Carbometallation Reactions

Abstract

Carbon-carbon bond formation by means of organometallics was developed mostly after the work of Barbier and Grignard, and has commonly been achieved by their named reactions with polar carbon electrophiles. In the search for new types of selective organometallic carbon-carbon bond formation, and following the pioneering Ziegler addition of some anionic initiators to nonpolarized carbon-carbon bonds [I], controlled carbometallation emerged as a new tool. Since then, reactions which result in the addition of the carbonmetal bond of an organometallic 1 across a carbon-carbon multiple bond 2, leading to a new organometallic 3 in which the newly formed carbon-metal bond can be used for further synthetic transformations (see Scheme 7l), are called carbometallation reactions. 1 2 3 Scheme 7-1 Carbornetallation.To be synthetically useful, the new organometallic 3 must have a reactivity different from that of 1 in order to avoid the polymerization of the carbometallated substrate [2]. So, the carbometallation ability of 1 must be higher than that of 3, except for an intramolecular carbometallation reaction, in which case the entropy factors favor the mono-addition even if the starting organometallic and the product have similar reactivities. Since an outstanding number of additions of organometallics to carbon-carbon multiple bond have been reported and reviewed [3-51, we will focus this chapter on the more recent advances in this field (from 1991 until the present time), both from our own and from other research groups. Carbometallation of Alkynes Intermolecular CarbometallationAlkynes are carbometallated with several organometallic compounds under mild conditions [3] but carbocupration has probably the greatest synthetic possibilities [4], associated with the zirconium-catalyzed methylalumination [5] reaction: both proceed with very high stereoselectivity and afford the syn addition product as described in Scheme 7-2. 1 Metal-catalyzed Cross-coupling ReactionsEdited by François Diederich, Peter J. Stang Scheme 7-2 Carbometallation of alkynes.However, the stereoselectivity of the carbocupration (syn addition) can be inverted by using the 1,2-metallate rearrangement [6], to lead to the organometallic copper species 4 [7] (Scheme 7-3). In every case examined, the stereochemistry of the polysubstituted alkenes formed corresponds to > 99% stereoselectivity. * 1. 2tBuLi. nC~H12 / Et2O 2. Warm to r.t. EtEt 70% Scheme 7-11 Internal carbolithiation of a substituted alkyne.The synthesis of substituted spiro[2.4]heptanes was also recently accomplished by treatment of functionalized iodocyclopropanes as described in Scheme 7-12 [ 161. Carbometallation of Alkynes277 Li OH nBuLi, EtzO -78 "C to r.t. t Me3Si Me3si@ 79% Scheme 7-12 Spirocyclization via carbolithiation.An extension of this intramolecular carbolithiation was recently disclosed for the preparation of bis-exocyclic 1,3-dienes by the 5-exo-dig cyclization of d-acetylenic vinyllithiums. Through subsequent Diels-Alder chemistry, they serve as useful precursors of polycyclic r...

Advances in Carbolithiation

“…The carbolithiation reaction is defined as the addition of an organolithium reagent 1 across a carbon-carbon π-bond resulting in the concomitant formation of new carbon-carbon and carbon-lithium σ-bonds in a newly formed organolithium compound 3 [1]. To be synthetically useful, the latter organolithium intermediate must have lower reactivity toward the substrate 2 than the initial organolithium compound in order to avoid oligomerization or anionic polymerization processes (Scheme 11.1, path B) [2,3].…”

Pd-Catalyzed Highly Regio- and Stereoselective Formation of C–C Double Bonds: An Efficient Method for the Synthesis of Benzofuran-, Dihydrobenzofuran-, and Indoline-Containing Alkenes

“…On the other hand, the intramolecular carbometalation of alkenes − initiated from the oxidative addition of C­(sp 2 )–X provides an efficient method to construct benzo-fused saturated nitrogen/oxygen heterocycles such as indolines − and dihydrobenzofurans, − which are prominent in a variety of natural products and biologically active compounds. − In 2002, Grigg and co-workers reported an interesting Pd-catalyzed queuing processes by employing allene as a relay switch and secondary amines as nucleophiles . Inspired by these precedents and our continued interest in the palladium-catalyzed cross-coupling of N -tosylhydrazones, − we conceived that the alkyl-Pd species generated from intramolecular carbopalladation of alkene may be trapped by a diazo substrate to form a Pd carbene species, which would undergo migratory insertion and β-hydride elimination to afford the polysubstituted olefins (Scheme c).…”

Carbocyclisation of zinc enolates onto unactivated double bonds: a mechanistic point of view

“…Although inter-and intramolecular carbometalation reactions (addition of organometallic species onto unactivated multiple bonds) have been widely developed [10,11], much little is known concerning the carbometalation of unactivated alkenes by stabilized enolate-type organometallics. Addition of ketones and malonates on styrenes under t-BuOK catalysis [12] is reported, as well as the intramolecular cyclisation of lithium enolates on (g 2 -alkene)Fe complexes [13][14][15][16], (g 4 -diene)Fe complexes [17][18][19], and of sodium malonates on (g 4 -diene)Mo complexes [20][21][22].…”