Substitution Reactions with Copper-Zinc Reagents

Substitution Reactions with Copper-Zinc Reagents 

4 Trcmsmetalation of Functionalized Organozinc Reagents 63, NHBoc 1.CuCN-2LiCI 

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Substitution Reactions with Copper-Zinc Reagents... 

Scheme 2.41. Substitution reactions with copper-zinc reagents by addition-elimination mecha-...

The related zinc cuprates formed from diorganozinc reagents and copper(I) cyanide also undergo smooth SN2 substitution reactions with propargyl oxiranes in the presence of phosphines or phosphites (Scheme 2.12). These transformations can also be performed with catalytic amounts of the copper salt since no direct reaction between the organozinc reagent and the substrate interferes [31, 34], and therefore should also be applicable to functionalized organozinc compounds. 

Copper catalysed substitution reactions require high reaction temperatures and polar solvents like NMP.9 With activated alkenyl iodides bearing electron-withdrawing groups, copper-zinc reagents react readily leading to addition-elimination products.10-11 This method can be used to prepare a range of polyfunctional unsaturated molecules (Scheme 10.3).10-12... 

An example of an SN2 substitution reaction with a mixed zinc-copper reagent is shown in Scheme 22.22. The product 9 was used to prepare the bicyclic enone 10. In this example the starting alcohol gave rise to the asymmetric induction. The substitution was anti-selective.152... 

Tetrafluoropyridyl organometallic reagents can be prepared by reaction of 4-bromotetra-fluoro- or tctrafluoro-4-iodopyridine with zinc or cadmium in dimethylformamide at room temperature.83 Metathesis of these reagents with copper(l) bromide affords the (2.3,5,6-tetra-fluoro-4-pyridyl)copper reagent. The latter species undergoes high-yield substitution reactions with allyl halides, vinyl iodides, aryl iodides, and alkanoyl halides. 

Another type of o-aminobenzyl synthon is based on o-(bis-trimethylsilylaminobenzyl)copper-zinc reagents <89TL4795>. These are prepared from the corresponding benzylic bromides by reaction with zinc, followed by addition of cuprous cyanide. These reagents react with acid chlorides to give 2-substituted indoles. Since the reactions proceed by C-acylation rather than iV-acylation, the conditions required for cyclization are mild and typically the C-acylated intermediates are not isolated. 

As well as alkenylstannanes [106-108], other classes such as a-heteroatom-substituted alkyltributylstannanes [109] and, more importantly, allylic stannanes [110, 111] also undergo these Sn-Cu transmetalations. Otherwise difficult to prepare, allylic copper reagents may, however, be obtained by treatment of allylic stannanes (produced in turn from organolithium, magnesium, or zinc organometallics) with Me2CuLi LiCN. They enter into cross-coupling reactions with alkyl bromides [110] or vinyl triflates (Scheme 2.52) [111]. 

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