Reagents organozinc

In contrast to the polar nature of C-Li and C-MgX bonds, the C-Zn bond is highly covalent and hence less reactive, allowing the preparation of functionalized derivatives. Utilization of organozinc reagents in organic synthesis has mainly centered around the preparation and utilization of functional organozinc compounds in organic syntheses (Reformatsky reaction), cyclopropanation (Simmons-Smith reaction), and transmetalations with transition metals. 

Primary and secondary alkylzinc iodides (RZnI) are best prepared by direct insertion of zinc metal (zinc dust activated by 1,2-dibromoethane or chlorotrimethylsilane) into alkyl iodides or by treating alkyl iodides with Rieke zinc. The zinc insertion shows a remarkable functional group tolerance, permitting the preparation of polyfunctional 

Unfunctionalized dialkylzincs (R2Zn) are obtained by transmetalation of zinc halides, such as ZnCl2, with organolithium or Grignard reagents. Iodide-zinc exchange reaetions catalyzed by Cul provide a practical way for preparing functionalized dialkylzincs. 

The Reformatsky reaction involves condensation of ester-derived zinc enolates with aldehydes or ketones to furnish the con-esponding [3-hydroxy esters. The zinc enolates are generated by addition of an a-haloester in THF, DME, Et20, benzene, or toluene to an activated zinc, such as a Zn-Cu couple or zinc obtained by reduction of zinc halides with potassium (Rieke zinc). An example of a Reformatsky condensation using Rieke zinc is shown below.  

An important application of the Reformatsky reaction is the conversion of P-hydroxy esters to a, P-unsaturated esters. Acid-catalyzed dehydration usually leads to a mixture of a, P- and P, y-unsaturated esters. However, conversion of the initially formed p-hydroxy esters to their corresponding acetates by treatment with acetyl chloride, followed by base-catalyzed dehydration with NaOEt, produces conjugated esters in high purity. This sequence of reactions provides an alternative route to the Homer-Wads worth-Emmons olefmation of ketones (see Chapter 8). 

Catalyst = (PPh2)4Ni from Ni acac)2/PPh3/Bu 2AIH or PPh3)2PdCl2andBu 2AIH 

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The reaction of 2,3-butadienyl acetate (843) with soft carbon nucleophiles such as dimethyl malonate gives dimethyl 2,3-butadienylmalonate (844)[520]. On the other hand, the reaction of the 2,3-butadienyl phosphate 845 with hard carbon nucleophiles such as Mg and Zn reagents affords the 2-allcyl-1,3-butadiene 846[520,521]. The 3-methoxy-1,3-butadiene 848 is obtained by the reaction of the 2-methoxy-2,3-butadienyl carbonate 847 with organozinc reagent. 

The 2-(l-alkynyl)oxirane 78 reacts with an organozinc reagent yielding the /9-allenylic alcohol 79[35]. 

Organozinc reagents aie not nearly as reactive towaid aldehydes and ketones as Grig-nai d reagents and organolithium compounds but are intermediates in certain reactions of alkyl halides. 

Heterocycles in reactions with organozinc reagents 96MI8. 

Formation of heterocycles in reactions using organozinc reagents 96MI8. 

Design of chiral catalysis and asymmetric autocatalysis for diphenyl-(l-methyl-pyrrolidin-2-yl) methanol-catalyzed enantioselective additions of organozinc reagents 97YGK994. 

Copper-catalyzed Enantioselective Conjugate Addition Reactions of Organozinc Reagents... 

To conclude die study, combinations of differently substituted substrates and di-organozinc reagents were investigated iSclieme 8.23). 

The addition usually takes place from the sterically less hindered side of the alkene. The stereochemical course of the addition can be controlled by suitably positioned oxygen center that can coordinate to the organozinc reagent. For example the reaction with 4-hydroxycyclopentene 6 as substrate exclusively yields the c -3-hydroxybicyclo [3.1.0] hexane 7 ... 

As demonstrated, the organozinc reagent provides exclusively the Cram product, while the organomagnesium reagent shows poor diastereofacial selectivity in the addition to 1 and even reverses the selectivity in the addition to 4. 

Numerous chiral non-S-coordinating bis(sulfonamides) have been successfully involved in the enantioselective addition of various organozinc reagents to aldehydes since the first use of tr<2 5-l(i ),2(i )-bis(trifluoromethanesulfo-namido)cyclohexane reported in 1989 by Ohno et These authors demonstrated the usefulness of this ligand in the Ti-catalysed enantioselective addition of ZnR2 to a variety of aldehydes, allowing enantioselectivities of up to 99% ee to be obtained (Scheme 3.37). 

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