Asymmetric functionalization of aromatic C-H bonds of N,N-disubstituted anilines with diazo compounds and imines is reported for the efficient construction of α,α-diaryl benzylic quaternary stereocenters in good yields with high diastereoselectivities and excellent enantioselectivities. This Rh(II)/chiral phosphoric acid cocatalyzed transformation is proposed to proceed through a metal-carbene-induced zwitterionic intermediate which undergoes electrophilic trapping. To the best of our knowledge, this is the first asymmetric example of metal carbene-induced intermolecular functionalization of aryl C-H bonds.

Enantioselective α-aminomethylation of carbonyl compounds constitutes a powerful protocol for introducing aminomethyl groups to simple organic molecules. However, current strategies rely on nucleophile-based enantioselective activation with inherently activated substrates only, and enantioselective protocol based on the activation of in situ-generated unstable formaldimines remains elusive, probably owing to their unstable nature and the lack of steric environment for efficient stereocontrols. Here, based on a rhodium/chiral phosphoric acid cooperative catalysis, we achieved an enantioselective three-component reaction of α-diazo ketones with alcohols and 1,3,5-triazines. A dual hydrogen bonding between the chiral phosphoric acid catalyst and two distinct active intermediates was proposed to be crucial for the efficient electrophile-based enantiocontrol. A series of chiral β-amino-α-hydroxy ketones including those derived from simple aliphatic alcohols, allylic alcohol, propargyl alcohol, complicated natural alcohols and water could all be prepared in high efficiency and enantioselectivity.

An unprecedented catalytic asymmetric allylation of isatins and isatin-derived ketimines is reported enabled by agold and chiral organocatalyst cooperative catalysis strategy. This method offers expeditious access to chiral 2,5-disubsituted alkylideneoxazolines containing vicinal stereogenic centers, mainly in optically pure form, and which are otherwise impossible to access.Mechanistic evidence reveals the presence of an alkylgold intermediate,and an X-raycrystal structure of the allylgold species illuminates its unique stability and reactivity.A na symmetric formal hetero-ene reaction of this gold intermediate,i nvolving ad earomatization process,i s enabled with assistance of aq uinine-derived squaramide catalyst. This novel discovery extends the synthetic applications of gold complexes and the versatility of gold catalysis. Scheme 1. Gold-catalyzed transformations of N-propargylamides.

Asymmetric functionalization of aromatic C À H bonds of N,N-disubstituted anilines with diazo compounds and imines is reported for the efficient construction of a,a-diaryl benzylic quaternary stereocenters in good yields with high diastereoselectivities and excellent enantioselectivities. This Rh II /chiral phosphoric acid cocatalyzed transformation is proposed to proceed through a metal-carbene-induced zwitterionic intermediate which undergoes electrophilic trapping. To the best of our knowledge, this is the first asymmetric example of metal carbene-induced intermolecular functionalization of aryl CÀH bonds.Carbene-induced C À H functionalization by transitionmetal-catalyzed decomposition of diazo compounds is among the most efficient and reliable synthetic tools for the construction of CÀC bonds.[1] Within this context, by taking advantage of a broad selection of transition-metal catalysts, both non-asymmetric and asymmetric functionalizations of C(sp 3 ) À H bonds have been extensively studied over the past several decades.[1b-e] However, while non-asymmetric functionalization of aromatic C(sp 2 )ÀH bonds have also been developed to some extent, [2][3][4][5] the asymmetric version of metal-carbene-induced functionalization of aromatic C(sp 2 )À H bonds remains unexplored except for intramolecular examples [6] or those starting from heteroarenes. [7] Unlike the carbene-induced C(sp 3 ) À H functionalization in which efficient asymmetric control could be achieved by chiral transition-metal catalysts via a concerted nonsynchronous transition state, [1b,d, 8] the functionalization of aromatic CÀH bonds is generally considered to proceed through the formation of a zwitterionic intermediate from electrophilic addition of a metal carbene to the aromatic ring and a subsequent rapid proton transfer (Scheme 1, path a). [1b] This stepwise mechanism makes it very challenging to achieve efficient enantioselective control by means of chiral transition-metal catalysts, [9] probably owing to the difficulty in controlling enantioselectivity during the asymmetric protonation step.[10] As part of our continuous research efforts in exploring new transformations based on asymmetric electrophilic trapping of active intermediates generated from metal carbenes, [11,12] we became interested in developing catalytic asymmetric functionalization of aromatic C À H bonds with a similar strategy. We envisioned that the proposed metalcarbene-induced zwitterionic intermediate could be intercepted by electrophiles such as active imines prior to 1,2-proton transfer to give formal CÀH insertion products (Scheme 1, path b). With such a strategy, asymmetric control could be realized during the trapping process by introducing chiral cocatalyst such as chiral phosphoric acid (PPA; Scheme 1, path b).[13] Herein, we report the successful development of a catalytic asymmetric functionalization of aromatic CÀH bonds from a novel three-component reaction of arenes, diazo compounds, and imines in the presence of a rhodium(II)/chiral PPA cat...

An efficient and novel rhodium-catalyzed formal C−O insertion reaction of alkyne-tethered diazo compounds for the synthesis of 3H-indol-3-ols is described. A type of donor/donor rhodium carbene generated in situ via a carbene/alkyne metathesis (CAM) process is the key intermediate and terminates in a unique transformation different from donor/acceptor carbenoids. In addition, 18 O-labeling experiments indicate that intramolecular oxygen-atom transfer from the amide group to the carbon−carbon triple bond occurs during this transformation.