We present here a highly efficient NHC-catalyzed kinetic resolution of a wide range of 1,1'-biaryl-2,2'-diols and amino alcohols to provide them in uniformly ≥99% ee. This represents the first highly enantioselective catalytic acylation of axially chiral alcohols. The aldehyde backbone that is incorporated into the chiral acyl azolium intermediate was found to have a significant effect on the enantioselectivity of the process.

We present herein an unprecedented stereo­selective synthesis of bridged biaryls with defined axial and central chirality from readily available starting materials. This N-heterocyclic carbene-catalyzed method proceeds through propargylic substitution of azolium enolates followed by two-directional cyclization, as supported by DFT calculation. A range of benzo­furan/indole-derived bridged biaryls bearing an eight-membered lactone are accessed with uniformly high stereo­selectivity (>98:2 dr, mostly >98% ee).

In contrast to the well-established kinetic resolution of secondary alcohols, [1] use of the tertiary alcohol kinetic resolution has remained limited with only a handful of systems reported in the literature including enzymatic and chemical methods. [2] During our studies, we became interested in the synthesis of 3-hydroxy-3-substituted oxindoles (I, Scheme 1), which represent the core structure of a large number of biologically significant natural products and are themselves important targets in medicinal chemistry. [3] It is shown that the identity of the substituent at the 3-position has significant influence on the biological activity of these natural products. [4] Not surprisingly, extensive efforts have been focused on their asymmetric synthesis and many successful systems have been developed. [5] One general catalytic asymmetric method that can tolerate a wide range of 3-substituents, however, remains elusive. We hope to address this issue using an unprecedented and alternative approach, namely the catalytic kinetic resolution of this important class of tertiary alcohols that are readily available in racemic form. [6] Considering the strategies applicable to our goal, we were particularly attracted to asymmetric esterification of alcohols employing chiral acyl azolium species (II, Scheme 1) [7] generated from aldehydes catalyzed by a N-heterocyclic carbene (NHC). [8] This novel catalytic generation of activated carboxylates, either from internal redox reactions of functionalized aldehydes (such as a,b-unsaturated aldehydes or a-halo aldehydes) [9] or from simple aldehydes under oxidative conditions, [10] has added a powerful dimension to NHC catalysis. Application of these new concepts to enantioselective CÀC bond formation has met with great success; the use of the chiral acyl azolium to induce asymmetric induction of the alcohol counterpart, however, has lagged behind. In fact, only a few isolated examples for the secondary alcohol kinetic resolution (selectivity S up to 7.3) [9e, 10g] or diol desymmetrization (up to 83 % ee) [9b, 10b] were reported in the literature. [11] Simple tertiary alcohols (e.g., tert-butanol), on the other hand, showed no reactivity towards the acyl azolium species. Asymmetric induction for tertiary alcohols using NHC catalysis, to the best of our knowledge, is not known.We initiated our studies by examining the reaction of racemic 1 a with a,b-unsaturated aldehydes catalyzed by triazolium-based NHCs in the absence of an external oxidant (Scheme 1). After extensive experimentation, no significant conversion to the desired saturated ester was obtained and the selectivity remained low (S < 5). When MnO 2 was included in the reaction between 1 a and cinnamaldehyde catalyzed by NHC derived from azolium 3, [12] 32 % conversion to ester 2 a and a good level of selectivity (S = 21) were obtained (entry 1, Table 1). The identity and equivalent of the base turned out to be essential for the reaction (entries 2-4), with 1.0 equiv DBU being the optimal choice (S = 30). The screening o...

The importance of axial chirality in enantioselective synthesis has been widely recognized for decades. The practical access to certain structures such as biaryl amino phenols known as NOBINs in enantiopure form, however, still remains a challenge. In drug delivery, the incorporation of axially chiral molecules in systematic screening has also received a great deal of interest in recent years, which calls for innovation and practical synthesis of structurally different axially chiral entities. Herein we present an operationally simple catalytic N -alkylation of sulfonamides using commercially available chiral amine catalysts to deliver two important classes of axially chiral compounds: structurally diverse NOBIN analogs as well as axially chiral N -aryl sulfonamides in excellent enantiopurity. Structurally related chiral sulfonamide has shown great potential in drug molecules but enantioselective synthesis of them has never been accomplished before. The practical catalytic procedures of our methods also bode well for their wide application in enantioselective synthesis.

Herein we present a highly efficient N-heterocyclic-carbene (NHC)-catalyzed atroposelective acylation of amino bisphenols to provide access to a wide range of 1,1′-biaryl-2,2′-amino alcohols (NOBIN analogs) in high yield and with uniformly excellent enantioselectivity. This catalytic system is shown to proceed through a combination of desymmetrization and secondary kinetic resolution to produce the axially chiral products in excellent enantioselectivity.

Presented herein is an unprecedented transition-metal-free propargylic substitution reaction with either azolium enolates or acyl anions, which are generated from aldehydes under N-heterocyclic carbene catalysis. This new catalytic activation operates on readily available cyclic propargylic carbamates through decarboxylation, and generates reactive allene intermediates that can undergo divergent cyclization pathways to deliver skeletally diverse polycyclic compounds with high levels of efficiency and excellent enantioselectivities.

Described is an unprecedented NHC-catalyzed (NHC=N-heterocyclic carbene), stereoselective ring opening of epoxy and cyclopropyl enals to deliver valuable compounds bearing multiple stereocenters. A straightforward three-step procedure involving two catalytic enantioselective transformations has been developed and leads to a regio- and stereodivergent synthesis of either 1,2-amino alcohols/diamines or 1,4-fluoro alcohols with excellent diastereo- and enantiopurity.

We present here a highly efficient NHC-catalyzed kinetic resolution of a wide range of 1,1'-biaryl-2,2'-diols and amino alcohols to provide them in uniformly ! 99 % ee. This represents the first highly enantioselective catalytic acylation of axially chiral alcohols. The aldehyde backbone that is incorporated into the chiral acyl azolium intermediate was found to have a significant effect on the enantioselectivity of the process.