Alkenylcoppers

A conceptually surprising and new route to prostaglandins was found and evaluated by C.R. Johnson in 1988. It involves the simple idea to add alkenylcopper reagents stereo-selectively to a protected chiral 4,5-dihydroxy-2-cyclopenten-l-one and to complete the synthesis of the trisubstituted cyclopentanone by stereoselective allylation of the resulting enolate. 

Unique chemistry is associated with the cyclopentenone all five carbon atoms can be functionalized, and the endo-methyl groups of the acetonide assure clean stereoselective addition of the alkenylcopper reagent from the convex side. The use of the acetonide group to control enolate regioselectivity and to mask alcohols should be generally applicable. 

Direct transmetalation of organoboranes to organocopper reagents is not a general reaction. Because of dieir similar bond energies and electronegativities, diis trans-nietalation is linided to die preparation of alkenylcopper and unfiinctionalized... 

The alkenylcopper adducts can be worked up by protonolysis, or they can be subjected to further elaboration by alkylation or electrophilic substitution. 

Mixed copper-zinc reagents also react with alkynes to give alkenylcopper species that can undergo subsequent electrophilic substitution. 

Scheme 8.6. Generation and Reactions of Alkenylcopper Reagents from Alkynes... 

This method can be extended to the preparation of alkenylcopper compounds. Thus, treatment of the iodoalkenyl azide 10 with nBuLi at —100 °C (Scheme 2.3), followed by transmetalation with Znl2 in THF and then by a second transmetalation with CuCN-2LiCl, produces the copper species 11. This then effects a cis-selective carbocupration of ethyl propiolate to furnish the ( , ) diene 12 in 81% yield. 

Scheme 2.3. Preparation of an azido-alkenylcopper reagent from an alkenyl iodide. 

The transmetalation of dialkenylchloroboranes of type 52 with methylcopper (3 equiv.) provides an alkenylcopper compound 53, which undergoes cross-coupling with allylic halides to produce mixtures of Sn2 and Sn2 products. Interestingly, this method is also useful for the preparation of functionalized alkenylcoppers such as 54 (Scheme 2.14) [31]. 

Scheme 2.14. Allylation of alkenylcopper species derived from alkenylboranes.

Scheme 2.15. Alkynylation of alkenylcopper reagents obtained from alkenylboranes.

Scheme 2.16. Preparation of fluorinated ketones by way of fluorinated alkenylcopper species.

Scheme 2.18. Michael additions using alkenylcopper species derived from alkenylaluminiums.

Alternatively, by performing a zirconium-catalyzed Negishi methylalumination on 1-hexyne, it is possible to produce stereochemically pure alkenylcopper species 62, which adds to enones in a 1,4-fashion, to give compounds such as 63 (Scheme... 

Scheme 2.19. Michael addition of a functionalized alkenylcopper species.

Scheme 2.49. Cyclization of alkenylcopper compounds generated from organostannanes.

Transmetalation of this type has also been used to assist palladium(0)-catalyzed cross-coupling reactions in sterically congested substrates. Transmetalation of stan-nanes into alkenylcopper intermediates considerably accelerates subsequent palladium(0)-catalyzed cross-coupling with arylsulfonates (Scheme 2.50) [103]. 

The reaction of stereomerically well-defined alkenylcopper species 91 obtained by a carbocupration followed by treatment with (KTFjiZn leads to a selective double methylene insertion providing the chelate-stabiUzed alkylzinc reagent 92, which leads after deuteriation with D2O to the unsaturated sulfoxide 93 in 80% yield. This method has been elegantly extended by Marek, Knochel and coworkers (Scheme 32). ... 

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