, contact SAFC™ at 1-800-244-1173 (USA), or visit www.safcglobal.com. References 14

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Scheme 13isshown inthenextcolumn. method ofpreparation seereference 28in thisissue).Thecorrected via Eschweiler-Clarke reaction from either amino groups (-NH correct catalystsmusthavedimethylaminogroups (-NMe 39867 Page 7,Paragraph4,Scheme13.The diaminecatalysts Desymmetrization – Alkaloids Cinchona Organocatalysis” ChemFiles Vol. 6No.4“Asymmetric Additions andCorrections to (1) References

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(7) (i) (a) (b) (h) (a) (e) Paquin, J.-F.Paquin, al. et (b) (d) (g) (b) (c) (a) (a) (b) (c) (e) (d) (c) (b) (j) Paras, N. A.; MacMillan, D. W.D. C. MacMillan, A.; N. Paras, (d) (c) (i) Imamoto, T.;Yoshida,Imamoto, K.; Sugita, K. (c) Yu. S. et al. Yu.et (c) S. (g) Paquin, J.-F.Paquin, al. et 124 T.Imamoto, al. et 127 (f) (a) Defieber,al. et C. (h) (f) Syntheses of vaulted biaryls: vaulted of Syntheses (a) T.Imamoto, al. et (b) Fischer,al. et C. mentionedinthetextdonotproduce theindicatedresults. The Imamoto, T.Imamoto, al. et Bao, J.; Wulff,W.J.; D. Bao, Bao, J.; Wulff,W.J.; D. Bao, Xiao, D. et al. et D. Xiao, Mauleón, P.;Mauleón, C. Carretero,J. Tang,W.;X. Zhang, Hayashi, T.Hayashi, al. et Tang,W.;X. Zhang, Mezzetti, A. et al. et A. Mezzetti, Zhang, Y.Zhang, al. et Lei, A. et al. et A. Lei, Zhang, Z. et al. et Z. Zhang, 64 41 al. et J. Weinkauff,D. Bolshan, Y.Bolshan, al. et Heller,P.D. al. et Mezzetti, A. et al. et A. Mezzetti, Kurth, V.Kurth, al. et Hamada, Y.Hamada, al. et Tang,W.al. et van Leeuwen, P.Leeuwen, van al. et W.M. N. Lautens, M.; Rovis, T.Rovis, M.; Lautens, Duursma, A. et al. et A. Duursma, Eur.X. Zhang, D.; Liu, Tang,W.al. et Tang,W.al. et Bao, J. et al. et J. Bao, T.Imamoto, T.Imamoto, al. et Miyaura, N. et al. et N. Miyaura, Spagnol, M. et al. et M. Spagnol, , 11934. , , 7894. , , 3996. , , 1612. , 2

). Thesediaminecatalystscaneasilybe synthesized Org. Lett. Org. J. Org. Chem. Org. J. J. Am. Chem. Soc. Chem. Am. J. J. Am. Chem. Soc. Chem. Am. J. J. Am. Chem. Soc. Chem. Am. J. Org. Lett. Org. J. Am. Chem. Soc. Chem. Am. J. Lett. Org. Org. Lett. Org. J. Am. Chem. Soc. Chem. Am. J. Soc. Chem. Am. J. Eur.Chem. Inorg. J. Angew. Chem. Int. Ed. Engl. Ed. Angew.Int. Chem. Lett. Org. Soc. Chem. Am. J. J. Org. Chem. Org. J. Org. Lett. Org. TetrahedronLett. Org. Lett. Org. J. Am. Chem. Soc. Chem. Am. J. TetrahedronLett. J. Am. Chem. Soc. Chem. Am. J. Tetrahedron:Asymmetry Soc. Chem. Am. J. Organometallics Organometallics Chem. Eur.Chem. J. Org. Lett. Org. Org. Lett. Org. Engl. Ed. Angew.Int. Chem. TetrahedronLett. Soc. Chem. Am. J.

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Int. Ed. Enríquez-García, A.;Lomberget,T.; Bernardinelli, G.T. 14, Reference (28).Thefollowingreference ismissing:(b)Kündig,E.P.; missing: Zhong,G. Page 14,Reference (5)(c)a-Aminoxylation.Thefollowingreference is References pending). patents International and (US researchmarket the for Chemical Nippon with collaboratrion in sold are ligands †QuinoxP* (35) (31) (30)

(19) (18) (29) (20) (28) (26) (22) (33) (23) (16) (36) (17)

Paquette, L. A.; Braun, A. Braun, A.; L. Paquette, Morimoto, Y.Morimoto, al. et For a review, see: Pàmies, O.; Bäckvall, J.-E. Bäckvall, O.; review,Pàmies, a see: For therein. Evans, D. A.; Bartroli, J.; Shih, T.Shih, J.; Bartroli,L. A.; D. Evans, Crimmins, M. T.;C. M. A. Crimmins, DeBaillie, Ward, R. S. Ward,R. (c) (e) Patwardhan, A. P.A. Patwardhan, (e) al. et Wulff,W.C.; D. Loncaric, (c) Wulff,W.C.; D. J. Antilla, (b) Johnson, R. A.; Sharpless, K. B. In B. K. Sharpless, A.; R. Johnson, (a) Antilla, J. C.; Wulff,W.C.; D. J. Antilla, (a) (d) 2nd Ed. Ojima, I., Ed.; Wiley-VCH: New York,New 2000; Wiley-VCH: Ed.; I., Ojima, Ed. 2nd Shvo, Y.Shvo, al. et Wiseman, J. M. et al. et M. J. Wiseman, Shu, L.; Shi, Y.Shi, L.; Shu, (d) Patwardhan, A. P.A. Patwardhan, (d) al. et Velàzquez,F.; F.H. Olivo, al. Storer,et I. R. (a) York,4.2. New Chapter VCH: 1993; Ed.; I., Ojima, Hodge, M. B.; Olivo, H. F.H. Olivo, B.; M. Hodge, Jacobsen, E. N. In N. E. Jacobsen, 6A. Chapter Arpin, A. et al. et A. Arpin, 128 T.M. al. Crimmins, et 103 103 Suenaga, K. et al. et K. Suenaga, T.;M. Crimmins, Chaudhary, K. Xue, S. et al. et S. Xue, Prabhakaran, R. Prabhakaran, Rowland, G. B. et al. et B. G. Rowland, (b)

2006 Wang, Z.-X. et al. et Wang,Z.-X. Tu,Y. al. et 44 39 121 Shi, Y.Shi, Acc. Frohn, M.; Shi, Y.Shi, M.; Frohn, , 4936. , 2127. , , 3247. , , 6169. , 4518. , , , 5099. , 45 (OC) , 98–101. Tetrahedron:Asymmetry 3

Angew. Chem.Int.Ed. Angew. Chem., Int. Ed. Angew.Int. Chem., Cr

J. Am. Chem. Soc. Chem. Am. J. Tetrahedron J. Am. Chem. Soc. Chem. Am. J. Chem. Res. Chem. Org. Lett. Org. Synlett J. Am. Chem. Soc. Chem. Am. J. Catalytic Asymmetric Synthesis, Asymmetric Catalytic J. Nat. Prod. Nat. J. OH OH J. Am. Chem. Soc. Chem. Am. J. Synthesis J. Am. Chem. Soc. Chem. Am. J. J. Am. Chem. Soc. Chem. Am. J. Org. Lett. Org. J. Org. Chem. Org. J.

Me 2004 1 CH

Curr.Chem. Org. 2 2006 eq H

Tetrahedron N H TetrahedronLett. s

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2004 3 Org. Lett. Org. Cl . Angew. Chem., Int. Ed. Angew.Int. Chem., . Et C 10 mol 2001 2 eq , -40°,21 , 2048, and referencecitation and 2048, , 3 Org. Lett. Org. N J. Am. Chem. Soc. Chem. Am. J. N, MS4A Angew. Chem., Int. Ed. Angew.Int. Chem., . BzCl

, 2000 1998

% Org. Lett. Org. 2005 8 , H

J. Am. Chem. Soc. Chem. Am. J. , 1986

, 1359. , 37 1996 Catalytic Asymmetric Synthesis, Asymmetric Catalytic 57 h J. Am. Chem. Soc. Chem. Am. J.

, 488. , , 1979. , 2006

2003 , 2001

, 5213. , 1995 , (OC) 2001 2005 61

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, 3155. , 108 3 , 515. , 2005 1997 Cr 118 89%, 99%ee

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6 , Chem. Rev.Chem. , 7400. , 40 7 , 1997 , 9806. , , , 1475. , 127 , 2201. , 69 , 4247–4250.Page , , 894. , , 3 OB OH , 2271. , , 84. , 127 119 , 3675. , , Angew. Chem. , 9397. , z

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,

New Chiral Building Blocks from Sigma-Aldrich

(R)-(−)-3,3’-Bis-(3,5-dimethylphenyl)- 8 (S)-(4-Fluorophenyl)oxirane 8 (S)-(+)-1-Fmoc-3-pyrrolidinol 8

5,5’,6,6’,7,7’,8,8’-octahydro-1,1’-bi-2-naphthol C8H7FO O C19H19NO3 OH C36H38O2 CH3 FW: 138.14 FW: 309.36 N FW: 502.69 [134356-74-4] F [215178-39-4] Fmoc CH3 76477-250MG-F 250 mg 654647-1G 1 g OH 76477-1G-F 1 g OH 654647-5G 5 g

CH3 (R)-(−)-1,2,3,4-Tetrahydro- 8 1-naphthylamine (R)-(−)-1-Cbz-3-pyrrolidinol 8 C12H15NO3 OH CH3 C10H13N NH2 FW: 147.22 FW: 221.25 669180-100MG 100 mg [100858-33-1] N [23357-46-2] Cbz (S)-(+)-3,3’-Bis-(3,5-dimethylphenyl)- 8 668818-5G 5 g 654655-1G 1 g 5,5’,6,6’,7,7’,8,8’-octahydro-1,1’-bi-2-naphthol 668818-25G 25 g 654655-5G 5 g

C36H38O2 CH3 FW: 502.69 (S)-(+)-1,2,3,4-Tetrahydro- 8 Z-D-Prolinol 8 1-naphthylamine CH3 C H NO 13 17 3 OH C10H13N NH2 OH FW: 235.28 FW: 147.22 N OH [72597-18-3] Cbz [23357-52-0] CH3 673102-1G 1 g 668796-5G 5 g 668796-25G 25 g CH3 (R)-2-Piperazinecarboxylic acid 8 dihydrochloride 669172-100MG 100 mg (R)-1-Boc-3-methylpiperazine 8 C H N O · 2HCl H 5 10 2 2 N C10H20N2O2 H N CH3 FW: 203.07 R-(+)-3,3,3-Trifluoro-1,2-epoxypropane 8 FW: 200.28 OH [126330-90-3] N C3H3F3O [163765-44-4] N H O O FW: 112.05 Boc CF 67176-1G-F 1 g [143142-90-9] 3 08571-1G-F 1 g 67176-5G-F 5 g 667005-250MG 250 mg 08571-5G-F 5 g 667005-1G 1 g (S)-(+)-3-Piperidinecarboxylic acid 8 (S)-1-Boc-3-methylpiperazine 8 C6H11NO2 O C H N O H (S)-(−)-3,3,3-Trifluoro-1,2-epoxypropane 8 10 20 2 2 N CH FW: 129.16 FW: 200.28 3 OH C3H3F3O [59045-82-8] O N FW: 112.05 [163765-44-4] N H [130025-34-2] CF3 Boc 656364-1G 1 g 63207-1G-F 1 g 665797-250MG 250 mg 656364-10G 10 g 63207-5G-F 5 g 665797-1G 1 g (R)-(−)-3-Aminopiperidine 8 (R)-(−)-1-Fmoc-3-pyrrolidinol 8 (R)-(4-Fluorophenyl)oxirane 8 dihydrochloride C19H19NO3 OH C H FO O C H N · 2HCl NH 8 7 FW: 309.36 5 12 2 2 FW: 138.14 FW: 173.08 [215178-39-5] N N · 2 HCl [134356-73-3] F Fmoc [334618-23-4] H 41609-250MG-F 250 mg 654639-1G 1 g 666297-250MG 250 mg 41609-1G-F 1 g 654639-5G 5 g 666297-1G 1 g

These new building blocks may all be purchased in custom-packaged kits with other compounds of your choice and in weights and vials of your choice through DiscoveryCPR.

• Chiral Epoxides • Chiral Primary Ring Amines CPR • Protected Amino Alcohols • Mono-BOC-Diamines Discovery • Chiral Unnatural Amino Acids

Contact us at [email protected] to request your kit today!

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