Polarity inversion is the hallmark of N-heterocyclic carbene (NHC) organocatalysis, with the generation and reaction of acyl anion equivalents known for more than 70 years. In contrast, polarity inversion through 1,4-addition of NHCs to conjugate acceptors was first applied in a catalytic reaction in 2006. This sub-field of NHC-organocatalysis has developed steadily over the subsequent years, enabling novel coupling reactions, enantioselective cycloisomerizations, polymerizations, and other reactions. In this review, this emerging area of NHC-organocatalysis is discussed with comprehensive coverage. In addition, notes regarding the use of other Lewis base catalysts for related reactions, and comments regarding NHC selection for this type of catalysis, are provided.

A new method for the formation of covalently linked DNA conjugates is described. The method involves installation of a 5´-hydroxylamine nucleophile onto synthetic DNA and condensation with a suitable electrophilic carbonyl compound to form an oxime linkage. Various protection strategies for the hydroxylamine group and their merits are discussed and the formation of an oligonucleotide–peptide conjugate is described.

The use of silyl nitronates is reported for the isothiourea-catalyzed synthesis of -nitro-substituted silyl esters containing up to two contiguous stereocenters in good yield and with excellent enantioselectivity (up to 93% yield, 99:1 er). The serendipitously-discovered formation of silyl ester products in this reaction demonstrates a novel platform for catalyst turnover in α,β-unsaturated acyl ammonium catalysis.

Direct polarity inversion of conjugate acceptors provides av aluable entry to homoenolates.N -heterocyclic carbene (NHC) catalyzedr eactions,i nw hich b-unsubstituted conjugate acceptors undergo homoenolate formation and C À C bond formation twice,h ave been developed. Specifically,t he all-carbon (5+ +1) annulations give ar ange of mono-and bicyclic cyclohexanones (31 examples). In the first family of annulations, b-unsubstituted acrylates tethered to ad ivinyl ketone undergo cycloisomerization, providing hexahydroindenes and tetralins.I nt he second, partially untethered substrates undergo an intermolecular (5+ +1) annulation involving dimerization followed by cycloisomerization. While enantioselectivity was not possible with the former,t he latter proved viable,a llowing cyclohexanones to be produced with high levels of enantiopurity (most > 95:5 e.r.)a nd exclusive diastereoselectivity (> 20:1 d.r.). Derivatizations and mechanistic studies are also reported. Scheme 1. Backgrounda nd mechanistic framework. EWG = electronwithdrawinggroup.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

Direct polarity inversion of conjugate acceptors provides a valuable entry to homoenolates. N‐heterocyclic carbene (NHC) catalyzed reactions, in which β‐unsubstituted conjugate acceptors undergo homoenolate formation and C−C bond formation twice, have been developed. Specifically, the all‐carbon (5+1) annulations give a range of mono‐ and bicyclic cyclohexanones (31 examples). In the first family of annulations, β‐unsubstituted acrylates tethered to a divinyl ketone undergo cycloisomerization, providing hexahydroindenes and tetralins. In the second, partially untethered substrates undergo an intermolecular (5+1) annulation involving dimerization followed by cycloisomerization. While enantioselectivity was not possible with the former, the latter proved viable, allowing cyclohexanones to be produced with high levels of enantiopurity (most >95:5 e.r.) and exclusive diastereoselectivity (>20:1 d.r.). Derivatizations and mechanistic studies are also reported.