RESUMO
The preparation of an advanced intermediate on route towards the synthesis of tedanolide C is reported here. It is based on the coupling of two fragments of similar size and complexity, which in turn are prepared by highly stereoselective substrate-controlled titanium-mediated aldol reactions from chiral ketones.
Assuntos
Macrolídeos/química , Macrolídeos/síntese química , Técnicas de Química Sintética , Cetonas/química , EstereoisomerismoRESUMO
A novel substrate-controlled aldol reaction of a chiral isopropyl ketone is reported. The outstanding regioselective enolization by TiCl4-i-Pr2NEt provides a chelated enolate that can participate in highly diastereoselective additions to a wide array of aldehydes favouring the corresponding 2,5-syn adducts.
Assuntos
Álcoois/síntese química , Pentanonas/química , Titânio/química , Álcoois/química , Catálise , Cristalografia por Raios X , Modelos Moleculares , Estrutura Molecular , EstereoisomerismoRESUMO
Substrate-controlled titanium-mediated aldol reactions from (S)-4-benzyloxy-3-methyl-2-butanone provide satisfactory levels of 2,5-syn asymmetric induction if they are carried out in the presence of a second equivalent of TiCl(4). Such reactions give high yields and excellent diastereoselectivity with a wide array of achiral and chiral aldehydes without needing other sources of chirality. This procedure is thus of interest for the synthesis of natural products. Furthermore, spectroscopic studies and analyses of the reacting species have revealed a possible mechanism to account for the experimental results.