Diastereoselective, vinylogous mukaiyama aldol additions of silyloxy furans to cyclic ketones: annulation of butenolides and gamma-lactones.

Efficient preparation of 3-substituted-furan-2(5H)-ones and their direct vinylogous aldol addition

γ-Regioselectivity of lithiated 2-buten-4-olide towards aromatic aldehydes: a simple synthesis of γ-arylidenebutenolides

A stereoselective vinylogous aldol reaction of N-monosubstituted tetronamides with aldehydes is described. The procedure is simple and scalable, works well with both aromatic and aliphatic aldehydes, and affords mainly the corresponding syn-aldol adducts. In many cases, the latter are obtained essentially free of their anti-isomers (dr > 99 : 1) in high yields (70–90%). Experimental and computational studies suggest that the observed diastereoselectivity arises through anti–syn isomer interconversion, enabled by an iterative retro-aldol/aldol reaction.

Thermodynamically driven, syn-selective vinylogous aldol reaction of tetronamides

All four chiral pestalotin diastereomers were synthesized in a straightforward and divergent manner from common (R)-glycidol. Catalytic asymmetric Mukaiyama aldol reactions of readily-available bis(TMSO)diene (Chan’s diene) with (S)-2-benzyloxyhexanal derived from (R)-glycidol produced a syn-aldol adduct with high diastereoselectivity and enantioselectivity using a Ti(iOPr)4/(S)-BINOL/LiCl catalyst. Diastereoselective Mukaiyama aldol reactions mediated by catalytic achiral Lewis acids directly produced not only a (1′S,6S)-pyrone precursor via the syn-aldol adduct using TiCl4, but also (1′S,6R)-pyrone precursor via the antialdol adduct using ZrCl4, in a stereocomplementary manner. A Hetero-Diels-Alder reaction of similarly available mono(TMSO)diene (Brassard’s diene) with (S)-2-benzyloxyhexanal produced the (1′S,6S)-pyrone precursor promoted by Eu(fod)3 and the (1′S,6R)-pyrone precursor Et2AlCl. Debenzylation of the (1′S,6S)-precursor and the (1′S,6R)-precursor furnished natural (−)-pestalotin (99% ee, 7 steps) and unnatural (+)-epipestalotin (99% ee, 7 steps), respectively. Mitsunobu inversions of the obtained (−)-pestalotin and (+)-epipestalotin successfully produced the unnatural (+)-pestalotin (99% ee, 9 steps) and (−)-epipestalotin (99% ee, 9 steps), respectively, in a divergent manner. All four of the obtained chiral pestalotin diastereomers possessed high chemical and optical purities (optical rotations, 1H-NMR, 13C-NMR, and HPLC measurements).

Divergent Asymmetric Total Synthesis of All Four Pestalotin Diastereomers from (R)-Glycidol

The chelation effect in the aldol reaction of dianion of tetronic acid with ketones was investigated to give the erythro adduct, predominantly, via the six-membered chelation transition state. The carbon-carbon bond formation occured at the 5-position siteselectively in this reaction

Chelation controlled aldol reaction of tetronic acid dianion with ketones

The aldol reaction of lithium enolates of tetronates with (R)-2,3-O-cyclohexylideneglyceraldehyde afforded the chelation controlled products stereoselectively. The conversion of the aldol products into arabitol and ribitol was also described.

Chelation Control in the Aldol Reaction of Tetronic Acid. Application to the Synthesis of Pentoses, Arabitol and Ribitol

A Stereoselective Synthesis of (.+-.)-Pestalotin.

Chelation Controlled Aldol Reaction of Tetronic Acid Dianion with Ketones.

The aldol reaction of lithium enolates of tetronates with (R)-2,3-O-cyclohexylideneglyceraldehyde afforded the chelation controlled products stereoselectively The conversion of the aldol products into arabitol and ribitol was also described

Akihiko Okuyama

Papers

Chelation controlled aldol reaction of tetronic acid dianion with ketones

Chelation Control in the Aldol Reaction of Tetronic Acid. Application to the Synthesis of Pentoses, Arabitol and Ribitol

A Stereoselective Synthesis of (.+-.)-Pestalotin.

Chelation Controlled Aldol Reaction of Tetronic Acid Dianion with Ketones.

Chelation Control in the Aldol Reaction of Tetronic Acid. Application to the Synthesis of Pentoses, Arabitol, and Ribitol.