Fused vs. spiro: Kinetic, not thermodynamic preference may direct the reaction of α-carbonyl oxonium ylides

Spirocyclizations Involving Oxonium Ylides Derived from Cyclic α-Diazocarbonyl Compounds: An Entry into 6-Oxa-2-azaspiro[4.5]decane Scaffold

“…1 H NMR (400 MHz, CDCl 3 ) δ 8.44 (dd, J = 7.8, 1.7 Hz, 1H), 8.34 (s, 1H,  CH), 7.56−7.49 (m, 2H), 7.48−7.39 (m, 4H), 7.06 (td, J = 7.6, 1.1 Hz, 1H), 6.97 (dd, J = 8.4, 1.0 Hz, 1H), 4.61 (ddd, J = 12.6, 11.4, 2.6 Hz, 1H), 4.12 (dd, J = 11.5, 4.5 Hz, 1H), 3.92 (s, 3H, OCH 3 ), 2.44−2.28 (m, 1H), 2.22 (td, J = 14.1, 4.2 Hz, 1H), 1.91−1.76 (m, 1H), 1.77−1.67 (m, 3H). 13 Yield of CH-insertion product 6h: 47 mg (28%), dr 3:1, white amorphous solid. Diastereomers were separated by HPLC.…”

“…All commercial reagents were used without purification. NMR spectrum were recorded using a Bruker Avance III spectrometer in CDCl 3 ( 1 H: 400.13 MHz, 13 C: 100.61 MHz, 19 F: 376.50 MHz); chemical shifts are reported as parts per million (δ, ppm); the residual solvent peak (CHCl 3 ) was used as internal standard: 7.26 for 1 H and 77.16 ppm for 13 C; multiplicities are abbreviated as follows: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad, dd = doublet of doublets, dt = doublet of triplets, ddd = doublet/doublets of doublets; and coupling constants, J, are reported in Hz. Mass spectra were recorded using a Bruker microTOF spectrometer (ionization by electrospray, positive ion detection).…”

“…1 H NMR (400 MHz, CDCl 3 ) δ 7.80 (d, J = 1.9 Hz, 1H), 7.61 (dd, J = 8.0, 1.7 Hz, 2H), 7.53−7.36 (m, 5H), 7.24− 7.17 (m, 2H), 4.44 (ddd, J = 8.2, 6.3, 3.9 Hz, 1H), 4.34 (dd, J = 3.9, 2.0 Hz, 1H), 3.89−3.78 (m, 1H), 3.73 (td, J = 7.7, 5.6 Hz, 1H), 1.97−1.79 (m, 3H), 1.66−1.57 (m, 1H). 13 Syntheses of compounds 2a and 6a on a 2 mmol scale: performed according to the general procedure from 1a (615 mg, 2 mmol). Reaction time: 1 h; yield of 2a 474 mg (67%), yield of 6a 182 mg (26%) obtained as a diastereomeric mixture (dr 3.8:1).…”

“…Until recently, only two examples of such spirocyclizations were reported in literature: (a) carbene insertion into the C–O bond of tetrahydrofuran under photochemical conditions and (b) Rh 2 (OAc) 4 -catalyzed C–O insertion of 6-diazopenicillinate into the benzofuran core . We reasoned that this gaping synthetic methodology void (particularly puzzling in light of the recently reported thiaspirocycle synthesis from cyclic sulfonium ylides) could be attributed to the possible preference of the respective oxonium ylides to follow pathway b , i.e., [1,4]-shift, rather than the Stevens rearrangement, and afford a fused bicyclic rather than a spirocyclic system. , However, in 2019, we discovered and reported the first systematically studied example of Rh­(II)-catalyzed spirocyclization of α-diazo homophthalimides with cyclic ethers and demonstrated, using quantum chemical calculations performed at the B3LYP/6-31G* level of theory, that said spirocyclization (Stevens type rearrangement, pathway a ) was indeed preferred over the formation of a fused bicycle ([1.4]-shift, pathway b ) . Inspired by this significant advancement in the oxonium ylide chemistry, we continued searching for cyclic α-diazocarbonyl compounds capable of undergoing similar spirocyclizations with cyclic ethers.…”

“…6a,b However, in 2019, we discovered and reported the first systematically studied example of Rh(II)-catalyzed spirocyclization of α-diazo homophthalimides with cyclic ethers 12 and demonstrated, using quantum chemical calculations performed at the B3LYP/6-31G* level of theory, that said spirocyclization (Stevens type rearrangement, pathway a) was indeed preferred over the formation of a fused bicycle ([1.4]-shift, pathway b). 13 Inspired by this significant advancement in the oxonium ylide chemistry, we continued searching for cyclic α-diazocarbonyl compounds capable of undergoing similar spirocyclizations with cyclic ethers. Recently, we 14 and others 15 reported the preparation of (E)-3-arylidene-4-diazopyrrolidine-2,5-diones 1 from N-substituted maleimides via the Wittig reaction and Regitz diazo transfer reaction.…”