Three-Component Photochemical 1,2,5-Trifunctionalizations of Alkenes toward Densely Functionalized Lynchpins

Abstract

Radical remote 1,n-difunctionalization reactions (n > 2) of alkenes are powerful tools to efficiently introduce functional groups with selected distances into target molecules. Among these reactions, 1,5-difunctionalizations are an important subclass, leading to sought-after scaffolds, but typically suffer from tailored starting materials and strict limitations for the formed functional group in 2-position. Seeking to address these issues and to make radical 1,5-difunctionalizations of alkenes more applicable, we report a novel three-component 1,2,5-trifunctionalization reaction between imine-based bifunctional reagents and two distinct alkenes, driven by visible light energy transfer-catalysis. Key to achieving this selective one-step installation of three different functional groups via the choreographed formation of four bonds was the utilization of a 1,2-boron shift and the rigorous capitalization of radical polarities and stabilities. Thorough mechanistic studies were carried out, and the synthetic utility of the obtained products was demonstrated by various downstream modifications. Notably, in addition to the functionalization of individual functional groups, their interplay gave rise to a unique array of cyclic products.

γ-Amino Alcohols via Energy Transfer Enabled Brook Rearrangement

“…Visible light induced energy transfer (EnT) processes are well-known for their ability to induce excited state reactivity under mild conditions. , Based on our group’s expertise in this field, we chose to investigate an innovative approach in this stride, as to date, there exist no reports leading to 1,3-amino alcohols by using this strategy. Photocatalysis-driven N–X (X = O and S) bond homolysis has gained wide recognition in the past few years. − This neat strategy enables the installation of two fragments of interest across the alkenes for difunctionalization reactions (Figure C). The primary barrier to the ease of such simultaneous addition reactions would be a nondesired radical–radical homocoupling, which may be intercepted by a kinetic phenomenon known as the persistent radical effect (PRE) .…”

“…In this scenario, the challenge comprises the construction of a 1,3-linkage across a double bond to achieve the targeted γ-amino alcohols, since previous reports have illustrated only 1,2 additions and 1,4 additions in cases of two distinct alkenes. There is a recent stand-alone report of a 1,2,5-trifunctionalization across two alkenes; however, this is a special case with a 1,2-boron shift within an allylic boronic species, which stands of course as a prerequisite . While it is established that bifunctional reagents containing a photolabile N–X bond form chemically distinct entities that stay intact during the addition across an olefin, we desired for an exception.…”

N -Heterocyclic carbene catalytic 1,2-boron migrative acylation accelerated by photocatalysis

“…While extensive research has been conducted on 1,2-migrations involving tetracoordinated borate species, investigations into radical-induced 1,2-boron migrations have remained relatively limited ( 24 – 26 ). In 1999, Batey and Smil ( 27 ) reported the first radical strategy for 1,2-boryl migration.…”

Photoredox-Catalyzed Strain-Release-Driven Synthesis of Functionalized Spirocyclobutyl Oxindoles

“…Although the complete suppression of the direct addition product was achieved by employing S-phenyl 4-fluorobenzenesulfonothioate 2b, the yield of the desired product was not improved (Figure 1 did not provide the desired spirocyclobutyl oxindole product 3a (Figure 1, columns 3 and 4). The lack of reactivity observed with 2c could be due to its high reduction potential (E 1/2 = −2.03 V vs SCE), 14 whereas the lack of reactivity of the radical precursor 2d can be attributed to its poor solubility in acetonitrile. Next, our focus shifted toward employing N-(diphenylmethylene)-4-fluorobenzenesulfonamide (2e), previously used by the groups of Glorius 15a and Du 15b for the difunctionalization of olefins via energy transfer photocatalysis.…”

“…The excellent reactivity of 2e can be attributed to its low reduction potential (E 1/2 = −1.22 V vs SCE). 14 These promising results encouraged us to optimize the reaction conditions further by employing tunable metalbased photocatalysts. Among the photocatalysts screened (Figure 1, columns 6−10), Ir(ppy) 3 emerged as the best photocatalyst with the quantitative formation of the desired product 3a.…”