Copper© cyanide, transmetalation

A further improvement in the cuprate-based methodology for producing PGs utilizes a one-pot procedure (203). The CO-chain precursor (67) was first functionalized with zirconocene chloride hydride ia THF. The vinyl zirconium iatermediate was transmetalated direcdy by treatment with two equivalents of / -butyUithium or methyUithium at —30 to —70° C. Sequential addition of copper cyanide and methyUithium eUcited the /V situ generation of the higher order cyanocuprate which was then reacted with the protected enone to give the PG. 

The lithium enolate 2a (M = Li ) prepared from the iron propanoyl complex 1 reacts with symmetrical ketones to produce the diastercomers 3 and 4 with moderate selectivity for diastereomer 3. The yields of the aldol adducts are poor deprotonation of the substrate ketone is reported to be the dominant reaction pathway45. However, transmetalation of the lithium enolate 2a by treatment with one equivalent of copper cyanide at —40 C generates the copper enolate 2b (M = Cu ) which reacts with symmetrical ketones at — 78 °C to selectively produce diastereomer 3 in good yield. Diastereomeric ratios in excess of 92 8 are reported with efficient stereoselection requiring the addition of exactly one equivalent of copper cyanide at the transmetalation step45. Small amounts of triphcnylphosphane, a common trace impurity remaining from the preparation of these iron-acyl complexes, appear to suppress formation of the copper enolate. Thus, the starting iron complex must be carefully purified. 

Reaction of the lithium enolate 2 with prochiral aldehydes at low temperature proceeds with little selectivity, producing all four possible diastereomers 3, 4, 5, and 6 in similar amounts50. Transmetalation of the lithium enolate by treatment with three equivalents of diethylaluminum chloride or with one equivalent of copper cyanide generates the corresponding cthylaluminum and copper enolates which react at — 100°C with prochiral aldehydes to produce selectively diastereomers 1 and 2, respectively50. The reactivity of tin enolates of iron- propanoyl complexes has not been described. 

In contrast, transmetalation of the lithium enolate at —40 C by treatment with one equivalent of copper cyanide generated a species 10b (M = Cu ) that reacted with acetaldehyde to selectively provide a 25 75 mixture of diastereomers 11 and 12 (R = CH3) which are separable by chromatography on alumina. Other diastereomers were not observed. Similar transmetalation of 10a (M = Li0) with excess diethylaluminum chloride, followed by reaction with acetaldehyde, produced a mixture of the same two diastereomers, but with a reversed ratio (80 20). Similar results were obtained upon aldol additions to other aldehydes (see the following table)49. 

Concerning the lithium-zinc transmetallation from intermediate 331, it has been used (THF, room temperature) to perform a palladium-catalyzed Negishi cross-coupliug reaction with aryl bromides - and a 8 2 regioselective allylation in the presence of copper cyanide. 346 and 347 were, respectively, obtained (Scheme 101). 

A novel asymmetric synthesis of a-amino acids via electrophilic amination has been demonstrated by Zheng and Armstrong and co-workers.94 No +NHBoc was observed when lithium tert-butyl-A-tosyloxycarbamate (LiBTOC) was reacted with zinc and lithium enolates of 48. Transmetallation of the lithium enolate with copper cyanide was necessary to generate a reactive amide cuprate, which then added efficiently to the electrophile. The electrophilic amination of chiral cuprates with LiBTOC provided an expedient approach to a-amino acids with predictable absolute configuration in high enantiomeric purity and good yield (Scheme 24.23). 

Substituted gem-dimetallic compounds, readily obtained via allylation of alkenyl organometallics, react with aldehydes in the presence of BF3-Et20 but do not react with ketones. When alkylidenemalonates are used instead of aldehydes, the Z-olefins see (E) (Z) Isomers) are obtained with a very high stereoselectivity (Scheme 35). A transmetallation reaction with copper cyanide significantly increases the reactivity of gm-dimetallic derivatives via formation of 1,1-zinca cyanocuprates. Indeed, when these compounds react with... 

Addition of aldehydes to the lithium enolate derived from propanoyl complex 6 requires prior transmetallation for optimum results. In particular, the use of diethylaluminium chloride has proved to be most valuable when the anti-aldol adduct 14 is required, whilst copper cyanide is the transmetallation reagent of choice when the syn-aldol adduct 15 is the target (Scheme 4.8). Oxidative cleavage and formation of the threo and erythro -hydroxy acids, respectively, is easily achieved by treatment with aqueous bromine solution or CAN. The aluminium(III)-mediated sequence has been employed in the synthesis of an enantiomerically pure degradation product of a marine cyclic peroxide, thereby proving its absolute configuration. ... 

The moderate intrinsic reactivity of zinc organometallics can be increased by transmetalation with various transition metal salts. Especially useful is the transmetalation of diorganozincs or organozinc halides with the THF-soluble complex of copper(I) cyanide... 

Neutral alkynylcopper compounds are not prepared by transmetalation of alkynyllithium compounds. Rather, they are obtained by partially deprotonating terminal alkynes with amines and capturing the ammonium acetylide formed at equilibrium with Cul (—> R-C=C-Cu + R3NH I example Figure 16.7). Copper(I) cyanide couples with aryl iodides and -bromides in a similar fashion as alkynylcopper compounds (which may well be conceived as their carba analogs). 

The reaction was applied to the formation of arylcopper used for homocoupling and coupling reactions, which have already been described in Section IV.B.2. In addition, it was established that the simple use of copper(I) salts in polar solvents permitted the transmetallation from tin to copper. The transient vinylcopper reagent was subjected to various intramolecular reactions such as coupling with vinyl halides , addition to a, /S-unsaturated ketones , to a, /3-unsaturated esters and addition to a, /3-alkynic esters . In addition to copper(I) halides, the reaction can be mediated by copper(I) cyanide and... 

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