A chiron approach to (1R,2R,5S,7R)-2-hydroxy-exo-brevicomin, a component of the volatiles produced by the male mountain pine beetle, Dendroctonus ponderosae

Article abstract of DOI:10.1016/j.tetlet.2004.08.086

A chiron approach to a synthesis of (1R,2R,5S,7R)-2-hydroxy-exo-brevicomin 1, a component of the volatiles obtained from male mountain pine beetles, Dendroctonus ponderosae has been achieved. Our synthesis started with commercially available d-mannitol and involved Wittig olefination, acid catalysed one-pot hydrogenation and internal acetalization as key steps.

Full text of DOI:10.1016/j.tetlet.2004.08.086

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 7713–7714
A chiron approach to (1R,2R,5S,7R)-2-hydroxy-exo-brevicomin,
a component of the volatiles produced by the male mountain
pine beetle, Dendroctonus ponderosaeI
D. Naveen Kumar and B. Venkateswara Rao*
Organic Chemistry Division III, Indian Institute of Chemical Technology, Hyderabad 500007, India
Received 15 July 2004;revised 2 August 2004;accepted 13 August 2004
Abstract—A chiron approach to a synthesis of (1R,2R,5S,7R)-2-hydroxy-exo-brevicomin 1, a component of the volatiles obtained
from male mountain pine beetles, Dendroctonus ponderosae has been achieved. Our synthesis started with commercially available
D-mannitol and involved Wittig olefination, acid catalysed one-pot hydrogenation and internal acetalization as key steps.
Ó 2004 Elsevier Ltd. All rights reserved.
In 1996 Francke et al.1 identified several new oxygen-
ated derivatives of 6,8-dioxabicyclo[3.2.1]octane in the
head space volatiles obtained from the male mountain
pine beetle, Dendroctonus ponderosae, which are destruc-
tive pests causing damage to coniferous forests in the
northern hemisphere. These compounds are mainly ste-
reoisomers of 7-ethyl-5-methyl-6,8-dioxabicyclo[3.2.1]oct-
an-2-ol and 1-(5-methyl-6,8-dioxabicyclo- [3.2.1]octyl)-
ethanol such as A–D and 1.
approach to the synthesis of 1. This target has been syn-
thesized twice since its discovery. The first synthesis by
Francke et al.1 was based on a kinetic resolution using
a Sharpless asymmetric epoxidation. The second by Mori
and co-workers3 used a Sharpless asymmetric dihydr-
oxylation as the key step. Our approach describes a synthe-
sis of 1 starting from D-mannitol as depicted in Scheme 1.
1,2;3,4-Di-O-isopropylidene-D-mannitol 2 was prepared
according to the literature procedure.4 The vicinal diol 2
was converted into olefin 3 in 71% yield using triphenyl-
phosphine, imidazole and iodine.5 Selective hydrolysis
of the terminal acetonide in 3 with 50% aq AcOH at
0°C for 4h gave 4 in 73% yield. Selective silylation of
Recently we reported an asymmetric synthesis of A and B
and a formal synthesis of (+)-exo-brevicomin starting
from a-picoline.2 In continuation of our interest in syn-
thesis of other members of the family, we report a chiron
OH
O
O
O
O
O
O
C
A
B
OH
OH
OH
OH
O
O
O
O
1
D
q IICT Communication Number: 040709.
*
Corresponding author. Tel./fax: +91 40 271 605 12;e-mail: venky@iict.res.in
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.08.086

7714
D. Naveen Kumar, B. V. Rao / Tetrahedron Letters 45 (2004) 7713–7714
O
O
OH
O
iii
OH
i
ii
HO
O
O
O
HO
O
O
O
O
3
4
2
O
O
O
iv
vi
v
TBSO
TBSO
HO
O
O
O
BnO
HO
BnO
7
6
OH
5
O
O
O
vii
O
+
O
O
O
BnO
BnO
O
1
8
Scheme 1. Reagents and conditions: (i) PPh3, imidazole, I2, toluene, reflux, 4h, 71%;(ii) 50% aq AcOH, 0 °C, 4h, 73%;(iii) TBSCI, imidazole, DCM,
rt, 3h, 90%;(iv) NaH, benzyl bromide, THF, 77%;(v) 1M TABAF in THF, THF, 80%;(vi) a. TEMPO, NaOCl, toluene, ethyl acetate, water;b.
Ph3PCHCOCH3, DCM, 76% (for two steps);(vii) H 2–Pd/C and catalytic aq HCl, 62%.
the primary hydroxyl of 4 gave 5 in 90% yield. Com-
pound 5 was subjected to benzylation using NaH, ben-
zyl bromide to give compound 6 in 77% yield.
Desilylation of compound 6 using 1M TBAF solutions
in THF gave compound 7. The primary alcohol was
oxidized to the aldehyde using TEMPO and the alde-
hyde subsequently treated with Ph3PCHCOCH3 to give
8 in 76% yield as a 0.9:1.1 cis,trans-diastereomeric
mixture (by NMR). Hydrogenation of 8 in the presence
of catalytic aq HCl using Pd/C, MeOH gave directly the
target 1 in 62% yield in the form of a colourless oil. The
physical and spectral data of compound 1 were in good
agreement with the reported values.6 In the final step,
debenzylation, hydrogenation of the double bonds,
hydrolysis of acetonide and internal acetalization were
successfully carried out in one pot by adding a catalytic
amount of aq HCl.
the late Dr. A. K. Singh for their support and
encouragement.
References and notes
1. Francke, W.;Schroder, F.;Philipp, P.;Meyer, H.;Sinnwell,
V.;Gries, G.
374.
Bioorg. Med. Chem. 1996, 4, 363–
2. Naveen Kumar, D.;Rao, B. V. Tetrahedron Lett. 2004,
44, 2227–2229.
3. Takikawa, H.;Shimbo, K.-i.;Mori, K. Liebigs Ann./Recueil
1997, 821–824.
4. Wiggins, L. J. Chem. Soc. 1946, 13–14.
5. Garegg, P. J.;Samuelsson, B.
470.
Synthesis 1979, 469–
29:2
6. Spectral data for compound 1: colourless oil; ½aꢀD ꢁ79:38
19
(c 1, CHCl3), {lit.1 ½aꢀD ꢁ18 (c 1.91, CHCl3) and lit.3
24
½aꢀD ꢁ79:5 (c 1.94, CHCl3)};IR (film cm ꢁ1): 3440, 2965,
In conclusion we have demonstrated a chiron approach
for the synthesis of 1 starting from D-mannitol.
2936, 1450, 1384, 1240, 1200, 1180, 1044, 1028, 967, 875
and 850; 1H NMR (300MHz, C6D6): d 0.77 (t, 3H,
J = 7.32Hz), 1.37 (s, 3H), 1.17–1.77 (m, 6H), 2.10 (br,
1H, OH), 3.22 (br s, 1H), 3.42 (t, 1H, J = 6.46Hz), 3.82 (br
s, 1H); 13C NMR (75MHz, C6D6): d 9.67, 24.95, 25.51,
28.68, 31.61, 66.00, 79.36, 82.53, 107.85;EI-MS m/z: 143
[M+ꢁ29], 129, 115, 114, 113, 112, 101, 99, 97, 85, 84, 83, 81,
73, 71, 70, 69, 61, 59, 58, 57, 56, 55, 43.
Acknowledgements
D.N.K. thanks the UGC New Delhi for financial assist-
ance (S.R.F). We are grateful to Dr. J. S. Yadav and