Synlett 2005(3): 532-534  
DOI: 10.1055/s-2005-862357
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Three-Component Synthesis of (1,3-Oxazol-2-yl)-1,2-dihydro(iso)quinoline and its further Structural Diversifications

Gian Cesare Trona, Jieping Zhu*b
a Dipartimento di Scienze Chimiche, Alimentari, Farmaceutiche e Farmacologiche, Università degli Studi del Piemonte Orientale, V. Le Ferrucci 33, 28100, Novara, Italy
b Institut de Chimie des Substances Naturelles, CNRS, 91198 Gif-sur-Yvette Cedex, France
Fax: +33(1)69077247; e-Mail: zhu@icsn.cnrs-gif.fr;
Further Information

Publication History

Received 27 November 2004
Publication Date:
04 February 2005 (online)

Abstract

A Reissert-type three-component synthesis of 1,3-oxazol-2-yl-1,2-dihydro(iso)quinoline is developed using α-isocyano β-phenyl propionamide as an isonitrile input. The structure of this multicomponent adduct is further diversified taking advantage of the rich chemistry of oxazole.

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The role of molecular sieve is unknown. It may remove adventitious water or act as a scavenger of HCl produced in situ. It is worthy of note that the same reaction did not occur in the presence of triethylamine.

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Typical Procedure for the Synthesis of 4.
To a solution of isoquinoline (1, 97.0 µL, 105.7 mg, 0.82 mmol) in dry CH2Cl2 (2.0 mL) at -40 °C were added powdered molecular sieves (4 Å, 200 mg) and methyl chloroformate (2, 155.0 mg, 126.7 µL, 1.64 mmol,) successively. The resulting yellow solution was stirred for 5 min and a solution of α-isocyano β-phenyl propionamide (3, 200.0 mg, 0.82 mmol) in dry CH2Cl2 (3.0 mL) was added drop-wise. After being stirred for 1.5 h, the reaction was quenched by addition of sat. aq NaHCO3 solution and extracted with CH2Cl2. The combined organic extracts were washed with HCl (2 N), sat. aq NH4Cl solution, dried over Na2SO4, and the volatile was evaporated under reduced pressure. The crude product was purified by flash chromatography (heptane-EtOAc = 6:4) to give 4 as a yellowish solid (263.0 mg, 76%): mp 110-112 °C. IR: 1713, 1633, 1440, 1347, 1235, 1113, 970 cm-1. 1H NMR (300 MHz, CDCl3): two rotamers, δ = 7.27-7.06 (9 H, m), 6.95, 6.91 (1 H, d, J = 7.7 Hz), 6.41, 6.29 (1 H, br s), 5.82 (1 H, d, J = 7.7), 5.75 (1 H, d, J = 7.7), 3.75, 3.71 (2 H, s), 3.66 (3 H, s), 3.53 (4 H, m), 2.74 (4 H, m). MS (ESI): m/z (%) = 454 (100) [M + Na+].