Regioselective Synthesis of
Highly Functionalized Arylphosphonates by Cyclocondensation
of 1,3-Bis(trimethylsilyloxy)buta-1,3-dienes with 3-Ethoxy-2-phosphonylalk-2-en-1-ones

Olumide Fatunsin; Mohanad Shkoor; Abdolmajid Riahi; Peter Langer

doi:10.1055/s-0029-1219950

LETTER

Regioselective Synthesis of Highly Functionalized Arylphosphonates by Cyclocondensation of 1,3-Bis(trimethylsilyloxy)buta-1,3-dienes with 3-Ethoxy-2-phosphonylalk-2-en-1-ones

Olumide Fatunsin^a, Mohanad Shkoor^a, Abdolmajid Riahi^a, Peter Langer*^a,b
^a Institut für Chemie, Universität Rostock, Albert Einstein Str. 3a, 18059 Rostock, Germany
^b Leibniz-Institut für Katalyse an der Universität Rostock e.V., Albert Einstein Str. 29a, 18059 Rostock, Germany
Fax: +49(381)4986412; e-Mail: peter.langer@uni-rostock.de;

Abstract

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Abstract

Highly functionalized arylphosphonates were prepared by TiCl₄-mediated cyclocondensation of 3-ethoxy-2-phosphonylalk-2-en-1-ones with 1,3-bis(trimethylsilyloxy)buta-1,3-dienes.

Key words

cyclizations - regioselectivity - phosphonic acid derivatives - silyl enol ethers

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References and Notes

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Diethyl (1-Ethoxy-3-oxobut-1-en-2-yl)phosphonate (2a)
A mixture of 1a (1.10 g, 1.0 mL, 5.55 mmol), triethyl orthoformiate (1.1 mL, 6.62 mmol) and Ac₂O (1.5 mL, 16.0 mol) was stirred for 2 h at 120 ˚C and subsequently for 2 h at 140 ˚C. The resulting mixture was distilled to give 2a as a brownish oil (1.20 g, 86%). ^¹H NMR (300 MHz, CDCl₃): δ = 1.21-1.24 (m, 6 H, 2 × OCH₂CH ₃), 1.36 (t, ^³ J = 6.9 Hz, 3 H, OCH₂CH ₃), 2.25 (s, 3 H, CH₃), 4.04-4.08 (m, 4 H, 2 × OCH ₂CH₃), 4.23 (q, ^³ J = 7.2 Hz, 2 H, OCH ₂CH₃), 7.70 (d, ^³ J _P,H = 11.4 Hz, 1 H, CH). ^¹³C NMR (CDCl₃, 75 MHz): δ = 15.0, 15.9, 16.0, 20.6 (CH₃), 62.2, 62.4, 73.0 (OCH₂), 107.3 (d, J _C,P = 191 Hz,C_q), 169.9 (d, J _CH,P = 25.5 Hz, CH), 195.0 (CO). ^³¹P NMR (250 MHz, CDCl₃): δ = 19.64. GC-MS (EI, 70 eV): m/z (%) = 250 (5) [M⁺], 235 (47), 221 (12), 207 (43), 205 (13), 179 (42), 177 (11), 151 (100), 123 (23), 121 (15), 105 (11), 81 (11), 53 (13), 43 (13), 29 (10). HRMS (EI): m/z calcd for C₁₀H₁₉O₅P [M]⁺: 250.09646; found: 250.09666.

Diethyl (1-Ethoxy-3-oxo-3-phenylprop-1-en-2-yl)phosphonate (2b)
A mixture of 1b (1.50 g, 1.27 mL, 5.85 mmol), triethyl orthoformiate (1.70 mL, 10.24 mmol), and Ac₂O (1.56 mL, 16.61 mmol) was stirred for 36 h at 140 ˚C. The mixture was cooled to 20 ˚C and purified by column chromatography to give 2b as a brownish oil (1.350 g, 74%). ^¹H NMR (300 MHz, CDCl₃): δ = 1.08 (t, ^³ J = 7.1 Hz, 3 H, OCH₂CH ₃), 1.21 (t, ^³ J = 7.0 Hz, 6 H, 2 × OCH₂CH ₃), 3.94 (q, ^³ J = 7.1 Hz, 2 H, OCH ₂CH₃), 4.01-4.10 (m, 4 H, 2 × OCH ₂CH₃), 7.34-7.48 (m, 5 H, CH_Ar), 7.80-7.82 (m, 1 H, CH). ^³¹P NMR (250 MHz, CDCl₃): δ = 16.25 Hz. ^¹³C NMR (75 MHz, CDCl₃): δ = 15.1, 16.1, 16.2 (CH₃), 62.3, 62.4, 71.4 (OCH₂), 106.4 (d, J _P,C = 189.3 Hz), 128.2 (2 × CH_Ar), 129.3 (2 × CH_Ar), 133.0 (CH_Ar), 137.6 (d, J _P,C = 4.3 Hz), 163.5 (d, J _P,C = 21.0 Hz, CH), 192.2 (d, J _P,C = 4.8 Hz, CO). IR (neat): 3060 (w), 2982 (w), 2932 (w), 2905 (w), 1716 (w), 1660 (m), 1597 (m), 1448 (m), 1391 (m), 1305 (w), 1244 (s), 1204 (m), 1145 (m), 1050 (m), 1016 (s), 959 (s), 853 (m), 790 (s), 723 (m), 690 (m), 659 (m), 564 (m), 534 (m) cm^-¹. GC-MS (EI, 70 eV): m/z (%) = 312 (4) [M⁺], 297 (3), 283 (11), 267 (53), 239 (25), 211 (17), 183 (21), 159 (14), 151 (34), 129 (45), 105 (100), 77 (54). ESI-HRMS: m/z calcd for C₁₅H₂₂O₅P [M + H]⁺: 313.1199; found: 313.1198.

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<A NAME="RD04210ST-16">16</A> Nguyen VTH. Bellur E. Appel B. Synthesis 2006, 2865

General Procedure for the Synthesis of Arylphosphonates 4a-l To a CH₂Cl₂ solution (2 mL/1.0 mmol of 2a,b) of 2a,b was added 3a-k (1.1 mmol) and, subsequently, TiCl₄ (1.1 mmol) at -78 ˚C. The temperature of the solution was allowed to warm to 20 ˚C over 12 h with stirring. To the solution was added HCl (10%, 20 mL), and the organic and the aqueous layer were separated. The latter was extracted with CH₂Cl₂ (3 × 20 mL). The combined organic layers were dried (Na₂SO₄), filtered, and the filtrate was concentrated in vacuo. The residue was purified by chromatography (silica gel, n-heptane-EtOAc) to give 4a-l.

Methyl 3-(Diethoxyphosphoryl)-6-hydroxy-2-methyl-benzoate (4a)
Starting with 2a (0.375 g, 1.5 mmol) and 3a (0.429 g, 1.65 mmol), 4a was isolated after chromatography (silica gel, heptanes-EtOAc) as a yellowish oil (0.217 g, 48%). ^¹H NMR (300 MHz, CDCl₃): δ = 1.24 (m, 6 H, 2 × OCH₂CH ₃), 2.65 (s, 3 H, CH₃), 3.91 (s, 3 H, OCH₃), 3.99-4.07 (m, 4 H, 2 × OCH ₂CH₃), 6.83 (dd, ^³ J _H,H = 8.6 Hz, ⁴ J _P,H = 3.3 Hz, 1 H, CH_Ar), 7.90 (dd, ^³ J _H,H = 9.0 Hz, ^³ J _P,H = 14.0 Hz, 1 H, CH_Ar), 11.0 (s, 1 H, OH). ^¹³C NMR (75 MHz, CDCl₃): δ = 16.2, 16.2, 20.6 (CH₃), 52.5 (OCH₃), 62.0, 62.0 (OCH₂), 114.9 (d, J _P,CH = 15.2 Hz, CH_Ar), 115.9 (d, J _P,C = 16.1 Hz), 119.0 (d, J _P,C = 193.0 Hz), 139.3 (d, J _P,CH = 11.0 Hz, CH_Ar), 145.8 (d, J _P,C = 13.5 Hz), 164.0 (d, J _P,C = 3.4 Hz, COH), 171.2 (d, J _P,C = 2.4 Hz, CO). ^³¹P NMR (250 MHz, CDCl₃): δ = 19.56. IR (neat): 2920 (m), 2851 (m), 1733 (m), 1660 (w), 1636 (w), 1580 (m), 1456 (m), 1437 (m), 1376 (w), 1308 (m), 1285 (m), 1199 (m), 1161 (m), 1158 (m), 1016 (s), 961 (m), 906 (m), 844 (m), 793 (m), 741 (m), 678 (w), 614 (w), 535 (m) cm^-¹. GC-MS (EI, 70 eV): m/z (%) = 302 (65) [M]⁺, 287 (50), 274 (20), 270 (48), 259 (17), 242 (100), 229 (18), 227 (13), 214 (84), 197 (43), 186 (21), 167 (17), 161 (31), 158 (23), 134 (15), 105 (19), 77 (27), 65 (10), 51 (12), 29 (14). HRMS (EI): m/z calcd for C₁₃H₁₉O₆P [M]⁺: 302.09138; found: 302.09139.