Radical‐Mediated 1,2‐Formyl/Carbonyl Functionalization of Alkenes and Application to the Construction of Medium‐Sized Rings

Abstract

An ovel radical 1,2-formylfunctionalization of alkenes involving 1,2(4,5)-formyl migration triggered by addition of various carbon-and heteroatom-centered radicals to alkenes has been developed for the first time,thus providing straightforwarda ccess to diverse b-functionalized aldehydes with good efficiency,r emarkable selectivity,a nd excellent functional group tolerance.A nalogous transformations mediated by ak eto-carbonyl migration have also been effected under similar conditions.This method was used to access ring systems including various benzannulated nine-, ten-, and eleven-membered rings,c omplex 6-5(6,7)-6(5) fused rings, and bridged rings with diverse functionalities.

Ring‐Expansion Approach to Medium‐Sized Lactams and Analysis of Their Medicinal Lead‐Like Properties

“…The expansion of smaller ring systemsi sa na ttractive alternativef or the constructiono fl arger ring compounds,m ost notably becauset he difficult end-to-end cyclisation step that blights traditional approachesc an be completely avoided. [14,15] In 2015, our group reported one such approach, that enables the insertion of aminoa cid and hydroxy acid derivedthree-or four-atomf ragments into cyclic b-keto estersv ia at elescoped acylation/ring expansion sequence to form lactamsa nd lactones (1 + 2!4;S cheme 1). [16] An otable featureo ft his method is that the cyclic b-keto ester motif present in the startingm ateriali sr eplicatedi nt he ring-enlarged product, hence,s uccessive ring expansion (SuRE) reactionsc an be performed (e.g., 4!5); repeating the same C-acylation/ring-expansion sequence with different amino/hydroxy acidf ragments on the product meanst hat rings of any size are potentially accessible.…”

Direct Photocatalytic Synthesis of Medium‐Sized Lactams by C−C Bond Cleavage

“…Nonetheless,c ompared with the first type,t hese two normally require multistep preparation of expansion substrates from cyclic ketones.B esides,a ll these three types of methodologies fail to provide ap ractically efficient route toward eight-membered lactams,w hich have raised recent synthetic interest. [6h] With our continuing efforts [10] in developing radical-initiated skeletal reorganization for the construction of carbo-and heterocyclic systems, [11] we herein report ag eneral and efficient two-step N + 3r ingexpansion strategy for convenient access to all ring members of medium-sized, that is,8 -11-membered, lactams from readily available cyclic (hetero)aryl ketones under mild visible-light conditions [12] (Scheme 2d)b yarare remote radical (hetero)aryl migration from Ct oN . [13] On this basis, we have also developed an N + 4r ing-expansion strategy leading to 13-15-membered macrolactams upon further onestep manipulation.…”

A remote C–C bond cleavage–enabled skeletal reorganization: Access to medium-/large-sized cyclic alkenes

“…Further screening of reaction parameters ( Table 1 , entries 2 to 15), through variation of the copper catalysts, the molar ratio of the reactants, organic solvents, reaction temperature, and time, has led to the identification of the optimal reaction conditions as follows: The reaction of 1A and 2 with a molar ratio of 1.0:2.4 ( 2 was added in two portions with a time interval of 10 hours) in the presence of CuCN (10 mol %) in 1,4-dioxane at 80°C for 20 hours to afford 3A in 69% yield (entry 15). Note that the intramolecular radical 1,3-migration process of other carbon-based groups has rarely been achieved in previously reported processes, probably due to the strained four-membered cyclic transition state involved in this process ( 26 , 31 ). In sharp contrast, the present radical vinyl migration process was surprisingly viable enough to accommodate such an unfavorable pathway, thus substantially expanding the scope of carbon-based functional group migration process.…”