Metallacycle-mediated cross-coupling with substituted and electronically unactivated alkenes

Abstract

This perspective surveys the history of- and recent advances in- metallacycle-mediated coupling chemistry of substituted alkenes. While the reaction of preformed metal–π complexes with ethylene was reported nearly 30 years ago, the generalization of this mode of bimolecular C–C bond formation to the regio- and stereoselective union of complex substrates has only recently begun to emerge. This perspective discusses early observations in this area, the challenges associated with controlling such processes, the evolution of a general strategy to overcome these challenges, and a summary of highly regio- and stereoselective convergent coupling reactions that are currently available by metallacycle-mediated cross-coupling with substituted alkenes.

Imines in the Titanium Coordination Sphere: Highly Reactive Titanaaziridines and Larger Titanacycles Formed by Subsequent C–C Coupling Reactions

“…[1,10,[18][19][20][21][22][23]36] In such a way, the titanoceneaziridine 5 undergoes insertion with carbonyl derivatives, whereas insertion reactions with olefins, acetylenes, nitriles, ketones, and aldehydes are found for the (methyleneaniline)titanium complex 6. [1,10] For these reasons, we were interested in the relationship between the substitution pattern of the imine ligand as well as the nature of the titanium fragment and the reactivity of the corresponding titanaaziridine.…”

Stereoselective Alkylation of Allylic Alcohols: Tandem Ethylation and Functionalization

“…Enantioselective synthesis of a 4,4-dialkyl-2-cyclohexenone. a) ClTi(OiPr) 3 (1 equiv), EtMgBr (3 equiv), Et2O, À78!À5 8C; then ClTi(OiPr) 3 (3 equiv); CH 2 = CHCHO. and cyclic allylic alcohols with the ethyl Grignard reagent in the presence of a titanium alkoxide.…”

“…[7] In light of the known instability of alkyl homologues of MeTi(OiPr) 3 , [8] the temperature control of the reaction was first examined, and it was optimal to warm the reaction mixture from À78 8C up to À10 or À5 8C, to set the stage of the trapping step. The presence of a scavenger for magnesium alkoxides in the reaction mixture was necessary prior to addition of an aldehyde to prevent an aldol condensation.…”

5.34 Early Transition Metal Mediated Reductive Coupling Reactions

“…As illustrated in Scheme 47B, this approach to controlling the course of metallacycle-mediated cross-coupling is quite effective in realizing highly selective alkyne-alkene-coupling reactions. 90,112 In the first case depicted, one can see that the hydroxymethyl substituent on the cyclohexene offers a means to control both the regio-and stereochemical course of cross-coupling. Here, C-C bond formation occurs distal to the hydroxymethyl group, with complete control of stereoselection (C-C bond formation occurs on the same face of the cyclohexene as the directing group).…”

“…88 Recognizing that Ti-alkoxides are compatible with metallacycle-mediated C-C bond formation and that alkoxide ligand exchange should be fast and reversible at Ti, led to a broad exploration of the use of tethered alkoxides as directing groups to control the course of metallacycle-mediated C-C bond formation. 89,90 These pursuits have indeed defined a collection of unique and complex coupling reactions not possible with other metal systems (catalytic or stoichiometric), while establishing a suite of technology capable of forging C-C bonds in the presence of free hydroxyls -a particularly compelling feature of this class of convergent coupling chemistry.…”