Zinc-copper reagents, 1,4-addition

The diastereoselective formation of dienol tricarbonyliron complexes on treating rf-2,4-pentadienal)Fe(CO)3 with functionalized zinc-copper reagents has been investigated (equation 49)66. Cyano-substituted complexes undergo intramolecular nucleophilic additions when treated with lithium diisopropylamide (LDA) as shown in equation 50. 

The same mechanism is operative for the preparation of squaric acid derivatives of type 112. Treatment of 3,4-dicMorocyclobutene-l,2-dione with two different zinc-copper reagents provides the double addition-elimination product 112 in 67% yield (Scheme 2.41) [87]. 

Scheme 2.45. Addition of zinc-copper reagents to nitroolefins.

SCHEME 84. Addition of functionalized zinc-copper reagents to cationic chromium complexes and subsequent cyclization... 

SCHEME 86. Addition-elimination reaction with zinc-copper reagents... 

Interestingly, bis(methylthio)-l-nitroethylene (380) reacts with dimetallic zinc-copper species leading to the corresponding exo-methylene cycloalkenes, such as 381 (Scheme 100) . / -Disubstitutcd nitroolefins are especially difficult to prepare by nitroaldol condensation. The addition of zinc-copper reagents to nitroolefins followed by a reaction with phenylselenyl bromide produces, after IFO, oxidation, EtZ mixtures of -disubstituted nitroalkenes, such as 382 (Scheme 100) . 

Michael-addition reactions can be performed with various zinc/copper reagents derived from organozinc halides. (3-Monosubstituted enones react in... 

Addition reaction of zinc-copper reagents to nitro olefins is a versatile method for preparing polyfunctional nitroalkanes.20 A direct ozonolysis of the intermediate zinc nitronate furnishes the corresponding ketone (Nef-reaction).20... 

The addition of zinc-copper reagents to an activated nitro olefin like 2-nitro-3-acetoxypropene is complete within a few minutes at -55 °C (Scheme 10.7).21... 

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. 

The reaction of 1,4-bis-zinc derivatives with CuCN-2LiCl allows the preparation of a range of new polyfunctional zinc-copper reagents.309 They undergo selectively 1,4-additions on a,/3-ethylenic ketones in the presence of TMSC1 providing a new zinc-copper reagent, which can react with another electrophile (Equation (175)). 

Stereoselective Michael addition of lunctionalized zinc-copper reagents to cycloheptatrienone iron tricarbonyl complexes is observed (Scheme 146). A pendant nitrile can participate in an alkylation reaction of the intermediate enolate forming a fused bicyclic ring system (Scheme 147). Addition in a 1,2- or 1,4-fashion depends on the nucleophile. Harder nucleophiles tend to form 1,2-adducts (Scheme 148). 

The extension of this cross-coupling to iodoalkenes is also possible. If the iodo-, bromo-, or chloroalkene is further conjugated with an electron-withdrawing group, a facile substitution via an addition-elimination mechanism is observed. Typically, 3-iodo-2-cyclohexen-l-one 24 [55] reacts with a zinc-copper reagent such as 25 furnishing the expected cross-coupling product 26 (see Section 9.6.5 Scheme 25) [13]. 

This addition-elimination reaction can be applied to the preparation of squaric acid derivatives. Thus, the treatment of 3,4-dichlorocyclobutene-l,2-dione 27 with two different zinc-copper reagents furnishes polyfunctional squaric acid derivatives like 28, provided the first zinc-copper reagent bears a secondary or tertiary alkyl group (Scheme 9-26) [56]. 

One approach that was influential in our research on the synthesis and applications of allylboronates to access a-methylene y-lactones, which was reported by Sidduri and Knochel, utilize a mixed zinc copper reagent that allowed for the one-pot preparation of a-methylene y-lactones (Equation 10). The desired copper-based allylation reagents are formed with high selectivity through a cfs-carbocupration, and the diastereoselectivity of aldehyde addition is high, which suggests a Type I chair-Uke transition state similar to allylboration reactions (see Section 5.1). 

Polyoxygenated metabolites of unsaturated fatty acids have been prepared via the addition of functionalized zinc-copper reagents such as 477 to unsaturated aldehydes in the presence of BF3-OEt2, providing allylic alcohols of type 478 (Scheme 2-142, (eq. 

---