skip to main content

Title: Rhodium(III)‐Catalyzed Synthesis of N ‐(2‐Acetoxyalkyl)isoquinolones from Oxazolines and Alkynes through C−N Bond Formation and Ring‐Opening

An atom‐economic approach for the synthesis ofN‐(2‐acetoxyalkyl)isoquinolones from oxazolines and alkynes through rhodium(III)‐catalyzed auto‐tandem reactions involving C−H bond functionalization/C−N bond formation/ring opening/nucleophilic substitution is described. This protocol features high regioselectivity, tolerance of various functional groups, and retention of absolute configuration of chirality. Exploration of the reaction mechanism reveals that Cu(OAc)2not only acts as the oxidant, but also provides acetate to promote the reaction in this process.

magnified image

more » « less
Author(s) / Creator(s):
 ;  ;  ;  ;  
Publisher / Repository:
Wiley Blackwell (John Wiley & Sons)
Date Published:
Journal Name:
Advanced Synthesis & Catalysis
Page Range / eLocation ID:
p. 214-218
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract

    The direct formation of aryl C−O bonds via the intramolecular dehydrogenative coupling of a C−H bond and a pendant alcohol represents a powerful synthetic transformation. Herein, we report a method for intramolecular arene C−H etherification via an umpoled alcohol cyclization mediated by an I(III)N‐HVI reagent. This approach provides access to functionalized chromane scaffolds from primary, secondary and tertiary alcohols via a cascade cyclization‐iodonium salt formation, the latter providing a versatile functional handle for downstream derivatization. Computational studies support initial formation of an umpoled O‐intermediate via I(III) ligand exchange, followed by competitive direct and spirocyclization/1,2‐shift pathways.

    magnified image

    more » « less
  2. Abstract

    With sunlight or blue LEDs irradiation, regioselective decarboxylative alkylation of various non‐aromatic heterocycles has been realized via C(sp3)‐centered radical C(sp2)−C(sp3) bond formation under oxidant‐free conditions at room temperature. This reaction readily incorporates various functional alkyl groups into heterocyclic compounds without observation of any alkyl radical rearrangement and represents a mild and general tool for the preparation of valuable alkyl group‐functionalized heterocyclic compounds.

    magnified image

    more » « less
  3. Abstract

    A series of various solvents and additives were tested in enantioselective hydroamination/cyclization reactions of aminoalkenes catalyzed by a binaphtholate yttrium catalyst. The functional group tolerance of the catalyst and the influence on the reaction rate and enantioselectivity was studied. Some weakly coordinating polar solvents, such as Et2O, MTBE, and chlorobenzene led to slightly increased reaction rates compared to the less polar solvent benzene, presumably due to a better stabilization of the polar transition state. Stronger binding solvents and additives, such as THF, DMAP, pyrrolidine,n‐propylamine, and 1‐phenylethylamine, decrease the reaction rate and diminish the enantioselectivity of the hydroamination product. Some additives, such as THF, Et2O, MTBE, chloro‐ and bromobenzene, as well as (+)‐sparteine resulted in slightly higher enantioselectivities in the cyclization of the model substrateC‐(1‐allylcyclohexyl)methylamine, although this observation was not generally true for other aminoalkene substrates. The reaction rates and enantioselectivities were depressed in the presence of (−)‐sparteine using the (R)‐binaphtholate‐ligated catalyst. In case ofC‐(1‐allylcyclohexyl)methylamine, the enantioselectivity was switched from 76% ee favoring the (S)‐enantiomer of the hydroamination product when using (+)‐sparteine to 22% ee in favor of the (R)‐enantiomer when (−)‐sparteine was used. The rates of cyclization of aminoalkenes and the resulting enantioselectivities significantly depend on substrate concentration with the highest rate (13.6 h−1) and enantioselectivity (68% ee) observed in dilute conditions (0.05 M) compared to a concentrated solution (0.5 M, 5.0 h−1, 35% ee) for 2,2‐dimethylpent‐4‐enylamine. These observations indicate that the reaction mechanism is shifted in favor of a slower, less enantioselective catalytic cycle involving a higher coordinate species when higher substrate concentrations or stronger binding additives are present.

    magnified image

    more » « less
  4. Abstract  
    more » « less
  5. Abstract

    Benzofused lactams, especially indolin‐2‐one and dihydroquinolin‐2‐one are popular structural motives in durgs and natural products. Herein, we developed a room temperature and robust synthesis of benzofused lactams through cobalt(III)‐catalyzed C(sp2)−H amidation. In this protocol, in‐situ formation of Cp*Co(III)(ligand) catalyst from Cp*Co(CO)I2and ligand simplify the synthetic effort of cobalt complexes. Simple and readily synthesized 1,4,2‐dioxazol‐5‐ones underwent room temperature intramolecular C−H amidation and afforded a wide variety of functionalized benzofused lactams in up to 86% yield. The scalability of the reaction is also be demonstrated.

    magnified image

    more » « less