A Short and Efficient Synthesis of Isoindolin-1-ones

Takayuki Tsuritani; Satoshi Kii; Atsushi Akao; Kimihiko Sato; Nobuaki Nonoyama; Toshiaki Mase; Nobuyoshi Yasuda

doi:10.1055/s-2006-933114

LETTER

A Short and Efficient Synthesis of Isoindolin-1-ones

Takayuki Tsuritani*^a, Satoshi Kii^a, Atsushi Akao^a, Kimihiko Sato^a, Nobuaki Nonoyama^a, Toshiaki Mase^a, Nobuyoshi Yasuda^b
^a Process Research, Banyu Pharmaceutical Co. Ltd., 9-1, Kamimutsuna 3-Chome, Okazaki, Aichi 444-0858, Japan
^b Merck Research Laboratories, Department of Process Chemistry, P.O. Box 2000, Rahway, NJ 07065, USA
Fax: +81(564)517086; e-Mail: takayuki_tsuritani@merck.com;

Abstract

Alle Artikel dieser Rubrik

Abstract

Here, we report a short and efficient synthesis of isoindolin-1-ones. Base-induced cyclization of o-hydroxymethylbenzamides, which was easily prepared from the corresponding phthalides and amines, led predominantly to N-alkylation in good yield. The reaction proceeded under mild conditions and bromine and nitrile substituents were tolerated. The selectivity is explained by HASB theory.

Key words

lactams - cyclizations - lactones - phosphate - N-selective alkylation

Volltext

Referenzen

References and Notes

1a Luzzio FA. Piatt Zachert D. Tetrahedron Lett. 1998, 39: 2285

1b Campbell JB. Dedinas RF. Trumbower-Walsh SA. J. Org. Chem. 1996, 61: 6205

1c Decroix B. Pigeon P. . Tetrahedron Lett. 1996, 37: 7707

1d Decroix B. Pigeon P. Othman M. Tetrahedron 1997, 53: 2495

1e Allin SM. Northfield CJ. Page MI. Slawin AMZ. Tetrahedron Lett. 1997, 38: 3627

1f Kundu NG. Khan MW. Tetrahedron Lett. 1997, 38: 6937

1g Kitching MS. Clegg W. Elsewood MRJ. Griffin RJ. Golding BT. Synlett 1999, 997

2a Nannin G. Griraldi PN. Molgora G. Biasoli G. Spinelli F. Logemann L. Dradi E. Zanni G. Buttinoni A. Tommasini R. Arzneim. Forsch. 1973, 23: 1090

2b

Hisamitsu Pharmaceutical Co., Inc. Japan Kokai Tokyo Koho 149257, 1980; Chem. Abstr. 1981, 94, 174879; address: P. J. Kocienski, School of Chemistry, Univerity of Leeds, Leeds LS2 9JT, UK.

3 Schmahl H.-J. Denker L. Plum C. Chahoud I. Nau H. Arch. Toxicol. 1996, 11: 749

4 Plowman J. Paull KD. Atassi G. Harrison S. Dykes D. Kabbe N. Narayan VL. Yoder O. Invest. New Drugs 1988, 6: 147

5a Ganesan A. Wang H. Tetrahedron Lett. 1998, 39: 9097

5b Anzani M. Capelli A. Vomero S. Heterocycles 1994, 38: 103

6 Horii Z. Iwata C. Tamura Y. J. Org. Chem. 1961, 26: 2273

7 Orito K. Horibata A. Nakamura T. Ushito H. Nagasaki H. Yuguchi M. Yamashita S. Tokuda M. J. Am. Chem. Soc. 2004, 126: 14342

8 Hoarau C. Couture A. Deniau E. Grandclaudon P. Synthesis 2000, 655

9a Späth E. Lintner J. Ber. Dtsch. Chem. Ges. B 1936, 69: 2727

9b Barrios I. Camps P. Comes-Franchini M. Muñoz-Torrero D. Ricci A. Sánchez L. Tetrahedron 2003, 59: 1971

10 See for mechanical study: Decker M. Nguyen TTH. Lehmann J. Tetrahedron 2004, 60: 4567

11 Lesimple P. Bigg DCH. Synthesis 1991, 306

12

See ref. 6 for preparation of 6i.

13 Kornblum N. Smiley RA. Blackwood RK. Iffland DC. J. Am. Chem. Soc. 1955, 77: 6269

14

When 1 equiv of Grignard reagent was employed, O-protected compound 8 was obtained predominantly in entry 5.

15

Typical Experimental Procedure. To a three-necked 50-mL round-bottomed flask equipped with dropping funnel were charged DMI (15 mL) and o-hydroxymethylbenzamide 6a (1.35 g, 5.00 mmol). The resulting solution was cooled to 0 °C, and then 1.98 M of i-PrMgCl-THF (5.63 mL, 11.15 mol, 2.23 equiv to 6a) was added dropwise. The resulting solution was warmed to ambient temperature and stirred for 0.5 h. The solution was cooled to 0 °C, and then ClP(O)(NMe₂)₂ (0.94 mL, 6.50 mmol, 1.3 equiv to 6a) was added dropwise. The mixture was warmed to ambient temperature, and stirred for 14 h. The resulting solution was quenched by 2 N aq HCl (10 mL). The mixture was extracted with i-PrOAc (3 × 10 mL), and the combined i-PrOAc extracts were washed with H₂O (2 × 10 mL) and dried over anhyd Na₂SO₄. Removal of the solvent and subsequent silica gel chromatography (heptane and EtOAc) afforded the corresponding lactam 1a in a pure form.

16

Spectroscopic Data for New Compounds.
Compound 6c: IR (neat): 1673, 1608, 1510, 1451, 1411, 1356, 1308, 1274, 1242, 1175, 1033, 1007, 837, 813, 768, 673 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 3.79 (s, 3 H), 4.22 (s, 2 H), 4.72 (s, 2 H), 6.86 (d, J = 8.5 Hz, 2 H), 7.24 (d, J = 8.5 Hz, 2 H), 7.53 (s, 1 H), 7.60 (d, J = 8.1 Hz, 1 H), 7.74 (d, J = 8.1 Hz, 1 H). ¹³C NMR (CDCl₃): δ = 45.82, 48.77, 55.27, 114.18, 125.21, 125.93, 126.12, 128.75, 129.50, 131.47, 131.72, 142.97, 159.21, 167.38.
Compound 6f: IR (neat): 1658, 1460, 1409, 1367, 1303, 1234, 1057, 764, 737, 686 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 4.86 (s, 2 H), 7.18-7.21 (m, 1 H), 7.41-7.46 (m, 2 H), 7.48-7.53 (m, 2 H), 7.58-7.60 (m, 1 H), 7.86-7.89 (m, 2 H), 7.92-7.94 (m, 1 H). ¹³C NMR (CDCl₃): δ = 50.71, 119.46, 122.59, 124.15, 124.46, 128.37, 129.14, 132.05, 133.24, 139.50, 140.09, 167.49.
Compound 6g: IR (neat): 2227, 1677, 1610, 1447, 1409, 1230, 1060, 877, 839, 770, 677 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.32 (d, J = 6.8 Hz, 6 H), 4.41 (s, 2 H), 4.69 (sept, J = 6.8 Hz, 1 H), 7.76 (d, J = 8.2 Hz, 1 H), 7.77 (s, 1 H), 7.94 (d, J = 8.2 Hz, 1 H). ¹³C NMR (CDCl₃): δ = 20.75, 43.12, 44.90, 114.56, 118.31, 124.45, 126.75, 132.09, 137.32, 141.51, 165.88.