Three-component couplings, alkyl group

Three-component coupling. Addition of AIBN to a benzene solution of an allylic stannane, an alkyl iodide, and an electron-deficient alkene initiates a radical process that results in 1,2-addition of the alkyl and allyl groups to the alkene.4 Example ... 

In this context, an elegant alkylative carbonylation of alkenes accompanied by phenylselenyl transfer is described by Ryu and Sonoda. This three-component coupling involves the addition of a methoxycarbonylmethyl radical to an alkene, the trapping of the produced alkyl free radical by CO, and termination of the reaction by phenylselenenyl group transfer from the starting material. Yields are... 

The Lee group originated rhodium alkenylidene-mediated catalysis by combining acetylide/alkenylidene interconversion with known metal vinylidene functionalization reactions [31], Thus, the first all-intramolecular three-component coupling between alkyl iodides, alkynes, and olefins was realized (Scheme 9.17). Prior to their work, such tandem reaction sequences required several distinct chemical operations. The optimized reaction conditions are identical to those of their original two-component cycloisomerization of enynes (see Section 9.2.2, Equation 9.1) except for the addition of an external base (Et3N). Various substituted [4.3.0]-bicyclononene derivatives were synthesized under mild conditions. Oxacycles and azacycles were also formed. The use of DMF as a solvent proved essential reactions in THF afforded only enyne cycloisomerization products, leaving the alkyl iodide moiety intact. 

Another useful reaction for the difunctionalization of olefins involves a group transfer carbonylation starting from a a-(phenylseleno)carbonyl (or related derivatives) and a terminal alkene under 80 atm of CO. An alkyl radical is first formed by the photocleavage of a C-SePh bond. The addition of this radical to the olefin, followed by the incorporation of CO and radical coupling with PhSe-, gave substituted selenoesters via a three-component coupling reaction [74], The intermolecular formation of C—C bonds via phenylseleno group transfer has been likewise adopted in the reaction between ester-substituted O,Se-acetals and an olefin [75],... 

Alkylative carbonylation of alkenes accompanied by a phenylselenyl group transfer has been used to prepare selenoesters via a three component coupling process [87]. 

Larock developed a powerful approach to isoquinolines which involves copper-catalyzed hydroamination of A -ferf-butyl-2-(l-alkynyl)benzaldimine accompanied by elimination of ferf-butyl group (Eq. 4) [55-59]. Asao and Yamamoto reported a novel synthesis of 1,2,3-trisubstituted isoquinolines through attack of a carbon nucleophile to the carbon-nitrogen double bond of iV-alkyl-2-(l-alky-nyl)benzaldimine and simultaneous hydroamination catalyzed by transition metal [60]. They also achieved isoquinoline synthesis by transition metal-free three-component coupling (Eq. 5) [61]. Takemoto and Yanada reported a related isoquinoline formation by a catalysis of carbophilic Lewis acids such as indium(III), Ni(II), or Au(I)/Ag(I) [62, 63]. Oikawa succeeded in palladium-catalyzed three-component... 

A possible mechanism for this copper-catalyzed three-component reaction was proposed in Scheme 7.21. First, coupling of 37 with hydrazine hydrochloride provides A in the presence of base (K3PO4). Copper-catalyzed coupling of A with alkyl 2-cyanoacetate (C-aiylalion) gives B, intramolecular nucleophilic attack of the NH of the pyrazolo group to cyano in B leads to C, and isomerization of C affords the target product 38. 

Muller s group developed a one-pot three-step four-component process for the construction of dihydropyrindines and tetrahydroquino-lines [96]. Through a coupling-isomerization-Stork-enamine alkylation-cyclocondensation sequence of an electron poor (hetero)aryl halide, a... 

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