Aldehydes MeMgBr addition

With aldehydes (140a) and (140b) in hand, further 1,2-additions of Me2CuLi have been examined and found to afford results (Scheme 25) opposite to those obtained with, for example, MeMgBr, in good yields (>85%). The preference is explained on the basis of attack onto the chelated bicyclic compound... 

Nonchelation-controlled addition reactions can be very useful in organic synthesis. - An example drawn from carbohydrate chemistry is particularly significant in diis regari (Scheme 8)." Due to chelation, the aldehyde (89) reacts with MeMgBr to give a mixture of the diastereomeric alcohols (91) and (92) in 88 12 molar ratio, whereas, in the reaction with MeTi(OPH)3 under nonchelation control, only the Felkin-Anh product (92) is observed. 2,3-O-Isopropylidene-o-glyceraldehyde (93 equation 33) is also reported to react under noncheladon-controlled conditions with several RTi(OPr )3 reagents. Oddly, PhTi(OPr )3 favors the formation of the syn product, a unique result that is difficult to rationalize. 

In a synthetic effort directed toward a segment of erythronolide A, the addition of (2) to aldehyde (22) gave, after treatment with MeMgBr/CuI, an approximately 80 20 mixture of ring-opened products (23) and (24 equation ll). Interestingly, direct alkylation of this aldehyde (as a mixture of double bond isomers) with ethyllithium gave an 18 82 mixture of adducts. The factors responsible for the complementary face selectivity shown by (2) versus ethyllithium are unclear. Comparisons are particularly difficult due to the fact that most organolithium additions to carbonyl compounds are irreversible, kinetically controlled processes, whereas reactions of (2) can be reversible. 

The union of fragments 78 and 81 was performed by treatment of 81 with t-BuLi to induce a bromine-lithium exchange, followed by transmetal lation to the cerium reagent [49] and finally the addition of aldehyde 78 (Scheme 17). The coupled product was obtained in 85% yield as a diastereomeric mixture of alcohols. Swem oxidation [50] and reaction with MeMgBr at -78 °C provided the tertiary alcohol stereoselectively in 98% yield. A final deprotection with tosic acid gave venustatriol (2). 

An efficient enantio-selective catalytic system for the addition of MeMgBr to aldehydes (with up to 96% ee) has been developed using binaphthyl derivative (11) as 0 chiral ligand and an excess amount of titanium tetraisopropoxide. 

The procedure involves copper(I)-catalysed conjugate addition of MeMgBr to an a,p-unsaturated thioester 4, followed by reduction to the corresponding aldehyde and subsequent olefination to elongate the chain. This yields anew a,p-unsaturated thioester 6, which, in turn, can be subjected to the next catalytic reaction (Scheme 5). 

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