Synlett 2019; 30(10): 1204-1208
DOI: 10.1055/s-0037-1611791
cluster
© Georg Thieme Verlag Stuttgart · New York

Diastereodivergent Synthesis of Bromoiminolactones: Electrochemical and Chemical Bromoiminolactonization of α-Allylmalonamides

,
Keiko Ishimaru
,
Satoshi Mizuta
,
Daishirou Minato
,
,
Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan   Email: onomura@nagasaki-u.ac.jp
› Author Affiliations

This research was supported by JSPS KAKENHI (16K08167, 15K07862, and 17H06961).
Further Information

Publication History

Received: 31 January 2019

Accepted after revision: 24 March 2019

Publication Date:
18 April 2019 (online)


Published as part of the Cluster Electrochemical Synthesis and Catalysis

Abstract

A diastereodivergent synthesis of N-substituted iminolactones by bromoiminolactonization of α-substituted α-allylmalonamides is reported. Whereas bromocyclization under conventional chemical conditions provided cis-bromoiminolactones, electrochemical conditions exhibited complementary diastereoselectivity to afford the trans-products. A variety of substituents on the nitrogen atoms and an α-position of the malonamide were tolerated under both sets of conditions to afford the corresponding iminolactones in excellent yields and high diastereoselectivities.

Supporting Information

 
  • References and Notes

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  • 23 Bromoiminolactonization of Compounds 1; General Procedure under Chemical Conditions NBS (178 mg, 2.0 equiv) was added to a solution of 1 (0.5 mmol) in toluene (6 mL), and the mixture was stirred at rt until all the starting material was consumed (TLC). The reaction was quenched with sat. aq Na2S2O3, and the resulting mixture was extracted with EtOAc. The combined organic layers were dried (MgSO4), filtered, and concentrated under reduced pressure. The residue was purified by column chromatography [silica gel, hexane–EtOAc] to afford 2 and 2′. Bromoiminolactonization of Compounds 1; General Procedure under Electrochemical Conditions In a beaker-type undivided cell, substrate 1 (0.5 mmol), Et4NBr (322 mg, 2.0 equiv), Zn(OTf)2 (18.2 mg, 10 mol%), and 2,2′-bipyridine (7.8 mg, 10 mol%) were dissolved in CH2Cl2 (6 mL), and the mixture was stirred for 20 min. The reaction vessel was fitted with a Pt plate electrode (1.0 × 2.0 cm2), and 4 F/mol of electricity was supplied under constant-current conditions (20 mA). The reaction was then quenched with sat. aq Na2S2O3 and the resulting mixture was extracted with CH2Cl2. The combined organic layers were dried (MgSO4), filtered, and concentrated under reduced pressure. The residue was purified by column chromatography [silica gel, hexane–EtOAc] to afford 2 and 2′. (cis)-5-(Bromomethyl)-3-ethyl-N-phenyl-2-(phenylimino)tetrahydrofuran-3-carboxamide (2b) (Prepared under Chemical Conditions) Colorless oil; yield: 187 mg (93%). IR (ATR): 692, 756, 1198, 1445, 1487, 1551, 1599, 1686, 3065 cm–1. 1H NMR (400 MHz, CDCl3): δ = 10.66 (s, 1 H), 7.59 (dd, J = 8.5, 1.2 Hz, 2 H), 7.39–7.32 (m, 4 H), 7.26–7.24 (m, 2 H), 7.18–7.14 (m, 1 H), 7.13–7.09 (m, 1 H), 4.76–4.69 (m, 1 H), 3.50 (d, J = 5.4 Hz, 2 H), 2.79 (dd, J = 13.9, 8.0 Hz, 1 H), 2.48 (dd, J = 13.7, 6.8 Hz, 1 H), 2.19–2.05 (m, 2 H), 1.10 (t, J = 7.3 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 168.2, 163.0, 144.5, 137.8, 128.9, 128.7, 124.8, 124.1, 123.2, 119.5, 78.1, 56.5, 35.0, 34.9, 33.7, 9.25. HRMS (EI): m/z [M]+ calcd for C20H21 81BrN2O2: 402.0766; found: 402.0763. (trans)-5-(Bromomethyl)-3-ethyl-N-phenyl-2-(phenylimino)tetrahydrofuran-3-carboxamide (2b′) (Prepared under Electrochemical Conditions) Colorless oil; yield: 146 mg (73%). IR (ATR): 692, 756, 1198, 1443, 1489, 1541, 1599, 1684, 3323 cm–1. 1H NMR (400 MHz, CDCl3): δ = 9.49 (s, 1 H), 7.56 (d, J = 8.3 Hz, 2 H), 7.37–7.33 (m, 4 H), 7.23 (t, J = 9.0 Hz, 2 H), 7.16–7.10 (m, 2 H), 4.62–4.56 (m, 1 H), 3.66 (dd, J = 10.7, 4.8 Hz, 1 H), 3.57 (dd, J = 11.2, 3.9 Hz, 1 H), 3.34 (dd, J = 13.2, 6.3 Hz, 1 H), 2.32–2.22 (m, 1 H), 2.10–1.96 (m, 2 H), 1.05 (t, J = 7.3 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 167.0, 163.6, 145.1, 137.7, 129.0, 128.7, 124.6, 124.3, 123.1, 119.3, 78.6, 58.3, 34.0, 33.6, 33.1, 9.5. HRMS (EI): m/z [M]+ calcd for C20H21 81BrN2O2: 402.0766; found: 402.0763.