Ynolate Chemistry. Jeff Kallemeyn October 22, 2002

Transcription

1 Ynolate Chemistry While enolates have numbered among the most important reagents of organic chemistry for more than a century, ynolates have hitherto remained unknown although their chemistry should be certainly no less interesting than that of the former class of compounds. -Urlich Schöllkopf and Inga oppe, Angew. Chem. Int. Ed. 1975, 765. Jeff Kallemeyn ctober 22, 2002

2 Ynolates ' base ' ' Enolate base M M Ynolate Ph N = Ph or BuLi Ph N Li 1) 30 min 2) TMSCl TMS 41% Schöllkopf, U., oppe, I. Angew. Chem. Int. Ed. 1975, 765.

3 Preparation of Ynolates: From Silylketenes Me 3 Si 1) BuLi 2) Me 3 SiCl Me 3 Si Me 3 Si 0.5 M, -78 o C 28% 0.5 M, -100 o C 60-65% 0.1 M, -100 o C 80-90% athke, M. W. et al. J. rg. Chem. 1978, 43, 376. TBDMS BuLi TF, -100 o C TBDMS Li ECl TBDMS E + TBDMS 1 2 E E Conditions: -100 o C, 1h, then: 1 2 TMS -70 o C, 3h 96 0 TBDMS -50 o C, 6h 0 65 TBDMS -70 o C, 3h, MPA (1 equiv.) 55(38) 0 TIPS -50 o C, 6h 0 50 TIPS -70 o C, 3h, MPA (1 equiv.) 30(6) 0 Silyl ynolates formed easily, relatively unreactive Kita, Y. et al. J. Chem. Soc.. Perkin Trans , 1705.

4 Preparation of Ynolates: From Ester * LiCBr Li 2 * Et Br Br t-buli -78 o C to r.t. TF Li * Br Li Li * ' * ' Li * Li * ' -13 C enriched material gave no scrambling of 13 C center. nly carbon migration. -Isoelectronic to the ofmann earrangement ' * + Li' -Effective 1-carbon homologation of ester. = t-bu, Ph, Cy = Me, Et, Bn, 50-72% yield Nucleophilic-Electrophilic-Nucleophilic character of ynolate Kowalski, C. J., Fields, K. W., J. Am. Chem. Soc. 1982, 104, 321

5 Preparation of Ynolates: From a-bromoester 1) LDA 2) NBS Method A -Dianion was trapped with either TMSCl or PhC. -Method B is preferred since no amine ispresent. Method B Bu Li + Bu Ph Ph = Me, Bu, Cy, Ph 4 equiv. Method A: 88% yield Method B: 85% yield Efficient synthesis of ynolate Shindo, M., Sato, Y., Shishido, K. Tetrahedron 1998, 54, 2411.

6 Concerted or Stepwise? ' [2 + 2] ' ' ' stepwise ' ' ' -No mechanistic study of reaction. -Ketene reaction with aldehyde believed to be stepwise by 13 C KIE and modeling. Effectively a [2 +2] cycloaddition, but most likely stepwise

7 b-lactone Formation Enolate more reactive than ynolate with aldehydes Shindo, M., Sato, Y., Shishido, K. Tetrahedron 1998, 54, 2411.

8 Mono-addition with ketone Ph C 5 11 C 5 11 Ph Not observed 2:1 ratio Enolate less reactive than ynolate with ketones Shindo, M., Sato, Y., Shishido, K. J. Am. Chem. Soc. 1999, 121, 6507.

9 b-lactone opening to alkenes Moderate to good selectivity for tri- and tetra-substituted alkenes. Shindo, M., Sato, Y., Shishido, K. Tetrahedron Lett. 1998, 39, 4857.

10 Stereoelectronic effect on ring opening Bu Ph Li Me "outward" Bu Ph Li Me E Bu Ph Li Me "inward" Bu Me Li Ph Z p-donating substituents prefer outward rotation Shindo, M., Sato, Y., Shishido, K. J. rg. Chem. 2000, 65, 5443.

11 Stereoelectronics in Cyclobutene pening Changes in E a for cyclobutane electrocyclic conrotatory ring opening. Better p-donating groups lower E a outward and raise E a inward. Conrotatory ring opening with smaller, but better p- donating group undergoing outward rotation. Activation energy differences vs. donating ability Electronic effects more important than steric effects ondon, N., ouk, K. J. Am. Chem. Soc. 1985, 107, Dolbier, W., Koroniak,., ouk, K., Sheu, C. Acc. Chem. es. 1996, 29, 471.

12 Stereoelectronics in Cyclobutene pening Electron Acceptor SM Electron Donor p-donor stabilizes s * with outward rotation p-acceptor destabilizes s with inward rotation Ground State Transition State ondon, N., ouk, K. J. Am. Chem. Soc. 1985, 107, Dolbier, W., Koroniak,., ouk, K., Sheu, C. Acc. Chem. es. 1996, 29, 471.

13 Z-selective Formation of Acylsilanes Vacant silicon orbital directs ring opening Shindo, M., Mastsumoto, K., Mori, S., Shishido, K. J. Am Chem. Soc. 2002, 124, 6841.

14 Tandem [2 + 2] and Dieckmann Condensation Shindo, M., Sato, Y., Shishido, K. J. rg. Chem. 2001, 66, 7818.

15 Tandem [2 + 2] and Dieckmann Condensation Et etroaldol if ketone is not reduced Synthesis of substiuted 2-naphthols Wide diversity of products is obtained through tandem reaction Shindo, M., Sato, Y., Shishido, K. J. rg. Chem. 2001, 66, 7818.

16 Tandem [2 + 2] and Michael Addition Single Diastereomer Proposed Transition State 1:1 to 4:1 Diastereomeric ratios of 8 Shindo, M., Sato, Y., Shishido, K. rg. Lett. 2001, 3, 2029.

17 1,3 Dipolar Addition with Nitrones Access to trans products with thermodynamic protonation Shindo, M., Itoh, K., Sato, Y., Shishido, K. rg. Lett. 2002, 4, 3119.

18 1,3 Dipolar Addition with Nitrones b-amino acids after hydrogenation Shindo, M., Itoh, K., Sato, Y., Shishido, K. rg. Lett. 2002, 4, 3119.

19 Additions to Electrophiles: Formation of Lactones Me 3 Al essential to opening of epoxide Kai,., Iwamoto, K., Chatani, N., Murai, S. J. Am. Chem. Soc. 1996, 118, 7634

20 Additions to Electrophiles: Lactams Me 3 Al not needed Kai,., Iwamoto, K., Chatani, N., Murai, S. J. rg. Chem. 2001, 66, 169

21 Tandem Lactam Formation/Peterson lefination Kai,., Iwamoto, K., Chatani, N., Murai, S. J. rg. Chem. 2001, 66, 169

22 Conclusion -Ynolates are simple nucleophiles. -Give an extra point of diversity compared to enolates. -Much future work is needed: Mechanistic Studies Non-tethered enolate additions Exploration of enatioselective reactions

23 Cyclobutene