Zinc reagents carbonyl reactions

Conditions for controlling the regiochemistry of the addition reactions between benzyl zinc reagents and 2,4-dichloroquinoline under palladium-catalyzed conditions were developed <99JOC453>. Similarly, the regiochemistry of the palladium-catalyzed carbonylation of 4,7-dichloroquinoline was evaluated <99TL3719>. 

SCHEME 91. Reaction of allenic, propargylic and allylic zinc reagents with carbonyl derivatives... 

SCHEME 93. Addition reactions of zinc and copper-zinc reagents to carbonyl compounds... 

In 1984, Fried et al. reported the reaction of bromodifluoroacetate with carbonyl substrates in the presence of zinc. The a,a-difluoro /1-hydroxyester was obtained in good yield without isolation of the Reformatsky reagent [240, 241] (Scheme 80) Later, this zinc reagent has also been prepared via reaction of ethyl bromodifluoroacetate with zinc amalgam in triglyme [242] or reaction of methyl iododifluoroacetate with zinc in acetonitrile [243]. 

Reaction of halodifluoroacetates with carbonyl compounds in the presence of zinc gives a,a-difluoro-(3-hydroxyesters (Equation 4.9).21-23 The intermediate zinc reagent is typically trapped in situ with aldehydes (Barbier conditions). 

The terpene menthol is widely used in organic synthesis, and serves as a chiral auxiliary for several asymmetric reactions [39]. (-)-Menthol 53 could be produced in one step from isopulegol 55 by hydrogenation of the carbon-carbon double bond, and the latter compound could be prepared by a Lewis acid-induced carbonyl-ene reaction [40] of f-(y )-citronellal 54. Nakatani and Kawashima examined that the ene cyclization of citronellal to isopulegol with several Lewis acids in benzene (Sch. 22) [41]. The zinc reagents were far superior to other Lewis acids for obtaining... 

We remarked that the first step of the radical-anion chain mechanism (Fig. 4) can be considered as a reduction of the halide by the nucleophile. Consequently, we tried to use well known reductants such as zinc. However, no reaction occurred when the halide is placed in the presence of zinc in various solvents. By analogy with the thiophenoxide condensation, we attempted the transformation in DMF under slight pressure. Consumption of the reagents was only observed when electrophilic substrates, such as carbonyl compounds, are present since the beginning of the reaction. These Barbier like condensations started more easily in pyridine than in DMF (ref. 19). Moderate yields were obtained with aldehydes as substrates (Fig. 6). 

The carbonyl group of an ester function can be converted to the corresponding methylene compound using Tebbe s reagent. The reaction can thus be considered as a general method of enol ether synthesis. An example of this reaction is given in Scheme 5. The same conversion can be achieved by reagents prepared from the reduction of 1,1-dibromoalkanes with zinc and TiCU in the presence of TMEDA. °... 

There appear to be no examples of intramolecular ene reactions with carbonyl groups where absolute stereochemical control is dictated with a removable chiral auxiliary, and only one example with an external chiral agent. In this case, the chiral zinc reagent 4 effected practical levels of control with 3,3,7-trimethyl-6-octenaI106. 

---