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Synlett 2006(13): 2087-2088  
DOI: 10.1055/s-2006-948190
LETTER
© Georg Thieme Verlag Stuttgart · New York

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

Kavirayani R. Prasad*, Pazhamalai Anbarasan
Department of Organic Chemistry, Indian Institute of Science, Bangalore, 560 012, India
e-Mail: prasad@orgchem.iisc.ernet.in;
Further Information

Publication History

Received 28 April 2006
Publication Date:
09 August 2006 (online)

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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

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.