Convenient preparation of carbonyl compounds from 1,2-diols utilizing Mitsunobu conditions

Article abstract of DOI:10.1016/S0040-4039(00)00071-X

1,1-Disubstituted 1,2-diols are efficiently converted into carbonyl compounds by reaction with triphenylphosphine and diethyl azodicarboxylate. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00071-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 1959–1962
Convenient preparation of carbonyl compounds from 1,2-diols
utilizing Mitsunobu conditions
Alejandro F. Barrero,∗ Enrique J. Alvarez-Manzaneda and R. Chahboun
Instituto de Biotecnología, Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Granada,
18071 Granada, Spain
Received 4 August 1999; revised 6 January 2000; accepted 11 January 2000
Abstract
1,1-Disubstituted 1,2-diols are efficiently converted into carbonyl compounds by reaction with triphenylphos-
phine and diethyl azodicarboxylate. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: Mitsunobu reactions; diols; aldehydes.
The Mitsunobu reaction is a useful synthetic tool which allows the conversion of an alcohol function
into a wide variety of functional groups.1–8
ROOC–N_N–COOR + Ph3P + R0OH + Nu : → Nu-R0 + Ph3PO + ROOC–NH–NH–COOR
Cyclic compounds are formed when the alcohol molecule contains a suitably placed nucleophile.
Epoxides are obtained from acyclic 1,2-diols under the Mitsunobu conditions9 and from cyclic trans-
1,2-diols.10–13 Under the same conditions triphenylphosphoranes resulted from cyclic cis-1,2-diols.11–14
Methyl shikimate (8a), having cis- and trans-diol groups, leads to the corresponding epoxide 8b, under
these conditions.15
During our research on the synthesis of bioactive compounds from labdane diterpenes we have
found that diol 12a is transformed with excellent yield into drimenal (12b)16 when it is treated with
triphenylphosphine (TPP) and diethyl azodicarboxylate (DEAD) in benzene. In order to elucidate the
scope and synthetic application of this reaction the behaviour of a variety of 1,2-diols with these reagents
has been studied. The results obtained are summarized in Table 1 and compared with those previously
reported. As may be seen, monosubstituted and disubstituted 1,2-diols are converted into epoxides or
phosphoranes, depending on whether the hydroxyl groups adopt an antiperiplanar (cyclic trans-diols and
acyclic diols) or an eclipsed conformation (cis-diols), respectively. The formation of phosphorane 3b
from diol 3a can be attributed to the bulky dioxolane groups which prevent the hydroxyl groups from
adopting the anti disposition. 1,1-Disubstituted-1,2-diols lead to the formation of aldehydes or ketones,
depending on whether the less substituted carbon is primary or secondary. Even acyclic 1,1-disubstituted
∗
Corresponding author.
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00071-X
tetl 16351

1960
Table 1
Reactions of 1,2 diols with the TPP–DEAD system

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Table 1 (continued)
diols, such as 4a, yield a significant amount of carbonyl derivative (4c), along with the expected epoxide
(4b); in the case of benzyl derivatives, such as 15a, the carbonyl compound is favoured.
The relative stereochemistry of compounds 9a–b, 10a–b, 11a–b and 14a–b was established on the

1962
basis of spectroscopic evidence and through NOE experiments.18 The 1H NMR spectrum of 9b showed
overlapped signals, making analysis of the NOE experiments difficult. This compound undergoes easy
oxidation by air to the corresponding acid 9c, whose spectrum was unequivocally assigned. Diols
11a–13a are intermediates of our synthetic research and were chemically correlated. Compounds 12b
and 13b showed identical properties to those reported in the literature.16,17
In summary, this reaction, which takes place under neutral conditions, constitutes a mild alternative
for preparing carbonyl derivatives from alkenes.
Acknowledgements
The authors thank the CYCYT (Project PB98-1365) for financial support.
References
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12. Mengel, R.; Bartke, M. Angew. Chem., Int. Ed. Engl. 1978, 17, 697–780.
13. Kinoshita, M.; Taniguchi, M. Bull. Chem. Soc. Jpn. 1988, 61, 2147–2156.
14. Kimura, J.; Fujisawa, Y.; Sawada, T.; Mitsunobu, O. Chem. Lett. 1974, 691–692.
15. McGowan, D. A.; Berchtold, G. A. J. Org. Chem. 1981, 46, 2381–2383.
16. Razmilic, I.; Sierra, J. R.; Cortés, M. Chem. Lett. 1985, 1113.
17. Simmons, D. P.; Reichlin, D.; Skuy, D. Helv. Chim. Acta 1988, 71, 1000–1006.
18. All new compounds were fully characterized spectroscopically and had satisfactory high resolution mass spectroscopy
data. Compound 9a: 1H NMR (400 MHz, CDCl3): δ 0.90 (s, 3H, Me-C2), 0.99 (s, 3H, Me-C2), 1.10 (bd, J=10.1 Hz, H-7),
1.22–1.46 (m, 3H, H-5, H-6), 1.54 (m, 1H, H-5), 1.72 (bs, 1H, H-1), 2.01 (bd, J=10.1 Hz, 1H, H-7), 2.09 (dd, J=4.7, 1.3 Hz,
1H, H-4), 2.55 (bs, 2H, OH), 3.56 (d, J=11.2 Hz, 1H, CH2OH), 3.68 (d, J=11.2 Hz, 1H, CH2OH). Observed NOEs: 3.56 and
3.68 with 0.90; 0.99 with 2.01. Compound 9b: 1H NMR (400 MHz, CDCl3): δ 1.10 (s, 3H, Me-C2), 1.13 (s, 3H, Me-C2),
1.28 (dt, J=9.9, 1.5 Hz, 1H, H-7), 1.34–1.51 (m, 2H, H-5, H-6), 1.59–1.74 (m, 3H, H-5, H-6, H-7), 1.89 (dd, J=3.2, 1.5 Hz,
1H, H-4), 2.09 (ddd, J=3.8, 2.3, 2.3 Hz, 1H, H-3), 2.53 (t, J=4.2 Hz, 1H, H-1), 9.84 (d, J=2.3 Hz, 1H, CHO). Compound
9c: 1H NMR (400 MHz, CDCl3): δ 1.03 (s, 3H, Me-C2), 1.12 (s, 3H, Me-C2), 1.25 (bd, J=10.1 Hz, 1H, H-7), 1.33 (m, 1H,
H-5), 1.41 (m, 1H, H-6), 1.63 (d, J=10.1 Hz, 1H, H-7), 1.68 (m, 1H, H-5), 1.86 (bs, 1H, H-4), 1.97 (m, 1H, H-6), 2.38 (bs,
1H, H-3), 2.44 (bs, 1H, H-1), 10.32 (s, 1H, COOH). Observed NOE: 2.38 with 1.25. Compound 10b: 1H NMR (400 MHz,
CDCl3): δ 0.70 (s, 3H, Me-C6), 1.20 (s, 3H, Me-C6), 1.25 (m, 1H, H-5), 1.80–1.95 (m, 3H, H-3, H-4, H-5), 2.10 (m, 1H,
H-3), 2.25 (m, 1H, H-5), 2.38 (m, 1H, H-7), 2.53 (m, 1H, H-1), 2.74 (m, 1H, H-2), 9.75 (s, 1H, CHO). Observed NOEs:
9.75 with 0.70 and 1.20. Compound 11b: 1H NMR (300 MHz, CDCl3): δ 0.74 (s, 3H, Me-16), 0.79 (s, 3H, Me-15), 0.86 (s,
3H, Me-14), 1.20–1.60 (m, 10H, H-2, H-20, H-6, H-60, H-7, H-1, H-3, H-9, H-11), 1.71 (m, 2H, H-3, H-11), 1.95 (m, 1H,
H-7), 2.33 (m, 1H, H-2), 2.43 (bt, J=5.0 Hz, 1H, H-8), 3.62 (t, J=6.4 Hz, 2H, H-12), 4.48 (d, J=12.0 Hz, 1H, OCH2Ph), 4.55
(d, J=12.0 Hz, 1H, OCH2Ph), 7.38 (m, 5H, Bn), 10.01 (s, 1H, H-13). Observed NOE: 10.01 with 0.74. Compound 14b: 1H
NMR (400 MHz, CDCl3): δ 0.03 (s, 3H, Me-Si), 0.04 (s, 3H, Me-Si), 0.83 (s, 3H, Me-13), 0.85 (s, 3H, Me-14), 0.87 (s, 9H,
t-Bu-Si), 0.94 (dt, J=13.0, 3.9 Hz, 1H, H-1α), 1.04 (d, J=6.4 Hz, 3H, Me-12), 1.12 (m, 1H, H-9), 1.14 (s, 3H, Me-15), 1.17
(dd, J=13.5, 3.9 Hz, 1H, H-3α), 1.19 (d, J=3.8 Hz, H-5), 1.42 (bd, J=12.6 Hz, 1H, H-3β), 1.47 (dq, J=13.1 Hz, 1H, H-2α),
1.64 (dt, J=13.7, 10.4, 3.4 Hz, 1H, H-2β), 1.86 (bd, J=13.1 Hz, 1H, H-1β), 2.31 (d, J=13.9 Hz, 1H, H-6), 2.36 (dd, J=13.9,
3.8 Hz, 1H, H-6), 2.65 (dq, J=12.2, 6.4 Hz, 1H, H-8), 3.59 (dd, J=11.0, 4.1 Hz, 1H, H-11), 3.85 (dd, J=11.0, 1.7 Hz, 1H,
H-11).