JACS 1982: A Survey of Papers with a Focus on Synthetic Organic Chemistry

Transcription

1 JAC 1982: A urvey of Papers with a Focus on ynthetic rganic Chemistry Baran Lab Group eting 15 ctober 2003 Carlos A. Guerrero

2 eagents and thods 1 2 [] PhC, Et 3 2 [] By 1982, the [3 + 2] cycloaddition of alkenes and nitrile -oxides was well known. owever, this chemistry had never been applied to the synthesis of b-hydroxy ketones. The major obstacle to implementing this reaction as an aldol equivalent is over-reduction to give the b-amino alcohol. Curran found that catalytic any nickel under an 2 atmosphere and addition of a buffer cleanly give imino alcohols that readily hydrolyze to give the desired compounds. yn and anti ratios are never a problem because 1) the cycloaddition is syn and 2) the alkene geometry is fixed. D. P. Curran

3 eagents and thods 2 AlCl mediated heteroene reactions of aldehydes and alkenes: Al 2 Cl Cl Al The reaction of methylenecyclohexane with certain aldehydes demonstrates the utility of this reaction: aldehyde, 2 AlCl = (91), = i-bu (74), = Ph (69), = (80), = t-bu (93) The moderate to high yields obtained highlight the mild nature of this transformation. ther protic or Lewis acids usually isomerize the alkene. 1, 1-disubstituted alkenes are most reactive. Ene reactions with tri- and tetrasubstituted alkenes also occur readily, but due to their slower rates, two competing reactions may take place. The first, methyl addition to the aldehyde, occurs with hindered and aromatic aldehydes. The second, aldol reaction, occurs with some aliphatic aldehydes. Alkenes which would give a secondary carbocation do not react with aldehydes other than formaldehyde. B. B. nider, D. J. odini, T. C. Kirk,. Cordova. 555.

4 eagents and thods The Evans asymmetric alkylation reaction was discovered in The focus of his paper in 1982 was transformations of the imides that resulted after the reaction. M E X E E E Li E E LiAl 4 E Ph 2 B; [] ab 4 D. A. Evans, M. D. Ennis, D. J. Mathre

5 eagents and thods Davis oxaziridines: reagents that serve as chiral sources of electrophilic oxygen: 2 Ar 2 Ar,, The oxaziridines are made in the following way: Et Ar Et 2 Ar m-cpba chiral (diastereisomeric) oxaziridines ee's for sulfide oxidations are modest (maximum of 46%). owever, the reagents have been applied to asymmetric hydroxylation of enolates. In the case of a chiral enolate (Evans imide), the group does not need to be chiral. F. A. Davis,.. Jenkins Jr.,. B. Awad,. D. tringer, W.. Watson, J. Galloy

6 eagents and thods a-lithiomethylenetriphenylphosphorane, a ighly eactive Ylide Equivalent Ph Ph Ph P Li Ph Ph Ph P Li The reagent is generated by treating methyltriphenylphosphonium bromide with 2 eq. of s-buli or by treating methylenetriphenylphosphorane with 1 eq. t-buli. eactivity: Ph Ph Ph P Li PhC, 1st eq. Ph Li PPh 3 PhC, 2nd eq. Ph Ph Ph Ph Ph P Li C 5 11 Ph 3 P Li C 5 11 PhC Ph C 5 11 E. J. Corey, J. Kang

7 tructure Determinations Vancomyin: 2 Cl Cl C 2 C. M. arris, T. M. arris

8 tructure Determinations 1: palytoxin 2 "Palytoxin can now be defined as structure 1!" Y. Kishi, D. Uemura, Y. irata, et al

9 Total yntheses geranyl bromide Br five steps n-buli, MPA, TMEDA, MM MM 75% C 2 MM C 2 1. a; Tf 2 2. LiCu 2 1. LiAl 4 2. MsCl, Et 3 ; LiBr 81%, two steps 95%, two steps MM aq. Cl C 65% C 1., Ts 2. TBA phenoxide TBA I 3 ; MMCl MM I CuC 90% MM C E. J. Corey, J, Das

10 Total yntheses MM MM MM C K 92% C 2 s 4, py 40% C 2 aq. Cl; 0.02% Ts, ; Ts, 2, 2-methoxypropane 90% MM MM 2 4, aac C MM i-bu 2 Al; aq. Cl C C aq. Cl 87% C K-76 E. J. Corey, J, Das

11 Total yntheses MM 2 4, aac MM chanism? aac 1 2 a 3 + Ac E. J. Corey, J, Das

12 Total yntheses triptolide key intermediate 1. Li/ 3 ; isoprene; (Et) 2 ()PCl; Li, Et 2, t-bu C 2, LiB; I 81% B = then Cl 84%, two steps LDA, MPA, TBCl t-bu TB t-bu C 2 C 2 then Cl 89% from butenolide L. C. Grover, E. E. van Tamelen. 867.

13 Total yntheses C 2 1. I, a 2. Li 3. MsCl, Et 3 4. Li/ % m-cpba 100% LDA 91% Cl 2 1. KAc 2. a 84% 72% 2 80% Cl 2 C 1. m-cpba 2. Li(TM) 2 ; aq. Cl 80% Cr 3 25% L. C. Grover, E. E. van Tamelen. 867.

14 Total yntheses 2 80% 2 C L. C. Grover, E. E. van Tamelen. 867.

15 Total yntheses TB C 2 C 2 then Cl 89% from butenolide C 2 TB C 2 C 2 L. C. Grover, E. E. van Tamelen. 867.

16 Total yntheses Ph 2 t-bui steps TL, 1981, 2059 pseudomonic acid A C 2 8 key intermediate C 2, 2 AlCl 72% Ac 2, py Ac C 2, Et 2 AlCl 100% 35-40% Ac Ph 2 t-bui 1. s 4, M 2. c-hexanone, it-buph 2 Ts, Cu 4 82% 1. PCC, aac 2. MgBr 3. t-buph 2 icl, Et 3, DMAP 4. PCC 52% Ac B. B. nider, G. B. Phillips

17 Total yntheses Et dl-aspidospermidine C Ph 2 Et Ph 100% Ph 140 C 33% Et Ph = C Et T. Gallager, P. Magnus, J. C. uffman

18 Total yntheses Ph m-cpba Ph TFAA; D Ph Et 97% Et 81% Et aney i LiAl 4 81% Et 54% Et dl-aspidospermidine = C T. Gallager, P. Magnus, J. C. uffman

19 Total yntheses albene I TM + C 2 C 2 () 3 P, Pd(Ac) 2 63% 2 C C 2 LiAl 4 93% 3 ; DM 82% K(TM) 2, MPA, ( 2 ) 2 ()PCl ()P( 2 ) 2 Li, Et 2 54% (2 ) 2 P() ()P( 2 ) 2 82% albene B. M. Trost, P. enaut

20 Total yntheses B aplasmomycin vinyl MgBr, CuI s 4, M 88% 76% 1. LiAl4 2. actone, Ts 3. PCC 70% m-cpba 83% 3 Al, propane-1,3- dithiol 87% E. J. Corey, B. C. Pan, D.. ua, D.. Deardorff

21 Total yntheses 3 Al, propane-1,3- dithiol 87% 2 Al 2 Al Al 2 Al 2 Al 2 2 Al 2 Al When the following orthoester was subjected to the reaction conditions, no product was formed, proving it is not involved in the mechanism: E. J. Corey, B. C. Pan, D.. ua, D.. Deardorff

22 Total yntheses MTM 3 ; DM; propane- 1, 3-dithiol, BF 3 Et 2 ; 2, 2- dimethoxypropane, Ts 80% 73% 1. Ac 2. BzC, Et 3 3. MsCl, Et 3 4. n-bu 4 80% DM, Ac, aac, Ac 2 TsCl, py 1., aq. Cl 2. ai 4, ac 3 C 91% 96% from d-mannose diacetonide and Li E. J. Corey, B. C. Pan, D.. ua, D.. Deardorff

23 Total yntheses C PPh 3, CBrCl 3 Cl Cl n-buli 1., aq. Cl 2. TIPCl, DMAP 3. Tf 2, py 99%, two steps 1. n-bu 4 I 2. ab 4, n-bu 3, hu n-bu 3 n n-bu 3 n, AIB 1. n-buli eq. CuC; epoxide Tf TIP 56%, five steps TIP 75% TIP 89% bsr epoxide TIP MTM 1. TBTf, 2, 6-lut 2. Ag 3, 2, 6-lut 3. TBTF, 2, 6-lut. 85% TIP TB TB n-buli, TMEDA, MPA; dimethyl oxalate 96% TIP TB TB E. J. Corey, B. C. Pan, D.. ua, D.. Deardorff E. J. Corey, D.. ua, B. C. Pan,. P. eitz

24 Total yntheses TIP TB TB LiI, 2, 6-lut 100% TIP TB TB TBAF 97% TB TB BPCl, Et 3 98% TB TB TB TB 1. LiI, 2, 6-lut 2. TBAF 3. BPCl, Et 3 65% TIP TB TB TB TB E. J. Corey, D.. ua, B. C. Pan,. P. eitz

25 Total yntheses TB TB TB TB 1. ab % F 3. gcl 2 94%, 1:1 mixture of diastereomers B() 3 75% B aplasmomycin E. J. Corey, D.. ua, B. C. Pan,. P. eitz