Carbometallation/vinylation

Three possible mechanisms may be envisioned for this reaction. The first two i.e. 1) Michael addition of R M to the acetylenic sulfone followed by a-elimination of LiOjSPh to yield a vinyl carbene which undergoes a 1,2 aryl shift and 2) carbometallation of the acetylenic sulfone by R M followed by a straightforward -elimination, where discarded by the authors. The third mechanism in which the organometallic reagent acts as an electron donor and the central intermediates is the radical anion ... 

The mechanism of carbometallation has been explored computationally.77 The reaction consists of an oxidative addition to the triple bond forming a cyclic Cu(m) intermediate. The rate-determining step is reductive elimination to form a vinyl magnesium (or zinc) reagent, which then undergoes transmetallation to the alkenyl-copper product. 

The vinyl metal intermediate arising from intermolecular nucleophilic addition of an oxygen nucleophile to a metal-alkyne complex has been harnessed for further transformations prior to protonation. An example is the ruthenium-catalyzed benzannulation of 1,5-enedyines that occurs through a tandem sequence involving hydroalk-oxylation, carbometallation, and protonation (Equation (82)).293... 

Radical cyclization of polyfunctional 5-hexenyl halides mediated by Et2Zn and catalyzed by nickel or palladium salts has been demonstrated to produce stereoselectively polyfunctional 5-membered carbo- and heterocycles [56, 57]. Based on this strategy a formal synthesis of methylenolactocin (11) was achieved (Scheme 20). The acetal 130, readily being built up by asymmetric alkylation of aldehyde 127 followed by reaction with butyl vinyl ether and NBS, served as the key intermediate for the construction of the lactone ring. Nickel(II)-catalyzed carbometallation was initiated with diethylzinc to yield exclusively the frans-disubstituted lactol 132, which could be oxidized directly by air to 134. Final oxidation under more forcing conditions then yielded the lactone (-)-75 as a known intermediate in the synthesis of (-)-methylenolactocin (11) [47aj. 

Yttrocene complexes catalyze the cascade cyclization/hydrosilylation of trienes to form saturated silylated bicyclic compounds.For example, reaction of the 4-silyloxy-4-vinyl-l,6-hexadiene 69 and phenylsilane catalyzed by Gp 2YMe(THF) at room temperature for 1 h followed by oxidation of crude 70a gave [3.3.0]bicyclic diol 70b in 73% yield over two steps as a single diastereomer (Scheme 18). Selective conversion of 69 to 70a presumably requires initial 1,2-hydrometallation of one of the less-hindered G=G bonds to form alkylyttrium alkene complex II (Scheme 18). Selective S-exo carbometallation of II in preference to -exo carbometallation would form cyclopentyl-methylyttrium complex III (Scheme 18). Gyclization of III via a chairlike transition state would form the strained /r< /75 -fused alkylyttrium complex IIIl, which could undergo silylation to form 70a. 

The carbomagnesiation of vinyisiianes is a powerful method for the generation of synthetically useful a-silyl carbanions. However, simple vinyisiianes such as trimethyl(vinyl) silane do not undergo carbometalation with Grignard reagents (Scheme 59) °. In early days, only limited success had been achieved by using perfluorovinylsilanes °°. 

The first diastereoselective carbometallation of vinyl metals bearing a chiral auxiliary was reported in 1998 (equation 42)44b. 

In contrast to the carbometallation with aryl-Grignard reagents to unfunctionalized alkynes, this reaction does not require a co-catalyst such as copper. Only in one example, applying PhMgBr, was CuBr added in accord with the protocol reported by Hayashi s group. Although the nature of the catalytically active species remains unclear, an alkoxide-directed carbometallation which yields a (vinyl)iron intermediate is proposed. 

The insertion of alkene to metal hydride (hydrometallation of alkene) affords the alkylmetal complex 34, and insertion of alkyne to an M—R (R = alkyl) bond forms the vinyl metal complex 35. The reaction can be understood as the cis carbometallation of alkenes and alkynes. 

Apparently, the simplest approach would be the carbometalation reaction or, more specifically, the vinylmetalation of alkynes [1-8]. The addition of organo-metallic reagents to functionalized or nonfunctionalized, terminal or nonterminal alkynes, in which the resulting organometallic compound can react with electrophiles, is defined as the carbometalation reaction (Scheme 1). It has been widely explored and applied in the regio- and stereoselective preparation of numerous vinyl metal species. 

The Pd-catalyzed cross-coupling reaction of vinyl(2-pyridyl)silanes 5.48 with organic halides gave substituted vinyl(2-pyridyl)silanes 5.49 in high yields. The mechanism of this reaction involves the carbometallation pathways (Scheme 5.18). 

The fruitfulness of the idea of a stepwise addition with an independent variation of the addends was brilliantly illustrated by Normant s studies, which resulted in the elaboration of a general method of alkene synthesis based on the reaction of alkyne carbometallation. Basically this reaction represents a case of the well-known nucleophilic addition to a carbon-carbon triple bond. In the Normant reaction, however, the initial addition of a nucleophile (an organome-tallic reagent) across the triple bond results in the formation of a stabilized carbanion-like intermediate equivalent to a vinyl carbanion. This intermediate can similarly be further reacted with an external electrophile. Most typically, copper-modified Mg or Li reagents, which are unable to react with acidic acetylenic hydrogens, are used in this sequence. 

The retro-Wittig reaction (i) (Scheme 2.39), with disconnection across the double bond, seems to be an obvious candidate for models containing disubstituted double bonds. In these cases, the steric outcome of the reaction can be easily controlled. An alternative route of disconnection at the vinyl bonds (ii) corresponds to a retro-carbometallation reaction. This disconnection is generally applicable to double bonds with any substitution pattern and is especially useful owing to the high stereoselectivity of the carbometallation step. Route (iii) involves a retrosynthetic dehydrogenation leading to the immediate acetylenic precursor, which can be conventionally disassembled into a parent acetylide and a pair of electrophiles as shown. 

The carbometallation of vinyl metals can be also applied to the addition of substituted propargyl bromides [107] (Scheme 7-99). 

Carbometallation of alkynes by Cp2TiMe2 affords vinyl complexes which serve as intermediates for the formation of titanacyclobutenes (Scheme 546). Alkyne insertion to form the vinyl species followed by oxidative addition into the 7-C-H bond and reductive elimination of methane is proposed.1437... 

The proposed mechanism involves die carbometalation of an alkynylstannane with an a-stannylketone, protonation of fhe resultant gem-bisstannylated intermediate, and double bond shift to an allylmetal species. In contrast, the GaCl3-mediated addition of SEE to trimefhylsilylefhyne forms /i. j -unsaturated ketones, vinylation products, without isomerization to u,/I-urisaluraled ketones [272]. A similar mechanism via a gem-bismetalated intermediate formed by carbometalation has been postulated for fhe GaCh-mediated vinylation. 

Hydrometallation or carbometallation of alkynyl silanes 186 is easier because of the presence of the silicon atom as the metal prefers to be at the silylated end of the resulting alkene 187. Trapping these intermediates with electrophiles allows the stereochemically controlled synthesis of almost any vinyl silane 188. The metal can be Li, Mg, Al, or Cu and both 187 and 188 are single geometrical isomers (whether E or Z depends on priorities of M and the various R groups).30... 

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