Organozinc functionalized

Cross-coupling between functionalized zin or l-bromoalky nes is very fast [83]. This st temperatures i-55 C) and offers bigli stet( condary organozinc-coppet reagents suCli a... 

The carbonyl substrate 3 to be reacted with the organozinc compound 2 can be an aldehyde or ketone that may contain additional functional groups. With a vinylogous halo ester—i.e. a y-halocrotyl ester—the corresponding y-crotylzinc derivative is formed. 

In the presence of Lil, TMS-C1, and a catalytic amount of (CH3)2CuCNLi2, conjugate addition of functionalized organozinc reagents occurs in good yield. 

Organozinc compounds are more reactive nucleophiles requiring no activation for the trans-metalation step, while allowing for much wider functionality to be present in the molecule than in organomagnesium compounds. However, organozinc compounds cannot be stored without special precautions, and therefore should be generated immediately prior to use, which makes... 

The general utility of the oxidative addition of functionalized organic halides to zinc was demonstrated by the formation of organozinc iodides 28 from protected (3- and 7-amino acids (Scheme 26).73 The organozinc iodides prepared in this manner were neither sufficiently stable nor sufficiently reactive in THF, but excellent yields were obtained in more polar aprotic solvents, such as DMF and DMSO. 

Perhaps the most investigated reaction of organozinc compounds is their addition to the carbonyl group of aldehydes. A broad range of simple and functionalized diorganozincs and a great variety of aldehydes have been studied in this transformation. The reaction furnishes chiral secondary alcohols, which are essential building blocks in the synthesis of natural products and other important compounds. Recent studies of this transformation have been devoted to its asymmetric catalytic versions (Scheme 103). 

A theoretical study of the reaction mechanism for addition of organozincate complexes to aldehydes was recently performed using density functional theory.298 It has been suggested that the addition takes place through formation of a four-centered transition state and, therefore, it can be considered a typical nucleophilic reaction. 

All alkyl halides used in the couplings were primary, although some of them were branched or had an ester functionality. Some of the dialkylzincs had a functional group without affecting the outcome of the reaction. For example, organozinc derivative 302 with a silyl enol ether group reacted with alkyl iodide 303, affording the desired product 304 in 65% yield (Scheme 153). 

Inspired by the well-established nickel-catalyzed co-oligomerization of 1,3-dienes with CO2, which proceeds via bis-TT-allyl intermediate, Mori has developed a powerful intramolecular version of this process (Scheme 103). After insertion of C02 into the bis-vr-allyl complex, a transmetallation with an organozinc reagent takes place to generate the Ni(0) catalyst. Highly functionalized carbo- and heterocyclic compounds with complete stereocontrol can372 be synthesized by this method. 

Feringa and co-workers described the tandem addition-aldol cyclization protocol leading to the formation of 6,6-, 6,7-, and 6,8-annulated bicyclic systems (Scheme 68).39 Using Cu(n)-29 as catalyst and functionalized organozinc reagents as nucleophiles, the conjugate addition reaction followed by aldol cyclization can offer highly enantioselec-tive annulation products (up to 98% ee). This method can be used in the synthesis of carbocyclic compounds, such as steroids, terpenes, and other natural products. 

Recent notable improvements by Knochel and co-workers include iron-catalyzed cross-coupling reactions of various acid chlorides 148 with dialkylzinc reagents (Equation (24))324 as well as the iron-catalyzed arylation of aroyl cyanides 149 with Grignard reagents (Equation (25)).3 5 In the first case Knochel s reaction conditions tolerate ester groups on the organozinc compounds, while in the latter case ester, aryl alkyl ether, cyano, and chloro functionalities on the aromatic moieties are compatibles with the reaction conditions. 

Table 11.12. Functionally substituted N,N-dibenzylcyclopropylamines 83 from N,N-dialkylformamides and organozinc precursors (see Scheme 11.23).

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