An N-heterocyclic carbene (NHC) catalyzed domino reaction triggered by a δ-LUMO activation of α,β-γ,δ-diunsaturated enal has been developed for the formal [4 + 2] construction of multisubstituted arenes and 3-ylidenephthalide. These two products, formed in a highly chemo- and regioselective manner, were obtained via different catalytic pathways due to a simple change of the substrate. The activation of the remote δ-carbon of unsaturated aldehydes expands the synthetic potentials of NHC organocatalysis.

Multisubstituted arenes such as indanes with attached all-carbon quaternary centers are unique scaffolds in synthetic functional molecules and sophisticated natural products.Akey challenge in preparing such molecules lies in the enantioselective installation of the quaternary carbon centers.C onventional methods in this direction include asymmetric substitution reactions and substrate-controlled cyclization reactions.T hese reactions lead to poor stereoselectivities and/or require long and tedious synthetic steps.Disclosed here is ao ne-step organic catalytic strategy for enantioselective access to this class of molecules.T he reaction involves an Nheterocyclic carbene catalyzedp rocess for direct benzene construction, indane formation, remote-carbon desymmetrization, and excellent chirality control. This approach will enable the concise synthesis of arene-containing molecules,i ncluding those with complex structures and challenging chiral centers.

Multisubstituted arenes such as indanes with attached all-carbon quaternary centers are unique scaffolds in synthetic functional molecules and sophisticated natural products.Akey challenge in preparing such molecules lies in the enantioselective installation of the quaternary carbon centers.C onventional methods in this direction include asymmetric substitution reactions and substrate-controlled cyclization reactions.T hese reactions lead to poor stereoselectivities and/or require long and tedious synthetic steps.Disclosed here is ao ne-step organic catalytic strategy for enantioselective access to this class of molecules.T he reaction involves an Nheterocyclic carbene catalyzedp rocess for direct benzene construction, indane formation, remote-carbon desymmetrization, and excellent chirality control. This approach will enable the concise synthesis of arene-containing molecules,i ncluding those with complex structures and challenging chiral centers. Figure 1. Arenes bearing challenging chiral centers.

Significance: Song, Chi and co-workers report an N-heterocyclic carbene (NHC) catalyzed synthesis of multisubstituted benzenes and 3-ylidenephthalides. Starting from readily accessible α,β-γ,δ-diunsaturated aldehydes and 1,3-diketones or β-keto esters, the target compounds were obtained in moderate to good yields using 10 mol% of precatalyst A in the presence of an excess of oxidant B under basic conditions. Comment: As pointed out by previous reports on the NHC-based activation of conjugated dienals, nucleophilic attacks preferably occur in the β-position of such systems. The authors have successfully circumvented this problem by 'blocking' the corresponding carbon atom with an additional substituent (R 1 ), thus resulting in a preferred 1,6-addition of the nucleophile.

N-Heterocyclic Carbene-Catalyzed -Carbon LUMO Activation of Unsaturated Aldehydes. -(ZHU, T.; MOU, C.; LI, B.; SMETANKOVA, M.; SONG*, B.-A.; CHI, Y. R.; J. Am. Chem. Soc. 137 (2015) 17, 5658-5661, http://dx.doi.org/10.