Fragment Coupling and the Construction of Quaternary Carbons Using Tertiary Radicals Generated Fromtert-AlkylN-Phthalimidoyl Oxalates By Visible-Light Photocatalysis

Abstract

The coupling of tertiary carbon radicals with alkene acceptors is an underdeveloped strategy for uniting complex carbon fragments and forming new quaternary carbons. The scope and limitations of a new approach for generating nucleophilic tertiary radicals from tertiary alcohols and utilizing these intermediates in fragment coupling reactions is described. In this method, the tertiary alcohol is first acylated to give the tert-alkyl N-phthalimidoyl oxalate, which in the presence of visible-light, catalytic Ru(bpy)3(PF6)2, and a reductant fragments to form the corresponding tertiary carbon radical. In addition to reductive coupling with alkenes, substitution reactions of tertiary radicals with allylic and vinylic halides is described. A mechanism for the generation of tertiary carbon radicals from tert-alkyl N-phthalimidoyl oxalates is proposed that is based on earlier pioneering investigations of Okada and Barton. Deuterium labeling and competition experiments reveal that the reductive radical coupling of tert-alkyl N-phthalimidoyl oxalates with electron-deficient alkenes is terminated by hydrogen-atom transfer.

Oxalates as Activating Groups for Alcohols in Visible Light Photoredox Catalysis: Formation of Quaternary Centers by Redox-Neutral Fragment Coupling

“…Inspired by Barton’s introduction of tert -alkyl N -hydroxypyridine-2-thionyl oxalates for generating carbon radicals from alcohols, 2b Overman et al recently introduced N -phthalimidoyl oxalate derivatives of tertiary alcohols for the reductive coupling of tertiary radicals with Michael acceptors using visible light and [Ru(bpy) 3 ](PF 6 ) 2 (eq 1). 3–5 Though this method was shown to possess a wide substrate scope, its mechanism necessitates the use of a stoichiometric reductant to produce the tertiary alkyl radical and forms phthalimide as a byproduct. Also, the inherent…”

Photoredox radical conjugate addition of dithiane-2-carboxylate promoted by an iridium(iii) phenyl-tetrazole complex: a formal radical methylation of Michael acceptors

“…5–7 Tetrabutylammonium was selected as the counterion to increase the solubility of the carboxylates in acetonitrile and in order to have the same cation as that of the supporting electrolyte used for the electrochemical experiments. 25 …”

“…, 1 and 2 ) are strongly oxidizing species once excited to their lowest excited state. 5–7 The excited-state redox potential of these molecules can be roughly estimated using a simplified version of the so-called Rehm–Weller equation: 26 where E 00 is the energy gap between the ground and excited states determined spectroscopically (see Fig. S4† for details about its determination).…”

“…Recently, Overman et al have also explored N -phthalimidoyl oxalate derivatives of tertiary alcohols for reductive coupling of tertiary radicals with Michael acceptors, using visible light and [Ru(bpy) 3 ][PF 6 ] 2 . 7 The key relevant characteristics of both the Overman and MacMillan radical generation methodologies were recently merged in a new powerful protocol. 8 A typical procedure entails the addition of 1–2 mol% of the photocatalyst Ir[dF(CF 3 )ppy] 2 ( t Bu-bpy)[PF 6 ] ( 1 , Fig.…”

Photoredox-catalyzed procedure for carbamoyl radical generation: 3,4-dihydroquinolin-2-one and quinolin-2-one synthesis

“…Based upon the reported procedure, 14,36 oxalyl chloride (3.81 g, 2.54 mL, 30.0 mmol) was added drop-wise to a solution of Nhydroxyphthalimide (979 mg, 6.0 mmol) in THF (100 mL) at -78 ˚C.…”