Alkenylcopper reagents

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. 

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

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

Scheme 2.15. Alkynylation of alkenylcopper reagents obtained from alkenylboranes.

The synthetic applications of alkenylcopper reagents have been reviewed in detail by Normant and Alexakis.3 The high synthetic potential of these reagents has been summarized in Scheme. t is important to notice that the reactivity of alkenylcoppers and dialkenylcuprates is not the sai21 e a being more reactive. Thus, some electrophiles3 do not react readily with alkenylcoppers, u on y wi... 

Enynes were prepared in good yield from alkynyl iodonium salts and alkenylcopper reagents, stereospecifically. This approach was suitable for the synthesis of conjugated enynes, using a trisubstituted alkene with complete retention of its geometry [47], 1,3-Diynes were similarly obtained by coupling alkynyl iodonium... 

Burton has investigated the alkylation of allyl halides with perfluoroorganocoppers. Both perfluoroalkylcoppers and perfluoroalkenylcoppers couple with allyl bromide in high yield the former also couples effectively with allyl chloride (equation 38)51 13. Doublebond stereochemistry is preserved with alkenylcopper reagents, while issues of a-/y-regio-selectivity of attack on the allyl unit have yet to be addressed. 

Alkylation Formation of Optically Active 4-Methyi-cyclohexylideneaikanes. Alkenylcopper reagents can be alkylated by treatment with alkyl halides and other electrophiles. Reaction of (S)-4-methylcyclohexylidenemethylcopper (enantiomer of the title reagent) with lodomethane gives (+)-(S)-4-(methylcyclohexylidene)ethane with 98% retention of configuration (eq 3). Alkylation of (R)-4-methylcyclohexylidenemethylcopper with methyl iodide and other alkyl halides is expected to show similar stereospecificity. 

The method was made considerably more general by inclusion of a catalytic amount of a palladium(O) complex during addition of the organometallic. Alkenylcopper reagents actually react relatively slowly with acid halides but, in a fashion analogous to other alkenyl metal species (see Section 1.13.4), they may be readily transmetallated to form an acylpalladium(II) complex which then undergoes reductive elimination to the product (Scheme 29)." A further discussion of acylation mediated by palladium complexes is included in Section 1.13.4. Interestingly, a,P-unsaturated acid chlorides react under these conditions to form divinyl ketones. 

Guneratne, R.D., and Burton, D.J., Preparation and functionalization of an alkenylcopper reagent formed by the syn addition of (dialkoxyphosphinyl)difluoromethylcopper to hexafluoro-2-butyne, J. Fluorine Chem., 98, 11, 1999. 

Whereas the direct reaction of a-substituted alkenylzirconocene reagents with chlorophosphines does not lead to the related alkenylphosphines, two groups have now shown that if the reactions are carried out in the presence of copper(I) chloride the desired phosphines are obtained, initially as copper-complexes, from which they can be liberated by treatment with appropriate reagents. It is thought that alkenylcopper reagents are involved in these reactions, and, using this approach, new alkenylphosphines have been prepared, e.g., (41)," and the diphosphines (42)." ... 

---