Diazo Strategy for Intramolecular Azirine Ring Expansion: Rh(II)-Catalyzed Synthesis of 2-Hydroxy-3-oxo-2,3-dihydro-1H-pyrrole-2-carboxylates

Abstract

A diazo strategy for the intramolecular azirine ring expansion was developed. Azirinyl-substituted diazodicarbonyl compounds, prepared from diazoacetylazirines, were converted in excellent yields to 2-hydroxy-3-oxo-2,3-dihydro-1H-pyrrole-2-carboxylates under Rh catalysis in the presence of water. According to DFT calculations, the formation of only pyrrolinone derivatives and the absence of O−H insertion products of Rh carbene into water are due to the low Gibbs free energy of the transition state for the concerted opening of the azirine ring and recyclization to pyrrolone in intermediate Rh complexes.

Divergent Diazo Approach toward Alkyl 5/4-Hydroxy-3H-benzo[e]indole-4/5-carboxylates

“…Mesitylene was commercial grade and used as received. Physical and spectral data of 2-diazoacetyl-2 H azirines 7a – 7e , 7g – 7e , and methyl 2-diazo-3-oxo-3-(2 H -azirin-2-yl)­propanoates 1a , 1k prepared according to the published procedures were in agreement with previously reported values. Diketones 8a–8d were commercial and used as received.…”

“…Compound 1f was prepared following the slightly modified published procedure from 2-diazo-1-(3-(3,4-dimethoxyphenyl)-2 H -azirin-2-yl)­ethan-1-one 7f (500 mg, 2.04 mmol), methyl iodide (2.54 mL, 40.8 mmol), and Cs 2 CO 3 (1.33 g, 4.08 mmol) in acetonitrile (20 mL) at 75 °C (oil bath temperature) for 24 h to give a pure product in 580 mg (94% yield), after column chromatography on silica (light petroleum/ethyl acetate, 10:1 (v/v)) as a light brown solid: mp 103–104 °C (light petroleum/ethyl acetate); 1 H NMR (CDCl 3 , 400 MHz) δ 7.44–7.43 (m, 1H), 7.40–7.38 (m, 1H), 6.99–6.97 (m, 1H), 4.11 (s, 1H), 3.96 (s, 3H), 3.95 (s, 3H), 3.93 (s, 3H); 13 C­{ 1 H} NMR (CDCl 3 , 100 MHz) δ 189.4 (C), 162.0 (C), 155.8 (C), 153.7 (C), 149.6 (C), 125.6 (CH), 114.5 (C), 111.7 (CH), 111.0 (CH), 56.12 (CH 3 ), 56.10 (CH 3 ), 52.4 (CH), 34.0 (CH 3 ); HRMS (ESI) m / z [M + Na] + calcd for C 14 H 13 N 3 NaO 5 + 326.0747, found 326.0756.…”

“…Earlier, an approach to substituted 4-hydroxybenzo­[ e ]­indoles and their heteroanalogues was found via an intramolecular aromatic substitution reaction of 2-(diazoacetyl)­pyrroles, derived from 2-(diazoacetyl)-2 H -azirines . Recently, a method has been developed for the preparation of their alkoxycarbonyl-substituted analogues, alkyl 2-diazo-3-oxo-3-(2 H -azirin-2-yl)­propanoates 1 . We hypothesized that pyrroles 2 , derived from azirines 1 and 1,3-dicarbonyl compounds, could be potentially used for the preparation of 3 H -benzo­[ e ]­indoles with 4/5-alkoxycarboxyl and 5/4-hydroxyl ( 4 and 6 ) substituents (Scheme , eq 3).…”

“…6f Recently, a method has been developed for the preparation of their alkoxycarbonyl-substituted analogues, alkyl 2-diazo-3-oxo-3-(2H-azirin-2-yl)propanoates 1. 7 We hypothesized that pyrroles 2, derived from azirines 1 and 1,3-dicarbonyl compounds, could be potentially used for the preparation of 3H-benzo [e]indoles with 4/5-alkoxycarboxyl and 5/4-hydroxyl (4 and 6) substituents (Scheme 1, eq 3).…”

I2‐DMSO‐Mediated Cascade Cyclization of β‐Ketosulfoxonium Ylides and β‐Enaminones: Synthesis of Quaternary‐Carbon‐Centered 2‐Hydroxy‐pyrrol‐3(2H)‐ones

“…In order to avoid keto‐enol tautomerism, a quaternary carbon center has been introduced into the 1 H ‐pyrrol‐3(2 H )‐ones at the position 2, which serves to overcome these issues. Very recently, Khlebnikov and co‐workers described an elegant strategy for the preparation of 2‐hydroxy‐pyrrol‐3(2 H )‐one scaffold via exploiting intramolecular diazo azirine derivatives ring expansion catalyzed by Rh(II)‐catalyst [7a] . Despite notable progress, the development of a simple, flexible, and metal‐free synthetic strategy for these molecules remains highly desirable due to its immense potential in discovering biologically active compounds.…”