Spirocycles Containing All-Carbon Quaternary Centers Baran Group Meeting Emily Cherney

Alkylations Continued Suresh- Synthesis (2008) v. 7, 1065-1068 Ficini- Tetrahedron Lett. (1981) v. 22, 629-632 O CO2Me O Me Me DME, rt H Me Me Me Me Me N H 44% N Ph N CO Me O 2 O MeO2C MgBr2, ACN, 70 °C O O O MeO2C 60-70% O O Ph N O Gravel- Org. Lett. (2010) v. 12, 5772-5775 • Me single diast. "Domino Stetter-Aldol-Aldol reaction" N Ph Br Me O O Et N S (30 mol %) H DBU (1 eq), Tanner- Tetrahedron (1989) v 45, 4309-4316 Me (CH2)2OH Me H H DCM, rt, NaH, DMF, Me 20 min TsHN Ts TsN Ts Stetter 0 to 50 °C O O (2 eq) TfO 71% Me O O O O Me nBuLi, THF, (±)-acoradiene H H HMPA, -20 °C O Aldol O 69% O Ts O HO HN Na(Hg), NaH2PO4, MeOH HO TsN H (+)-nitramine 74% OH O

Aldol/ Sum it up! Common Akylation Strategies: J. Chem. Soc., Chem. Commun. (1995) 955-956 Elimination O 1 - double alkylation of bis-halide or other bis- O electrophile !- to , malonate, etc. BF3•OEt2, DCM 2 - intramolecular cyclizations onto epoxides, O halides, or other electrophiles OH 3 - intramolecular Michael or Aldol reactions to HO Me O form quaternary centers 85% ee O 4- intramolecular Sakurai allylations to form OH O quaternary centers 86% 5- use of chiral to form chiral enamines for diastereoselective Aldol and Michael 71% reactions 6-I didn't cover oxidative dearom/intramolecular dr 1:1 Prins-type closure. This is included later! Spirocycles Containing All-Carbon Quaternary Centers Baran Group Meeting Emily Cherney

Transition Metal-Based Methods Rainey- JACS (2012) v. 134, 3615-3618 Moreto- JACS (1992) v.114, 10449-10461 Pd(OAc)2 (10 mol %) Chiral Bronsted Acid (20 mol %) O O Me 5- Me HO 1,4-benzoquinone (2 eq.) Me Ni Ni(CO)4, exo- PhCF3 MeOH trig i Br 2,4,6-tri PrPh 71% 50% O MeO C Chiral O O 86% ee OH OH 2 P HO Bronsted O OH yield modest b/c 6- Acid: endo competes Mori- JACS (1997) v. 119, 7615-7616 2,4,6-triiPrPh MgCl Stephenson- Org. Lett. (2011) v. 13, 6320-6323 Bu Bu Cp* Cp* HO O ZrCp*, Me Pd(OAc)2 (10 mol%) BuMgCl Zr Zr Authors propose a MgCl Selectfluor(2 eq.) II/IV ACN, rt, 12 h Pd catalytic cycle NBn H H N Me 43% Me N N 46%, Bn Bn Bn 86% ee OH O H Negishi- Tetrahedron Lett. (1996) v. 37, 3803-3806 Note: The first assymetric Heck reactions were described in 1989 by Shibasaki and Overman. We will see many more examples demonstrating the power of the assymetric Heck in Part 2. Overman- JACS (1998) v. 120, 6477-6487 Et2AlCl, Ti(OiPr) (cat.) Et Pd2(dba)3 (5 mol%) 4 M Hexanes Et M (R)-BINAP (11%) Me Ag3PO4 (2 eq), DMA A I Me 49% Me H 99% and MeN 72% ee MeN Me O Et Et Et M O O Busacca developed new phosphine ligands to improve ee for this reaction. See: Org. Lett. (2003) OH 2 v.5, 595-598 OH and B Mikami- JACS (2003) v. 125, 4704-4705 B H 1:1 dr A H H CO2Me [(MeCN)4Pd](BF4)2 (5 mol%) MeO C (S)-BINAP (10 mol%) 2 O Buchwald- JACS (2011) v. 133, 9282-9285 HCO2H (1 eq) O DMSO, 100 °C, 1hr OH O [Pd(cinnamyl)Cl2] (1 mol%) N 99% Ligand (3 mol%) Ts O 99% ee N K2CO3, Dioxane Ts MeO L Toste- JACS (2007) v. 129, 2764-2765 MeO MeO * Pd OTIPS O Ligand = PCy2 ((R)-Binaphane)Pd(OH2)2(OTf)2 73% OMe BnN 100:1 Et2O/AcOH, rt, 20 min BnN Br racemic* 80% 98% ee * Preliminary assymetric results were obtained with chiral phosphine ligands providing up to 74% yield, 81% ee on the substrate shown. Mechanistic studies support Pd-alkyne activation followed by silyl ether addition. Spirocycles Containing All-Carbon Quaternary Centers Baran Group Meeting Emily Cherney

Rearrangement Methods Hwu- JOC (1992) v. 57, 922-928 Silicon-Facilitated Ring Contraction Me Kita- Tetrahedron Lett. (1995) v. 36, 3219-3222 Epoxide Rearrangement FeBr3, DCM, Me Me "-silicon effect F3B O -60 °C OCOPh OCOPh OCOPh Me stabilizes positive BF3•OEt2, O TMS 54% charge build up during DCM, O °C ring contraction HO O Me rearrangement Me 95% Me Me 91% ee Me Me Me Me Kido- J. Chem. Soc., Perkin Trans. 1 (1992) 229-233 [2,3]-Sigmatropic Rearr. Burnell- JOC (1998) v. 63, 5708-5710 Acyloin Condensation/Ring Expansion Me Me Me Me Me Me O Cl Rh (OAc) , O 2 4 TMSO BCl , DCM, HF, MeOH; O PhH, reflux O 3 B TFA -78 °C O O 87% Me 85% 72% 2 steps EtO2C O TMSO Me O PhS S N2 EtO2C SPh Me Ph EtO2C O Me Kuroda- Tetrahedron Lett. (1994) 6895-6896 Nazarov Tu- J. Chem. Soc., Perkin Trans. 1 (2000) 3791-3794 Semipinacol Rearr. TMS O

HO O FeCl , DCM, -60 °C ZnBr2 (4 mol%) -bond that shifts should be 3 DCM, rt anti to the alcohol from the 67% O epoxide opening 91 % O OH >99:1 dr For enantioselective version of semipinacol shift onto enone instead of epoxide with chiral iminium Frontier- JACS (2011) v. 133, 6307-6317 Nazarov/ Wagner Meerwein Shifts catalysis see: Tu- JACS (2009) v. 131, 14626-14627 O Marshall- JOC (1970) v. 35, 192-196 Dienone Ring Contraction CO2Me LA O O CO2Me [Cu(II)(box)](SbF6)2 DCM, rt, 5 hrs O Me Me Me h!, AcOH, Ac2O, dioxane H2SO4 79% OMe Me Ar H Ar O 66% O Me Me O Ar=2,4,6-triMeO-Ph Ar Me Me Me Conversion of Bridged Systems Trost- JACS (1996) v. 118, 12541-12554 Vinylcyclobutane Rearrangement Marshall- Tetrahedron Lett. (1969) 1387-1390 Grob on [3.2.1]bicycle JACS (1988) v. 110, 6556-6558 Vinylcyclopropane Rearrangement OMs O TMSOTf (1 eq.) O OTMS (0.7 eq) -free OH can be OH tBuOK OMe DCM OMe used for the vinyl- 60% OMe 64% cyclobutane Me Grob Fragmentation rearrangements Me Spirocycles Containing All-Carbon Quaternary Centers Baran Group Meeting Emily Cherney

Conversion of Bridged Systems-Continued 2: Don't be a Whimp- If you have set yourself up with proper functionality Make that Quat. Center! on your ring, this should be a piece of cake. You Sakai- J. Chem. Soc., Chem. Commun. (1990) 1778-1779 Grob on Bicycle have many reaction to choose from--here are the OH most popular: HO OH O O H HO (5 eq.) O H O BF3•OEt2 (7 eq.) - Alkylation with an Electrophile: deprotonate at the future spirocarbon (or go DCM through an enamine) usually works (unless you are dealing with maoecrystal V) - Allylation: assymetric or not, there are a methodologies devoted to doing just (80%) HO HO Me this. It is sort of under the category of alkylation, but so much work has been Me Me Me done in this area, it get's its own line. O Me Me - Addition of a Nucleophile: if you are adding to a Michael acceptor you are all Janaki- J. Chem. Soc., Perkin Trans. 1 (1997) 195-200 Ox. Cleavage set, if you are adding to a ketone you still have work to do - Claisen Rearrangement: works in tough situations to make sterically hindered O OH O quaternary centers O 3. Follow through and All you have to do is make one last bond--it doesn't RuCl3, NaIO4 Close the Second Ring! even necessarily have to be a C-C bond. Did I mention that everything is intramolecular? As they 75% - Dieckmann Condensation - Acyloin Condensation say, "it's like falling off a log." Common reactions are listed along with the following "bold" disconnection: Me Me -Wittig olefination, etc. Iyer- Tetrahedron Lett. (1985) 5393-5396 Ozonolysis of Bicycle -RCM CHO -Aldol Condensation LiH, DMF, hydroquinone, O -Lactonization !, 69% nBu N, 190 C O3, DCM; DMS 3 ° O 78% 68% F N H2N O H Husson- ACIE (1998) v. 37 104-105 Reduction of Hemiaminal Fleming- Letrahedron Lett. (1982) v. 23, 2053-2056 Cycloaddition Methods OH Ph OH NaSO2Tol, HO Norman- JOC (1975) v. 40, 1602-1606 Diels-Alder on Exocyclic Olefins CHO CHO N O LAH ZnBr2 N 82% SnCl4•5H2O, 51% Ts Ts Me Me O Ph NH2 O Ph rt Me O Ring Closure of Geminially Disubstituted Cyclic Systems 48% Rather than showing a bunch of boring transformations I will sum up this section visually: Me 1: Start with a Ring Your functional group handle can be many things--anything that has a handle! that you can form a quaternary center from. Some popular Smith- JOC (1984) v. 49, 832-836 Intramolecular [2+2]/cleavage choices in the literature are: FG RuO4, NaIO4, n NR2 OR OR O h , ACN H O, CCl FG " 2 4 O 23% nBu O n FG R 2 steps CO2H FG MeO OMe R O nBu nBu O O O O O O issue with this approach: always have to cleave the cyclobutane to get to the FG S n R spirocycle. The same is true for intramolecular cyclopropanations. For examples see: J. Chem. Soc., Chem. Commun. (1976) 978 and Can. J. Chem. (1970) 3273-3274 Spirocycles Containing All-Carbon Quaternary Centers Baran Group Meeting Emily Cherney

Cycloaddition Methods Continued Oppolzer- Helv. Chim. Acta (1977) v. 60, 2388-2401 Ene Reaction Me Me Tokunaga- J. Chem. Soc., Chem. Commun. (1995) 955-956 [3+2] Cycloadd. 3:2 280 °C, 72 hr O Bn EtO C N O H 2 68% Toluene, Bn Me Me N O EtO2C EtO2C 180 °C Bintz-Guidecelli- Tetrahedron Lett. (1997) v. 38, 2841-2844 Ene Reaction Me N Me Me Bn Me Me Me Me OS(O)p-tol Me Me 3:2 o-DCB, CaCO , Me 3 Ts Ts 130 °C Knolker- Synlett. (1996) 1155-1158 [3+2] Cycloaddition Me Me 85% Me Me Me Me TIPS O O TIPS 4:1 Conia- Bull. Chim. Soc. France (1966) 278-281 Conia Ene Reaction Me TiCl4, DCM, -78 °C Me Me O Me O Me O Me O Me Me Me Me Me 98% Me 220- 300 °C Trost- JACS (2006) v. 128, 13328-13329 [3+2] Cycloaddition Pd(dba) (5 mol%) Me 2:3 Me O 2 O Chiral Ligand (10 mol%) toluene, -25 °C Radical Cyclization Methods Ph Srikrishna- Letrahedron Lett. (1994) 7841-7844 Me SnBuCl (0.15 eq) Me Ph OMe Me OMe Me NaCNBH3, O 94% AIBN (cat.), tBuOH Ligand= P N O O O 92% ee TMS OAc Br 83% H H Greene- JACS (1996) v. 118, 9992-9992 Motherwell- Shibata- JACS (2006) v. 128, 13686-13687 [2+2+2] Cycloaddition Me Me O O Tet. (1992) 8031-8052 O Me O Me Me [Rh(cod)2]BF4 (5 mol %) Mn(OAc)3, Me O (xylyl)-BINAP (5 mol %) O EtOH O OXan O DCE, 60 °C TsN TsN 61% Me 89% H H O O Me (10 eq)* 99% ee Me Back- JOC (1996) v. 61, 3806-3814 Me *substrates with C(CO2Bn)2 instead of NTs require only 3 eq Me Cossy- JOC (1997) v. 62, 7106-7113 Ene Reaction TMS O O O O Me h!, 254 nm, Bu3SnH, AIBN, Me Me Ph 79% Ph Ph benzene benzene Me Me O O H H N Me H N O toluene H N 87% 150 °C PhSe N N dr>20:1 Me N 90% PhSe Me O 77:23 O TMS Spirocycles Containing All-Carbon Quaternary Centers Baran Group Meeting Emily Cherney

Part 2-Total Synthesis White- JOC (2010) v. 75, 3569-3577 Quaternary centers derived from spirocycles and all-carbon spirocycles are highlighted in red. MeO CO2Et MeO Indole Alkaloids NH Strychnine: Woodward- JACS (1954) v. 76, 4749 (total synthesis) N CO2Et h!, EtOH NTs N N CO Et N 60% 2 CO Et N CO2Et TsCl, 2 Boc Boc H CO2Et H pyr. H N Perophoramidine: Retro- N Mannich H 64% Qin- JACS (2010) v. 132, 14051-14054 N H O single OMe OMe diastereomer Me NH OMe N O OMe Cl N MeO CO2Et Guillou- Org. Lett. (2007) v. 9, 3101-3103 (method) 1) Pd dba ,Et N, DMA 2 3 3 O N CO2Et O O 2) 1N HCl Boc 3) Boc O, Et N, DMAP Bn Br 2 3 BnNH2, Cl N N 4) SeO2, AcOH, tBuOH MeOH; O N H 5) Boc2O, Et3N, DMAP NaOH O R* R* I 57% 79% NPhth O 4 steps N AgClO4 (4.5 eq) NPhth N N O N O N H Cl toluene, -78 °C H Boc Boc O Strychnofoline: Carreira- JACS (2002) v. 124, 14826 (total synthesis 80% OTBDPS N Me BocHN Br Br N (3 eq) N N H Me Boc O N R*=(S)-tBuSO H BnO N O H H Bn Funk- JACS (2004) v. 126, 5068-5069 N HO N Me MgI2 (1 eq.) N 55% TIPSO N3 H H THF, 80 °C N3 Cs CO , TIPSO Br 2 3 Br DCM, rt N OTBDPS O H 89% N N Br NH H H O O N BnO N single Horsfoline: Bn diastereomer 1) NaH, Boc2O Trost- Org. Lett. (2006) v. 8, 2707-2730 2) PPh3, THF, H2O [Pd(C H )Cl] (0.25 %) Me 2 5 2 TIPSO NH NH2 CO3Et ligand* (1 mol %) TIPSO N EtO C O Br MeO TBAT (15 mol%) MeO 2 MeO allyl acetate OTIPS O O N 96% 84% ee N Br NBoc N N O N Ar Ar N H Ar= 2,4-diOMeBn H H Boc Spirocycles Containing All-Carbon Quaternary Centers Baran Group Meeting Emily Cherney

Gelsemine: Cliffnotes on the Spirooxindole Strategies: Indole Alkaloids Continued 1) Intramolecular Heck 3) Photo Induced Spirotryprostatin A/B: Trost- Org. Lett. (2001) v. 9, 2763-2766 (Overman and Speckamp)/ Radical Cyclization O 2) Radical Cyclization (Johnson) O O O Me (Hart) H N Pd2(dba)3 (10 mol%) N N HN N Me HN N O Trost Ligand MeO N HN HN (89% X dr: 16:1 O O regio: 14:1 Me N R Me Gong- Org. Lett. (2011) v. 13, 2418-2421 Me H N O N EtO C Me O Me H2N CO2Et 2 Chiral Bisphosphoric EtO2C NH OHC Me 5) Divinylcyclopropane 4) Eschenmoser Claisen CO Et Acid, toluene, 3A MS 2 CO2Me rearrangement Rearrangement 94% (Fukuyama) (Danishefsky) CO Me N > 99:1 dr 2 O H N Me Me MeO NO2 O O 2 > 99:1 ee H Me MeO NO2 NH Marcfortine B: Trost- JACS (2007) v. 129, 3086-3087 CO H 2 H TMS O Me O Me CO Me N NH2 Me Me 2 H HN TMS OCO2Me I Me O Pd(OAc)2 (5 mol%) Note: Fukuyama recently used a similar transformation in the synthesis of Gelsemoximine: JACS (2011) v. 133, 17634-17637 Me N O P(OiPr)3 (35 mol%) Me BocN Alkaloids (Other) N OMe 93% O Boc dr 1:1 Nakadomarin A: Nishida- JACS (2003) v. 125, 7484-7485 OMe MeO OMe 1) PhSO Cl, NaHCO O HN Chimonanthrine and Calycanthine: 2 3 H OH 2) allyl-Br, K2CO3 Overman- JACS (1999) v. 121, 7702-7703 3) ethylene glycol, TsOH O O O RO OR H N 77%- 3 steps N O 2 Bs N CO2Me 4) resolve CO2Me Me R= TBDPS R= acetonide Cl Me (PPh ) PdCl I I (PPh ) PdCl H 3 2 2 Bn Bn 3 2 2 N Et3N, DMA N N Et3N, DMA H 71% 90% Me H H O O N N Me Me TBDPSO OTBDPS Williams- Org. Lett. (2004) v. 6, 4539-4541 O O O Ph O O O The diastereomer Ph O O O O on the left leads O H to meso- N chimonanthine Ph N Bs NBn Ph N -H2O NBoc and the right one BnN H N N N N leads to H chimonanthine NBn O N 35% O H Me Bn O O Bn single H O CO2Et and calycanthine O O Me Boc chimonanthine diast. Me O O Me Me Spirocycles Containing All-Carbon Quaternary Centers Baran Group Meeting Emily Cherney

Alkaloids (Other) Continued Kishi- JACS (1998) v. 120, 7647-7648 NOTE: Kishi made ent-pinnatoxin, but I didn't have time to draw the other enantiomer. Sorry. Nakadomarin A: Kerr- JACS (2007) v. 129, 1465-1469 Me Me Me Me MeO PMB O AllocHN HN OH Yb(OTf)3 (15 mol%) N OBn AllocHN OBn 4A MS O O TBDPSO O CO tBu Br 87% 2 CO2Me CO2tBu CO2Me DABCO, TEA, PhH; CO2Me OMs OHC Br dodecane, 70 °C CO2Me O OTBDPS H Dixon- JACS (2009) v. 131, 16632-16633 O OTBS 34% O O O plus other DA O isomers O OTBS O CO Me H Me 2 Chiral Urea O Me Me O (15 mol%) cat. H N TESO O controlled H 57% Inoue- ACIE (2004) v. 43, 6505-6510 N dr 91:9 O O N MeO2C Me Me 2 O Me Me condensation/ TIPSO TIPSO O N 2 nitro-Mannich/ 68% H H lactamization NC NC Gymnodimine: H2N MsO KHMDS, THF, 0 C; HO KHMDS, 0 °C to rt Romo- ACIE (2009) v. 48, 7402-7405 HO HO 72% Me N HO H O O Me O O O MOMO O MOMO Me O2N H O O Ph Ph Zakarian- JACS (2008) v. 120, 3774-3776 Me Me H Me OH N N Ph Me O O O O O BnO TsN OTBS Pinnatoxins: Me TIPSO O Me Me Me OPMB OMOM O 85% CuCl2 (20 mol%) Me Me Me N dr > 19:1 Chiral Box Ligand (22 mol%) F3C NLi 95% ee AgSbF (40 mol%) 94% O 6 R N BnO Ts Ph OPMB N O H then TMSCl HO O TMSO Ph O Me Ireland- O H O O Et Claisen O O OH R O OTBS HO Me 1 OMOM Me Me R R3 Me 2 OTIPS Spirocycles Containing All-Carbon Quaternary Centers Baran Group Meeting Emily Cherney

Alkaloids (Other) Continued Futoenone: Angle- JOC (1993) v. 58, 5360-5369 Pinnatoxins: Hashimoto- ACIE (2008) v. 47, 7091-7094 OMe O O OMe O OMe OBn (10 eq) O OTBDPS Me OMe Me OMe O 4A MS, p-xylene, O Me 160 °C, 12 h O O Me Me TiCl4, DCM O Me 35% Me O (+ 46% other O OTBDPS 85% O isomers) H O O OTBS R TESO Me OTBS OTBS Me O OTBS Siculine: Node- Tetrahedron (2004) v. 60, 4901-4907 O OTBS OH O Elatol: Stoltz- JACS (2008) v.130, 810-811 HO Me Cl Pd(dmdba) (10 mol%) O 2 PIFA, trifluoro- Chiral Phosphine N ethanol, -25 °C Cl Ligand (10 mol%), 11 °C Me O O N 78% N HO 82% COCF3 COCF3 Me 87% ee Br Me O Me Cl MeO MeO MeO OtBu Me Me OH OBn OBn Me Stepharinine: Honda- Org. Lett. (2006) v. 8, 657-659 Salvileucalin B: OtBu Me MeO MeO MeO Chen- Org. Lett. (2011) v. 13, 4410-4413 (Studies Toward) O PIFA, trifluoro- NH N NH O OH MeO MeO ethanol, 0 °C, OTBS COCF3 MeO O NaBH4 O ZnI2 90% O 85%

To see many other similar examples: O MeO2C Discorhabdin GM O OH O HMDS, µW, Non-Nitrogen Containing [5.5]Spirocycles 78% 250 °C; Cyanthiwigin AC: O HF•Pyr, ACN Reddy- Org. Lett. (2006) v. 8, 5585-5588 O OH Me OTBS O See Also: Reisman- JACS (2011) v. 133, 774-776 95% NaH, THF,O HO Me OMs reflux, 3h; Me Cu(hfacac) Me B (2 eq) O 2 O 60% 65% B O N2 H Me O OTBS NC CO2Me O MsO Me Me O O CN Spirocycles Containing All-Carbon Quaternary Centers Baran Group Meeting Emily Cherney

Non-Nitrogen Containing [5.5]Spirocycles Continued Acutimine: Castle- JACS (2009) v. 131, 6674-6675 Maoecrystal Z: Reisman- JACS (2011) v. 133, 14964-14967 MeO O O OH (Bu Sn) OH CO CH CF 3 2 Me 2 2 3 Me Cl h!, Cl HO O Cp TiCl , Zn0, Me 2 2 TBSO Cl Et3Al (3 eq) Me OAc 2,4,6-collidine•HCl I 3-Ph-2-SO Ph- Me Me O TBSO 2 O O 74% O NMe TBSO O O OTBS single diast. 62% Non-Nitrogen Containing [5.4]Spirocycles O OMe BnO OMe BnO OMe See Vetivane GM-Bruns and Ingenol GM- Seiple for many examples OMe OMe Platensimycin: Nicolaou- ACIE (2006) v. 45, 7096-7090/ JACS (2009) 16905 OMe 1) LDA, OH OEt OEt Vannusals A and B: Nicolaou- JACS (2010) v. 132, 7153-7176 O O Br OTBS Me O 2) LDA, propargyl-Br O HO2C N Me H Me OH O 89% O H 2 steps Me OH O O Me TBSO OR Me H There are over a dozen total OAc H OH sythesis and studies toward 50% TMSI, HMDS papers on this molecule. To O O the best of my knowledge, the 1) KH, (MeO)2CO (20 eq) O Nicolaou approach is the only THF, 85 °C one that goes through a [Rh(cod)Cl ] (5 mol%) 2) Mn(OAc) , Cu(OAc) , 2 OMe 3 2 spirocycle. Most go through a (S)-BINAP (11 mol %) HOAc, 80 °C fused 6,6- or 5,5-system en AgSbF (20 mol%) O OMe route to the cage structure. 6 MeO 72% 91% TBSO O O 95% ee Fredericamycin: Kelly- JACS (1988) v. 110, 6471 CO Me O OBn OBn 2 O OH O MeO CO2Me Non-Nitrogen Containing [4.4]Spirocycles O OH OMe OMOM OMe O Dimethyl Gloiosiphone A: Takahashi- JOC (2007) v. 72, 3667-3671 (Formal) O OH HO N OBn OBn O PhO2S OMe OMPM PhO2S O N EtO H Pd(OAc)2 (10 mol%) DIBAL PPh3 (40 mol%) OEt O OMe OBn HO 66% BnO O OMe dr 60:40

PhO2S O Swern O OAc OMPM MOMO PhO S MOMO 2 40% OBn 2 steps OBn O Spirocycles Containing All-Carbon Quaternary Centers Baran Group Meeting Emily Cherney

Non-Nitrogen Containing [4.4]Spirocycles Continued Miscellaneous Fredericamycin: Clive- JACS (1994) v. 116, 11275-11286 SNF4435 C and D: Parker- JACS (2004) v. 126, 15968-15969 O N O O N O MeO MeO 2 Me 2 Me Ph Ph Me Me Ph3SnH, Et3B, O O MeO O2 MeO PhSe H H O H H O OMe 50% OMe OMe OMe Me H Me H O O Me Me Fredericamycin: Bach- JACS (1994) v. 116, 9921-9926 C D O Me Me OH EtS TMSO OH NO O SEt 2 Me Hg(OCOCF3)2 O Me 54% O Pd(CH3CN)2Cl2, Me TMSO DMF, rt SNF4435 C Me H O OMe 53% and D Fredericamycin: Boger- JACS (1995) v. 117, 11839-11849 Me 4:1 ratio MeO MeO Me C to D I Me3Sn HO TFAA, DMSO, HO BnO DBU BnO Me Lideraspirone A and Bi-linderone: Wang- Org. Lett. (2011) v. 13, 2192-2195 OMe > 68% OMe Me O OH O lindaspirone A O 42% Me O Me Me O O Me Fredericamycin: Kita- JACS (2001) v. 123, 3214-3222 CpCOO CpCOO O O OMe OMe OMe OMe O O Me Me h!- 365 nm BF OEt , DCM 3• 2 Me N N O Me O Me Me O O O 94% O O O 99% de Me Me Me O Me O

O O

bi-linderone Me Me 24% O O