Catalytic olefin metathesis--through which pairs of C = C bonds are reorganized--transforms simple molecules to those that are complex and precious. This class of reactions has noticeably enriched chemical synthesis, which is the art of preparing scarce molecules with highly desirable properties (for example, medicinal agents or polymeric materials). Research in the past two decades has yielded structurally well-defined catalysts for olefin metathesis that are used to synthesize an array of molecules with unprecedented efficiency. Nonetheless, the full potential of olefin metathesis will be realized only when additional catalysts are discovered that are truly practical and afford exceptional selectivity for a significantly broader range of reactions.

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.

Metal-free, nucleophilic activation of a B-B bond has been exploited in the development of a highly efficient method for conjugate additions of commercially available bis(pinacolato)diboron to cyclic or acyclic α,β-unsaturated carbonyls. Reactions are readily catalyzed by 2.5-10 mol % of a simple N-heterocyclic carbene (NHC). A variety of cyclic and acyclic unsaturated ketones and esters can serve as substrates. Transformations deliver β-boryl carbonyls bearing tertiary as well as quaternary B-substituted carbons in up to >98% yield. Preliminary studies indicate that, although related Cu-NHC-catalyzed reactions are equally efficient, the metal-free variant is more functional group tolerant; in contrast to the Cu-catalyzed reactions, the metal-free processes proceed readily in the presence of a terminal alkyne and do not promote concomitant diboration of an aldehyde. Representative functionalization of the resulting boron enolates demonstrates the strong influence of the Lewis acidic B of the β-boronate.Development of metal-free catalytic processes is critical to advancement of modern chemical synthesis; such protocols are valuable even in cases where a metal-catalyzed variant is available. The two reaction classes often proceed by mechanistically distinct pathways and can give rise to complementary reactivity and selectivity patterns. It is thus noteworthy that C-B bond formation has remained exclusively in the domain of metal-based catalysis. 1 Pt-, 2 Rh-, 3 Ni-4 and Cu-catalyzed 5 conjugate additions of diborons 6 with unsaturated esters have been disclosed; these transformations are largely or entirely limited to reactions of acyclic substrates E-mail: E-mail: amir.hoveyda@bc.edu. (with achiral and chiral catalysts, respectively). In only three cases is the formation of quaternary B-substituted carbons reported (all with acyclic enones). 4 Herein, we introduce a method for efficient C-B bond formation through transformations that are catalyzed by 2.5-10 mol % of a readily available N-heterocyclic carbene (NHC). Cyclic and acyclic α,β-unsaturated ketones or esters serve as substrates; β-boryl carbonyls with tertiary or quaternary B-substituted carbons are obtained in up to >98% yield. We illustrate that boron conjugate addition under metal-free conditions delivers reactivity and site-selectivity levels not attainable through the use of a Cu-catalyzed variant. 5 NIH Public AccessThe present investigations are based on the principle that a nucleophilic NHC 7 might associate with a Lewis acidic boron of commercially available bis(pinacolato)diboron (1) (Scheme 1). 8 The resulting electronic reorganization 9,10 could lead to activation of the B-B bond, promoting reaction with an appropriate electrophilic site through the general pathway in Scheme 1.To initiate our studies, we subjected cyclohexenone and bis(pinacolato)diboron (1) to a premixed solution of commercially available imidazolinium salt 2 and NaOt-Bu (10 mol % of each) in THF at 22 °C. As shown in entry 1 of Table 1, 66% conversion to the desire...

H-bonding interactions have been exploited extensively in the design of catalysts for stereoselective synthesis but have rarely been utilized in the development of metal-catalyzed processes. Studies described herein demonstrate that intramolecular H-bonding interactions can significantly increase the rate and levels of stereochemical control in Ru-catalyzed olefin metathesis reactions. The utility of H-bonding in catalytic olefin metathesis is elucidated through development of exceptionally facile and highly diastereoselective ring-opening/cross-metathesis (DROCM) reactions, involving achiral Ru catalysts and enantiomerically enriched allylic alcohols. Transformations proceed to completion readily (> 98% conversion, up to 87% yield), often within minutes, in the presence of < or = 2 mol % of an achiral catalyst to afford synthetically versatile products of high stereochemical purity (up to > 98:2 dr and 11:1 E:Z).

Chiral olefin metathesis catalysts enable chemists to access enantiomerically enriched small molecules with high efficiency; synthesis schemes involving such complexes can be substantially more concise than those that would involve enantiomerically pure substrates and achiral Mo alkylidenes or Ru-based carbenes. The scope of research towards design and development of chiral catalysts is not limited to discovery of complexes that are merely the chiral versions of the related achiral variants. A chiral olefin metathesis catalyst, in addition to furnishing products of high enantiomeric purity, can offer levels of efficiency, product selectivity and/or olefin stereoselectivity that are unavailable through the achiral variants. Such positive attributes of chiral catalysts (whether utilized in racemic or enantiomerically enriched form) should be considered as general, applicable to other classes of transformations.