Copper reagents, alkenyl

The dienone 858 is synthesized by coupling of the alkenyl copper reagent 856 with crotyl chloride (857) in the presence or absence of ZnCl2[731], Tetrabutyllead (859) reacts with benzoyl chloride to afford butyl phenyl ketone[732]. 

Another recent disclosure examined silicon-to-copper transmetallation as a mild means of synthesizing alkenyl-copper reagents from stable precursors. The method requires activation of the silyl group by an allylic alcohol. Again, the silanes in this work are produced by circuitous means but should be accessible by ruthenium-catalyzed hydrosilylation. Treatment of the silyl alcohol with a stoichiometric amount of copper(l) /rz -butoxide results in the C-to-O migration of the silyl group to produce a vinylcuprate shown to be competent for subsequent allylation to produce 1,4-diene products (Scheme 17). 

With glyceraldehyde-derived enones and enoates, it has been found that addition of aryl or alkenyl copper reagents is almost independent of the enone geometry [24, 25]. In agreement with the modified Felkin-Anh model, Z enoates usually provide high levels of anti selectivity (Scheme 6.11). Hence, the Z derivative 64 reacted with complete stereochemical control, whereas the -enoate 64 gave a lower selectivity of 4 1 in favor of the anti-conjugate adduct [25]. 

Attempted preparation of fluorinated alkenyl copper reagents from the corresponding alkenyl iodides with copper powder was not successful. The symmetric dimer was obtained in good yield [172-179] (Scheme 62). 

A practical method for preparation of fluorinated alkenyl copper reagents has been recently developed from cuprous halides metathesis of the corresponding zinc or cadmium reagents [180]. These copper reagents exhibit excellent stability at room temperature and undergo a variety of coupling reactions with methyl, allyl, vinyl, aryl and acid halides [180] (Scheme 63). More recently, preparation of cyclic perfluoroalkenyl copper reagents has been reported by the same route [156-158]. 

Alkenyl copper reagents, such as 87-%, also prepared via vinyl iodides such as 85 or %, have proven to be reliable reagents for the introduction of the standard as well as many modified p-chains (22,23.26.29.31.32.34-37,72). The alkenyl-copper reagents are of three types lithio divinylcuprates (87), lithio mono vinylcuprates (%, ) containing an inert ligand, and vinylcopper reagents (90) which have received little synthetic attention (Scheme 16). scheme is... 

The copper species formed depends on the solvent, and three different species were detected by F NMR, although the structure of each species was not elucidated [245 This copper reagent undergoes a variety of coupling reactions with aryl, alkenyl, allyl, and acetylenic halides [244, 245 (equation 162)... 

The reaction of propargylic chiral acetals with a catalytic copper reagent (RMgX/5% CuX) provides the expected alkoxy allenes in quantitative yield (Table 3)61. The diastereomeric excess is highly dependent on the size of the ring of the acetal and on the type of substituents it contains. The best diastereomeric excess is 85% with the acetal derived from cyclooctanediol. The use of lithium dimethylcuprate results in 1,2-addition lo the triple bond and the resulting lithium alkenyl cuprate bearing a cyclic acetal does not eliminate even at reflux temperature ( + 35°C). 

Another type of copper reagent was prepared from RZnI/CuCN, and this was shown to couple with alkenyl halides." ... 

The mechanism of carbometallation has been explored computationally.77 The reaction consists of an oxidative addition to the triple bond forming a cyclic Cu(m) intermediate. The rate-determining step is reductive elimination to form a vinyl magnesium (or zinc) reagent, which then undergoes transmetallation to the alkenyl-copper product. 

In addition to alkenylboron compounds, alkenylalane, alkenylzirconium, alkenyltin, alkenyl copper, and alkenylmagneslura reagents are reported to undergo a related alkenyl-alkenyl coupling reaction to give l,3-a1kad1enes. 

Reaction of methyl iododifluoroacetate with copper in HMPA affords the carboalkoxydifluoromethylene copper reagent, which couples with aryl, alkenyl, alkyl, alkynyl and allyl halides to give the corresponding 2,2-difluoroester derivatives [261] (Scheme 87). 

A stereoselective synthesis of substituted pyrrolidines has been achieved by a sequential domino Michael addition and intramolecular carbozincation. The intermediate zinc-copper reagent obtained after cyclization can be trapped with an electrophile such as allyl bromide (Scheme 18).180 Addition of zincated hydrazones 52 on alkenyl boronates, followed by a trapping with an electrophile, provides adduct of type 53 with good yield and high diastereoselectivity (Scheme 19).181 By this addition/trapping sequence, several contiguous stereogenic centers are created in one step. 

Alkynylation of zinc-copper compounds has been used for the synthesis of polyfunctional acetylenic ethers [84] and for the preparation of building blocks for pharmaceutically active compounds [85]. Whereas cross-coupling between non-activated iodoalkenes and zinc-copper reagents only proceeds at elevated temperatures and in polar solvents such as NMP or DMPU (60 12 h) [86], alkenyl... 

A transition metal catalyzes a similar carbomagnesation reaction, which has broaden the synthetic usefulness of this method for synthesis of alkenyl Grignard reagents. Among several transition metal salts that were reported to catalyze carbomagnesation of acetylenes [7,51,82 84], copper salts are most popular [7,13-15]. A variety of acetylenes, including acetylene itself [85], as well as substituted ones participated in this reaction. Some representative reactions are summarized in Table 11. 

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