Diastereoselective carbocupration

Scheme 7-115 Regio- and diastereoselective carbocupration of a strained C=C bond.

Scheme 10.125 Diastereoselective carbocupration/ketone allylzincation of terminal unactivated alkynes [106].

Carbocupration of chiral alkynylsulfoxides 47 in a regio- and stereospecific manner produces alkenyl organocopper 48, which is subsequently reacted with bis(iodomethyl) zinc in the presence of aldehydes or imines. The zinc carbenoid homologation step leads to 49, the conformation of which is controlled by intramolecular chelation 49 reacts with the aldehyde or imine before it can undergo a -elimination (cf. equation 20). The final product 63 is generally obtained with high diastereoselectivity and in good overall yield (Table 8). 

Chiral homoallylic alcohols and amines were prepared by using a four-component condensation reaction based on a zinc homologation followed by a trapping with an aldehyde or an imine.301 A regio- and stereospecific carbocupration reaction on alkynyl sulfoxide provides the corresponding metallated /3,/3-dialkylated a,/ -ethylenic sufoxide 98. Addition of aldehydes or imines, followed by addition of the bis(iodomethyl)zinc carbenoid, provides adducts 99 in good overall yield and with very high diastereoselectivity (Scheme 36). 

Finally, the carbometallation reaction of spirocyclic cyclopropenes with a chiral ketal attached to the substrate was described. Thus, carbocupration of the chiral cyclopropene 96 proceeded with 96% diastereoselectivity with a higher-order organocuprate [134] (Scheme 7-114). 

One approach that was influential in our research on the synthesis and applications of allylboronates to access a-methylene y-lactones, which was reported by Sidduri and Knochel, utilize a mixed zinc copper reagent that allowed for the one-pot preparation of a-methylene y-lactones (Equation 10). The desired copper-based allylation reagents are formed with high selectivity through a cfs-carbocupration, and the diastereoselectivity of aldehyde addition is high, which suggests a Type I chair-Uke transition state similar to allylboration reactions (see Section 5.1). 

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