REACTIONS OF DIENOLATES FROM (R)-2-TERT-BUTYL-6-METHYL-4H-1,3-DIOXIN-4-ONE WITH ALDEHYDES AND KETONES - A CHIRAL ACETOACETIC ESTER D4-REAGENT

Dienolate derivatives 2 of the readily available (R)-2-tert-butyl-6-methyl-4H-1,3-dioxin-4-one (1) were generated with Li, Na, or K hexamethyldisilazamide or from the corresponding silyldienol ethers [2, M = SiMe3, Si(tBu)Me2]. The lithium dienolate reacts with acetaldehyde at C-5 to give 3 (diastereoselectivity 20:1). In contrast, products 6a-g of hydroxy-benzylation at the exocyclic C-1' position are formed highly regioselectively with aromatic aldehydes and ketones (diaster-eoselectivity less-than-or-equal-to 3:1). Surprisingly, a 1,2-adduct at the exocyclic position (such as 8) was obtained only in the reaction of alpha,beta-unsaturated aldehydes with silylenol ethers 2-SiMe3 or -Si(tBu)Me2 in the presence of Lewis acids. The same aldehydes combine with the Li dienolate in a Michael addition at the exocyclic carbon (a3/d4 coupling, diastereoselectivity 20:1, products 10), with the new stereogenic center being formed in a 1,5-position remote from the stereogenic center of the dienolate reagent. The configurational assignments rest upon chemical correlation and upon NOE measurements. The stereochemical course of the dienolate reactions is discussed.