Aryl cuprates

Asymmetric conjugate addition of dialkyl or diaryl zincs for the formation of all carbon quaternary chiral centres was demonstrated by the combination of the chiral 123 and Cu(OTf)2-C H (2.5 mol% each component). Yields of 94-98% and ee of up to 93% were observed in some cases. Interestingly, the reactions with dialkyl zincs proceed in the opposite enantioselective sense to the ones with diaryl zincs, which has been rationalised by coordination of the opposite enantiofaces of the prochiral enone in the alkyl- and aryl-cuprate intermediates, which precedes the C-C bond formation, and determines the configuration of the product. The copper enolate intermediates can also be trapped by TMS triflate or triflic anhydride giving directly the versatile chiral enolsilanes or enoltriflates that can be used in further transformations (Scheme 2.30) [110],... 

Scheme 54 shows the synthesis reported by Cox et al. of the pyrazoline compound 198 [98]. The Weinreb amide (e.g., 199) was reacted with a terminal alkyne followed by a reaction of the resulting alkyl ketone (200) with an aryl cuprate to produce the pyrazoline 198. Cox et al. employed the use of microwave technology in this reaction. Kidwai and Misra also employed microwave technology to produce pyrazoline compounds [99]. 

Recently, the direct transformation of allyl- 206272 and aryl tellurides 209273 into the corresponding organocopper species 207 and 210 by tellurium-copper exchange was described. The resulting allyl 207 or aryl cuprates 210 were captured by coupling with vinyl triflates 208272 or by 1,4-addition to enones 211,273 respectively (Scheme 112). 

A vinyl halide with an aryl cuprate, preserving the stereochemistry of the vinyl halide. 

A variation involves an aryl cuprate coupled with a vinyl halide, leading eventually to the /3-methylenedihydrobenzo-furan complex (equation 103). Cyclization occurs spontaneously upon fluoride-induced removal of the silyl protecting... 

A new route to 3,4-disubstituted piperidines employs diastereoselective 1,4-addition of N-nicotinoyl thiazolidinethiones with aryl cuprates <05TL8673>. Treatment of the pyridinium salt, prepared from chiral nicotinic amide 165 and phenyl chloroformate, with... 

Cobalt(II) catalyses the coupling of Grignard reagents with chloropyridines"° and of aryl cuprates with aryl halides. This reaction shows unusual substrate reactivity patterns and the mechanism is thought to involve a radical intermediate at the oxidative addition step. 

Fig. 9 shows some examples, the list of which might be expanded almost arbitrarily. The only limitation hes in the reactivity of the aryl cuprates, which means that pyridyl or thienyl residues cannot be introduced yet. On the other hand the flexibility of the bisepoxide method is demonstrated by the synthesis of 2,3-diamino-propionic acid (p-amino-alanine) which is a constituent of antibiotic cyclo-peptides like tuberactinomycin A or, in form of the N-methyl derivative L-BMAA, occurs in the seeds of the local sago palm and had notoriously caused the Guam disease [8], with a certain kind of Alzheimer and Parkinson symptoms, until the American conquest of the island in World War II led to a change in nutrition (Fig. 10). 

Co(II)-catalyzed cyclizations were among the first metal-catalyzed oxidative cyclizations to be studied [38]. Sinha and coworkers have recently reported the synthesis of a library of mono- and bis-tetrahydrofuran substrates using a Co(II)-catalyzed cyclization (Scheme 40) [39]. It is worth noting that the readily available cycliza-tion precursors came from the addition of alkyl or aryl cuprates to 1,2-epoxyhexene 152. 

Scheme 4-223. Biaryls by iron-catalyzed coupling of aryl cuprates with or// o-carbamoyl-substituted aryliodides or 8-iodoquinolinones.

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