Iterative Synthesis of Polydeoxypropionates Based on Iridium-Catalyzed Asymmetric Hydrogenation of α-Substituted Acrylic Acids

Abstract

A novel iterative protocol for the synthesis of polydeoxypropionates was developed based on iridium-catalyzed asymmetric hydrogenation of α-substituted acrylic acids. The catalyst loading can be as low as 0.01 mol %, and the overall yield for one iterative cycle is >76%. The reaction conditions are mild, and no organometallic reagents or chromatography steps are required. Using this protocol, (+)-phthioceranic acid and the polydeoxypropionate motifs of ionomycin and borrelidin were synthesized in high yield.

Enantioselective Total Synthesis of (−)‐Doliculide Using Catalytic Asymmetric Hydrogenations

“…Our group has developed a number of highly effective catalytic asymmetric hydrogenation reactions. [15] [16] We wish to use Ir-catalyzed asymmetric hydrogenation of a β-keto ester [17] to construct a 1,3diol unit and Ir-catalyzed asymmetric hydrogenation of α-acrylic acid, [18] [19] to build the 1,3-methyl unit of deoxypropionates. By varying the configuration of catalysts, the absolute and relative configuration of newly formed stereogenic centers can be controlled.…”

“…Subsequently, acid 15 was converted to α-substituted acrylic acid 17 in 65 % yield by means of the protocol we developed previously, that are carboxymethylation with Meldrum's acid, alkenylation with Eschenmoser's salt. [18] The TBS protecting group is intact under the acidic reaction conditions. The asymmetric hydrogenation of compound 17 was performed to generate the second methyl-substituted stereogenic center.…”

“…The acid 21 with a new methyl-substituted stereogenic center was obtained in high yield with 97.3 : 2.7 dr by carboxymethylation with Meldrum's acid, alkenylation with Eschenmoser's salt, and asymmetric hydrogenation catalyzed by (R)cat-2c. [18] The acid 21 was treated with glycine tertbutyl ester hydrochloride in the presence of diethyl phosphorocyanidate (DEPC) to provide amide 22. The selective deprotection of MOM of amide 22 produced compound 23 by using 2.5 equivalent of B-bromocatecholborane in dichloromethane at À 78°C, while the TBS was intact in this condition.…”

Chemical Synthesis of Cell Wall Constituents of Mycobacterium tuberculosis

“…Since their first reported total syntheses , phthioceranic and hydroxyphthioceranic acids have attracted a lot of attention. Over the past years, due to their exquisite and synthetically challenging 1,3-methyl ramification, five more stereoselective syntheses were reported by four different groups. − This intriguing target motif has sparked the creativity of the chemical community to develop highly efficient and elegant solutions to the synthesis of the 1,3-methyl array.…”

Stereodiverse Iterative Synthesis of 1,3-Polyol Arrays through Asymmetric Catalytic Hydrogenation. Formal Total Synthesis of (−)-Cyanolide A

“…Inspired by an iterative protocol that we developed to synthesize deoxypropionates, 13 we conceived an iterative fourstep protocol for preparing 1,3-polyols (Scheme 2). We began by focusing on elongating the carbon chain of keto ester 2.…”