No abstract

Cu-catalyzed methods for site-selective hydroboration of terminal alkynes, where the internal or α-vinylboronate is generated predominantly (up to >98%) are presented. Reactions are catalyzed by 1-5 mol % of N-heterocyclic carbene (NHC) complexes of copper, easily prepared from N-aryl-substituted commercially available imidazolinium salts, and proceed in the presence of commercially available bis(pinacolato)diboron [B(2)(pin)(2)] and 1.1 equiv of MeOH at -50 to -15 °C in 3-24 h. Propargyl alcohol and amine and the derived benzyl, tert-butyl, or silyl ethers as well as various amides are particularly effective substrates; also suitable are a wide range of aryl-substituted terminal alkynes, where higher α-selectivity is achieved with substrates that bear an electron-withdrawing substituent. α-Selective Cu-catalyzed hydroborations are amenable to gram-scale procedures (1 mol % catalyst loading). Mechanistic studies are presented, indicating that α selectivity arises from the structural and electronic attributes of the NHC ligands and the alkyne substrates. Consistent with suggested hypotheses, catalytic reactions with a Cu complex, derived from an N-adamantyl-substituted imidazolinium salt, afford high β selectivity with the same class of substrates and under similar conditions.

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A Cu-catalyzed method for efficient boron-copper addition processes involving acyclic and cyclic disubstituted aryl olefins are reported. Reactions are promoted with 0.5-5 mol % of a readily available N-heterocyclic carbene (NHC) complex; the presence of MeOH promotes in situ protonation of the C-Cu bond and leads to efficient catalyst turnover, constituting a net Cu-catalyzed hydroboration process. Reactions proceed in >98:<2 site-selectivity, and furnish secondary organoborane isomers that complement those obtained through reactions of boron-hydride reagents or by Rh-or Ir-catalyzed hydroborations (benzylic secondary C-B bonds). Initial observations regarding processes catalyzed by chiral NHC complexes, delivering products in up to 99:1 enantiomeric ratio, are disclosed.Development of efficient and stereoselective catalytic hydroboration reactions is a compelling objective in chemical synthesis; 1 a number of challenges, however, are yet to be addressed. For example, reactions of disubstituted olefins, furnishing regioisomers not accessible through the existing methods, have not been introduced. As part of studies regarding the development of N-heterocyclic carbenes (NHCs) 2 for facile site-and enantioselective synthesis, 3 we have begun to probe the ability of the derived metal complexes as catalysts for C-B bond formation. Herein, we disclose a protocol for catalytic boron-copper addition to acyclic and cyclic aryl olefins. Reactions are promoted by 0.5-5 mol % of a readily available NHC-Cu complex, proceed with >98:<2 site-selectivity, and afford boronate isomers that complement those obtained through transformations with borohydride reagents or catalyzed by Rh-and Ir-based E-mail: amir.hoveyda@bc.edu. Our studies were guided by previous disclosures on boron-copper addition to styrenes with stoichiometric amounts of an NHC-Cu complex and bis(pinacolato)diboron (1), affording secondary C-Cu and primary C-B bonds. Development of a catalytic version, where protonation of the C-Cu bond constitutes net hydroboration, 5 required us to identify an efficient procedure with the substantially less reactive disubstituted alkenes to obtain chiral alkylboranes. NIH Public AccessWe first established that treatment of (E)-β-methylstyrene with Cu complex 2 (1 equiv), diborane 1 and NaOt-Bu delivers a complex mixture, only 20% of which is boronate 5 (after quench; entry 1, Table 1). We then noted a report on reactions of α,β-unsaturated esters with 1, promoted by phosphine-Cu complexes. 6 An alcohol additive was used to protonate the resulting C-Cu bond to generate a catalytically active Cu-alkoxide, enhancing reaction efficiency. Such considerations led us to determine that subjection of (E)-β-methylstyrene to 0.5 mol % 2 and NaOt-Bu, 1.1 equivalents of 1 in the presence of 2.0 equivalents of MeOH results in >98% conversion to 5 at 22 °C within ten minutes (entry 2, Table 1); 5 is isolated in >98% yield and >98% site-selectivity. It should be noted that reaction of (E)-β-methylstyrene with BH 3 •THF or 9-BBN delive...

A Cu-catalyzed protocol for conversion of terminal alkynes to enantiomerically enriched diboronates is reported. In a single vessel, a site-selective hydroboration of an alkyne leads to the corresponding terminal vinylboronate, which undergoes a second site-selective and enantioselective hydroboration. Reactions proceed in the presence of two equivalents of commercially available bis(pinacolato)diboron [B2(pin)2] and 5–7.5 mol % of a chiral bidentate imidazolinium salt, affording diboronates in 60–93% yield and up to 97.5:2.5 enantiomeric ratio (er). The enantiomerically enriched products can be functionalized to afford an assortment of versatile organic molecules. Enynes are converted to unsaturated diboronates with high chemo- (>98% reaction of alkyne; <2% at alkene) and enantioselectivity (e.g., 94.5:5.5 er).

A one-pot condensation of isotryptamines and aldehydes that affords enantiomerically enriched 4-substituted tetrahydro-γ-carbolines is reported. The reaction is induced by a chiral thiourea/benzoic acid dual catalyst system. Purification of the N-Boc-protected products by trituration or crystallization provides the optically pure tetrahydro-γ-carboline derivatives in a scalable and highly practical procedure.

No abstract

Catalytic enantioselective allylic substitution (EAS) reactions, which involve the use of alkyl- or aryl-substituted vinylaluminum reagents and afford 1,4-dienes containing a quaternary carbon stereogenic center at their C-3 site, are disclosed. The C–C bond forming transformations are promoted by 0.5–2.5 mol % of sulfonate bearing chiral bidentate N-heterocyclic carbene (NHC) complexes, furnishing the desired products efficiently (66–97% yield of isolated products) and in high site- (>98% SN2′) and enantioselectivity [up to 99:1 enantiomer ratio (er)]. To the best of our knowledge, the present report puts forward the first cases of allylic substitution reactions that result in the generation of all-carbon quaternary stereogenic centers through the addition of a vinyl unit. The aryl- and vinyl-substituted vinylaluminum reagents, which cannot be prepared in high efficiency through direct reaction with diisobutylaluminum hydride, are accessed through a recently introduced Ni-catalyzed reaction of the corresponding terminal alkynes with the same inexpensive metal-hydride agent. Sequential Ni-catalyzed hydrometallations and Cu-catalyzed C–C bond forming reactions allow for efficient and selective synthesis of a range of enantiomerically enriched EAS products, which cannot cannot be accessed by previously disclosed strategies (due to inefficient vinylmetal synthesis or low reactivity and/or selectivity with Si-substituted derivatives). The utility of the protocols developed is demonstrated through a concise enantioselective synthesis of natural product bakuchiol.