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

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).…”

“…[25][26][27][28][29] Installing heteroatoms can eliminate 1,5-C-H insertion however this introduces the possibility of nucleophilic attack on the carbene by the heteroatom. 17,19,24 This reaction forms an ylide that undergoes the Stevens rearrangement (or a Stevens-type rearrangement when the heteroatom is oxygen), forming a ve-membered ring (5). 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.…”

“…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).…”

Rh-Catalyzed Intermolecular Reactions of α-Alkyl-α-Diazo Carbonyl Compounds with Selectivity over β-Hydride Migration

“…38a With Rh 2 ( S -PTTL) 4 , at temperatures below –40 °C, β-hydride migration was suppressed and tetrahydropyrans were formed in high yields. Ligand and temperature effects are displayed in Scheme 24.…”

“…38b He demonstrated α-diazopropionates combine with 1,4-cyclohexadiene with good selectivity over β-hydride migration. However, in the case α-diazobutanoates and α-diazopentanoates, β-hydride migration dominated (Scheme 25).…”