K. Suyama, Y. Sakai, Kazuhiro Matsumoto
Jan 18, 2010
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Angewandte Chemie
Abstract
a-Hydroxy phosphonates and a-hydroxy phosphonic acids are an important class of molecules that are widely used in biological applications. The asymmetric hydrophosphonylation of aldehydes with phosphonates is a powerful and direct method for synthesizing enantioenriched a-hydroxy phosphonates. Thus, intense research has been devoted to developing highly enantioselective catalysts for this reaction, and it is now becoming an emerging area in organic chemistry. A variety of chiral Lewis acid and heterobimetallic catalysts have been reported and high enantioselectivities have been achieved. However, most of these methods require relatively high catalyst loading and a longer reaction time to obtain the products in acceptable yields. Dialkyl phosphonates exist in equilibrium between their phosphite and phosphonate forms. The phosphite form is thought to be the active species; however, under neutral conditions the equilibrium lies predominantly toward the phosphonate form, which leads to sluggish reactivity. Consequently, the facilitation of phosphite–phosphonate tautomerization is essential for achieving hydrophosphonylation with low catalyst loading. For example, Abell and Yamamoto utilized the reactive reagent (CF3CH2)2PO(OH) to achieve a highly enantioselective hydrophosphonylation with only 1 mol% of catalyst. Ooi and co-workers applied chiral triaminoiminophosphoranes as organic base catalysts and achieved high yield and enantioselectivity with low catalyst loading at 98 8C. 8] These results further highlighted the importance of rapid phosphite-phosphonate tautomerization. A simple technique for accelerating the phosphite– phosphonate tautomerization is the deprotonation of phosphonates using a base. However, the hydrophosphonylation of aldehydes is a well-known base-mediated process, and the participation of the base-mediated pathway is a critical problem for the enantioselective reaction. Nevertheless, we believed that a judicial choice of base and catalyst would facilitate the Lewis acid catalyzed asymmetric hydrophosphonylation reaction without eroding the enantioselectivity, presuming that the trapping of the phosphite anion by the catalyst and release of the hydrophosphonylation product could proceed rapidly enough for the catalytic process to exclusively occur before the non-catalytic process (Scheme 1). Herein, we report that inorganic bases significantly enhance the rate of reaction of the Al(salalen)catalyzed asymmetric hydrophosphonylation of aldehydes, in which high enantioselectivities ranging from 93 to 98 % ee were achieved for the reactions of both conjugated and nonconjugated aldehydes.