Enantioselective Palladium‐Catalyzed [3+2] Cycloaddition of Trimethylenemethane and Fluorinated Ketones

Abstract

A nitrile‐substituted trimethylenemethane (TMM) donor undergoes palladium‐catalyzed [3+2] cycloadditions with fluorinated ketones to generate tetrasubstituted trifluoromethylated centers in high enantioselectivity under mild conditions. The generation of the palladium–TMM complex was achieved by a self‐deprotonation strategy, which shows remarkable improvements in regiocontrol, efficiency, and atom economy of asymmetric [3+2] cycloadditions. Moreover, the versatility of the nitrile group provides direct access to a variety of synthetically useful intermediates, including amides, aldehydes, and esters. The developed reaction conditions allow for the synthesis of a wide variety of aromatic, heteroaromatic, and aliphatic fluorinated dihydrofurans in excellent regio‐ and enantioselectivities.

Stereoselective synthesis of functionalized azepines via gold and palladium relay catalysis

“…We initiated the investigation of suitable reaction conditions by using enynamide 1a and cyano-TMM donor 2 15 as the model substrates. In the presence of a bimetallic catalytic system consisting of Ph 3 PAuCl/AgPF 6 and Pd 2 (dba) 3 /Feringa ligand L1 16 (Table 1, entry 1), the desired fused azepine product 3a was obtained in 46% yield with modest diastereoselectivity (1.5 : 1 dr) and enantioselectivity (31%/44% ee).…”

Highly Regio‐, Diastereo‐, and Enantioselective Assembly of Azepino[2,3‐b]indoles viaPalladium‐Catalyzed [4 + 3] Cycloaddition†

“…Initially, the model [4 + 3] cycloaddition of indoline‐derived aza‐diene 1a with cyano‐TMM donor 2a [ 12 ] was studied by employing Pd 2 (dba) 3 /Feringa ligand L1 [ 13 ] as the catalyst in toluene at room temperature (Table 1, entry 1). Pleasingly, the target azepino[2,3‐ b ]indole compound 3a was obtained as an exclusive product in 84% yield with good diastereo‐ and enantioselectivity (7 : 1 dr, 64% ee).…”

Direct access to α,α-chlorofluoro arylketones via mild electrophilic heterohalogenation of arylalkynes

“…2 Ketones represent a class of useful building blocks ubiquitously applied in the production of medicines, functional materials, ligands, chemosensors, agrochemicals, etc. 3 As such, the search for new approaches enabling the selective synthesis of fluorinated ketones 4 would be highly desirable, as it would pave the way for further development of functional products.…”

“…To date, although there have been many approaches reported for the synthesis of α-fluoro ketones, 4 the construction of α,α-chlorofluoro ketones is far more challenging due to the difficulty in controlling the reaction chemoselectivity. In this regard, the first example of the synthesis of α,α-chlorofluoro ketones was reported by Jutand et al, and the products are formed via the initial transformation of arylaldehydes into 1-aryl-2,2-dichloro-2-fluoroethyl alcohols in the presence of a CFCl 3 /SnCl 2 system followed by hydroxyl oxidation (Scheme 1a).…”