Pd-Catalyzed Photochemical Alkylative Functionalization of C═C and C═N Bonds

Abstract

The development of excited-state palladium-catalyzed alkylative cyclization of acrylamides and the alkylation of quinoxalinones is described. The application of a variety of primary, secondary, and tertiary unactivated alkyl halides as alkyl radical precursors and the use of a simple catalyst system are the highlights of this reactivity manifold. The reactions exhibit wide scope, occur under mild conditions, and furnish the products in excellent yields.

Cascade Cyclizations Triggered by Photochemically Generated Carbamoyl Radicals Derived from Alkyl Amines

“…The ortho -cyano-substituted acrylamide motif is being actively studied by the synthetic community as it leads to the quinoline dione substructure, which is present in a plethora of important biologically active molecules. ,− Among methods that provide access to different derivatives of quinoline diones, a sulfonylative cyclization was reported by Yu and Li groups wherein the Yu group demonstrated a metal-free sulfonylative cyclization, and the Li group utilized Cu-catalyzed sulfonylation under conditions that were applicable to a larger selection of radicals for the annulation of 2-cyanoacrylamides. − Among other strategies for cyclization of acrylamide precursors, phosphorylation, , trifluoromethylation, difluoromethylation, , azidation, thiomethylation, and silylation are methods that have been well received by the scientific community. Our group has reported the visible light-mediated functionalization of CC and CN bonds ,, including the addition of carbamoyl radicals to quinone methides (Scheme b). We contemplated that photochemical carbamoylation represents several advantages over peroxide-promoted generation and use of carbamoyl radicals, such as application to aliphatic amines, use of precursors with other functionalities such as olefins and alkynes, and applicability to acrylamides containing other heteroatoms and flanking groups, ultimately resulting in a significantly greater product diversity (Scheme c).…”

“…39−43 Among other strategies for cyclization of acrylamide precursors, phosphorylation, 44,45 trifluoromethylation, 46 difluoromethylation, 40,47 azidation, 48 thiomethylation, and silylation 49 are methods 50 that have been well received by the scientific community. Our group has reported the visible light-mediated functionalization of C�C and C�N bonds 33,46,51 including the addition of carbamoyl radicals to quinone methides (Scheme 1b). We contemplated that photochemical carbamoylation represents several advantages over peroxide-promoted generation and use of carbamoyl radicals, such as application to aliphatic amines, 21 use of precursors with other functionalities such as olefins and alkynes, and applicability to acrylamides containing other heteroatoms and flanking groups, ultimately resulting in a significantly greater product diversity (Scheme 1c).…”

Photocatalytic Alkylation/Arylative Cyclization of N-Acrylamides of N-Heteroarenes and Arylamines with Dihydroquinazolinones from Unactivated Ketones

“…1 H NMR (500 MHz, CDCl 3 ) δ (ppm) = 8.54 (d,J = 8.7 Hz,1H),6H),3H),7.29 (t,J = 7.6 Hz,1H),7.02 (t,J = 7.6 Hz,1H),2.41 (dd,J = 14.2,7.8 Hz,1H),1.97 (dd,J = 14.1,4.9 Hz,1H),1.69 (s,3H),3H),2H),1H), 1.00−0.96 (m, 2H), 0.86−0.82 (m, 3H); 13 C{ 1 H} NMR (126 MHz, CDCl 3 ) δ (ppm) = 173. 9,139.3,134.4,134.4,132.4,130.4,129.9,129.4,128.3,128.2,126.8,126.5,125.9,125.4,125.2,124.5,120.0,119.5,116.9,76.9,49.5,47.8,35.0,34.5,33.3,30.9,26.3,26.2,26.2;HRMS (ESI): m/z calc. for (C 30 H 28 Br 1 N 1 O 1 Na 1 ) [M + Na] + : 520.1246; found: 520.1245; IR (ATR) (ν cm −1 ): 3082, 29393082, , 28643082, , 17063082, , 1615…”

“…Driven by such a notion, the motivation was further inflamed by a number of documented synthetic methods for cascade alkylation/cyclization of various N-acrylamides, en route to indolo-and benzimidazolo[2,1-a]isoquinolines or 2-oxindoles, with different alkyl radical progenitors under thermo-(often elevated temperature), photo-, or electrochemical conditions. 9,10 Hence, augmenting the terrain of ketone C−C activation, herein, a visible-light photoredox-catalyzed cascade alkylation and intramolecular arylative cyclization of diverse methacrylamides�prepared from 2-arylindoles, 2-arylbenzimidazoles, or anilines�with dihydroquinazolinones is recognized to access distinct alkyl-substituted indolo-and benzimidazolo-[2,1-a]isoquinolines or 2-oxindoles (Scheme 1).…”

“…To fortify the foundation of a mechanistic hypothesis, a variety of crucial experiments were performed. To begin with, the reaction between 1a and 2a in the presence of 2,2,6,6tetramethylpiperidine (TEMPO) radical scavenger led to no formation of desired 3aa, rather detecting an adduct (9) by HRMS analysis (Scheme 5a). 11 Additionally, the radical clock experiment of dihydroquinazolinone 2n with 1a resulted in the formation of product 3an (14%), via the generation of (1cyclopropyl)methyl radical and subsequent rapid ring-opening to homoallylic radical (Scheme 5b).…”