Synthesis of chiral 4-substituted 2-hydroxypent-4-enoic acid derivatives via diastereoselective ene reaction promoted by ZnBr2

The diastereoselective carbonyl-ene reaction of various 1,1-disubstituted olefins with the chiral derivatives of glyoxylic acid, with Oppolzer’s sultam 1a and 8-phenylmenthol 1b auxiliaries, was studied. The reaction proceeds effectively under undemanding conditions in the presence of equimolar or catalytic amount of ZnBr2 in good yield and at 72–94% de. Diastereoselectivities are usually slightly better with 8-phenylmenthyl glyoxylate 1b, however, the use of hemiacetal 1a is preferred because the products are often crystalline.

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(2′S)-N-(2′-Hydroxy-4′-phenylpent-4′-enoyl)-(2R)-bornane-10,2-sultamC21H27NO4S[α]D24=-85.7 (c 1.5, CHCl3)Source of chirality: (2R)-bornane-10,2-sultamAbsolute configuration: (2′S)

(2′S)-N-(2′-Hydroxy-4′-methylpent-4′-enoyl)-(2R)-bornane-10,2-sultamC16H25NO4S[α]D24=-114.9 (c 1.5, CHCl3)Source of chirality: (2R)-bornane-10,2-sultamAbsolute configuration: (2′S)

(2′S)-N-(2′-Hydroxy-5′-methyl-4′-methylenehexanoyl)-(2R)-bornane-10,2-sultamC18H29NO4S[α]D24=-108.8 (c 0.5, CHCl3)Source of chirality: (2R)-bornane-10,2-sultamAbsolute configuration: (2′S)

(2′S)-N-(2′-Hydroxy-5′,5′-dimethyl-4′-methylenehexanoyl)-(2R)-bornane-10,2-sultamC19H31NO4S[α]D24=-93.4 (c 0.4, CHCl3)Source of chirality: (2R)-bornane-10,2-sultamAbsolute configuration: (2′S)

(2′S)-N-[3′-(Cyclopent-1-enyl)-2′-hydroxypropionyl]-(2R)-bornane-10,2-sultamC18H27NO4S[α]D24=-100.7 (c 1.2, CHCl3)Source of chirality: (2R)-bornane-10,2-sultamAbsolute configuration: (2′S)

(2′S)-N-[3′-(Cyclohex-1-enyl)-2′-hydroxypropionyl]-(2R)-bornane-10,2-sultamC19H29NO4S[α]D24=-106.1 (c 1.5, CHCl3)Source of chirality: (2R)-bornane-10,2-sultamAbsolute configuration: (2′S)