The Synthesis of Arylketones via Friedel-Crafts Acyldegermylation

Abstract

Electron-rich and electron-neutral aryl trialkylgermanes are shown to be competent precursors to aryl ketones via Friedel-Crafts acyldegermylation. Given the previously demonstrated greater stability towards basic/nucleophilic conditions of arylgermanes as compared to arylsilanes/stannanes, these reactions significantly expand the utility of group 14 acyldemetalation in synthesis. This is exemplified by the cleavage of Ge-based linker models for solid-phase synthesis (SPS).

arylgermanes - solid-phase synthesis - electrophilic aromatic substitution - Friedel-Crafts acylation - oligothiophenes

References

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For mention of acetyldegermylation of PhGeMe₃ see:

13a Maire J. Marrot J. Nabet R. Bull. Soc. Chim. Fr.  1981,  429 

13b For acetyldegermylation of trans-PhCH=CHGeEt₃ see: Marsubara S. Yoshino H. Utimoto K. Oshima K. Synlett  2000,  495 

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15 Boymond L. Rottlander M. Cahiez G. Knochel P. Angew. Chem. Int. Ed.  1998,  37:  1701 

16

Subjection of 2-TMG-4-methoxyacetophenone 12 to aluminium(III) chloride/AcCl to see if a second acyl group could be installed by ipso-degermylation resulted in the formation of no identifiable products.

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Data for Arylgermanes.

20a For compounds 2a, 2f, see: Moerlein SM. J. Organomet. Chem.  1987,  319:  29 

20b For compounds 2b, 2c, see: Bennett SW. Eaborn C. Jackson RA. Pearce R. J. Organomet. Chem.  1971,  28:  59 

20c

Compound 2d: a clear colourless oil, R _f = 0.71 (PE). ¹H NMR (250 MHz, CDCl₃): δ = 0.57 [9 H, s, (CH ₃)₃Ge], 2.48 (6 H, s, CH₃C), 7.01-7.04 (2 H, m, CH₃CCHCHCHCCH₃), 7.14-7.20 (1 H, m, CHCHCH). ¹³C NMR (63 MHz, CDCl₃): δ = 3.6 (q), 24.6 (q), 127.8 (d), 128.4 (d), 143.5 (s), one quaternary carbon not observed. IR (neat): 3052, 2968, 2909, 1566, 1448, 1236, 833, 768 cm^-1. MS (EI): m/z (%) = 224 (14)[M⁺], 209(100), 179 (7), 119 (20), 105 (39). HRMS: m/z calcd for C₁₁H₁₈ ⁷⁴Ge: 224.0620; found: 224.0622.
Compound 2e, a clear colourless oil, R _f = 0.74 (PE). ¹H NMR (250 MHz, CDCl₃): δ = 0.52 [9 H, s, (CH₃)₃Ge], 2.46 (6 H, s, CH ₃C), 7.11 (1 H, s, CH₃CCHCCH₃), 7.24 {2 H, s, CH₃CCHC[Ge(CH₃)₃]CHCCH₃}. ¹³C NMR (63 MHz, CDCl₃): δ = -1.7 (q), 21.5 (q), 130.1 (d), 130.7 (d), 137.3 (s), 142.4 (s). IR (neat): 2972, 2909, 1597, 1236, 1137, 828, 600 cm^-1. MS (EI): m/z (%) = 224 (11) [M⁺], 209 (100), 179 (11), 119 (8), 105 (16). HRMS: m/z calcd for C₁₁H₁₈ ⁷⁴Ge: 224.0620; found: 224.0623.

20d For compound 2g, see: Moerlein SM. J. Org. Chem.  1987,  52:  664 

20e For compound 2h, see: Riedmiller F. Jockisch A. Schmidbaur H. Z. Naturforsch., B: Chem. Sci.  1999,  54:  13 

21

(f) Compound 2i: a clear colourless oil, R _f = 0.79 (PE-EtOAc, 8:2). ¹H NMR (250 MHz, CDCl₃): δ = 0.46 [9 H, s, (CH ₃)₃Ge], 1.44 (3 H, t, J = 7.0 Hz, CH₂CH ₃), 4.43 (2 H, q, J = 7.0 Hz, CH ₂CH₃), 7.42-7.48 (1 H, m, GeCCHCHCHCCO₂Et), 7.67-7.71 (1 H, m, GeCCHCHCHCCO₂Et), 8.02-8.07 (1 H, m, GeCCHCHCHCCO₂Et), 8.21 (1 H, m, GeCCHCCO₂Et). ¹³C NMR (63 MHz, CDCl₃): δ = -1.8 (q), 14.4 (q), 60.8 (t), 127.8 (d), 129.4 (d), 129.9 (s), 133.9 (d), 137.4 (d), 143.0 (s), 166.9 (s). IR (neat): 2977, 2908, 1715, 1590, 1367, 1261, 1117, 826, 742 cm^-1. MS (EI): m/z (%) = 268 (1) [M⁺], 253 (100), 225 (48), 149 (17), 119 (31), 104 (28), 91 (34), 89 (32). HRMS (ESI⁺): m/z calcd for C₁₂H₁₉ ⁷⁴GeO₂: 269.0597; found: 269.0588.
For compounds 16, 17, see ref. 6b.

Data for Acetyl Derivatives.

22a For compounds 3, 5, 7, 9, see: Cacchi S. Fabrizi G. Gavazza F. Goggiamani A. Org. Lett.  2003,  5:  289 

22b For compound 4, see: Buchwald SL. Watson BT. Lum RT. Nugent WA. J. Am. Chem. Soc.  1987,  109:  7137 

22c For compound 6, see: Brook MA. Henry C. Tetrahedron  1996,  52:  861 

22d For compound 8, see: Friedman L. Koca RM. J. Org. Chem.  1968,  33:  1255 

22e

Compound 10: a clear colourless oil, R _f = 0.38 (PE-EtOAc, 9:1). ¹H NMR (400 MHz, CDCl₃): δ = 0.41 [9 H, s, Ge(CH ₃)₃], 2.58 (3 H, s, COCH ₃), 3.88 (3 H, s, OCH ₃), 6.89 (1 H, dd, J = 8.5, 3.0 Hz, CH₃OCCHCHCCOCH₃), 7.21 [1 H, d, J = 3.0 Hz, (CH₃)₃GeCCH], 7.91 (1 H, d, J = 8.5 Hz, CH₃COCCH). ¹³C NMR (63 MHz, CDCl₃): δ = 0.0 (q), 26.8 (q), 55.1 (q), 111.9 (d), 121.2 (d), 132.5 (d), 143.3 (s), 167.2 (s), two quaternary carbons not observed. IR (neat): 2964, 1677, 1587, 1563, 1269, 1227, 1045, 827 cm^-1. MS (EI): m/z (%) = 253 (100) [M - Me]⁺, 238 (11), 223 (27), 119 (23), 89 (18). HRMS (EI): m/z calcd for C₁₂H₁₈ ⁷⁴GeO₂: 268.0519; found: 268.0521.

22f

Compound 18: as colourless blocks, R _f = 0.54 (PE-EtOAc, 9:1); mp 29-31 °C. ¹H NMR (270 MHz, CDCl₃): δ = 0.086 (3 H, t, J = 7.0 Hz, CH ₃CH₂), 1.29-1.35 (6 H, m, CH ₂ CH ₂ CH ₂ CH₃), 1.53-1.58 (2 H, m, CCH₂CH ₂ ), 2.45 (3 H, s, COCH ₃), 2.92 (2 H, t, J = 8.0 Hz, CCH ₂CH₃), 7.13 (1 H, s, CH). ¹³C NMR (125 MHz, CDCl₃): δ = 14.1 (q), 22.6 (t), 29.2 (t), 29.8 (t), 30.2 (2 × t), 31.6 (t), 81.1 (s), 141.5 (d), 141.7 (s), 151.6 (s), 189.4 (s). IR (neat): 2955, 2855, 1653, 1401, 1237, 954 cm^-1. MS (CI⁺): m/z (%) = 337 (100) [M + H], 354 (51), 279 (9), 228 (17), 211 (23). HRMS (CI⁺): m/z calcd for C₁₂H₁₈OSI: 337.0123; found: 337.0120.