A Biphilic Phosphetane Catalyzes N–N Bond-Forming Cadogan Heterocyclization via P^III/P^V═O Redox Cycling

Abstract

A small ring phosphacycle (1,2,2,3,4,4-hexamethylphosphetane) is found to catalyze deoxygenative N-N bond-forming Cadogan heterocyclization of o-nitrobenzaldimines, o-nitroazobenzenes and related substrates in the presence of hydrosilane terminal reductant. The reaction provides a chemoselective catalytic synthesis of 2H-indazoles, 2H-benzotriazoles, and related fused heterocyclic systems with good functional group compatibility. On the basis of both stoichiometric and catalytic mechanistic experiments, the reaction is proposed to proceed via catalytic PIII/PV=O cycling, where DFT modelling suggests a turnover limiting (3+1) cheletropic addition between the phosphetane catalyst and nitroarene substrate. Strain/distortion analysis of the (3+1) transition structure highlights the controlling role of frontier orbital effects underpinning the catalytic performance of the phosphetane.

A General One‐Pot Synthesis of 2H‐Indazoles Using an Organophosphorus–Silane System

“…In stark contrast, substituents at the 7‐position of the 2‐nitrobenzaldehydes in the vicinity of the reacting center were apparently detrimental for efficient conversion, as 44 was obtained in only a low yield. This finding is in line with all described reductive cyclizations of 3‐substituted 2‐nitrobenzaldimines to 2 H ‐indazoles and shows that proximal substituents severely affect Cadogan‐type organophosphorus‐mediated cyclizations . Nonetheless, our procedure also reliably generated more complex 2 H ‐indazoles bearing base‐ or acid‐sensitive substituents on the benzene ring, such as N 2‐(1 H ‐indol‐1‐yl)‐2 H ‐indazole heterocycle 46 with two acetoxy groups and derivative 45 with an ester group, which were obtained in moderate yields (44–46 %), as well as terminal alkyne 47 (51 %).…”

“…Balancing the required reactivity versus the desired reaction selectivity of the intermediate was considered crucial to avoid undesired side reactions, that is, nonproductive reduction of the nitro group, the aldehyde, or imine functionality. Surprisingly, phenylsilane, which is a well‐established reagent for the reduction of tertiary phosphine oxides, was less efficient (55 % yield; Table , entry 8), whereas triphenylsilane and methyldiethoxysilane led to the desired product in only a trace amount or a very low yield (Table , entries 9 and 10). To our surprise, easily separable and inexpensive 2,4,6,8‐tetramethylcyclotetrasiloxane (TMCTS) was comparably effective to diphenylsilane and afforded 3 in 73 % yield (Table , entry 11).…”

“…Until very recent reports by Genung et al . and Radosevich et al., however, who preformed 2‐nitrobenzaldimines, neat conditions or at least large excess amounts of the phosphines or phosphites were required. Despite these advances, a direct one‐step conversion of 2‐nitrobenzaldehydes and amines into the corresponding 2 H ‐indazoles through a domino imine condensation/reductive cyclization reaction would be highly desirable.…”

Biphilic Organophosphorus-Catalyzed Intramolecular Csp2–H Amination: Evidence for a Nitrenoid in Catalytic Cadogan Cyclizations

“…In accord with our previous calculations on a related system, 18 computational models indicate a stepwise pathway for the initial deoxygenation of 1 by phosphetane 3 proceeding by (3+1) cheletropic addition ( TS1 , Δ G ‡ rel = +30.0 kcal/mol) to form pentacoordinate spiro-bicyclic dioxazaphosphetane species INT1 (Figures 7 and 8). Both the P–O (2.39 Å and 2.21 Å) and N–O (1.28 Å and 1.27 Å) bond distances in TS1 are indicative of a concerted mechanism in which the phosphorous concurrently attacks the two oxygen atoms of the nitro group.…”

“…17 In this vein, we recently reported that a simple trialkylphosphine catalyst containing a core four-membered ring, in combination with phenylsilane as a terminal reductant, provided a competent system for the catalytic reductive N–N bond forming heterocyclization of o -nitrobenzaldimines giving 2 H -indazoles. 18 In this chemistry, the phosphacyclic catalyst promotes reductive O -atom transfer from the nitroarene substrates by cycling in the P III /P V =O catalytic couple. The varied catalytic chemistry of phosphine oxides is experiencing rapid expansion, 19 and the potential of P III /P V =O redox methods 20 in particular to favorably impact the process intensity of otherwise stoichiometric phosphorus-mediated transformations has been specifically noted.…”