We report asymmetric dearomatization of phenols using Ag carbenoids from α-diazoacetamides. The Ag catalyst promoted intramolecular dearomatization of phenols, whereas a Rh or Cu catalyst caused C-H insertion and a Büchner reaction. Studies indicated Ag carbenoids have a carbocation-like character, making their behavior and properties unique. Highly enantioselective transformations using Ag carbenoids have not been reported. We achieved a Ag carbenoid-mediated chemo- and highly enantioselective phenol dearomatization with substrate generality for the first time.

Various nitrogen-bridged bicyclic skeletons are found in bioactive natural products and pharmaceuticals. The development of a new reaction to construct these molecular frameworks has attracted considerable attention in synthetic organic chemistry. We developed a novel synthetic method for obtaining a wide variety of nitrogen-bridged bicyclic compounds with a catalytic process, Rh-catalyzed formal carbenoid insertion into an amide C-N bond. Using 0.1-0.4 mol % Rh2(NHCO(t)Bu)4 catalyst, various azabicyclo[X.Y.Z]alkane derivatives were obtained in good to excellent yield, successfully demonstrating the broad substrate scope of the developed process. Experimental and computational studies to elucidate the reaction mechanism revealed that the formal insertion reaction of a carbenoid into an amide C-N bond proceeded via the formation of Rh-associated N-ylides, followed by an acyl group-selective Stevens [1,2]-shift through a concerted addition/elimination process on the sp(2)-hybridized carbon.

Although (+)-catharanthine is an attractive alkaloid for both clinical research and organic synthetic chemistry, only a limited number of approaches for its catalytic asymmetric synthesis exist. Herein, we describe a novel strategy for synthesizing a chiral intermediate of (+)-catharanthine via phosphoric acid-catalyzed asymmetric desymmetrization of a meso-isoquinuclidine possessing a 1,3-diol unit that was synthesized by a formal amide insertion reaction.

The past few decades have witnessed extensive efforts to discloset he unique reactivity of metal-nitrenes, because they could be ap owerful synthetic tool for introducing the amine functionality into unactivated chemical bonds. The reactivity of metal-nitrenes, however,i sc urrently mainly confined to aziridination (an insertion into aC =C bond) and CÀHa mination (an insertion into aC ÀHb ond). Nitrene insertion into an amide CÀNb ond, however,h as not been reported so far.I nt his work we have developedarhodium-catalyzed one-nitrogen insertion into amide CÀNa nd sulfonamideS ÀNb onds. Experimental and theoretical analy-ses based on density functional theory indicate that the formal amide insertion proceeds via ar hodium-coordinated ammonium ylide formed between the nitrene and the amide nitrogen, followed by acyl group transfer concomitant with CÀNb ond cleavage. Mechanistic studies have allowed rationalization of the origin of the chemoselectivity observed between the CÀHa nd amide insertion reactions. The methodology presented herein is the first example of an insertion of nitrene into amide bonds and provides facile access to unique diazacyclic systems with an NÀNb ond linkage.Scheme1.Reactions leadingt oN + ÀN À ylide formation from metal-nitrenes.Supporting information and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

Starting from bromo/iodobenzaldehyde derivatives, the corresponding (Z)- and (E)-(2-stilbenyl)­methanols could be prepared in 2–5 steps via Pd-catalyzed cross-coupling reactions (Sonogashira and Heck reactions) followed by aryllithium/aryl Grignard addition. For the (E)-stilbenes, subsequent acid-mediated cyclization using p-TsOH immobilized on silica (PTS-Si) at low temperatures furnished the 2,3-trans-1-indanols with complete stereocontrol at the C2–C3. Further oxidization of the alcohol provided the indanones, which are structurally related to the natural product paucifloral F. At higher temperatures, 1,2- and 2,3-disubstituted indenes could be selectively prepared in good to excellent yields. On the other hand, the (Z)-stilbenes, under similar conditions (PTS-Si), did not give the indanols; only the 1,2-disubstituted indenes could be obtained. To gain further insights into the stereochemistry at C2–C3 for the (Z)-stilbenes, hydride or azide was employed as a nucleophile; the corresponding indane products were obtained with the cis stereochemistry at the C2–C3. Thus, the (Z)- or (E)-olefin geometry of the substrate directed the stereoselective indanyl cyclization to furnish the cis or trans at the C2–C3 ring junction, respectively, while reaction conditions controlled the selectivity of the product types.