Rhodium Carbenoid Mediated C-H Activation of a Tertiary Methyl Group: An Enantiospecific Approach to the Angular Triquinanes Norsilphiperfolane and Norcameroonanes

Abstract

An enantiospecific synthesis of the angular triquinane system present in the sesquiterpenes cameroonanes and silphiperfolanes has been accomplished, starting from 5-isopropenyl-2-­methylcyclopent-1-ene-1-methanol [readily available in three steps from (R)-limonene] employing an intramolecular rhodium carbenoid insertion into the C-H bond of a tertiary methyl group for the construction of the triquinane system.

angular triquinanes - silphiperfolane - cameroonane - enantiospecific synthesis - rhodium carbenoid C-H insertion

References

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Yields refer to isolated and chromatographically pure compounds. All the compounds exhibited spectroscopic data (IR, ^¹H and ^¹³C NMR, and HRMS) consistent with their structures.
Selected Spectral Data1-{(1 S ,2 R ,5 S )-1,5-Dimethylbicyclo[3.3.0]octane-spiro[7.2′]-1,3-dioxolan-2-yl}ethanone (17)
[α]_D ^²² -69.6 (c 2.1, CHCl₃). IR (neat): ν_max = 2959, 2879, 1708 (C=O), 1452, 1354, 1331, 1238, 1161, 1114, 1091, 1070, 1040, 1019, 946, 894, 820, 727 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 3.95-3.65 (4 H, m, OCH₂CH₂O), 3.15 (1 H, dd, J = 9.2, 8.0 Hz), 2.24 (1 H, d, J = 14.4 Hz), 2.09 (3 H, s, CH₃C=O), 2.10-1.45 (7 H, m), 0.94 (3 H, s), 0.74 (3 H, s, 2 × tert-CH₃). ^¹³C NMR (100 MHz, CDCl₃): δ = 209.9 (C, C=O), 116.3 (C, C-7), 64.0 (CH₂), 63.7 (CH₂) [OCH₂CH₂O], 61.0 (CH, C-2), 52.1 (C), 51.4 (C), 50.7 (CH₂), 49.6 (CH₂, C-4), 37.8 (CH₂), 31.3 (CH₃, CH₃C=O), 24.4 (CH₂, C-3), 23.4 (CH₃), 18.5 (CH₃). HRMS: m/z calcd for C₁₄H₂₂O₃Na [M + Na]: 261.1467; found: 261.1465.
Ethyl 2-Diazo-3-{(1 S ,2 R ,5 S )-1,5-dimethylbicyclo-[3.3.0]octane-spiro[7.2′]-1,3-dioxolan-2-yl}-3-oxopropanoate (19)
[α]_D ^²5 -50.9 (c 3.0, CHCl₃). IR (neat): ν_max = 2960, 2878, 2136 (N=N), 1715 (OC=O), 1652 (C=O), 1470, 1455, 1378, 1334, 1301, 1206, 1116, 1092, 1043, 1020 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 4.29 (2 H, q, J = 7.1 Hz, OCH ₂CH₃), 4.02 (1 H, dd, J = 7.8, 7.1 Hz), 3.95-3.75 (4 H, m, OCH₂CH₂O), 2.21 (1 H, d, J = 14.2 Hz), 2.15-2.06 (1 H, m), 1.98 (1 H, d, J = 14.1 Hz), 1.92 (1 H, d, J = 14.9 Hz), 1.90-1.66 (4 H, m), 1.32 (3 H, t, J = 7.1 Hz, OCH₂CH ₃), 1.01 (3 H, s), 0.91 (3 H, s, 2 × tert-CH₃). ^¹³C NMR (100 MHz, CDCl₃): δ = 195.0 (C, C=O), 161.3 (C, OC=O), 116.4 (C, OCO), 64.1 (C, C=N₂), 64.0 (CH₂), 63.8 (CH₂, OCH₂CH₂O], 61.2 (CH₂, OCH₂CH₃), 56.4 (CH), 53.6 (C), 52.3 (CH₂), 51.2 (C), 49.9 (CH₂), 39.9 (CH₂), 26.7 (CH₂), 23.1 (CH₃), 19.9 (CH₃), 14.4 (CH₃, OCH₂ CH₃). HRMS: m/z calcd for C₁₇H₂₄N₂O₅Na [M + Na]: 359.1583; found: 359.1579
(1 S ,5 R ,8 S )-8-Methyltricyclo[6.3.0.0 ^¹,5 ]undecane-4,10-dione (21)
mp 147-149 ˚C; [α]_D ^²² +62.6 (c 2.5, CHCl₃). IR (neat): ν_max = 2961, 2875, 1736 (C=O), 1405, 1272, 1227, 1178, 735 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 2.61 (1 H, d, J = 18.7 Hz), 2.50-2.27 (4 H, m), 2.24 (2 H, s), 2.20-1.95 (2 H, m), 1.94-1.55 (4 H, m), 1.14 (3 H, s, tert CH₃). ^¹³C NMR (100 MHz, CDCl₃ + CCl₄): 220.7 (C, C=O), 217.0 (C, C=O), 58.7 (CH, C-5), 57.3 (C, C-1), 51.2 (CH₂), 50.2 (C, C-8), 50.1 (CH₂), 39.8 (CH₂), 37.7 (CH₂), 29.2 (CH₂), 26.7 (CH₂), 21.5 (CH₃, tert CH₃). HRMS: m/z calcd for C₁₂H₁₆O₂Na [M + Na]: 215.1060; found: 215.1048
(1 S ,5 S ,8 S )-4,10-Bismethylene-8-methyltricyclo-[6.3.0.0 ^¹,5 ]dodecane (22)
[α]_D ^²4 -35.7 (c 1.0, CHCl₃). IR (neat): ν_max = 3072, 2947, 2862, 1654, 1464, 1456, 1375, 1210, 879 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 4.82 (1 H, s), 4.76 (1 H, s), 4.75 (1 H, s), 4.72 (1 H, s, 2 × C=CH₂), 2.51 (1 H, d, J = 8.8 Hz), 2.40 (1 H, d, J = 15.4 Hz), 2.37-2.29 (2 H, m), 2.25 and 2.18 (2 H, 2 × d, J = 16.4 Hz), 2.10-1.88 (1 H, m), 1.68 (1 H, td, J = 12.4, 8.4 Hz), 1.65-1.35 (5 H, m), 1.00 (3 H, s, tert CH₃). ^¹³C NMR (100 MHz, CDCl₃): δ = 159.0 (C, C-4), 151.4 (C, C-10), 105.1 (CH₂), 104.4 (CH₂, 2 × C=CH₂), 62.9 (C, C-1), 56.2 (CH, C-5), 51.3 (C, C-8), 47.5 (CH₂), 46.2 (CH₂), 39.9 (CH₂), 35.2 (CH₂), 33.5 (CH₂), 31.6 (CH₂), 23.3 (CH₃). HRMS: m/z calcd for C₁₄H₂₀Na [M + Na]: 211.1463; found: 211.1475.

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