Baran Group Meeting Jacob T. Edwards JACS Year in Review: 1979 2/28/15

Volume: 101 Syntheses covered: H CO2Na OMe Issues: 26 Me NaO2C O OMe Articles: 2138 O O O O Most Cited Articles: O Br MeO O Me H Me Systematic ab initio gradient calculation of molecular geometries, Me OH Cl aplysistatin prephenic acid griseofulvin force constants, and dipole moment derivatives Peter Pulay , Geza Fogarasi , Frank Pang , James E. Boggs, 2550 - OMe 2560. (1811 citations) MeO OH H H HO Enhancement of nuclear magnetic resonance signals by H N O polarization transfer N Gareth A. Morris , Ray Freeman, 760 - 762. (1670 citations). H N MeO O Nobel Prize in Chemistry: Herbert C. Brown (USA) and Georg Wittig (Germany) OMe tylophorine δ-coniceine lycorine "A few times in the history of chemistry have new synthetic methods OH been deemed so important that the originators have been awarded the O Nobel Prize. This has once more happened, this year Brown and Wittig Me Me Me OH Me Me have been awarded the prize for chemistry for their development of HO Me CO2H O boron and phosphorus compounds, respectively, into important reagents O O Me H in organic synthesis." H Me Et O OH HO H H Other Notable Events: Me OH Queen releases "Don't Stop Me Now" (Jan. 5) Prelog-Djerassi Lactone methynolide aphidicolin Filming begins for Star Wars V: The Empire Strikes Back (Mar. 5) OH Me H Three Mile Island partial nuclear meltdown (Mar. 28) O OH O Me Sverdlovsk Anthrax Leak (Apr. 2) Me O Pittsburgh Pirates defeated Baltimore Orioles to win the World Series Me H Me H OH (Oct. 10 - 17) Me H Iran-United States Hostage Crisis (Nov. 4) O OH OH Saddam Hussein becomes the President of Iraq (Jul. 16) Me CO2H CO2H Star Trek: The Motion Picture is premiered at the Smithsonian Institution gascardic acid (Dec. 6) hirsutic acid C 4-demethoxydaunomycinone NC Top Song: My Sharona by The Knack Me Highest-grossing Movie: Kramer vs. Kramer Me Best-selling album: 52nd Street by Billy Joel i-Pr Popular TV Shows: M*A*S*H, The Dukes of Hazzard, Dallas 9-isocyanopupukeanane Baran Group Meeting Jacob T. Edwards JACS Year in Review: 1979 2/28/15 Total Synthesis of dl-Aplysistatin Vanadium-Catalyzed Epoxidation of Cyclic Allylic Alcohols. T. R. Hoye, M. J. Kurth. 5065 - 5067 Stereoselectivity and Stereocontrol Mechanism LDA, then T. Itoh, K. Jitsukawa, K. Kaneda, S. Teranishi. 159 - 169. Me OTs Ph HO OH OH O Me OBn O O VO(acac)2, 1. Me Me SPh TBHP CO2Me Hg(TFA) ; Me 2 CO Me PhS CO2Me SPh KBr; Br 2 83% H (97:3 cis:trans) 2. LDA, HMPA; Me Br2, LiBr, ZnCl , Me O , pyr. mixture of 4 diastereomers 2 2 44% Ph O CHO Selective epoxidation of eicosa-cis-5,8,11,14-tetraenoic 54% (2 steps) m-CPBA, RT; ~ 70% (arachidonic) acid and eicosa-cis-8,11,14-trienoic acid. Δ E. J. Corey, Haruki Niwa, J. R. Falck. 1586 - 1587. H Me Me OBn O O O CDI, CH2Cl2; CO2H H O CO2H Ph3CBF4, 2 2 O RT CO Me RT Br Br 2 Me H 51% H Me Me Me O A new olefin synthesis: condensation of aldehyde Cyclopropanation of Olefins with a Stable, Iron-Containing tosylhydrazones with stabilized carbanions Methylene Transfer Reagent E. Vedejs, J. M. Dolphin, W. T. Stolle. 249 - 251. S. Brandt, P. Helquist. 6474-6475. Me (CH ) OBF 1 1. Na(Hg) 3 3 4 CO R R1 - not very selective [CpFe(CO) ] S+ BF - LDA 2 2 CpFe(CO)2CH2SMe Cp Fe 4 N N for cis/trans (a few 2. 82% Me 1 NHTs NLiTs -LiTs, LiX, N R exceptions) Cl S CO A + 2 - does not tolerate Me 2 enolizable ketone 93% (2 steps) - air stable at RT R2 LDA Li R 2 tosylhydrazones Me R CO CO 1 2 X (Why not?) + - R R X S BF4 dioxane + X = CN, SO R, SPh Cp Fe Cp Fe CH2 2 Exception: R1 = Ph, X = CN Me Δ R1 R2 CO CO 5:95 cis:trans OHC OH CO Me CO2Me CHO 2 A Selenium Stabilized Carbanions. α-Lithio Selenoxides as Reagents for the Synthesis of Olefins, Allyl Alcohols, and Dienes 86% H. J. Reich, S. K. Shah, and F. Chow. 6648 - 6656. Me Me Tett. Lett., 1982, 23, 1871 - 1874. warburganal O O Me R1 Me Rearrangement in the palladium-catalyzed cyclization of α-substituted N- R2 X R2 O -undergoes syn acryloyl-o-bromoanilines R1 X Me M. O. Terpko, R. F. Heck. 5281 - 5283. + Se Me elimination H Ph R3 H 1 4 Pd(OAc)2, R Pd(OAc)2, N Me Li R N O H 1 Me P(o-tol)3 N R3 P(o-tol)3 O R O OH Me 100 °C 100 °C R3 R4 O R2 1 R1 = Me, Ph Br R = H R3 R2 R R2 = R3 = H Baran Group Meeting Jacob T. Edwards JACS Year in Review: 1979 2/28/15

Diels-Alder reactions of trans-1-methoxy-3-trimethylsilyloxy-1,3-butadiene Alkaloid Synthesis by the Intramolecular Imino Diels-Alder Reaction. S. Danishefsky, T. Kitahara, C. F. Yan, J. Morris. 7001 - 7008. δ-Coniceine and Tylophorine OMe S. Weinreb, N. A. Khatri, J. Shringarpure. 5073 - 5074. OMe H Me3SiCl 4 steps N OAc N Et3N, ZnCl2 TMSO OH O O 50 - 70% O Danishefsky's "A toluene solution of methylol acetate...was rapidly passed through a Diene 15-cm column of glass helices maintained at 370 - 390 °C..." 73% Synthesis of Disodium Prephenate and Disodium Epiprephenate. OMe Stereochemistry of Prephenic Acid and an Observation on the Base- MeO Catalyzed Rearrangement of Prephenic Acid to p-Hydroxyphenyllactic Acid H OMe H H S. Danishefsky, M. Hirama, N. Fritsch, J. Clardy. 7013 - 7018. 2 steps O N O N N CO2Me OMe CO2Me CO2Me 4 steps TMSO O Ph OMe MeO OMe + neat PhS S OMe - 100 °C; 31% (2 steps) O AcOH, EtOAc A Simple, Stereospecific Synthesis of the Skeleton of the Lycorine Alkaloids CO2Na NaO2C O O G. Stork, D. J. Morgans, Jr. 7110 - 7111. 1. PPh , CCl ; 3 4 O O O OH O NaOH, CO2Me O CO2Me 9-BBN HN MeOH O LiHMDS O 30% OMe N OMe O O 95% O OH HO O O 2. SO3•py., CO2H Et N, DMSO O O 3 A Stereospecific Synthesis of Griseofulvin OMe 73% (2 steps) O NaH S. Danishefsky, F. Walker. 7001 - 7008. P CO2Me 57% OMe (EtO) OMe O OMe O -O 2 1. LiBH4 S+ 2. CNSePh-NO , Cl 4 steps TMSO 2 Ph Bu P MeO2C PhMe 3 O 3. NaIO , MeO OH MeO Me 100 - 135 °C 4 O NaHCO3 O Cl Cl O OMe OMe N 52% O OMe OMe O O N exo [4+2] (3 steps) OTMS 140 °C H2, Pd/C 51% O O O O 58% 54% MeO O Me S+ Ph OH Cl Me -O H H H HO OMe O OMe O O H2, Pd/C H H H N N O "Thus with no serious attempt at optimization, griseofulvin O O O H was obtained in 21% overall yield...via simple reagents." MeO O O O O N Cl Me 7-oxo−α-lycorane lycorine Baran Group Meeting Jacob T. Edwards JACS Year in Review: 1979 2/28/15 Stereocontrolled Synthesis of the Prelog-Djerassi Lactone Macrolide Antibiotics. 1. Total Synthesis of the Prelog-Djerassi Lactone J. D. White, Y. Fukuyama. 226 - 228. and Methynolide O P. A. Grieco, Y. Ohfune, Y. Yokoyama, W. Owens. 4749 - 4752. Me Me 1. AcOH 2. H , Me O 2 O Me O 1. DIBAL-H O Pd/C Me 1. m-CPBA O Br Br Me O Me O 4 steps m-CPBA O O 86% O O O 53% Me 2. H , Pd/C Me O Me 2 Me (2 steps) 2. BF3•Et2O TBSO 93% 3. MsCl, pyr. O 84% (2 steps) H Me Me Me Me HO 66% (3 steps) 1. MsCl Me O O O CrO3, O 2. KO2CC6H5 Me 1. m-CPBA Me Me Me H2SO4, Me OH Me Me 3. K2CO3 60% Me 2. K CO , Me acetone, H2O 3 steps O (2 steps) 2 3 73% MeOH, H2O CO2H (3 steps) O O O 82% O O OH TBSO Me H H Me Me H Me Me Me HO TBSO TBSO Me Me O O Me Me CuLiMe2; Me 1. O3, O 1. 1. TBSCl TMSCl 2. NaBH Me O 4 Me Me Me Me 6 steps Me 2. LiTMP, (11 steps) I O PhSeCl O OTMS Me Me Me 3. H O , AcOH Me Me O O OH OMe n-Buli Me 2 2 H O OH 55% Me Me 2. MnO2 TBSO Me O OTBS (3 steps) Me 3. TsOH O Me Me Me 85% Et OTBS Me CrO3, H2SO4, Me Me 15% HCl O O (3 steps) Me acetone, H2O OH CO2H CH2OH Me Me 1. CrO3, H2SO4, O O O O CO2H H 12% from H Me Me acetone, H2O Me enone Me Me HO Me TFAA (1.2 eq) HO Me 90% O A Stereocontrolled Synthesis of the ( ) Djerassi-Prelog Lactonic Acid 2. 1M HCl, THF ± HO2C G. Stork, V. Nair. 1315 - 1316. Et O OH Et OH OTBS Me Me Me CHCl3, H H NaOH(aq), Me Me O OR OR J. Am. Chem. Soc. 1975, 97, 3513 - 3515. OEt 1. L-selectride Et3N•HCl HCl Me 83% Me 2. MOMCl Me 97% Reactions of Aniline with Olefins Catalyzed by Group 8 Metal 80% O O OMOM Complexes: N-Alkylation and Heterocycle Formation R = CH(CH )OC H S. Diamond, A. Szalkiewicz, F. Mares. 490 - 491. 3 2 5 Me Me Me (10 atm), 150 °C H O O 90% AcOH (aq), OR LDA; RhCl •H O N N Me TMSCl 1. CuLiMe2 NaOAc Cl 3 2 Et 2. Cr(ClO ) Cl Cl 4 2 82% Me 84% Me 60% Me NH2 30 turnovers < 1 turnover Me (2 steps) OMOM MOMO MOMO Me Me OTMS H CO H Me Me N N Me O ; CrO 2 Et 3 3 CO H 2 CO H Me 26% 2 Me O O (100 atm), 200 °C Me Me H 10 turnovers 20 turnovers MOMO HO Me PdCl2 Baran Group Meeting Jacob T. Edwards JACS Year in Review: 1979 2/28/15

A Total Synthesis of Aphidicolin Stereospecific Total Synthesis of Aphidicolin B. Trost, Y. Nishimura, K. Yamamoto, S. McElvain. 1328 - 1330. J. E. McMurry, A. Andrus, G. Ksander, J. H. Musser, M. A. Johnson. 1330-1332. - 1. Li, NH , O BF4 O 3 Me + Me O O t-amylOH; Me O O 1. t-BuLi, S Me O DIBAL-H Me Me O O NaH, TMSCl Me 1. LDA, Me Me Me t-AmOH (trace), 2. MeLi, 2. 3M HCl KOH methallyl iodide PhH, reflux O Me Me O CH2O (g) O 3. Acetone, H Me 68% H TsOH Me O 2. OsO4, 95% O Me Me O H (2 steps) OH 91% Me O Me H NaIO4 H Me 77% Me (3 steps) Me O Me O Me O O (2 steps) TMSO Me 1. LAH 86% OTMS 2. Hg(OAc) (2 steps) Me 2 Me 1. PhSeSePh, Me Me O O FVP NaBH4 O CHO Me H Me O 97% 2. Me H Me O O N OTMS 1. LAH; p-TsCl Me H Me H TMS Me O 2. Na Fe(CO) Me Me 2 4 Me O O Me 50 °C Me 360 °C Me Me O 56% Me H 18% O 20% Me H minor diastereomer (2:1) (3 steps) O (2 steps) H Me n-Buli, Me O Me H O HMPA; 35% Me allyl iodide OTHP OTHP Me O 85 °C O O A Convenient One-Step Synthesis of 2,2-Disubstituted Oxetanes from NH NH , KOH Ketones Me 2 2 3 steps 140 - 220 °C S. C. Welch, A. S. C. P. Rao. 6135 - 6136. Me H Me H Me H 91% O O O O O H H Me S CH2Na Me S CH2Na Me H Me Me NTs NTs O O O Me Me Me O (1.1 eq) O (3 eq) O 1 2 DMSO, 1 2 R R DMSO, R1 R2 R R 1. 0.5% TsOH RT 40 °C 68% (2 steps) 46 - 94% 2. PCC J. Am. Chem. Soc. 1973, 95, 4287 - 4291. Phenylseleno- and phenylsulfenolactonizations. Two highly efficient and OH O S synthetically useful cyclization procedures 1. Me Me K. C. Nicolaou , S. P. Seitz , W. J. Sipio , J. F. Blount. 3884 - 3893. OH 2. KOH 3. acetone, Me TsOH Me H CO H O Me H 4. 2M HCl, 2 [O] O PhSCl/ O MeOH H PhSeCl HO H Me O O O - OH Me [H ] Dalziel, W.; Hesp, B.; Stevenson, K. M.: and Jarvis, J. A. J. J. Chem. Soc., X O Perkin Trans. 1973, I, 2841. O Baran Group Meeting Jacob T. Edwards JACS Year in Review: 1979 2/28/15 Cyclization Reactions via Oxo- -allylpalladium(II) Intermediates Me Me π N NMe2 Y. Ito, H. Aoyama, T. Hirao, A. Mochizuki, T. Saegusa. 494 - 496. Me Me MeO2C CO2Me O X OTES Pd(OAc)2 PhH, RT MeO C Me 2 X = OMe MeCN CO2Me OTMS 87% Me Benzocyclobutenedione monoketal. A 1,4-dipole equivalent for Me anthracyclinone synthesis. Synthesis of (±)-4-demethoxydaunomycinone O O D. K. Jackson, L. Narasimhan, J. S. Swenton. 3989 - 3990. O O II Pd Pd(OAc)2 (0.1 eq) 74% II O MeO OMe O O OMe O Pd O2 Me Me Li O O O + R2 R2 Me Me Me Me MeO 1 1 CO2H O OMe R O OMe R Me H 1. NaBH Me 4 H OMe 2. MeI, OMe LDA; OMe Me CH OH Me 2 Br CO H NaH MoO , CO2Me O O O 2 Br CO2Me 5 Br Me 3. CH2N2 HMPA OH Me Carreira. Angew. Chem. Int. Ed. 2012, 51, 3474 - 3477. 71% indoxamycin B (3 steps) OMe O OMe OMe OMe OMe Diels-Alder Reactions of "Pull-Push"Activated Isoprenes O 1. M. Gillard, C. T'Kint, E. Sonveaux, L. Ghosez. 5837 - 5839. S M 55% Me Me Me Me 2. Al(Hg) (2 steps) N N+ Me Me ⋅ Me OMe O Reacts with X Reacts with MeO OMe 1.3 V electron-deficient electron-rich O O OMe O Br vs. Pt O OHBr dienophiles? dienophiles? Br HO Me Me 0.6 A Me X = NMe F X= Cl, I OH OH Me Me 2. KOH, MeOH OH TsOH, N Me Me 5 - 15 °C (CH3O)3CH, + Me Me MeO OMe OMe OMe Me N N OMe 2 hrs OMe OMe RT, 16 min X 1. n-Buli; R-CN Me Me O N N O X = Cl, I R R R = CH3, 2. HCl O Me Me O OMe O O OH O N Me Me Me N O Me Me Z X H O+ X Me Z 3 Me Z OH OH Z = CN, CO2Me O OH OH X = F, NMe2 O OMe OMe Baran Group Meeting Jacob T. Edwards JACS Year in Review: 1979 2/28/15 Anodic cyanation. Aromatic nucleophilic substitution of monomethyl- and A stereocontrolled total synthesis of (±)-hirsutic acid C dimethylnaphthalenes B. M. Trost, C. D. Shuey, F. DiNinno, Jr. 1284 - 1285. K. Yoshida. S. Nagase, 4268–4272. Br O CN O O 1. LDA, CN TMS ; Et3N PhMe, 1.7 V + KOH CO2Me Δ 70% NaCN 2. LDA, TMEDA, O CN CO ; CH N NC CO2Me 74% 6% CN 2 2 2 3. 2.5% HCl (aq) H2, 77% (3 steps) 80% CN CN 5% Pd/BaCO3 CN 1.5 V CN Zn, + + CN NaCN Br CO2Et NaOMe EtO2C Me Me 1.BH3•THF MeOH Me CN Me CO H 77% O 34% 5% 23% 2. Ac2O CO2Me 2 O CO2Me 2. NBS, CCl4 Regiocontrolled Anodic Cyanation of Nitrogen Heterocycles. Pyrroles and CN O 3. LiBr, Li2CO3, CN Indoles 130 °C PCC Me K. Yoshida. 2116 - 2121. Me 4. K2CO3, MeOH, 80% Me 0 °C N+I- 1.0 V 1.6 V 53% (5 steps) NC CN CO MeOH CHO HO N 64% CN 34% N 2 CO2Me N N S Me Me 1. K CO , Et3N, i-PrOH, Me Me 2 3 MeOH, H O Δ 2 67% 1.1 V 2. NaBH4 Me NC Me 0.6 V 77% O N 60% N CN 3. Ph3P, CN 1. HCl (dry), MeO C N Me Me Me O 2 N CO Me R MeOH 2

0.6 V CN 2. O3; DMS 92% MeO2C Me Me CN (3 steps) Me N 29% N N 3. BF3•Et2O,O O O Me MeSH Me Me 72% (3 steps) R CO Me Twofold cation-olefin cyclization. Synthesis of syn-[3.2.1]2- and [2.2.2]2 2 R = CH(SCH3)2 geminane 1. KOH, O O OH H. Park, P. F. King, L. A. Paquette. 4773 - 4774. W-5 H2O, THF Raney 75% 2. MeLi, -78 C; MeO C ° 2 Br Nickel O CH N , 0 °C Br Me 2 2 Me Me O SiO 1. LAH 2 3. PCC 2. DHP RT Al2O3 4. KOt-Am 3. PPh3Br2 83% 46% (4 steps) 66% (3 steps) Br CO2Me Br Me Me Me CO2Me CO2Me CO2H

+ H2, Pt + Tett. Lett., 1971, 40, 3703 - 3706. Tett. Lett., 1974, 43, 3745 - 3748.

syn-[3.2.1]2-geminane [2.2.2]2-geminane 3 : 1 Baran Group Meeting Jacob T. Edwards JACS Year in Review: 1979 2/28/15 A Total Synthesis of Gascardic Acid Total Synthesis of the Racemate of the Sesquiterpenoid Marine Allomone R. K. Boeckman, Jr. D. M. Blum. S. D. Arthur. 5060 - 5062. 9-Isocyanopupukeanane E. J. Corey, M. Behforouz, M. Ishiguro. 1608 - 1609. Me H 1. Li Me Me H O NC KOH, MeO2C Me Me 1. HCl, H O Me OMe 2 TosMIC, OMe H2O, H2O2; OMe O Me 2. CrO 3 KOt-Bu CH2N2 CuR Me 3. CH N 2 2 Me Me 52% Me O Me Me Me 65% (3 steps) O i-Pr 1:1 dr 2. O OMe Me i-Pr i-Pr R CO Me H2 LDA, HMPA, 90% OMe 2 (200 atm) MeI R = CH(OCH3)2 4 O AcOH, TMS 1. NaBH4 O 7% HClO4, CO2H CO2Me 3. Methanolic 2. OEt 72% (2 steps) Me H Me BBr , Me base Nishimura's OH 3 OMe Hg(OAc)2 -78 to -10 C 85% (3 steps) Catalyst ° Me H 47 hrs 82% H Me Me Me Me H 37% Me Me H i-Pr i-Pr i-Pr 1. CrO3 Me 1. LAH; 2. KI3, Me 68% (2 steps) O Me 160 °C 1. NH OH, NaHCO3 TsCl, pyr. Me 2 I Me 2. PCC EtOH, pyr. Me 68% Me R Me O 2. H (1 atm), NHCHO O (2 steps) Me OTs 2 Nishimura's Me CHOMe Me H O CO2Me O KOt-Bu i-Pr + Catalyst Me R = CH2CH2CH2CO2Me CO2Me Me 1. Na2CO3 (aq), 75% 3. O O NaOMe, 90% CH OH O MeOH 3 H Me i-Pr H 2. Me H Me O H H Me O Li i-Pr MsCl, pyr. Me Me Me -10 °C Me Ph S Me i-Pr H 80% NC BF •Et O NMe (minor) 3 2 Me (3 steps) Me Me Me 65% 3. Al(Hg) Me O 4. CH N Me Me 2 2 R O Me R 70% (4 steps) CO2Me i-Pr R CO2Me CO2Me Total Synthesis of (±) 9-Isocyanopupukeanane LiTMP 70% H Yamamoto, H. L. Sham. 1609 - 1611. 160 °C O OH PhH; AcOH:H O 3:1, Me H Me H TMSO 2 Me 5 steps 50 °C Me Me H OTHP Me 1. NaBH Me Me quant. 4 HO NaOH, Me 2. MsCl Me Me Me MeOH, H OH H Me 3. DBN, 80 °C Me 1. HO 60% THF H TsOH Me Me (2 steps) Me 68% 1. H , Ir 2. NCS, DMS; Me (3 steps) O 2 2. NH2OH 1. Me Li Et3N O NH2 O CO Me 3. TiCl3/DIBAL-H (3:1); CO2H 2 Me CO Me DIBAL-H Me Me O 2 Me Me Me Me 2. AcOH, H2O, i-Pr 60 °C O 3. MsCl, Et3N Baran Group Meeting Jacob T. Edwards JACS Year in Review: 1979 2/28/15

Syntheses not covered: Me Me OH O OH O H Me Me Me O Et H HO OH OH Me O Me Me H Et O OH Me CO H Me O H 2 O O OH Me Me

OH monensin erythronolide A (Kishi) (Corey)

O O Me O O Me O Me O Me O Me O Me Me

picrotoxinin isocomene periplanone B (Corey) (Pirrung) (Still)