121352-95-2Relevant academic research and scientific papers
Direct catalytic asymmetric aldol reaction
Yoshikawa, Naoki,Yamada, Yoichi M. A.,Das, Jagattaran,Sasai, Hiroaki,Shibasaki, Masakatsu
, p. 4168 - 4178 (2007/10/03)
The direct catalytic asymmetric aldol reaction using aldehydes and unmodified ketones is described for the first time herein. This reaction was first found to be promoted by 20 mol % of anhydrous (R)-LLB (L = lanthanum, L = lithium, B = (R)-binaphthol moiety) at -20 °C, giving a variety of aldol products in ee's ranging from 44 to 94%. This asymmetric reaction has been greatly improved by developing a new heteropolymetallic asymmetric catalyst [(R)-LLB, KOH, and H2O]. Using 3-8 mol % of this catalyst, a variety of direct catalytic asymmetric aldol reactions were again found to proceed smoothly, affording aldol products in ee's ranging from 30 to 93% and in good to excellent yields. Interestingly, the use of this new heteropolymetallic asymmetric catalyst has realized a diastereoselective and enantioselective aldol reaction using cyclopentanone for the first time. It is also noteworthy that a variety of aldehydes, including hexanal, can be utilized for the current direct catalytic asymmetric aldol reaction. Chiral aldehydes containing α-hydrogen including (S)-hydrocinnamaldehyde-α-d have been found to produce the corresponding aldol products with negligible racemization (0-4%) at the α-position. One of the aldol products has been successfully converted to the key synthetic intermediates of epothilone A and bryostatin 7. The possible structure of the heteropolymetallic catalyst is also discussed. Finally, mechanistic studies have revealed a characteristic reaction pathway, namely that the reaction is kinetically controlled and the rate-determining step is the deprotonation of the ketone. This is consistent with the fact that the reaction rate is independent of the concentration of the aldehyde.
Synthesis of Bryostatins. 1. Construction of the C(1)-C(16) Fragment
Blanchette, Mary A.,Malamas, Michael S.,Nantz, Michael H.,Roberts, John C.,Somfai, Peter,et al.
, p. 2817 - 2825 (2007/10/02)
The synthesis of fragment AB of bryostatin 1 is described.Two aldol coupling reactions involving (i) chiral fragment A with achiral B and (ii) chiral fragment A1 with achiral A2 constitute crucial steps in which an external chiral boron reagent is used to control stereoselectivity in the creation of a new stereogenic center.This type of double asymmetric synthesis, although rarely precedented, provides a powerful means of stereocontrol over the fragment assembly.
