Assembly of functionalized carbocycles or N-heterocycles through a domino electrocyclization–[1,2] migration reaction sequence

Abstract

The development of processes that streamline the synthesis of complex, functionalized carbocycles and heterocycles remains a hotly pursued topic because their scaffolds are present in a range of bioactive molecules and electronic materials. Although the Nazarov reaction has emerged to be useful in the synthesis of carbocycles and heterocycles, using an electrocyclization to trigger a migration remains underdeveloped. By constructing several bonds in one operation, domino reaction sequences are particularly effective at improving the efficiency of synthesis. The use of transition metal catalysts has the potential to render these processes stereoselective. This review examines the use of electrocyclization-[1,2] migrations to construct molecules and is organized by the type of ring constructed and the order of the two steps in this process.

Cyclisation Reactions Involving Alkyl Enol Ethers

“…Electrocyclic reactions are an important subclass of pericyclic reactions and have received much attention in organic synthesis owing to their inherent ability to rapidly generate molecular complexity with a high degree of stereospecificity. [63] As the above-described cycloadditions, they proceed in a concerted fashion with a cyclic array of π-electrons in the transition state. In electrocyclic ring closing reactions a new σbond is formed between the termini of an acyclic conjugated π-system, while a π-bond is broken.…”

TiCl3‐Mediated Synthesis of 2,3,3‐Trisubstituted Indolenines: Total Synthesis of (+)‐1,2‐Dehydroaspidospermidine, (+)‐Condyfoline, and (−)‐Tubifoline

“…We have recently reported an efficient synthesis of 2,3‐disubstituted indoles 9 by aqueous TiCl 3 ‐mediated reductive cyclization of 2‐nitrophenyl‐substituted alkenes 10 or 11 (Scheme c). The reaction was thought to go through the nitrone intermediates 12 and 13 , respectively The mild conditions (room temperature), functional‐group compatibility and high yield render it a valuable alternative to the classic Cadogan–Sundberg indole synthesis [P(OEt) 3 , reflux] . Aimed at the development of general and direct access to polycyclic 2,3,3‐trisubstituted indolenine 14 , a ubiquitous motif found in many MIAs, we became interested in investigating the reductive cyclization of tetrasubstituted alkenes 15 (Scheme d).…”

“…Ther eaction was thought to go through the nitrone intermediates 12 and 13,r espectively [7,8] Them ild conditions (room temperature), functional-group compatibility and high yield render it avaluable alternative to the classic Cadogan-Sundberg indole synthesis [P(OEt) 3 ,r eflux]. [9,10] Aimed at the development of general and direct access to polycyclic 2,3,3-trisubstituted indolenine 14,aubiquitous motif found in many MIAs,w eb ecame interested in investigating the reductive cyclization of tetrasubstituted alkenes 15 (Scheme 1d). Theh ypothetic pathway involved selective reduction of nitroarene 15 to nitroso compound 16 followed by 6p-electron-5-atom electrocyclization [11] and 1,2-alkyl migration of the resulting nitrone 17 to 18.R eduction of the latter would then afford the desired 2,3,3-trisubstituted indolenine 14 in as ingle operation.…”

Rh2(II)-Catalyzed Ring Expansion of Cyclobutanol-Substituted Aryl Azides To Access Medium-Sized N-Heterocycles

“…The development of processes that tease new reactivity out of catalytic intermediates continues to spur synthetic chemists toward innovative solutions that access N -heterocycles . Constructing these scaffolds using metal divalent catalytic intermediates to trigger domino reactions is rare despite the potential of these reactions to dramatically increase the complexity of the substrates . Azides are emerging as valuable precursors for nitrenes in transition-metal-catalyzed N-atom-transfer reactions, but an electron-withdrawing N-substituent is generally required for the best outcome. , Our investigations into the reactivity of rhodium N -aryl nitrenes have established them as valuable electrophilic catalytic intermediates for the synthesis of complex indoles from readily accessible styryl azides. , During the course of our studies, we were curious if the electrophilicity of 2 could be harnessed to participate in other bond-forming reactions instead of initiating electrocyclization–migration or C–H bond amination reactions.…”