Intramolecular carbocupration

The Conia-ene reaction is a thermal cyclization of an alkyl ketone with an alkyne to give the corresponding a-vinylated ketone.98 The catalytic version of this reaction has been reported to generalize the process to more functionalized substrates.99 The intramolecular carbocupration of alkyne 94 has been investigated under basic conditions in the presence of a catalytic amount of copper iodide (Scheme 28).100 The cyclic product 95 is obtained in high yield. 

The carbocupration of methoxyallene affords a (Z)- or (E)-enol ether depending on the solvent used [52], In THF, the reaction exhibits Z-selectivity because the coordination ability of THF excludes the intramolecular chelation effect of the methoxy group, which may be responsible for the E-selectivity for the reaction in ether (Scheme 10.49). 

Carbocupration of alkynes by zirconacyclopentane derivatives can be performed according to the same procedure. Thus, the zirconocyclopentane 135, obtained by treatment of Bu2ZrCp2 with 1,6-heptadiene, reacts at room temperature with phe-nylacetylene to afford the adduct 136 through a carbocupration-reductive elimination mechanism. Cross-coupling followed by intramolecular carbocupration takes place in the case of the reaction with 1-bromohexyne, producing 137 (Scheme 2.66) [143]. 

Carbocupration of chiral alkynylsulfoxides 47 in a regio- and stereospecific manner produces alkenyl organocopper 48, which is subsequently reacted with bis(iodomethyl) zinc in the presence of aldehydes or imines. The zinc carbenoid homologation step leads to 49, the conformation of which is controlled by intramolecular chelation 49 reacts with the aldehyde or imine before it can undergo a -elimination (cf. equation 20). The final product 63 is generally obtained with high diastereoselectivity and in good overall yield (Table 8). 

The conjugate addition of various propargyl alcohols [57] or propargyl amines [58] to gem-diactivated olefins such as 47 can be used in tandem with the intramolecular carbocupration reaction (Scheme 20). This sequential... 

Evano and colleagues disclosed a modular indole synthesis via the intramolecular carbocupration of N-aryl-ynamides (124 125) (130L3122).A series of indole derivatives was prepared by Jiao via the palladium-catalyzed aerobic oxidative intramolecular hydroamination and C-H functionalization of N-alkynylanilines (13T4408). Suh reported a microwave-assisted synthesis of 3-functionalized indoles via an intramolecular arene-alkene coupling of o-iodoanilino enamines (13T7211). 

Rao and Knochel have reported the addition of copper reagents prepared by transmetallation from polyfunctional organozinc iodides to reactive alkynes in a stereochemically well-defined syn-addition. Intramolecular carbocupration of functionalized alkynyl-substituted alkylcopper species such as 74 obtained from the alkyl iodide 75 allows the preparation of highly substituted five-membered car-bocylcles giving stereochemically pure exo-alkylidenecyclopentane derivatives such as 76. The lower reactivity compared to the lithium- or magnesium-copper reagents does not allow the reaction with unactivated terminal alkynes but tolerates ester, nitrile or chloride functions (Scheme 9.23) [34]. 

Scheme 9.23 Stereospecific preparation of five-membered carbocycles by intramolecular carbocupration.

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