Succinylation of Tertiary Alcohols under High Pressure

Abstract

The efficient succinylation of the sterically hindered tertiary alcohols 1 was performed by reaction with succinic acid monomethyl and monoallyl ester (4a and 4b), respectively, in CH₂Cl₂ in the presence of dicyclohexylcarbodiimide and 4-(dimethylamino)pyridine under high pressure to give the methyl and allyl succinates 5a and 5b, respectively, in high yields. The succinates 5a,b were efficiently converted into the hemisuccinate 3a by treatment with lithium propyl mercaptide or by palladium(0)-catalyzed deallylation.

Key words

succinates - hemisuccinates - acylation - tertiary alcohols - high pressure

References

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15

The alcohol 7 was prepared from the known lactone 6 [13] in two steps:(1)LAH, THF, 0 °C (90%);(2)BOMCl, i-Pr₂NEt, CH₂Cl₂, 0 °C to r. t. (79%). ¹H NMR (270 MHz, CDCl₃): δ = 0.92 (t, J = 6.7 Hz, 3 H), 1.20-1.80 (m, 10 H), 1.37 (s, 3 H), 1.42 (s, 3 H), 2.03 (s, 1 H), 3.54 (dt, J = 9.6, 6.3 Hz, 1 H), 3.60 (dt, J = 9.6, 6.3 Hz, 1 H), 3.87 (dd, J = 8.2, 7.8 Hz, 1 H), 3.93 (dd, J = 7.8, 6.1 Hz, 1 H), 4.03 (dd, J = 8.2, 6.1 Hz, 1 H), 4.60 (s, 2 H), 4.75 (s, 2 H), 7.25-7.40 (m, 5 H). ¹³C NMR (67.5 MHz, CDCl₃): δ = 14.2, 23.3, 23.5, 25.6, 25.8, 26.5, 31.0, 36.6, 64.6, 68.3, 69.3, 72.7, 79.8, 94.5, 108.7, 127.6, 127.7, 128.3, 128.4, 137.8.

16

The alcohol 10 was prepared from the known amide 9 [13] in four steps:(1)DIBAH, Et₂O, 0 °C (90%);(2)CBr₄, Ph₃P, 2,6-lutidine, CH₂Cl₂, 0 °C (80%);(3)BuLi, THF, -78 °C to r. t. (68%);(4)MeI, NaHCO₃, acetone, H₂O, 60 °C (83%). ¹H NMR (270 MHz, CDCl₃): δ = 0.92 (t, J = 6.7, 3 H), 1.22-1.36 (m, 4 H), 1.36 (s, 3 H), 1.42 (s, 3 H), 1.48-1.70 (m, 4 H), 1.97 (dd, J = 2.8, 2.8, 1 H), 2.22 (dddd, J = 16.6, 9.5, 7.2, 2.8, 1 H), 2.34 (dddd, J = 16.6, 9.2, 6.4, 2.8, 1 H), 3.87 (dd, J = 7.9, 7.9, 1 H), 3.97 (dd, J = 7.9, 6.4, 1 H), 4.06 (dd, J = 7.9, 6.4, 1 H). ¹³C NMR (67.5 MHz, CDCl₃): δ = 12.7, 14.2, 23.3, 25.5, 25.9, 26.4, 33.1, 36.2, 62.5, 64.6, 72.9, 79.4, 84.3, 108.9.

17

The alcohol 28 was prepared from the enantiomer of the amide 9 [12] using the same procedure for the preparation of 24 [13] : ¹H NMR (500 MHz, CDCl₃): δ = 0.77 (d, J = 6.4 Hz, 3 H), 0.92 (t, J = 6.9 Hz, 3 H), 1.05 (s, 9 H), 1.20-1.80 (m, 16 H), 2.00 (m, 1 H), 3.36 (ddd, J = 10.1, 101, 2.3 Hz, 1 H), 3.62 (ddd, J = 9.2, 8.7, 6.9 Hz, 1 H), 3.69 (dd, J = 9.6, 6.9 Hz, 1 H), 3.73 (ddd, J = 9.2, 9.2, 5.0 Hz, 1 H), 3.77 (s, 3 H), 3.77 (dd, J = 6.9, 6.0 Hz, 1 H), 3.85 (dd, J = 9.6, 6.9 Hz, 1 H), 4.47 (d, J = 11.5 Hz, 1 H), 4.52 (d, J = 11.5 Hz, 1 H), 6.86 (d, J = 8.7 Hz, 2 H), 7.28 (d, J = 8.7 Hz, 2 H), 7.30-7.80 (m, 10 H). ¹³C NMR (125 MHz, CDCl₃): δ = 14.2, 17.6, 19.1, 23.4, 24.7, 26.8, 28.0, 29.5, 30.6, 33.4, 33.7, 35.0, 35.1, 55.2, 63.6, 67.3, 71.2, 72.2, 72.8, 74.4, 95.0, 113.8, 127.8, 127.8, 129.3, 129.8, 129.9, 130.8, 132.7, 132.8, 135.6, 135.7, 159.1.

18

The reaction of 2-methyl-1-phenylpropan-2-ol with the succinic acid monomethyl ester (4a, 2 equiv), DCC (2.4 equiv) and DMAP (0.1 equiv) in CH₂Cl₂ at r. t. smoothly proceeded to give the methyl succinate 30 after 4.5 h in 98% yield even under atmospheric pressure: ¹H NMR (270 MHz, CDCl₃): δ = 1.45 (s, 6 H), 2.56 (m, 4 H), 3.06 (s, 2 H), 3.68 (s, 3 H), 7.15-7.35 (m, 5 H). The allyl succinate 31 was also prepared using the succinic acid monoallyl ester (4b) in the same manner in 96% yield: ¹H NMR (270 MHz, CDCl₃): δ = 1.44 (s, 6 H), 2.58 (m, 4 H), 3.05 (s, 2 H), 4.59 (ddd, J = 5.6, 1.4, 1.4, 2 H), 5.23 (ddt, J = 10.6, 1.4, 1.4, 1 H), 5.32 (ddt, J = 17.2, 1.4, 1.4, 1 H), 5.91 (ddt, J = 17.2, 10.6, 5.6, 1 H), 7.15-7.35 (m, 5 H).