Gilman’s cuprate

As recently highlighted by Woodward, enantioselective Sf/2 allylic substitution reactions are mechanistically related to conjugate addition reactions . Theoretical studies carried out by Nakamura and coworkers for the conjugate addition and allylic alkylation using Gilman s cuprates revealed profound mechanistic similarities between these two processes . ... 

The reaction can be alternatively carried out with TMSC1 as a Lewis acid and oiganocuprates [53]. (—)-Dihydro-pinidine, the enantiomer of an alkaloid from Pinas jeffrei, has been synthesized in excellent overall yield following this method. Piperidinone 46a was treated with Gilman s cuprate and trimethylsilylchloride in THF at -78 °C, such that the 2,6-disubstituted piperidinone 49a was obtained in high yield and diastereoselectivity. Its carbonyl group was reduced in a two-step procedure via formation of the dithiolane and subsequent desulfurization with Raney nickel. 

Preferential 1,2-addition of Gilman s cuprate to a ketone over the usually much more facile 1,4-mode occurs in the case of keto enone (,67) When Goldsmith and Sakano treated (67) with 2 equiv. of Me2CuLi at —78 C and quenched the reaction with acetic anhydride, enone (66) was formed. At higher temperatures Michael addition begins to take place, although the cuprate also generates products of ketone enolization (68) rather than carbon-carbon bond formation (Scheme 10). 

SCHEME 27.12 (Top) Structures of Gilman- and Lipshutz-type cuprates (bottom) stmcture of Gilman-type cuprates with the coordination of solvent (S, solvent molecule). 

Confirmation that cw-addition of alkyl copper complexes occurs in these reactions has been obtained by studies of lanthanide-induced shift H n.m.r. spectra of the products. Corey has now introduced (3-methyl-3-methoxybut-l-ynyl)copper in THF as a relatively inexpensive reagent for the generation of mixed cuprates (Gilman s reagents), which enable coupling reactions to occur in high yield with alkyl-lithium reagents. ... 

Since the preformed aggregate Bu3Cu2Li showed a diastereoselectivity of 83 17 in the presence of boron trifluoride16, the low diastereoselectivity noted above was presumably due to a faster addition reaction of butyllithium, which is formed by the treatment of the Gilman cuprate with the boron trifluoride-diethyl ether complex16,, s. 

The discovery of the Gilman cuprate Me2CuLi [5-8], and House s [6, 7] and Corey s [8] demonstrations of its synthetic potential, produced a major breakthrough in this area of chemistry. A major disadvantage of the application of this type of cuprate reagents in stoichiometric amounts, especially from the point of view of atom economy , is the fact that one equivalent of the (potentially valuable) organic component is usually not used in the reaction and ends up as chemical... 

An alternative route to milbemycin by Baker relies on a straightforward s uence of s m to obtain homochiral alkyne (150), beginning with (S)-methyl 3-hydroxy-2-methylprq>ionate (147). A Gilman cuprate delivers the mediyl group to (148) in a chelation-controlled manner resulting in threo (anri)... 

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