Dichlorotin oxide-catalyzed new direct functionalization of olefins: Synthesis of trans β-azidohydrins and 1,2-diols

Article abstract of DOI:10.1016/S0040-4039(00)00176-3

We have succeeded in developing direct syntheses of trans β- azidohydrins and trans 1,2-diol derivatives from olefins catalyzed by dichlorotin oxide. The regioselectivity of these reactions with tri- substituted olefins is high (10:1 in the synthesis of 1,2-diol derivatives) to excellent (>99:1 in the synthesis of azidohydrins). It has been found that these reactions do not proceed via epoxides. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00176-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 2415–2418
Dichlorotin oxide-catalyzed new direct functionalization of
olefins: synthesis of trans β-azidohydrins and 1,2-diols
Isao Sakurada, Shingo Yamasaki, Motomu Kanai and Masakatsu Shibasaki ∗
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Received 27 December 1999; revised 20 January 2000; accepted 21 January 2000
Abstract
We have succeeded in developing direct syntheses of trans β-azidohydrins and trans 1,2-diol derivatives from
olefins catalyzed by dichlorotin oxide. The regioselectivity of these reactions with tri-substituted olefins is high
(10:1 in the synthesis of 1,2-diol derivatives) to excellent (>99:1 in the synthesis of azidohydrins). It has been
found that these reactions do not proceed via epoxides. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: dichlorotin oxide; trans β-substituted alcohol; olefin.
Syntheses of trans β-substituted alcohols from olefins usually require two steps, epoxidation of an
olefin and the following opening of the epoxide. Although this two-step method is well-established,
only one inefficient example is known, where trans 1,2-diol derivatives are formed directly from
olefins.1 Therefore, the development of a direct trans β-substituted alcohol synthesis from olefins is
very important. We recently reported on the SnCl4-catalyzed direct trans chlorohydrin synthesis from
olefins using bis(trimethylsilyl) peroxide (BTSP) and trimethylsilyl chloride (TMSCl) (Scheme 1).2 The
active catalytic species of this reaction is dichlorotin oxide (Cl2SnO)n which is generated from SnCl4
by BTSP. From mechanistic studies, we proposed a catalytic cycle that involves the insertion of a C_C
double bond to dichlorotin oxide, nucleophilic attack of BTSP on Sn and regeneration of (Cl2SnO)n
by SN2 attack of TMSCl. Accordingly, it was expected that it would be possible to apply this catalytic
cycle to other trans β-substituted alcohol syntheses by using the corresponding trimethylsilyl reagents
((CH3)3SiX in Scheme 1). Herein, we report the direct syntheses of trans azidohydrins and trans 1,2-diol
derivatives from olefins catalyzed by dichlorotin oxide.
First, we tried the direct trans β-azidohydrin synthesis from cyclohexene (1.0 mmol) using SnCl4
(10 mol%), BTSP (2 mol equiv.) and trimethylsilyl azide (TMSN3) (2 mol equiv.). As expected, when
performing the reaction at ambient temperature for 7 h the reaction gave trans-2-azido-1-cyclohexanol
(1) (yield 43%), together with the undesired trans-2-chloro-1-cyclohexanol (yield 17%).3 This undesired
formation of the chlorohydrin could be reduced, using pre-generated dichlorotin oxide4 (20 mol%)
∗
Corresponding author. Fax: +81-3-5684-5206; e-mail: mshibasa@mol.f.u-tokyo.ac.jp (M. Shibasaki)
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00176-3
tetl 16456

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Scheme 1. Proposed mechanism
instead of SnCl4, to give the azidohydrin 1 in 52% yield and the chlorohydrin in 10% yield (Table 1,
entry 1).5 Other substrates (cyclic and acyclic olefins) also gave the corresponding trans β-azidohydrins
in acceptable yields (Table 1).6 Furthermore, 1-methyl-1-cyclohexene (Table 1, entry 6) gave 6 with
almost complete regioselectivity.7 To the best of our knowledge, this is the first example of a direct trans
β-azidohydrin synthesis starting with olefins.
Table 1
Synthesis of trans azidohydrins

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Next, we extended the reaction for the synthesis of trans 1,2-diol derivatives. We were pleased to find
that, by using trimethylsilyl acetate (TMSOAc) instead of TMSN3, cyclic and acyclic olefins were also
successfully converted to the corresponding trans β-acetoxy alcohols (Table 2, entries 1, 3, 5 and 6).6
Furthermore, in order to improve the yield, other trimethylsilyl carboxylates were investigated.9 As a
result, we found that trimethylsilyl methoxyacetate, which can coordinate to Sn because of the α-oxygen
atom, improved the yield in the case of cyclohexene and cyclopentene (Table 2, entries 2 and 4).10 Also
in this case, high regioselectivity (10:1) was obtained for 1-methyl-1-cyclohexene to give 13 as the major
product (Table 2, entry 7).
Table 2
Synthesis of trans 1,2-diol derivatives
Interestingly, it was found from the following experiment, that epoxides were not the intermediate
in these azidohydrin and acetoxy alcohol syntheses (Scheme 2). Thus, the reaction of a mixture of
cycloheptene and cyclohexene oxide using (Cl2SnO)n (20 mol%), BTSP (1.2 mol equiv.) and TMSN3
(2 mol equiv.) gave only 3, and 1 was not detected in the reaction mixture. The same reaction using
TMSOAc (2 mol equiv.) instead of TMSN3 gave only 11. In agreement with this result, the epoxide
1
derived from cycloheptene was not detected in the reaction mixtures by TLC and H NMR analyses.
Therefore, we postulate the reaction mechanism as shown in Scheme 1.11
In summary, we have developed a one-step procedure for the synthesis of azidohydrins and acetoxy
alcohols from olefins by the catalysis of (Cl2SnO)n. The development of a catalytic asymmetric version
of these reactions is currently under investigation.

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Scheme 2. Experiment using a mixture of olefin and epoxide
Acknowledgements
We thank CREST and RFTF for financial support.
References
1. trans 1,2-Diol synthesis from olefin (via dibenzoate): Wilson, C. V. In Organic Reactions; Adams, R., Ed.; John Wiley &
Sons, Inc.: New York, 1957; Chapter 6, Vol. 9, p. 350.
2. Sakurada, I.; Yamasaki, S.; Iida, T.; Göttlich, R.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc. in press.
3. The undesired chlorohydrin formation may be due to the in situ generation of TMSCl by the ligand exchange between SnCl4
(or even (Cl2SnO)n) and TMSX (X=N3, OCOR).
4. Preparation of dichlorotin oxide: To a solution of BTSP12 (0.94 M in CH2Cl2, 64 mL, 60 mmol, 3 mol equiv.) was added
SnCl4 (1.0 M in CH2Cl2, 20 mL, 20 mmol) at 0°C under argon. After the mixture was stirred at rt for 2 h, volatiles (solvent,
excess BTSP, chlorine, hexamethyldisiloxane) were evaporated in vacuo to afford dichlorotin oxide (2.4 g, 69%) as a white
powder.
5. General procedure of azidohydrin synthesis: To a CH2Cl2 solution (0.5 mL) of dichlorotin oxide4 (41.1 mg, 0.2 mmol) was
added BTSP (neat, 0.44 mL, 2.0 mmol), cyclohexene (101 µL, 1.0 mmol) and TMSN3 (265 µL, 2.0 mmol) at 0°C under
argon. After 24 h at rt, the reaction was quenched with AcOH–H2O–THF (1.5:1.0:4.0 mL). The mixture was stirred at rt for
10 min, and added dropwise to a mixture of sat. aq. NaHCO3 (20 mL) and 10% aq. Na2SO3 (4 mL) at 0°C. Extraction with
CHCl3 (10 mL×3), evaporation of the solvent and purification by silica gel column chromatography (hexane–AcOEt 10:1)
afforded 1 (74.0 mg, 52%).
6. The moderate isolated total yield of the products (azidohydrins or acetoxy alcohols+chlorohydrins) could be due to the
formation of unknown by-products, whose structure determinations are under investigation.
7. The regioselective synthesis of 6 from 1,2-epoxy-1-methylcyclohexane is usually difficult. (a) Mereyala, H. B.; Frei, B. Helv.
Chim. Acta 1986, 96, 415–418. (Et3Al/HN3, yield 68%; the ratio is not described). (b) Meguro, M.; Asao, N.; Yamamoto,
Y. Chem. Commun. 1995, 1021–1022. (cat. Yb(OiPr)3/TMSN3, total yield 95% (26:74); the regio isomer of 6 is the major
product). (c) Crotti, P.; Bussolo, V. D.; Favero, L.; Macchia, F.; Pineschi, M. Tetrahedron Lett. 1996, 37, 1675–678 [cat.
Hf(OTf)4/1,1,3,3-tetramethylguanidinium azide, total yield 72% (58:42)]. (d) Fringuelli, F.; Piermatti, O.; Pizzo, F.; Vaccaro,
L. J. Org. Chem. 1999, 64, 6094–6096 [NaN3/H2SO4/H2O (pH 4.2), yield 67% (80:20)].
8. The configuration of azidohydrins was determined by comparison with the literature data (compounds 1 and 2: Ref. 13;
compounds 7, 9 and 11: Ref. 2) or by preparing authentic samples from corresponding epoxides.
9. Trimethylsilyl benzoate, trimethylsilyl o-nitrobenzoate, trimethylsilyl chloroacetate or trimethylsilyl dichloroacetate gave
unsatisfactory results.
10. Unexpectedly, cycloheptene and cis-5-decene gave the corresponding trans carbonate in 42 and 46% yields, respectively.
The mechanism is not clear at present. The relative configuration was determined by a comparison with authentic samples
prepared from 11 and 12 [(1) 10% aq. NaOH/MeOH; (2) (Cl3CO)2CO/Et3N/CH2Cl2].
11. For a detailed discussion about the reaction mechanism, see Ref. 2.
12. Jackson, W. P. Synlett. 1990, 536.
13. Zhang, Z.; Scheffold, R. Helv. Chim. Acta 1993, 76, 2602–2615.