Organometallation of (R)-2,3-cyclohexylideneglyceraldehyde derived ketones: a simple and stereoselective strategy for the synthesis of (+)-tanikolide

Several metal mediated allylations and Grignard additions to ketones 3 and 5, both derived from (R)-2,3-cylcohexylideneglyceraldehyde, took place with very high diastereoselectivity producing the same tertiary carbinol 4b as the major product. Subsequently, 4b was exploited to synthesize (+)-tanikolide efficiently through a series of simple reactions employing an RCM strategy.

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(2R)-1,2-O-Cyclohexylidene tetradedacane-1,2-dihydroxy-3-oneC20H36O3[α]D22=+22.2 (c 0.12, CHCl3)Source of chirality: (2R)-2,3-cyclohexylideneglyceraldehydeAbsolute configuration: (2R)

(2R,3R)-1,2-O-Cyclohexylidene-3-undecyl-hex-5-en-1,2,3-triolC23H42O3[α]D22=+11.6 (c 0.8, CHCl3)Source of chirality: (2R-2,3-cyclohexylideneglyceraldehydeAbsolute configuration: (2R,3R)

(2R,3S)-1,2-O-Cyclohexylidene-3-undecyl-hex-5-en-1,2,3-triolC23H42O3[αD22=-5.3 (c 0.9, CHCl3)source of chirality: (2R)-2,3-cyclohexylideneglyceraldehydeAbsolute configuration: (2R,3S)

(5R)-5[(2′R)-1′,2′-O-Cyclohexylidene dihydroxyethyl]-hexadec-2-en-5-olideC22H40O4[α]D22=+2.7 (c 1.0, CHCl3)Source of chirality: (2R)-2,3-cyclohexylideneglyceraldehydeAbsolute configuration: (5R,2′R)

(5R)-5[(2′R)-Dihydroxyethyl]-5-hexadecanolideC18H34O4[α]D22=-12.1 (c 1.1, CHCI3)Source of chirality: (2R)-2,3-cyclohexylideneglyceraldehydeAbsolute configuration: (5R,2′R)