Crossed-Aldol condensation diastereoselective

The stereochemical course of several Co2(CO)6-mediated reactions has been studied. For example, although alkynyl aldehydes undergo crossed aldol condensation with trimethylsilyl enol ethers with little stereoselectivity, their hexacarbonyldicobalt derivatives react with moderate to excellent syn diastereoselectivity.96 101 The mechanism behind this selectivity has not been fully elucidated and is complicated by the lluxional nature of the intermediate cations. This stereoselective reaction has been successfully applied to the synthesis of /3-lactam antibiotics.100... 

In the studies on the synthesis of the antitumor agents esperamicin and calicheamicin by Magnus et al. [93], an aldol reaction was found suitable for macrocyclization after a number of unsuccessful attempts. Thus, as shown in Scheme 54, the diynene core structure (165) of the two antitumor agents was synthesized from the dicobalt hexacarbonyl derivative 163. When 163 was treated with n-BujBOTf/DABCO/EtjN in CHzClj-THF the aldol product 164 was isolated as a single stereoisomer in 45% yield. Although alkynyl aldehydes undergo similar crossed aldol condensation, their dicobalt hexacarbonyl derivatives react with moderate to excellent syn diastereoselectivity [94]. 

For Aldol and Related Reactions. The TMSI/(TMS)2NH combination can be used for the synthesis of polycyclic cyclobutane derivatives by tandem intramolecular Michael-aldol reaction. TMSI-induced diastereoselective synthesis of tetrahy-dropyranones by a tandem Knoevenagel-Michael reaction, has also been developed. More recently, the facile synthesis of a,a bis(substituted benzylidene)cycloalkanones has been reported, using TMSI (in situ generated) mediated cross-aldol condensations (eq 53). ... 

The lower yield may be explained by the fact that linear aldehydes also undergo self-aldol condensation, which is in direct competition with the crossed-aldol reaction. Aromatic aldehydes as the carbonyl component led to reduced diastereoselectivity. For example, the (.S )-prolinc-catalyzed aldol reaction of 4 with ort/tochlorobenzaldehyde proceeded with a good yield of 73%, but with an anti/syn ratio of only 4 1 and enantiomeric excesses of 86% ee (anti) and 70% ee (syn). 

Condensation Reactions. Boron trichloride converts ketones into (Z)-boron enolates at —95 °C in the presence of Diisopropyl-ethylamine. These enolates react with aldehydes with high syn diastereoselectivity (eq 2). A similar condensation of imines with carbonyl compounds also provides crossed aldols in reasonable yields. The reaction was extended to the asymmetric aldoi condensation of acetophenone imine and benzaldehyde by using isobornylamine as a chiral auxiliary (48% ee). ... 

LLC networks containing catalytic headgroups have also been shown to be useful for heterogeneous Lewis acid catalysis. The Sc(III)-exchanged cross-linked Hu phase of a taper-shaped sulfonate-functionalized LLC monomer has been shown to be able to catalyze the Mukaiyama aldol and Mannich reactions [115] with enhanced diastereoselectivity. This Sc(III)-functionalized Hu network affords condensation products with syn-to-anti diastereoselectivity ratios of 2-to-l, whereas Sc(III) catalysts in solution or supported on amorphous polymers show no reaction diastereoselectivity at all. 

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