An Expeditious Enantiospecific Synthesis of (+)-2-Hydroxy-exo-brevicomin

Abstract

An expeditious approach for the synthesis of Western pine beetle pheromone 2-hydroxy-exo-brevicomin from natural chiral pool l-(+)-tartaric acid was achieved. The key step involves a highly diastereoselective reduction of a keto-Weinreb amide and further elaboration to the title compound in high yields with complete stereocontrol.

Key words

pheromone - 2-hydroxy-exo-brevicomin - tartaric acid - stereoselective reduction

References and Notes

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9

Formation of the other diastereomer was not observed within detectable limits in the ¹H NMR spectrum of the crude reaction mixture.

10

E-Stereochemistry for the α,β-unsaturated ketone 10 was assigned based on ¹H NMR (J = 15.9Hz). Formation of the Z isomer was not observed within detectable limits. However, stereochemistry of the olefin is irrelevant as it is saturated in the next step.

11

All new compounds exhibited satisfactory spectral data.
Compound 7: [α]_D ²⁵ +7.8 (c 1.6, CHCl₃). IR (neat): 2985, 2940, 1720, 1670, 1382, 1087, 993, 852 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 4.99 (d, J = 4.5 Hz, 1 H), 4.80 (d, J = 4.5 Hz, 1 H), 3.68 (s, 3 H), 3.20 (s, 3 H), 2.80-2.48 (m, 2 H), 1.46 (s, 3 H), 1.41 (s, 3 H), 1.06 (t, J = 7.5 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 208.8, 169.7, 112.6, 82.1, 73.9, 61.6, 32.6, 32.4, 26.6, 26.2, 7.1. HRMS: m/z calcd for C₁₁H₁₉NO₅ + Na: 268.1161; found: 268.1151.
Compound 8: [α]_D ²⁵ -7.1 (c 3.5, CHCl₃). IR (neat): 2953, 2857, 1673, 1463, 1380, 1255, 1070, 836, 777 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 4.69 (br s, 1 H), 4.57-4.53 (m, 1 H), 3.74-3.70 (m, 1 H), 3.73 (s, 3 H), 3.19 (s, 3 H), 1.68-1.53 (m, 1 H), 1.49-1.33 (m, 1 H), 1.42 (s, 3 H), 1.41 (s, 3 H), 0.92 (t, J = 7.8 Hz, 3 H), 0.85 (s, 9 H), 0.04 (s, 6 H). ¹³C NMR (75 MHz, CDCl₃): δ = 170.5, 110.9, 79.9, 73.4, 72.4, 61.7, 32.2, 26.9, 26.2, 25.7, 25.6, 18.1, 10.2, -4.6. HRMS: m/z calcd for C₁₇H₃₅NO₅Si + Na: 384.2182; found: 384.2146.
Compound 10: [α]_D ²⁵ +11.6 (c 3, CHCl₃). IR (neat): 2931, 2857, 1681, 1471, 1369, 1253, 1089, 835, 775 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 6.72 (dd, J = 15.9, 5.1 Hz, 1 H), 6.34 (d, J = 15.9 Hz, 1 H), 4.51 (t, J = 6.9 Hz, 1 H), 3.82-3.69 (m, 2 H), 2.26 (s, 3 H), 1.76-1.63 (m, 1 H), 1.56-1.36 (m, 1 H), 1.43 (s, 3 H), 1.39 (s, 3 H), 0.94 (t, J = 7.2 Hz, 3 H), 0.89 (s, 9 H), 0.08 (s, 3 H), 0.06 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 197.9, 143.8, 130.6, 109.5, 82.8, 75.9, 73.0, 27.4, 26.9, 26.7, 25.8, 25.6, 18.1, 10.3, -4.1, -4.6. HRMS: calcd for C₁₈H₃₄O₄Si + Na: 365.2124; found: 365.2108.
Compound 11: [α]_D ²⁵ -11.3 (c 3.1, CHCl₃). IR (neat): 2931, 2857, 1720, 1463, 1369, 1253, 1160, 1078, 836, 775 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 3.90-3.82 (m, 1 H), 3.65-3.56 (m, 2 H), 2.74-2.50 (m, 2 H), 2.14 (s, 3 H), 2.03-1.90 (m, 1 H), 1.74-1.58 (m, 2 H), 1.47-1.36 (m, 1 H), 1.35 (s, 6 H), 0.92 (t, J = 7.2 Hz, 3 H), 0.88 (s, 9 H), 0.06 (s, 6 H). ¹³C NMR (75 MHz, CDCl₃): δ = 208.2, 135.6, 108.1, 82.8, 75.9, 73.4, 40.1, 29.9, 27.5, 27.3, 26.9, 25.9, 18.2, 10.3, -4.2, -4.6. HRMS: m/z calcd for C₁₈H₃₆O₄Si + Na: 367.2281; found: 367.2285.
2-Hydroxy-exo-brevicomin(4): [α]_D ²⁵ +32.5 (c 1.2, CHCl₃), {Lit. [7d] [α]_D ²⁵ +33.3 (c 1.94, CHCl₃)}. ¹H NMR (300 MHz, CDCl₃): δ = 4.16 (t, J = 6.6 Hz, 1 H), 3.99 (br s, 1 H), 3.97-3.88 (m, 1 H), 1.95-1.86 (m, 1 H), 1.78-1.46 (m, 5 H), 1.45 (s, 3 H), 0.93 (t, J = 7.8 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 106.9, 80.5, 77.2, 66.2, 34.9, 28.3, 26.6, 23.8, 9.7.