Solvent influence in the Rh-catalyzed intramolecular 1,6 C–H insertions: a general approach to the chromane and flavanone skeletons

Enantioselective synthesis of isochromans and tetrahydroisoquinolines by C–H insertion of donor/donor carbenes

“…15,16 Although C-H insertion reactions have been used in the synthesis of a wide variety of ve-membered ring (1,5-C-H insertion) heterocycles, 1,7,10 there are few examples of sixmembered ring (1,6-C-H insertion) formation and the substrates are limited to oxygen-containing rings. [17][18][19][20][21][22][23][24] Accessing 1,6-C-H insertion is difficult due to the kinetic favorability of 1,5-C-H insertion and the potential for rearrangement products when heteroatoms are present ( Fig. 1).…”

“…24,30 Despite these challenges, there are scattered reports of forming tetrahydropyran, chroman, and chromanone cores through 1,6-C-H insertion using donor/acceptor or acceptor carbenes. 18,20,[22][23][24][31][32][33] In 2012, Cossy and coworkers demonstrated the use of donor carbenes generated from cyclopropenes in the synthesis of tetrahydropyrans by C-H insertion, 22,31 further expanding the diazo-free insertion work demonstrated by Zhu. 34,35 In the cases where chiral catalysts were used, enantioselectivity was oen moderate; 19,20 it wasn't until 2015 when Hashimoto achieved higher levels of enantioselectivity using Rh 2 (S-PTTL) 4 (up to 97 : 3 er).…”

“… 18 , 20 , 22 – 24 , 31 – 33 In 2012, Cossy and coworkers demonstrated the use of donor carbenes generated from cyclopropenes in the synthesis of tetrahydropyrans by C–H insertion, 22 , 31 further expanding the diazo-free insertion work demonstrated by Zhu. 34 , 35 In the cases where chiral catalysts were used, enantioselectivity was often moderate; 19 , 20 it wasn't until 2015 when Hashimoto achieved higher levels of enantioselectivity using Rh 2 ( S -PTTL) 4 (up to 97 : 3 er). 24 We hypothesized that using donor/donor carbenes would reduce the electrophilicity of the rhodium carbene enough to allow C–H insertion to proceed selectively without interference by the heteroatom.…”

Diastereo- and enantioselective intramolecular 1,6-C–H insertion reactions of α-diazo esters catalyzed by chiral dirhodium(II) carboxylates

“…Recently, Rodríguez-García and co-workers reported that 1,6-C-H insertion of a-alkyl-a-diazo ester could compete with b-hydride elimination when hydrocarbons were used as a solvent. 17 In continuation of our studies on asymmetric C-H insertions, 6-9 we herein report a chemo-, diastereo-and enantioselective intramolecular 1,6-C-H insertion of a-diazo esters, in which Rh 2 (S-PTTL) 4 provides oxygen-containing six-membered heterocycles with up to 95% ee and perfect cis diastereoselectivity.…”

Effects of Axial Solvent Coordination to Dirhodium Complexes on Reactivity and Selectivity in C–H Insertion Reactions: A Computational Study

“…76 The effects of axial coordination by solvent on Rh-carbene reactivity and selectivity should be considered, since it has been shown that reaction outcome can highly depend on the solvent. 26,[77][78][79] Weakly Lewis basic and non-polar/low-polarity solvents, expected to be poorly coordinating, such as dichloromethane or hexane, are generally considered the most efficient reaction media for C-H functionalization. 29 Still, there are examples reported of C-H insertion 80,81 and cyclopropanation 82 reactions in water, a highly coordinating, polar solvent.…”