Synthesis of (R)-(+)-tanikolide through stereospecific C-H insertion reaction of dichlorocarbene with optically active secondary alcohol derivatives.
Stereospecific alpha C-H insertion reaction of protected chiral 1,2-glycols, (S)-1,2-isopropylidenedioxytridecane (3) and ethyl (S)-4,5-isopropylidenedioxy-pentanoate (4), prepared from (R)-glyceraldehyde acetonide (2), with dichlorocarbene generated from CHCl(3)/50% NaOH/cetyltrimethylammonium chloride (as ptc.) took place with complete retention of configuration to provide (S)-4-dichloromethyl-2,2-dimethyl-4-undecyl-1,3-dioxolane (5) and ethyl (S)-3-(4-dichloromethyl-2,2-dimethyl-1,3-dioxolan-4-yl)-propanoate (8), respectively. The ester (8) was transformed to 5 by elongation of the side chain. The glycol derivative (5) was converted into O-TBDPS-protected (S)-2-hydroxymethyl-2-undecyloxirane (16). Reaction of 16 with a cuprate reagent containing homoallylic carbon chain followed by oxidative manipulation of the terminal olefin afforded (R)-(+)-tanikolide (1).
Arasaki
Hideki
H
Gifu Pharmaceutical University, Japan.
Iwata
Masashi
M
Makida
Miyuki
M
Masaki
Yukio
Y
D000438:Alcohols / Q000138:chemical synthesis*; D006843:Hydrocarbons, Chlorinated / Q000138:chemical synthesis*; D007783:Lactones / Q000138:chemical synthesis*; D009904:Optical Rotation; D013237:Stereoisomerism
D000438:Alcohols; D006843:Hydrocarbons, Chlorinated; D007783:Lactones; C400156:tanikolide; C004260:dichlorocarbene