Mechanism of NHC-Catalyzed Conjugate Additions of Diboron and Borosilane Reagents to α,β-Unsaturated Carbonyl Compounds

Abstract

Broadly applicable enantioselective C–B and C–Si bond forming processes catalyzed by an N-heterocyclic carbene (NHC) were recently introduced; these boryl and silyl conjugate addition reactions (BCA and SCA, respectively), which proceed without the need for a transition metal complex, represent reaction pathways that are distinct from those facilitated by transition metal-containing species (e.g., Cu-, Ni-, Pt-, Pd- or Rh-based). The Lewis base (NHC) catalyzed transformations are valuable to chemical synthesis, as they can generate high enantioselectivities and possess unique chemoselectivity profiles. Here, the results of investigations that elucidate the principal features of the NHC-catalyzed BCA and SCA processes are detailed. Spectroscopic evidence is provided illustrating why the presence of excess base and MeOH or H2O is required for efficient and enantioselective boryl and silyl addition reactions. It is demonstrated that the proton sources influence the efficiency and/or enantioselectivity of NHC-catalyzed enantioselective transformations in several ways. The positive, and at times adverse, impact of water (biphasic conditions) on catalytic enantioselective silyl addition reactions is analyzed. It is shown that a proton source can facilitate non-enantioselective background reactions and NHC decomposition, requiring the catalyst to surpass such complications. Stereochemical models are presented that account for the identity of the observed major enantiomers, providing a rationale for the differences in selectivity profiles of BCA and SCA processes.

Cu‐NHC‐Catalyzed Enantioselective Conjugate Silyl addition to Indol‐1‐ylacrylate Derivatives

“…In this substrate screening (Table ), we turned to the acceptors having a Z configuration. The results pointed out the absolute configuration was the same as that products obtained from the E precursor, which is similar with Hoveyda's Cu‐NHC and NHC catalyzed sily addition to acyclic and cyclic α,β‐unsaturated carbonyls …”

Asymmetrische Synthese sekundärer und tertiärer Boronsäureester

“…[74,75] In Gegenwart katalytischer Mengen eines N-heterocyclischen Carbens (NHC) reagierte B 2 pin 2 über eine 1,4-Addition an die ungesättigten Systeme in hervorragender Ausbeute und Regioselektivitätz uc yclischeno der acyclischen sekundärer und tertiären Alkylboronsäureestern. [74,75] In Gegenwart katalytischer Mengen eines N-heterocyclischen Carbens (NHC) reagierte B 2 pin 2 über eine 1,4-Addition an die ungesättigten Systeme in hervorragender Ausbeute und Regioselektivitätz uc yclischeno der acyclischen sekundärer und tertiären Alkylboronsäureestern.…”

“…Eine wichtige Publikation von Hoveyda und Mitarbeitern aus dem Jahr 2009 behandelte ausführlich die b-Borylierung von a,b-ungesättigten Ketone in Abwesenheit eines Metallkatalysators. [74,75] [76] Während in der anfänglichen Studie racemische b-borylierte Produkte gebildet wurden, beschrieb Hoveyda später eine asymmetrische Variante mithilfe chiraler Imidazoliumsalze in Kombination mit einer organischen Base (Schema 20). [77] Hervorragende Ausbeuten und Enantioselektivitäten konnten fürd ie b-Borylierung einer großen Auswahl an Substraten erreicht werden, einschließlich a,b-ungesättigten Ketonen, Estern, Amiden und Aldehyden;ein späterer Bericht erweiterte die Methode auf b,b-disubstituierte Enone,w as einen Zugang zu optisch reinen tertiären Alkylboronsäureestern bot.…”

Formation of Quaternary Stereocentres by Copper-Catalysed Enantioselective Conjugate Addition Reaction

“…The mechanism of these NHC-catalysed boryl conjugate addition reaction in the absence of transition-metal complexes [115] will not be discussed here, as it is outside of the scope of this chapter.…”