Alkylcopper reagents

However, the use of ordinary achiral alkylcopper reagents instead of the chiral lithium bis(l-alkenyljcuprate also produced the same level of high diastereoselectivity, and thus it seems that the chirality at the y-position of 1 did not exert a significant influence upon the diastereoselectivity. The stereoselectivity was controlled by the stereogenic centers in the substrate. 

Alkylcopper reagents add to allenyl sulphoxides 555 to give the corresponding allylic sulphoxides 556 in moderate yields647 (equation 354). 

Addition of alkylcopper reagents to unsaturated carboxylic acids... 

Coupling of halo ketones with lithium alkylcopper reagents... 

Preparation from activated Cb(O).1 An activated Cu, prepared by lithium naphthalenide reduction of CuIPBu3 (12,140), reacts with primary alkyl bromides at -50 to -78° to form alkylcopper reagents that undergo 1,4-addition to cyclo-hexenone in moderate to high yield. This conjugate addition is facilitated by ClSi(CH3)3 and a phosphine. 

Scheme 2.34. Preparation of chiral alkylcopper reagents (Ipc = isopinocampheyl).

Addition of alkylcopper reagents to unsaturated carboxylic acids 5-22 Free-radical addition of acids to olefins... 

Coupling of halo ketones with lithium alkylcopper reagents 0-94 Acetoacetic ester synthesis and similar reactions... 

Acetylene may undergo two subsequent additions to form conjugated (Z,Z)-di-enylcuprates.515,518 High yields are achieved when acetylene reacts with a-substi-tuted vinylcuprates.518 The addition is faster in tetrahydrofuran than in diethyl ether, and even secondary and tertiary alkylcopper reagents participate in addition.519 Regioisomers, though, may be formed in some cases. 

In a parallel study, Wipf and Fritch11041 have shown that also urethane-protected (Boc), and even amino acid segments, are tolerated as acyl compounds on the aziridine nitrogen. The best results were obtained with alkylcopper reagents derived from CuCN and an alkyl-lithium in the presence of boron trifluoride-diethyl ether complex. Some 6-alkylated compounds (11-15%) were isolated as well. This work was extended to a solid-phase procedure that resulted in resin-bound alkene isosteres that could immediately be used in further peptide synthesis.11051 For this purpose, the 2-nitrophenylsulfonyl (oNbs) group was used for nitrogen protection and aziridine activation. It could be readily cleaved with benzenethio-late, which was compatible with the acid-sensitive Wang linker used. 

When terminal alkynes are used as substrates, alkylcoppermagnesium dihalides prepared from a cop-peril) bromide-dimethyl sulfide complex typically are used (e.g. equation 31134 and Scheme 7).135 The choice of a Grignard reagent, from which the alkylcopper(I) species is prepared, is important in this instance, alkyllithium-derived alkylcopper reagents usually are less satisfactory.10... 

CHj),SiCl also improves conjugate addition of stoichiometric alkylcopper reagents. 

Formation of metal-carbon bonds by addition of an organometallic reagent to an unsaturated compound or a diazonium compound is a little-used method in organocopper chemistry. Various alkylcopper reagents, (RCu + MgXg or LiX), add to acetylene or the alkynes, RC=CH, in a cis manner in ether or ether-pentane at low temperatures (223). A 7T-complex is a probable intermediate. The vinylcopper addition product obtained is dependent on the nature of the alkyne, being sensitive to electronic effects in the latter ... 

Addition to ot, -acetylenic esters and ketones (3, 108 6, 163-164). The addition of organocopper reagents to conjugated acetylenic carbonyl compounds is usually not stereospeciflc, although cis-addition predominates. Japanese chemists have found that the stereoselectivity in the reaction with alkylcopper reagents is markedly enhanced by use of the complex RCu BRj. Thus the reaction of dimethyl acetylenedicarboxylate with n-butylcopper complexed with tri-n-butylboron (or triethylboron) results in exclusive formation of the cis-adduct. In the absence of a trialkylborane the cis- and adducts are formed in the-ratio 85 15. 

Stereospeeific synthesis of IJ-dieues. Corey el al. have described a new synthesis of 1,3-dienes based on the highly stereospeeific cis addition of alkylcopper reagents to a,p-acctylenic carbonyl compounds (3, 108). Thus the reaction of methyl 4-trimethyl-siloxy-2-nonynoate (I ) in THF with divinylcopperlithium (1.25 cq.) at - 90° and then at — 78° affords the pure madduct (2) in > 90% yield. Treatment of (2) with melhanolic hydrochloric acid effects cleavage of the trimethylsilyl ether and lactonization to give (3). 

Use of TMSCl in combination with HMPA, DMAP, or TMEDA all favored 1,2-addition over 1,4-addition. Sequential ct-alkosyalkylcuprate conjugate addition, enolate trapping with TMSCl, and silyl enol ether alkylation provides a one-pot synthesis of tetrahydrofurans (Scheme 3.35) [129]. Cyclic enones afford ds-fused tetrahydrofurans, while acydic systems give complex mixtures of diastereomers. a-Alkoxj alkylcopper reagents also participate in allylic substitution reactions with ammonium salts [127]. 

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