Aldol reactions in the synthesis

Copper hydride species, notably Stryker s reagent [Ph3PCuH]6, are capable of promoting the conjugate reduction of a,( >-unsalurated carbonyl compounds [42], Taking advantage of this trustworthy method, Chiu et al. demonstrated in 1998 an intramolecular reductive aldol reaction in the synthesis of novel terpenoid pseudolaric acids isolated from Chinese folk medicine (Scheme 28) [43]. Two equivalents of [Ph3PCuH]6 enabled cycli-zation of keto-enone 104 to provide the bicyclic diastereomers 105 (66%) and 106 (16%). The reaction also was applied to the transformation of 107... 

Deslongchamps and coworkers [26] used a combination of a transannular Diels-Alder cycloaddition and an intramolecular aldol reaction in the synthesis of the unnatural enantiomer of a derivative of the (+)-aphidicolin (4-74), which is a diterpe-noic tetraol isolated from the fungus Cephalosporium aphidicolia. This compound is an inhibitor of DNA polymerase, and is also known to act against the herpes simplex type I virus. In addition, it slows down eukaryotic cell proliferation, which makes it an interesting target as an anticancer agent... 

Scheme 22 Proline-catalyzed aldol reaction in the synthesis of caUipeltoside C...

The Danishefsky group reported the use of an organocatalytic intramolecular aldol reaction in the synthesis of a key intermediate, 108, for preparation of optically active estrone and commercially relevant 19-norsteroids [118, 119]. In the presence... 

I. Paterson C. J. Cowden, D. J. Wallace, Stereoselektive Aldol Reactions in the Synthesis of Polyketide Natural Products, in Modem Carbonyl Chemistry, Ed. J. Otera, Wiley-VCH, Weinheim, 2000, 249-297. 

Stereoselective Aldol Reactions in the Synthesis of Polyketide Natural Products... 

Paterson I, Cowden CJ, Wallace DJ. Stereoselective aldol reactions in the synthesis of polyketide natural products. In Otera J, editor. Modern carbonyl chemistry. New York Wiley 2000. p 249-298. 

The aldol reaction plays a key role in biosynthesis of poly-ketide natural products. It is also one of the most used transformations for stereoselective C—C bond formation. Deslongchamps and co-workers described one of the early examples of transannular aldol reactions in the synthesis of (it)-ryanodol, a compact and highly functionalized polycyclic diterpenoid isolated from Ryania speciosa The 1,5-diketone 48 that was requisite for the transannular aldol reaction was generated in situ from 47 by ozonolysis of its alkene (Scheme 20.14). Conformational equilibration of 48 to the less strained conformer B was followed by a transannular aldol reaction to give 49 in 90% yield. The polycyclic molecular framework provided the conformational bias for stereoselective formation of 49, which was converted to ryanodol after additional transformations. 

SCHEME 20.21. The organocatalytic enantioselective transannular aldol reaction in the synthesis... 

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