Diastereoselective formation of anellated tetrahydrofurans using a nitrate radical induced oxidative, self-terminating radical cyclization cascade

Organic Photoredox Catalysis

“…The authors provide an additional example of alkyne reactivity in this system in the cyclization of alkyne 74.1a,b to give tetrahydrofuran 74.2a,b (Scheme 74). 312 This radical cascade was studied previously 330,331 and is thought be initiated by addition of NO 3 • to alkyne 74.1 to give a vinyl radical, which undergoes 1,5 HAT then a 5-exo cyclization. On the basis of significant bleaching of the Mes-Acr-Me + absorption, low yields were attributed to catalyst degradation, possibly by way of oxidation at the mesitylene portion of Mes-Acr-Me + .…”

Intermolecular Radical Additions to Alkynes: Cascade‐Type Radical Cyclizations

“…With larger ring sizes, both yields and diastereoselectivities were reduced. [26][27][28] A similar conformational restriction of the intermediate vinyl radical was also obtained using the Thorpe-Ingold effect 30 provided by two geminal ester groups (not shown). 31 The key step in NO 3 .…”

“…can be used for the oxidative cyclization of cycloalkyl-clamped alkynes 67 (Scheme 2.12). This reaction leads to formation of anelated tetrahydrofurans (68 with X ¼ O) [26][27][28] or pyrrolidines (68 with X ¼ NTs, NTf) 29 possessing four asymmetric centers in good to excellent yields through a cascade consisting of radical addition, rate-determining 1,5-HAT 69 ! 70, 26,28 5-exo cyclization 70 !…”

Self-Terminating, Oxidative Radical Cyclizations

“…To promote intramolecular reactions, a reduction of the possible conformations in the alkyne is essential, which could be simply achieved, for example, by the introduction of cycloalkyl bridges. Thus, following radical addition to the less hindered site of the alkyne bond, alkynyl ethers of type 21 were oxidatively cyclized with excellent diastereoselectivity to the tetrasubstituted tetrahydrofurans of type 22 ( Scheme 5 ) [ 33 ].The yield of this cyclization significantly depended on the conditions of radical generation, which also demonstrated the instability of the radical intermediates towards oxidation. Whereas the electrochemical formation of NO 3 • requires high potentials at the electrodes [ 34 ], a general reduction of the oxidizing environment was possible using the photolysis of CAN as NO 3 • source, because it enables the dosage of the oxidizing radical precursor in high dilution.…”