1,3-Asymmetric Induction in the Reaction of Organometallics to β-Hydroxy Ketones and β-Silyloxy Ketones

Abstract

High level of 1,3-asymmetric induction was realized in the reaction between β-hydroxy ketones and triisopropoxytitanium reagents to give anti-1,3-diols possessing tertiary alcohols. To the contrary, syn-1,3-diols were obtained by the addition reaction of organometallics to β-t-butyldimethylsilyloxy ketones.

Internal Lewis Acid Coordination as a Powerful Tool To Promote Highly Stereoselective Alkylation ofα-Alkyl-β-Hydroxy Ketones with Grignard Reagents

“…[4] Fujisawa et al [5] reported that the treatment of b-hydroxy ketones, which have a stereocenter in the b-position, with MeTiCl 3 and MeTi(OiPr) 3 yielded mainly anti-diols, whereas reactions of the corresponding b-silyloxy ketones with lithium, magnesium, and titanium reagents afforded isomeric mixtures in which syn-diols were predominant. Anti-diols, as the prevalent diastereoisomers, were obtained by Ruano et al [6] in the methylation of b-hydroxy ketones with MeLi in the presence of ZnBr 2 , while formation of syn-diols was observed when Me 3 Al was used as the methylating agent.…”

Synthetic Studies Toward Pectenotoxin 2. Part I. Stereocontrolled Access to the C10−C22 Fragment

“…Potentially, these mild conditions would also tolerate the presence of the nonanomeric AB spiroketal system in more advanced intermediates. Although hydroxyl-directed alkylations have rarely been used in total synthesis, the literature precedents were nevertheless encouraging …”

Synthetic Studies Toward Pectenotoxin 2. Part II. Synthesis of the CDE and CDEF Ring Systems

“…The aldol union of ketone 5 and aldehyde 16 yielded the β-hydroxyketone 17 with excellent selectivity (Scheme ) and good yield. However, the key hydroxyl-directed methyltitanation of 17 required a considerable amount of experimentation to obtain a reproducible protocol. The reaction was much more sluggish than with the simpler C 10 −C 22 precursor aldol system .…”