Enantioselective Alcohol C-H Functionalization for Polyketide Construction: Unlocking Redox-Economy and Site-Selectivity for Ideal Chemical Synthesis.
The development and application of stereoselective and site-selective catalytic methods that directly convert lower alcohols to higher alcohols are described. These processes merge the characteristics of transfer hydrogenation and carbonyl addition, exploiting alcohols and π-unsaturated reactants as redox pairs, which upon hydrogen transfer generate transient carbonyl-organometal pairs en route to products of C-C coupling. Unlike classical carbonyl additions, stoichiometric organometallic reagents and discrete alcohol-to-carbonyl redox reactions are not required. Additionally, due to a kinetic preference for primary alcohol dehydrogenation, the site-selective modification of glycols and higher polyols is possible, streamlining or eliminating use of protecting groups. The total syntheses of several iconic type I polyketide natural products were undertaken using these methods. In each case, the target compounds were prepared in significantly fewer steps than previously achieved.
Department of Chemistry, University of Texas at Austin , Austin, Texas 78712, United States.
Jiajie
J
Feng
Department of Chemistry, University of Texas at Austin , Austin, Texas 78712, United States.
Zachary A
ZA
Kasun
Department of Chemistry, University of Texas at Austin , Austin, Texas 78712, United States.
Michael J
MJ
Krische
D000438:Alcohols / Q000737:chemistry*; D006865:Hydrogenation; D007700:Kinetics; D010084:Oxidation-Reduction; D061065:Polyketides / Q000737:chemistry*; D013237:Stereoisomerism
D000438:Alcohols; D061065:Polyketides