Copper electrophilic addition

Photolytically generated carbene, as mentioned above, undergoes a variety of undiscriminated addition and insertion reactions and is therefore of limited synthetic utility. The discovery (3) of the generation of carbenes by the zinc-copper couple, however, makes carbene addition to double bonds synthetically useful. The iodo-methylzinc iodide complex is believed to function by electrophilic addition to the double bond in a three-center transition state giving essentially cis addition. Use of the... 

These zinc reagents also exhibit excellent thermal stability but still react with strong electrophiles [275-277]. With less reactive electrophiles, addition of catalytic cuprous bromide can improve the reaction with dialkoxyphosphiny-difluoromethyl zinc reagents [278, 279]. Presumably, this reaction involves a dialkoxyphosphinydifluoromethyl copper reagent intermediate (Scheme 95). 

Preparation of 3-(3-pivaloxypropyl)-1-zinca-2-oxacyclopentane by hydrozincation and its copper-mediated addition to an electrophile preparation of ethyl 2-(4-hydroxy-7-pivaloxy)acrylate13... 

Copper catalysed addition of a (3-zincated phosphonate to an electrophile preparation of dimethyl 2-(cyclohex-1-en-3-on-1-yUpentanephosphonate10... 

Copper catalysed addition of a 1,4-organodizinc reagent to an electrophile preparation of 4-(3-oxocyclohexyl)-1-(3-oxocyclohex-1-enyDbutane18... 

Copper catalysed addition of a functionalized benzylic organometallic to an electrophile preparation of 2-(3-carbethoxy-2-propenyl)-1,4-diacetoxynaphthalene14... 

Similar to the addition reactions of acceptor-substituted dienes (Scheme 16), the outcome of the transformation depends on the regioselectivity of the nucleophilic attack of the organocopper reagent (1,4- vs. 1,6-addition) and of the electrophilic capture of the enolate formed. The allenyl enolate obtained by 1,6-addition can afford either a conjugated diene or an allene upon reaction with a soft electrophile, and thus opens up the possibility to create axial chirality. The first copper-mediated addition reactions to Michael acceptors of this type, for example, 3-alkynyl-2-cyclopentenone 75,... 

Various functionalized alkynes can be submitted to carbocupration reactions, such as alkoxyalkynes,150 alkynyl carbamates,151 acetylenic orthoesters,152 and thioalkynes.153 The carbocupration of orthoesters, for example, 204, has been used to prepare a-substituted esters of the type 206 by acidic hydrolysis of the adduct 205 (Scheme 51).152 This allows the formation of regioisomers that are not accessible by copper-mediated addition to acetylenic esters. A stereoselective synthesis of trisubstituted alkenes has been described by Normant et al.lSd> starting from phenylthio-acetylene 207. Carbocupration with lithium di- -butylcuprate affords the intermediate 208 which, upon addition of /z-butyllithium, undergoes a 1,2-metalate rearrangement to the vinylcuprate 209. The latter can be trapped with various electrophiles, for example, ethyl propiolate, providing product 210 with complete regio- and stereocontrol. 

Vinylidene osmium(O) (187) (Section II,B,3,g) reacts with sulfur, selenium, or copper chloride to give complexes 233 via electrophilic addition to the osmium-carbon bond (116) (Scheme 18). Complex 187 also reacts with benzoylazide to form the five-membered metallacycle 234 (Z) which isomerizes 234 (E) on heating in benzene (141). 

On the basis of this concept the same group has developed a similar strategy using a copper-catalyzed addition of organozinc reagents to enones, followed by trapping of the resulting zinc-enolate by ketones, esters or nitriles as terminal electrophiles (Scheme 35) [83]. 

Reaction involving the formation of a sulfonium intermediate (80) followed by a sigmatropic rearrangement was formulated by Trost and Biddlecom (Scheme 8) and cyclization initiated by an allylic copper carbenoid (81) was proposed by Cohen and coworkers (Scheme 9). The common feature of all of these proposed mechanisms relies on the electrophilic addition of the donor to the acceptor prenyl pyrophosphate and is... 

Mechanistic studies of rhodium porphyrins as cyclopropanation catalysts have resulted in the spectroscopic identification of several potential intermediates in the reaction of ethyl diazoacetate with olefins, including a diazoniumfethoxy-carbonyl)methyl-rhodium complex formed by electrophilic addition of the rhodium center to the a-C atom of ethyl diazoacetate [29]. It is not known if analogous intermediates are also formed in analogous reactions of copper catalysts. However, the initial part of the catalytic cycle leading to the metal carbene intermediate is not of primary concern for the enantioselective reactions described herein. It is the second part, the reaction of the metal-carbene complex with the substrate, that is the enantioselective step. 

The a,(3-unsaturated ester (8), aldehyde (9), and nitro (10) compounds participate as electrophiles in a number of useful conjugate addition reactions. Copper-catalyzed addition of Grignard reagents provides access to aryl butanoic acid derivatives substituted with an oxetane (equation 1 in scheme 13.7). The ester, aldehyde, and nitro electrophiles also undergo mild Rh-catalyzed additions of aryl and vinyl boronic acids (equation 2 through equation 4 in scheme 13.7). Interestingly, the unsaturated aldehyde participates readily in an amine conjugate addition to afford oxetane substituted 3-amino-acetaldehyde derivatives. 

Scheme 18.7 Electrophilic addition of copper derivatives to enamine of imidazolidinone.

With alkynes, copper-catalyzed addition of the Grignard reagent (1) provides the allylsilane. The intermediate vinylcopper reagent can also be trapped with electrophiles. ... 

Janson PG, Ghoneim I, Ilchenko NO, Szabo KJ (2012) Electrophilic trifluoromethylation by copper-catalyzed addition of CF3-transfer reagents to alkenes and alkynes. Org Lett 14 2882-2885... 

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