title: Regioselective Reductive Cross-Coupling Reactions of Unsymmetrical Alkynes.
abstract: The present microreview summarizes our progress over the last few years in defining regioselective reductive cross-coupling reactions of unsymmetrical alkynes with terminal- and internal alkynes, aldehydes, and imines. We begin with a brief historical perspective of metal-mediated reductive dimerization reactions of aromatic alkynes and discuss the challenges associated with "crossed" versions of this mode of reactivity. Next, a collection of available methods that allow for regioselective reductive cross-coupling of internal alkynes with terminal and internal alkynes, aldehydes, and imines is summarized. After an examination of the requirements for regioselectivity in these cases, the logic behind our design of alkoxide-directed titanium-mediated reductive cross-coupling reactions is presented. A nomenclature is introduced to delineate the presumed mechanistic origin of regioselection associated with each reaction design, and a presentation of alkoxide-directed regioselective reductive cross-coupling reactions of alkynes follows. Throughout, principal issues related to reactivity and selectivity are discussed to assess scope and limitations of available methods and to describe the broad challenges that exist for defining complex fragment union reactions based on reductive cross-coupling chemistry.
authors.affiliation: Department of Chemistry, The Scripps Research Institute Scripps-Florida 130 Scripps Way #3A2 Jupiter, FL 33458.
authors.forename: Holly A
authors.initials: HA
authors.lastname: Reichard
authors.affiliation: Department of Chemistry, The Scripps Research Institute Scripps-Florida 130 Scripps Way #3A2 Jupiter, FL 33458.
authors.forename: Martin
authors.initials: M
authors.lastname: McLaughlin
authors.affiliation: Department of Chemistry, The Scripps Research Institute Scripps-Florida 130 Scripps Way #3A2 Jupiter, FL 33458.
authors.forename: Ming Z
authors.initials: MZ
authors.lastname: Chen
authors.affiliation: Department of Chemistry, The Scripps Research Institute Scripps-Florida 130 Scripps Way #3A2 Jupiter, FL 33458.
authors.forename: Glenn C
authors.initials: GC
authors.lastname: Micalizio
keywords: alkene synthesis; alkyne; carbometalation; reductive coupling; titanium