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

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.

phosphinamides - dearomatization - stereoselective synthesis - phosphorus amino acids - phosphorus heterocycles

References

1a Robichaud AJ. Meyers AI. J. Org. Chem.  1991,  56:  2607 

1b Hulme AN. Henry SS. Meyers AI. J. Org. Chem.  1995,  60:  1265 

2a Ahmed A. Bragg RA. Clayden J. Tchabanenko K. Tetrahedron Lett.  2001,  42:  3407 

2b Bragg RA. Clayden J. Bladon M. Ichihara O. Tetrahedron Lett.  2001,  42:  3411 

For some recent references see:

3a James B. Meyers AI. Tetrahedron Lett.  1998,  39:  5301 

3b Shindo M. Koga K. Tomioka K. J. Org. Chem.  1998,  63:  9351 

3c Saito S. Sone T. Shimada K. Yamamoto H. Synlett  1999,  81 

3d Shindo M. Koga K. Asano Y. Tomioka K. Tetrahedron  1999,  55:  4955 

3e Kolotuchin SV. Meyers AI. J. Org. Chem.  2000,  65:  3018 

3f Saito S. Sone T. Murase M. Yamamoto H. J. Am. Chem. Soc.  2000,  122:  10216 

3g Tomioka K. Shioya Y. Nagaoka Y. Yamada KI. J. Org. Chem.  2001,  66:  7051 

4a Padwa A. Filipkowski MA. Kline DN. Murphree S. Yeske PE. J. Org. Chem.  1993,  58:  2061 

4b Ahmed A. Clayden J. Rowley M. Chem. Commun.  1998,  297 

4c Ahmed A. Clayden J. Rowley M. Synlett  1999,  1954 

4d Aggarwal VK. Ferrara M. Org. Lett.  2000,  2:  4107 

4e Clayden J. Menet CJ. Mansfield DJ. Org. Lett.  2000,  2:  4229 

4f Clayden J. Tchabanenko K. Yasin SA. Turnbull MD. Synlett  2001,  302 

5 Fernández I. López-Ortiz F. Tejerina B. García-Granda S. Org. Lett.  2001,  3:  1339 

6a Aminophosphonic and Aminophosphinic Acids. Chemistry and Biological Activity   Kukhar VP. Hudson HR. John Wiley; New York: 2000. 

6b Chebib M. Johnston GAR. J. Med. Chem.  2000,  43:  1427 

7a

Compound 6a,b have been previously synthesized through the reaction of PCl₃ with the corresponding benzylamine. No yields were given. Our modification afforded the desired product quantitatively. The ¹H and ³¹P NMR spectra of the crude products indicated a purity higher than 97%. Therefore, the compounds were used without additional purification by distillation.

7b For 6a (bp 165 ºC/0.15 Torr) see: Imbery D. Friebolin H. Z. Naturforsch. B  1968,  23:  759 

7c For 6b (δ (³¹P, 30% CHCl₃) = 138.1 ppm) see: Gouesnard JP. Dorie J. Martin GJ. Can. J. Chem.  1980,  58:  1295 

8

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

9

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): ν_max = 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).

10

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.

11a Mann FG. Watson J. J. Org. Chem.  1948,  13:  502 

11b Imamoto T. Kikuchi S.-I. Miura T. Wada Y. Org. Lett.  2001,  3:  87 

12 Myers AG. Gleason JL. Yoon T. Kung DW. J. Am. Chem. Soc.  1997,  119:  656 

13 Woll MG. Lai JR. Guzei IA. Taylor SJC. Smith MEB. Gellman SH. J. Am. Chem. Soc.  2001,  123:  11077