Synlett 2002(5): 0781-0783
DOI: 10.1055/s-2002-25365
LETTER
© Georg Thieme Verlag Stuttgart · New York

Nucleophilic Napththalene Dearomatization of N-Alkyl-N-benzyl(dinaphthyl)phosphinamides. Application to the Synthesis of γ-(N-Alkylamino)(dihydronaphthalenyl)phosphinic Acids

Gloria Ruiz Gómez, Fernando López Ortiz*
Área de Química Orgánica, Universidad de Almería, Carretera de Sacramento, 04120, Almería. Spain
Fax: +34(950)215481; e-Mail: flortiz@ual.es;
Further Information

Publication History

Received 19 December 2001
Publication Date:
07 February 2007 (online)

Abstract

Lithiation of N-alkyl-N-benzyl(dinaphthyl)phosphinamides with s-BuLi at -90 ºC in THF promoted the dearomatization of one naphthalene ring through anionic cyclization. The intermediate lithium compounds were trapped with MeOH, MeI and allyl bromide affording benzo[e]-1-phosphaisoindoles with excellent stereoselectivities. Acid hydrolysis of the P-N linkage allowed to obtain γ-(N-alkylamino)phosphinic acids containing a dihydronaphthalene system. This structural fragment proved to be an element of conformational restriction.

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The structural analysis included 1D (1H, 13C, 31P, DEPT, selective TOCSY) and 2D (gHMQC, gHMBC and gNOESY) NMR experiments.

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s-BuLi (1.2 mL of a 1.3 M solution in cyclohexane, 1.56 × 10-3 mol) was added to a stirred solution of 9a (6.23 × 10-4 mol) in THF (30 mL) at -90 ºC. After 30 min of metallation MeOH (1.87 × 10-2 mol) was added and the reaction was stirred at -90 ºC for 20 min. Then the reaction mixture was poured into ice water and extracted with ethyl acetate (3 × 15 mL). The organic layers were dried over Na2SO4 and concentrated in vacuo. 1H, 1H{31P}, and 31P NMR spectra of the crude were measured in order to determine the stereoselectivity of the process. Precipitation from diethyl ether afforded 10a as a white solid, mp 201-203 ºC. IR (KBr): νmax = 1159 cm-1. 1H NMR (300.13 MHz, CDCl3): δ = 2.69 (d, 3 J PH = 7.8 Hz, 3 H), 3.78 (dddt, 3 J HH = 2.5, 3 J HH = 7.1 Hz, 3 J HH = 18.3, 3 J PH = 4.6 Hz, 1 H), 3.94 (dd, 3 J HH = 18.3, 2 J PH = 22.1 Hz, 1 H), 4.77 (dd, 3 J HH = 7.1, 3 J PH = 13.3 Hz, 1 H), 5.83 (dt, 3 J HH = 9.7, 3 J HH = 2.5, 4 J PH = 2.5 Hz, 1 H), 6.24 (dd, 3 J HH = 9.7, 4 J HH = 2.5 Hz, 1 H), 6.72 (dt, 3 J HH = 7.5, 4 J HH = 1.7 Hz, 1 H), 6.89 (dt, 3 J HH = 7.5, 4 J HH = 5 J PH = 1.7 Hz, 1 H), 6.96 (t, 3 J HH = 7.5 Hz, 1 H), 7.35 (d, 3 J HH = 7.5 Hz, 1 H), 7.40 (dt, 3 J HH = 7.1, 4 J HH = 1.7 Hz, 1 H), 7.47 (dd, 3 J HH = 7.9, 4 J PH = 2.7 Hz, 1 H), 7.50 (t, 3 J HH = 7.1 Hz, 2 H), 7.61 (ddd, 3 J HH = 8.1, 3 J HH = 6.9, 4 J HH = 1.2 Hz, 1 H), 7.66 (dd, 3 J HH = 7.1, 4 J HH = 1.7 Hz, 2 H), 7.78 (ddd, 3 J HH = 8.6 Hz, 3 J HH = 6.9, 4 J HH = 1.7 Hz, 1 H), 7.87 (ddd, 3 J HH = 7.1, 4 J HH = 1.4, 3 J PH = 15.7 Hz, 1 H), 7.91 (dd, 3 J HH = 8.2, 4 J HH = 1.7 Hz, 1 H), 8.01 (d, 3 J HH = 7.9 Hz, 1 H), 9.79 (d, 3 J HH = 8.6 Hz, 1 H) ppm. 13C NMR (75.47 MHz, CDCl3): δ = 29.54 (d, 2 J PC = 3.9 Hz, CH3), 42.39 (d, 2 J PC = 4.8 Hz, CH), 43.31 (d, 1 J PC = 92.8 Hz, CH), 66.60 (d, 2 J PC = 8.7 Hz, CH), 124.38 (d, 3 J PC = 14.1 Hz, CH), 126.41 (CH), 126.57 (d, 3 J PC = 21.3 Hz, C), 126.68 (CH), 126.80 (d, 1 J CP = 99.1 Hz, C), 126.84 (d, 3 J PC = 6.0 Hz, CH), 127.04 (CH), 127.16 (CH), 127.33 (CH), 127.56 (CH), 127.80 (CH), 127.98 (CH), 128.13 (2 CH), 128.84 (3 CH), 129.15 (CH), 130.22 (C), 133.67 (d, 4 J PC = 3.3 Hz, CH), 134.01 (d, 2 J PC = 9.0 Hz, C), 134.18 (d, 2 J PC = 10.5 Hz, CH), 135.62 (d, 3 J PC = 11.1 Hz, C), 137.54 (C) ppm. 31P NMR (121.50 MHz, CDCl3): δ = 45.74 ppm. Anal. Calcd for C28H24NOP: C, 79.82; H, 5.70; N, 3.32. Found: C, 79.83; H, 5.72; N, 3.31. MS (API-ES): m/z = 422 (M+1).

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The preference for the trans junction may be explained through the coordination of the lithium cation with the oxygen atoms of the methanol and the P-O linkage from the same face of the thicyclic system.