Regioselective and Stereospecific Azidation of 1,2- and 1,3-Diols by Azidotrimethylsilane via a Mitsunobu Reaction

Article abstract of DOI:10.1021/jo9906375

A one-pot regio- and stereospecific azidation reaction of 1,2- and 1,3-diols with azidotrimethylsilane (MB₃SiN₃) via a Mitsunobu reaction has been achieved. With 1,2- and 1,3-diols, the reaction of triphenylphosphine, diisopropyl azodicarboxylate, and Me₃SiN₃ in dichloromethane gave regioselective azidation at C-2 and C-3, respectively, in good yield (74-90% combined yield of 1a + 1b or of 2a + 2b). However, application of the same reaction conditions to a 1,4-diol led to the exclusive formation of the cyclic ether. The regioselectivity of this one-pot reaction is influenced by the solvent, the degree of steric bulk at C-2 of the 1,2-diol or at C-3 of the 1,3-diol, and the presence of electron-donating and electron-withdrawing groups near the secondary carbinol carbon. This selectivity is discussed in terms of the mechanistic model proposed by Mathieu-Pelta and Evans (Mathieu-Pelta, I.; Evans, S. A., Jr. J. Org. Chem. 1992, 57, 3409-3413), which involves reaction of the dioxaphospholane intermediate with Me₃SiN₃ to form oxyphosphonium ions 4 and 5.

Full text of DOI:10.1021/jo9906375

J . Org. Chem. 1999, 64, 6049-6055
6049
Regioselective a n d Ster eosp ecific Azid a tion of 1,2- a n d 1,3-Diols by
Azid otr im eth ylsila n e via a Mitsu n obu Rea ction
Linli He, Meni Wanunu, Hoe-Sup Byun, and Robert Bittman*
Department of Chemistry and Biochemistry, Queens College of The City University of New York,
Flushing, New York 11367-1597
Received April 16, 1999
A one-pot regio- and stereospecific azidation reaction of 1,2- and 1,3-diols with azidotrimethylsilane
(Me3SiN3) via a Mitsunobu reaction has been achieved. With 1,2- and 1,3-diols, the reaction of
triphenylphosphine, diisopropyl azodicarboxylate, and Me3SiN3 in dichloromethane gave regiose-
lective azidation at C-2 and C-3, respectively, in good yield (74-90% combined yield of 1a + 1b or
of 2a + 2b). However, application of the same reaction conditions to a 1,4-diol led to the exclusive
formation of the cyclic ether. The regioselectivity of this one-pot reaction is influenced by the solvent,
the degree of steric bulk at C-2 of the 1,2-diol or at C-3 of the 1,3-diol, and the presence of electron-
donating and electron-withdrawing groups near the secondary carbinol carbon. This selectivity is
discussed in terms of the mechanistic model proposed by Mathieu-Pelta and Evans (Mathieu-Pelta,
I.; Evans, S. A., J r. J . Org. Chem. 1992, 57, 3409-3413), which involves reaction of the
dioxaphospholane intermediate with Me3SiN3 to form oxyphosphonium ions 4 and 5.
In tr od u ction
SnCl2,9 SmI2,10 Bu3SnH/AIBN11). This approach is par-
ticularly important since several powerful enantioselec-
tive methods can be used to prepare epoxides12 and
vicinal diols,1d which are facile precursors of azidohy-
drins. Moreover, azides can be converted in situ to
carbamates,13 amides,14 and other derivatives.
A 2-amino-1-ol and 3-amino-1-ol substructure is a
common component of many natural products. Chiral 1,2-
and 1,3-amino alcohols are also versatile building blocks
for the synthesis of a wide range of biologically important
compounds and are precursors of ligands for asymmetric
reaction catalysis.1 Many synthetic methods are available
for the direct installation of the amino alcohol function-
alities into a substrate. Well-known methods for the
preparation of amino alcohols are opening of epoxides2
or cyclic sulfates3 by amines, reduction of R- and â-amino
acids,4 and asymmetric aminohydroxylation of olefins.5
Ring opening of epoxides by azide ion (NaN3, LiN3, or
Me3SiN3) in the presence of a promoter (e.g., LiClO4,15a
Al(i-PrO)3,15b Ti(OPr-i)4,15c,d BF3‚Et2O,15e MgSO4,2a and
NH4Cl2a) gives vicinal azidohydrins. However, in these
reactions azide ion generally attacks the C-1 position of
terminal epoxides and the C-3 position of 2,3-epoxy
alcohols. Ring opening of cyclic sulfates by azide ion gives
a similar regioselectivity.3 These methods are thus not
suitable when C-2 substitution is desired. The synthesis
of C-2 monoazido alcohols from diols is usually achieved
by a multistep reaction sequence involving selective
protection, activation, azide substitution, and deprotec-
tion. In 1992, an efficient regioselective and stereospecific
method was described for converting a 1,2-propanediol
into a 2-azido-1-silyloxypropane.16a This reaction utilized
formation of a 1,3,2-dioxaphospholane by reaction of 1,2-
propanediol and (EtO)2PPh3 (generated by reaction of
Azidohydrins are attractive precursors of amino alco-
hols because many efficient methods are known for the
conversion of an azide to an amine (e.g., Ph3P/THF-
H2O,6 LiAlH4, catalytic hydrogenation,7 H2S/pyridine,8
* To whom correspondence should be addressed. Tel.: (718) 997-
3279. Fax: (718) 997-3349. E-mail: robert_bittman@qc.edu.
(1) (a) Shioiri, Y.; Hamada, Y. Heterocycles 1988, 27, 1035-1050.
(b) Barlow, C. B.; Bukhari, S. T.; Guthrie, R. D.; Prior, A. M. In
Asymmetry in Carbohydrates; Dekker: New York, 1979; pp 81-99. (c)
Blaser, H.-U. Chem. Rev. 1992, 92, 935-952. (d) Kolb, H. C.; Van-
Nieuwenhze, M. S.; Sharpless, K. B. Chem. Rev. 1994, 94, 2483-2547.
(2) (a) Sharpless, K. B.; Behrens, C. H.; Katsuki, T.; Lee, A. W. M.;
Martin, V. S.; Takatani, M.; Viti, S. M.; Walker, F. J .; Woodward, S.
S. Pure Appl. Chem. 1983, 55, 589-604. (b) Behrens, C. H.; Sharpless,
K. B. Aldrichim. Acta 1983, 16, 67-79. (c) Askin, D.; Eng, K. K.;
Rossen, K.; Purick, R. M.; Wells, K. M.; Volante, R. P.; Reider, P. J .
Tetrahedron Lett. 1994, 35, 673-676. (d) Hanson, R. M. Chem. Rev.
1991, 91, 437-475. (e) Klunder, J . M.; Ko, S. Y.; Sharpless, K. B. J .
Org. Chem. 1986, 51, 3710-3712.
(8) (a) Adachi, T.; Yamada, Y.; Inoue, I. Synthesis 1977, 45-46. (b)
Becher, J .; Pluta, K.; Krake, N.; Brondum, K.; Christensen, N. J .;
Vinader, M. V. Synthesis 1989, 530-533.
(9) Maiti, S. N.; Singh, M. P.; Micetich, I. G. Tetrahedron Lett. 1986,
27, 1423-1424.
(10) (a) Huang, Y.; Zhang, Y.; Wang, Y. Tetrahedron Lett. 1997, 38,
1065-1066. (b) Goulaouic-Dubois, C.; Hesse, M. Tetrahedron Lett.
1995, 36, 7427-7430. (c) Benati, L.; Montevecchi, P. C.; Nanni, D.;
Spagnolo, P.; Volta, M. Tetrahedron Lett. 1995, 36, 7313-7314.
(11) (a) Samano, M. C.; Robins, M. J . Tetrahedron Lett. 1991, 32,
6293-6296. (b) Pupeiko, N. E.; Prikota, T. I.; Mikhailopulo, I. A. Synlett
1991, 342-342.
(12) Katsuki, T.; Martin, V. Org. React. 1996, 48, 1-300.
(13) Saito, S.; Nakajima, H.; Inaba, M.; Moriwake, T. Tetrahedron
Lett. 1989, 30, 837-838.
(14) Byun, H.-S.; Bittman, R. J . Org. Chem. 1996, 61, 8706-8708.
(15) (a) Chini, M.; Crotti, P.; Flippin, L. A.; Macchia, F. J . Org. Chem.
1990, 55, 4265-4272. (b) Emziane, M.; Lhoste, P.; Sinou, D. Synthesis
1988, 541-544. (c) Caron, M.; Sharpless, K. B. J . Org. Chem. 1985,
50, 1557-1560. (d) Chong, J . M.; Sharpless, K. B. J . Org. Chem. 1985,
50, 1560-1563. (e) Behrens, C. H.; Sharpless, K. B. J . Org. Chem. 1985,
50, 5696-5704.
(3) For a review, see: Lohray, B. B.; Bhushan, V. Adv. Heterocycl.
Chem. 1997, 68, 89-180.
(4) (a) Gage, J . R.; Evans, D. A. Org. Synth. 1988, 67, 77-82. (b)
Smith, G. A.; Gawley, R. E. Org. Synth. 1984, 63, 136-139. (c)
Poindexter, G. S.; Meyers, A. I. Tetrahedron Lett. 1977, 40, 3527-
3528. (d) Kokotos, G.; Noula, C. J . Org. Chem. 1996, 61, 6994-6996.
(e) Coppola, G. M.; Schuster, H. F. Asymmetric Synthesis: Construction
of Chiral Molecules Using Amino Acids; Wiley: New York, 1987.
(5) For asymmetric aminohydroxylation of olefins, see: Bruncko, M.;
Schlingloff, G.; Sharpless, K. B. Angew. Chem., Int. Ed. Engl. 1997,
36, 1483-1486 and references therein.
(6) For a review about the Staudinger reaction, see: Gololobov, Y.
G.; Zhmurova, I. N.; Kasukhin, L. F. Tetrahedron 1981, 37, 437-472.
(7) Scriven, E. F. V.; Turnbull, K. Chem. Rev. 1988, 88, 297-368.
10.1021/jo9906375 CCC: $18.00 © 1999 American Chemical Society
Published on Web 07/16/1999

6050 J . Org. Chem., Vol. 64, No. 16, 1999
He et al.
Ta ble 1. Regioselective Azid a tion of 1,2-Diols via a
Mitsu n obu Rea ction
Ta ble 2. Solven t Effects on th e Regioselectivity of
Azid a tion u n d er Mitsu n obu Con d ition sa
a
Typical reaction times required for the overall conversion of
a diol to 1a and 1b: 7 h in THF and CH2Cl2, 12 h in PhCH3.
a
The ratio was calculated from the isolated yields of 1a and
stirred at this temperature until azide substitution was
completed. After desilylation (n-Bu4NF in THF), the
products were purified by column chromatography.
The regioselectivity of the monoazidation of 1,2-diols
is summarized in Table 1. With one exception, the diols
shown in Table 1 gave 2-azido-1-ol 1a as the major
product. (Since the diol shown in entry 9 did not undergo
azide substitution even at room temperature, the reaction
mixture was heated to 70 °C; the primary azide 1b of
the protected mannose was obtained almost exclusively.)
The highest C-2 regioselectivity was observed when R
was n-hexyl (Table 1, entry 7). The possible reasons for
the lower regioselectivity found with glycerol derivatives
(Table 1, entries 1-5) and for the lower yield obtained
from benzylthioglycerol (Table 1, entry 4) are discussed
below.
Solven t Effect on th e Azid a tion of 1,2-Diols. The
influence of solvent on the reaction was studied. The
three substrates shown in Table 2 were randomly se-
lected, and three solvents commonly used in the Mit-
sunobu reaction19 were tested. It is clear that the
regioselectivity but not the yield of the reaction depends
on the solvent, with the highest degree of regioselectivity
taking place in toluene and the lowest in THF.
1b. Isolated yield. c During the reaction, rearrangement takes
b
place via an episulfenium ion intermediate to give (S)-3-azido-2-
d
benzylthio-1-propanol.26 The reaction with Me3SiN3 was carried
out at 70 °C.
Ph3P with diethyl peroxide) to activate the alcohol and
Me3SiX (X ) PhS, I, Br, Cl, CN, and N3) as nucleophiles,
mainly for the purpose of mechanistic study. In the course
of our efforts to convert a hindered secondary hydroxy
group to an azide under mild conditions, we found that
addition of Me3SiN3 to a mixture of diisopropyl azodi-
carboxylate (DIAD), triphenylphosphine, and a 1,3-diol
also provided the secondary azide in good yield and with
excellent stereocontrol. The use of DIAD rather than the
hazardous EtOOEt as the phosphine activator represents
a significant advantage. In view of the potential impor-
tance of azidation of diols, a detailed study has been
carried out, and herein we report some synthetic applica-
tions of this reaction.
Resu lts
Azid a t ion of 1,2-Diols (Der iva t ives of P r op a n e-
1,2-d iol a n d Glycer ol). Chiral 1,2-diols were prepared
either by catalytic asymmetric dihydroxylation (entries
1, 2, and 6-8 of Table 1)17 or by nucleophilic opening of
chiral glycidol (entries 3-5).18 The one-pot conversion of
a 1,2-diol to its azido alcohol was performed by adding
DIAD to a mixture of diol and Ph3P in THF at 0 °C. After
3 h, Me3SiN3 was injected, and the reaction mixture was
Azid a tion of 1,3- a n d 1,4-Diols. Similarly, the one-
pot azidation reactions of 1,3- and 1,4-diols were carried
out.20 It is obvious that under the same conditions
regioselective azide substitution also occurred at the more
hindered C-3 position of the 1,3-diols shown in Table 3.
However, with a 1,4-diol (R ) n-C14H29) a tetrahydrofuran
derivative was formed exclusively, presumably via an
(16) (a) Mathieu-Pelta, I.; Evans, S. A., J r. J . Org. Chem. 1992, 57,
3409-3413. (b) Pautard, A. M.; Evans, S. A., J r. J . Org. Chem. 1988,
53, 2300-2303.
(19) Hughes, D. V. Org. React. 1992, 42, 335-656.
(17) Byun, H.-S.; Erukulla, R. K.; Bittman, R. J . Org. Chem. 1994,
59, 2630-2633.
(20) Chiral 1,3-diols were synthesized via the following sequence of
reactions: (1) catalytic asymmetric dihydroxylation of R,â-unsaturated
esters, (2) formation of cyclic sulfates, (3) opening of the cyclic sulfate
with LiBr, (4) debromination of the R-bromide ester with Bu3SnH/
AIBN, and (5) ester reduction by DIBAL-H.
(18) (a) Erukulla, R. K.; Byun, H.-S.; Locke, D. C.; Bittman, R. J .
Chem. Soc., Perkin Trans. 1 1995, 2199-2200. (b) Byun, H.-S.;
Bittman, R. J . Org. Chem. 1994, 59, 688-671.

Azidation of 1,2- and 1,3-Diols by TMSN3, Ph3P, and DIAD
J . Org. Chem., Vol. 64, No. 16, 1999 6051
Ta ble 3. Regioselective Azid a tion of 1,3-Diols via a
Mitsu n obu Rea ction a
a
b
The starting diols were prepared as outlined in ref 20. The
ratio was calculated from the isolated yields of 2a and 2b.
c Isolated yield.
Ta ble 4. Ster eosp ecificity of Azid a tion
F igu r e 1. Partial 13C NMR spectra of (R)-(-)-MTPA esters
of 2-azido-1-hexadecanol (A-C) and 3-azido-1-octadecanol (D-
F). Mosher esters derived from: (A) a 1.00:1.13 mixture of (2R)-
2-azido-1-hexadecanol and (2S)-2-azido-1-hexadecanol; (B)
(2R)-2-azido-1-hexadecanol; (C) (2S)-2-azido-1-hexadecanol; (D)
a 1.19:1.00 mixture of (2R)-3-azido-1-octadecanol and (2S)-3-
azido-1-octadecanol; (E) (2R)-3-azido-1-octadecanol; and (F)
(2S)-3-azido-1-octadecanol.
Sch em e 1. Su ggested Mech a n ism for th e
F or m a tion of 1a a n d 1b via
1,3,2λ5-Dioxa p h osp h ola n es 3a a n d 3b
a
The enantiomeric excess of the starting diols was determined
by analysis of the 1H NMR spectra of the bis-MTPA esters. The
b
enantiomeric excess of the secondary azides was determined by
analysis of the 13C NMR spectra of the azido-MTPA ester (Figure
1).
intramolecular Mitsunobu reaction due to the facile
formation of a five-membered ring.
Ster eosp ecificity of Azid a tion . One representative
example of a 1,2- and 1,3-diol was selected to evaluate
the stereospecificity of the azidation. The enantiomeric
excess of the starting diols was determined by analysis
1
of the H NMR spectra of the bis-MTPA esters, while for
that of the azidohydrins, 13C NMR analysis of the
corresponding azido-MTPA ester was employed since
1
baseline separations were not obtained in their H NMR
spectra. The excellent stereospecificity of the reaction is
demonstrated in Table 4 and Figure 1. In each reaction,
the chiral purity of the product was as high as that of
the starting diol.
dorotation. (2) Silylation at the more basic P-O apical
oxygen21 leads to the formation of (silyloxy)phosphonium
ions 4 and 5, which was confirmed by 31P NMR spectros-
copy (δ 62.0 and 63.5 ppm, respectively16b). (3) The
transition state leading to 3b′ experiences severe steric
hindrance since the trimethylsilyl group is sandwiched
between the C-4 alkyl group and the equatorial PdC6H5
groups in the trigonal-bipyramidal array. Thus, forma-
tion of C-2 siloxyphosphonium ion 4 is favored. (4)
Subsequent SN2 displacement of Ph3PO by azide ion
affords the C-2-N3 regioisomer 1a as the major product.
Discu ssion
Mech a n ism . Although the reaction conditions in the
current study are different from those reported previ-
ously,16a our results support and extend the mechanism
proposed by Mathieu-Pelta and Evans.16a Scheme 1
illustrates the following steps: (1) The reaction of an
alkyl (S)-1,2-propanediol with triphenylphosphine and
DIAD furnishes two conformational isomers, 3a and 3b,
which undergo a rapid interconversion through a pseu-
(21) Luckenbach, R. Dynamic Stereochemistry of Pentacoordinated
Phosphorus and Related Elements; George Thieme: Stuttgart, FRG,
1973.

6052 J . Org. Chem., Vol. 64, No. 16, 1999
He et al.
Ta ble 5. Azid a tion vs Silyla tion of P r im a r y, Secon d a r y,
a n d Ter tia r y Alcoh ols w ith Me3SiN3 via a Mitsu n obu
Rea ction
Me3SiN3 a s a Sou r ce of Azid e Ion . It is well known
that cyclic sulfates are very reactive toward nucleophilic
ring opening.22 However, attempted reaction between
Me3SiN3 and the cyclic sulfate of (S)-1-(4′-methoxyphe-
-
nyl)glycerol revealed that little N3 was available from
Me3SiN3 in THF and CH2Cl2, since no ring opening
occurred at all, even after 48 h of reflux in THF (94% of
the starting cyclic sulfate was recovered). This result
suggests that dioxaphosphorane 3a or 3b first reacts with
Me3SiN3 to form the ion pair 3a ′ or 3b′, which then
generates (silyloxy)phosphonium ion 4 or 5 and azide ion.
Regioselectivity of Azid a tion . (a ) Ster ic Effect. We
propose that the regiochemistry of the reaction is con-
trolled not only by steric congestion presented in the
apical oxygen atom of dioxaphosphoranes 3a and 3b but
also by the rate of the azide displacement reaction with
4 or 5. As demonstrated in Tables 1 and 3, all of the
azidation reactions (except that in entry 9, Table 1)
-
showed a consistent attack of N3 at the more hindered
secondary carbinol position. This result suggests that
nucleophilic substitution by N3- is not the rate-determin-
ing step of the overall reaction. If so, 1b instead of 1a
would be the major product (Curtin-Hammett prin-
ciple).23
with PhSNa decreases from 1.0 to 0.18 and to 0.16 when
X is changed from CH3 to Cl and to F.25a This result may
explain why the regioselectivities in entries 1-5 (Table
1) and entry 1 (Table 3) are lower than those in entries
6 and 7 (Table 1) and entries 2 and 3 (Table 3),
respectively. The largest effect was observed in entries
1 and 2 (Table 1), where phenyloxy groups are stronger
electron-withdrawing groups than benzyloxy and alkoxy
groups (entries 3 and 5 of Table 1, respectively). Such
â-carbon electronic effects are also known to take place
in nucleophilic opening reactions of epoxides.2
Finally, part of the oxyphosphonium ion 4 derived from
benzylthioglycerol undergoes intramolecular displace-
ment to form a sulfenium ion, which after ring opening
by N3- leads to a 2-benzylthio-3-azide derivative (14%).26
Therefore, the yield of 1a is lower (entry 4, Table 1).
Solven t Effect. Although the solvent also plays a role
in determining the regioselectivity of the reaction, and a
nonpolar solvent seems to favor formation of the C-2-N3
product (Table 2), it is worthwhile to point out that
CH2Cl2 is the solvent of choice among the three studied
here. All of the diols studied have poor solubility in
toluene at 0 °C; therefore, prolonged reaction time is
required, and sometimes reaction is incomplete.
Ap p lica tion of th e Azid a tion to Sim p le Alcoh ols.
Azidation of simple alcohols by the Mitsunobu reaction
is well known using diphenylphosphoryl azide, hydrazoic
acid, and zinc azide/pyridine complex.19 Table 5 shows
the results of azidation of simple alcohols with Ph3P,
DIAD, and Me3SiN3. Since Me3SiN3 needs to be activated
prior to the azide substitution reaction, it was predictable
that the maximum yield of the azido derivative that could
be realized would be 50% (to get one N3- from Me3SiN3,
one alcohol will be consumed to form Me3SiOR). Azidation
of cetyl alcohol proceeded in 46% yield, whereas a
secondary alcohol bearing a 1,3-benzylidene group gave
a poor yield. The failure of the azidation reaction with a
tertiary alcohol (Table 5) may reflect the inability of this
substrate to react with Ph3P to form an oxyphosphonium
ion.
Steric hindrance in the R group causes the less
hindered apical oxygen21 of dioxaphosphorane 3a to
attack Me3SiN3 to give 3a ′; a similar attack after pseu-
dorotation would yield the hindered ion pair 3b′. After
ring opening, oxyphosphonium ion 4 is favored over 5.
Therefore, C-2-N3/C-3-N3 becomes the major product
(except in entry 9, Table 1). Although a bigger R group
is expected to give a higher ratio of 4/5, it would also slow
the subsequent SN2 reaction of 4 to a greater extent than
it would for that of 5. Hence, when the R group of the
16a
1,2-diol is changed from CH3 to n-C6H13 and to n-C14H29,
the regioselectivity (1a /1b ratio) decreases from >99:116a
to >50:1 and to 20:1, since 4 can interconvert to 5 prior
to undergoing direct reaction with N3-. When the R group
-
in a diol is very bulky, the approach of N3 at the
secondary carbinol carbon of 4 can be totally blocked. In
this case, nucleophilic displacement can only take place
at the primary position, and the C-1-N3 derivative would
become the major product. Entry 9 in Table 1 reflects
such a situation, where R is bulky and molecular model-
ing indicates that one of the methyl groups in the
isopropylidene moiety is positioned at the back of the
leaving Ph3PO.
(b) Electr on ic Effect. The data presented in Tables
1 and 3 suggest that, in addition to the steric effect
discussed above, a significant electronic effect is also
observed in the azidation of 1,2- and 1,3-diols. Since the
carbon atom bearing the leaving group is more electron-
deficient in the SN2 transition state than in the ground
state,24 most SN2 reactions are retarded by the presence
of electron-withdrawing substituents at the â-carbon
atom.25 For example, the relative SN2 rate of XCH2CH2Br
(22) Gao, Y.; Sharpless, K. B. J . Am. Chem. Soc. 1988, 110, 7538-
7539.
(23) For a discussion of the Curtin-Hammett principle, see: (a)
Carey, F. A.; Sundberg, R. J . In Advanced Organic Chemistry; Plenum
Press: New York, 1990; pp 215-216. (b) Seeman, J . I. Chem. Rev. 1983,
83, 83-134.
(24) Streitwieser, A., J r. Chem. Rev. 1956, 56, 571-752.
(25) (a) Hine, J .; Brader, W. H., J r. J . Am. Chem. Soc. 1953, 75,
3964-3966. (b) Bordwell, F. G.; Brannen, W. T., J r. J . Am. Chem. Soc.
1964, 86, 4645-4650. (c) Winstein, S.; Allred, E.; Heck, R.; Glick, R.
Tetrahedron 1958, 3, 1-13.
Con clu sion
The one-pot regio- and stereospecific azidation of 1,2-
and 1,3-diols with Ph3P, DIAD, and Me3SiN3 under
(26) Eames, J .; Warren, S. Tetrahedron Lett. 1996, 37, 3525-3528.

Azidation of 1,2- and 1,3-Diols by TMSN3, Ph3P, and DIAD
J . Org. Chem., Vol. 64, No. 16, 1999 6053
one-pot mode, the crude products were dissolved in a minimum
volume of hexane and transferred to a silica gel column for
chromatographic separation (elution first with 150 mL of
hexanes-EtOAc 50/1, then with the appropriate mixture of
hexanes-EtOAc).
Mitsunobu conditions has been achieved in good yield.
This mild method avoids a multistep protection and
deprotection procedure and is compatible with a broad
range of functional groups that may be present in the
diol. The regioselectivity of the reaction appears to be
sensitive to the size of the alkyl substituent, the electronic
distribution of the substrate, and the polarity of the
solvent. This reaction combination is not suitable for the
conversion of a simple alcohol to its azido derivative
because Me3SiN3 is a poor nucleophile.
(S)-2-Azid o-3-O-(4′-ch lor op h en yl)-1,3-p r op a n ed iol: mp
36.5-37.5 °C; [R]25 -22.1° (c 1.5, CHCl3); IR (CHCl3) 3611,
D
3442, 2125, 2110, 1511, 1235, 1040, 839 cm-1; 1H NMR δ 1.96
(br s, 1H), 3.75 (dd, 1H, J ) 11.4, 5.9 Hz), 3.88 (m, 2H), 4.07
(dd, 1H, J ) 9.7, 6.7 Hz), 4.12 (dd, 1H, J ) 9.8, 4.7 Hz), 6.83
(d, 2H, J ) 8.9 Hz), 7.23 (d, 2H, J ) 8.9 Hz); 13C NMR δ 61.99,
62.17, 68.07, 115.79, 126.40, 129.43, 156.68. Anal. Calcd for
C9H10O2N3Cl: C, 47.48; H, 4.43; N, 18.64; Cl, 15.57. Found:
C, 47.56; H, 4.21; N, 18.56; Cl, 15.27.
Exp er im en ta l Section
(R)-3-Azido-1-O-(4′-ch lor oph en yl)-1,2-pr opan ediol: [R]25
D
Gen er a l In for m a tion . See refs 14 and 17 for general
experimental protocols. 1H and 13C NMR spectra were recorded
at 400 and 100 MHz on a Bruker spectrometer, respectively,
and were referenced to the residual CHCl3 at 7.24 (1H) and
77.00 ppm (13C). Deuterated chloroform (CDCl3) was used as
the only solvent for all of the NMR analysis. (R)-(-)-R-
Methoxy-R-trifluoromethylphenylacetic acid chloride, DIAD,
TBAF, and Me3SiN3 were purchased from Fluka, Lancaster,
Aldrich, and Acros, respectively, and were used as provided
commercially without further purification. Elemental analyses
were carried out by Schwarzkopf Microanalytical Laboratory
(Woodside, NY). Melting points are uncorrected.
Gen er a l P r oced u r e for th e Azid a tion of 1,2- a n d 1,3-
Diols. Meth od A (On e-P ot Mod e). To a solution of a diol
(1.0 mmol) and Ph3P (342 mg, 1.3 mmol) (both thoroughly dried
overnight under vacuum of 0.7 Torr) in 18 mL of dry solvent
(THF, CH2Cl2, or PhCH3) was injected 311 µL (1.5 mmol) of
DIAD27 at 0 °C. After the yellow reaction mixture was stirred
at this temperature for 3 h under nitrogen, 211 µL (1.3 mmol)
of Me3SiN3 was injected. CAUTION: Me3SiN3 is sensitive to
H2O, releasing toxic hydrazoic acid on hydrolysis. Therefore,
Me3SiN3 should be used only in a well-ventilated hood, and
skin contact should be avoided. The reaction mixture (either
a clear solution or sometimes a suspension) was stirred at the
same temperature for 3 h and then allowed to warm to room
temperature. After removal of the solvent, the residue was
dissolved in 3 mL of THF and treated with 2.5 mL of a 1 M
TBAF solution in THF containing 5 wt % of H2O.28 The brown
reaction mixture was stirred at room temperature until all of
the silyloxy azides 1a -OTMS and 1b-OTMS were consumed
completely (TLC). Concentration gave a slurry, which was
dissolved in CH2Cl2 and passed through a pad of silica gel in
a sintered glass funnel to remove Ph3PO and salts. The pad
was washed with a mixture of hexanes-EtOAc (usually 6/1)
depending on the polarity of the products. The crude products
were purified by silica gel chromatography (elution first with
150 mL of hexanes-EtOAc 50/1 and then with the appropriate
mixture of hexanes-EtOAc).
+13.3° (c 1.4, CHCl3); IR (CHCl3) 3605, 3446, 2111, 1507, 1041,
1
830 cm-1; H NMR δ 2.24 (br s, 1H), 3.47 (dd, 1H, J ) 12.7,
6.1 Hz), 3.52 (dd, 1H, J ) 12.6, 4.6 Hz), 3.96 (d, 2H, J ) 5.2
Hz), 4.14 (m, 1H), 6.80 (d, 2H, J ) 8.9 Hz), 7.25 (d, 2H, J )
8.9 Hz); 13C NMR δ 53.30, 69.19, 69.32, 115.79, 126.38, 129.45,
156.78.
(S)-2-Azido-3-O-(4′-m eth oxyph en yl)-1,3-pr opan ediol: mp
52.5-53.0 °C; [R]25 -29.0° (c 1.2, CHCl3); IR (CHCl3) 3601,
D
3432, 2126, 2110, 1511, 1235, 1040, 825 cm-1; 1H NMR δ 1.92
(br s, 1H), 3.74 (dd, 1H, J ) 11.1, 5.8 Hz), 3.75 (s, 3H), 3.85
(m, 2H), 4.05 (dd, 1H, J ) 9.8, 6.4 Hz), 4.09 (dd, 1H, J ) 9.8,
4.7 Hz), 6.83 (m, 4H); 13C NMR δ 55.70, 62.12, 62.37, 68.58,
114.70, 115.60, 152.24, 154.33. Anal. Calcd for C10H13O3N3: C,
53.81; H, 5.87; N, 18.82. Found: C, 53.87; H, 5.72; N, 19.01.
(R)-3-Azid o-1-O-(4′-m et h oxyp h en yl)-1,2-p r op a n ed iol:
[R]25D +16.4° (c 4.3, CHCl3); IR (CHCl3) 3585, 3401, 2110, 1491,
1245, 1040, 820 cm-1; 1H NMR δ 2.40 (br s, 1H), 3.46 (dd, 1H,
J ) 12.7, 6.1 Hz), 3.52 (dd, 1H, J ) 12.7, 4.7 Hz), 3.75 (s, 3H),
3.95 (m, 2H), 4.12 (m, 1H), 6.82 (s, 4H); 13C NMR δ 53.36,
55.70, 69.38, 69.79, 114.71, 115.57, 152.32, 154.32.
(S)-2-Azid o-3-O-ben zyl-1,3-p r op a n ed iol: [R]25D -29.9° (c
1.5, CHCl3); IR (CHCl3) 3460, 2120, 2097, 1261, 1096 cm-1
;
1H NMR δ 2.31 (s, 1H), 3.60-3.73 (m, 5H), 4.55 (s, 2H), 7.29-
7.36 (m, 5H); 13C NMR δ 62.37, 62.61, 69.96, 73.47, 127.61,
127.84, 128.43, 137.37. Anal. Calcd for C10H13O2N3: C, 57.96;
H, 6.32; N, 20.28. Found: C, 58.21; H, 6.24; N, 20.57.
(R)-3-Azid o-1-O-ben zyl-1,2-p r op a n ed iol: [R]25D +11.5° (c
1.1, CHCl3); IR (CHCl3) 3565, 3472, 2097, 1272, 1102 cm-1
;
1H NMR δ 2.47 (br s, 1H), 3.30 (dd, 1H, J ) 8.6, 6.1 Hz), 3.40
(dd, 1H, J ) 8.6, 4.7 Hz), 3.47 (dd, 1H, J ) 9.6, 6.1 Hz), 3.51
(dd, 1H, J ) 9.6, 4.4 Hz), 3.94 (m, 1H), 4.54 (s, 2H), 7.27-7.37
(m, 5H); 13C NMR δ 54.85, 71.09, 72.69, 74.96, 129.25, 129.39,
129.94, 138.93.
(S)-1-Azid o-3-ben zylth io-2-p r op a n ol: [R]25D +42.9° (c 1.9,
CHCl3); IR (CHCl3) 3580, 3498, 2105, 1496, 1450, 702, 666
1
cm-1; H NMR δ 2.47 (m, 2H), 2.56 (s, 1H), 3.25 (dd, 1H, J )
12.6, 6.23 Hz), 3.32 (dd, 1H, J ) 12.6, 4.0 Hz), 3.65-3.77 (m,
3H), 7.21-7.32 (m, 5H); 13C NMR δ 35.50, 36.27, 55.10, 68.81,
127.25, 128.58, 128.78, 137.61.
Meth od B (Tw o-P ot Mod e). The only modification here
is that after the completion of the reaction among a diol, Ph3P,
DIAD, and Me3SiN3 and concentration the yellow residue was
dissolved in a minimum volume of CH2Cl2 and passed through
a pad of silica gel in a sintered glass funnel instead of the direct
addition of TBAF. The pad was rinsed with hexanes-EtOAc
(100/1 or 50/1) to collect the silyloxy azides. The excess yellow
DIAD served as an indicator, since silyloxy azides are less
polar than DIAD (except for the sugar derivative), and
therefore, they were eluted before DIAD. After concentration,
the residue was dissolved in 3 mL of dry THF and treated with
2.5 mL of TBAF. After the same workup procedure as in the
(R)-2-Azid o-3-ben zylth io-1-p r op a n ol: [R]25D -5.0° (c 1.42,
CHCl3); IR (CHCl3) 3500, 2110, 702, 666 cm-1; 1H NMR δ 1.71
(t, 1H, J ) 5.9 Hz), 2.55 (dd, 1H, J ) 13.8, 6.6 Hz), 2.60 (dd,
1H, J ) 13.8, 6.7 Hz), 3.48 (m, 1H), 3.59 (m, 1H), 3.71 (m,
1H), 3.76 (s, 2H), 7.23-7.34 (m, 5H); 13C NMR δ 31.79, 36.90,
63.35, 63.97, 127.36, 128.68, 128.94, 137.68. Anal. Calcd for
C
10H13ON3S: C, 53.79; H, 5.87; N, 18.82. Found: C, 53.59; H,
5.65; N, 18.71.
(S)-3-Azid o-2-ben zylth io-1-p r op a n ol: [R]25D +16.6° (c 0.8,
CHCl3); IR (CHCl3) 3478, 2105, 1496, 1455, 702, 666 cm-1; 1H
NMR δ 1.87 (br s, 1H), 2.81 (m, 1H), 3.37 (dd, 1H, J ) 12.6,
7.2 Hz), 3.42 (dd, 1H, J ) 12.6, 6.4 Hz), 3.61 (dd, 1H, J ) 11.5,
5.6 Hz), 3.67 (dd, 1H, J ) 11.5, 5.4 Hz), 3.79 (s, 2H), 7.24-
7.34 (m, 5H); 13C NMR δ 35.87, 47.37, 52.57, 62.27, 127.46,
128.75, 128.80, 137.67.
(27) It is important to use an excess of DIAD (about 1.15 equiv)
relative to Ph3P; otherwise, an excess amount of Ph3P can destroy the
azide group in the products by the Staudinger reaction.
(28) The reaction was generally carried out in a one-pot mode.
However, it is often helpful to pass the reaction mixture (before the
addition of KF or TBAF) through a pad of silica gel to remove the more
polar byproducts such as Ph3PO, dihydro-DIAD, and unreacted diol.
If this procedure is employed, it is also important to realize that the
trimethylsilyloxy group is not stable, and therefore, the reaction
mixture should not be allowed to remain in contact with silica gel for
a prolonged time.
(S)-2-Azid o-3-O-oct a d ecyl-1,3-p r op a n ed iol: mp 46.8-
47.4 °C; [R]25 +11.6° (c 1.78, CHCl3); IR (CHCl3) 3592, 2100,
D
1080 cm-1; 1H NMR δ 0.86 (t, 3H, J ) 7.0 Hz), 1.23 (m, 30H),
1.54 (m, 2H), 1.91 (br s, 1H), 3.45 (dt, 2H, J ) 6.6, 1.5 Hz),
3.58-3.75 (m, 5H); 13C NMR δ 14.10, 22.68, 25.97, 29.35, 29.41,
29.56, 29.59, 29.65, 29.68, 31.91, 62.18, 63.09, 71.01, 71.91.

6054 J . Org. Chem., Vol. 64, No. 16, 1999
He et al.
Anal. Calcd for C21H43O2N3: C, 68.25; H, 11.73; N, 11.37.
Found: C, 68.13; H, 11.55; N, 11.44.
33.70, 59.02, 59.42, 71.67, 73.51. Anal. Calcd for C16H33ON3:
C, 67.56; H, 11.62; N, 11.82. Found: C, 67.70; H, 11.75; N,
11.79.
(R)-3-Azid o-1-O-octa d ecyl-1,2-p r op a n ed iol: mp 38.9-
40.0 °C; [R]25 -5.2° (c 2.1, CHCl3); IR (CHCl3) 3580, 3440,
(R)-4-Azid o-1-O-h exa d ecyl-1,2-p r op a n ed iol: mp 33.5-
D
34.0 °C; [R]25 -5.7° (c 0.84, CHCl3); IR (CHCl3) 3562, 2097
2105, 1045 cm-1; 1H NMR δ 0.86 (t, 3H, J ) 7.0 Hz), 1.23 (m,
30H), 1.53 (m, 3H), 3.30-3.48 (m, 6H), 3.91 (m, 1H); 13C NMR
δ 14.10, 22.67, 26.06, 29.35, 29.44, 29.53, 29.57, 29.60, 29.65,
29.68, 31.91, 53.46, 69.64, 71.69, 71.76.
D
cm-1, H NMR δ 0.86 (t, 3H, J ) 7.0 Hz), 1.23 (m, 26H), 1.54
1
(m, 2H), 1.68 (dt, 2H, J ) 6.9, 6.8), 1.96 (br s, 1H), 3.28 (dd,
1H, J ) 9.5, 7.5 Hz), 3.41-3.51 (m, 5H), 3.89 (m, 1H); 13C NMR
δ 14.11, 22.68, 26.10, 29.36, 29.46, 29.60, 29.66, 29.69, 31.92,
32.29, 48.12, 67.72, 71.60, 74.61.
(S)-2-Azid o-1-h exa d eca n ol: mp 45.0-45.5 °C; [R]25D +9.9°
1
(c 1.2, CHCl3); IR (CHCl3) 3626, 3595, 2105 cm-1; H NMR δ
(R)-3-Azido-1-h exadecan ol: mp 37.0-37.5 °C; [R]25D -23.8°
(c 1.89, CHCl3); IR (CHCl3) 3610, 3460, 2105 cm-1; 1H NMR δ
0.86 (t, 3H, J ) 7.0 Hz), 1.20-1.24 (m, 22H), 1.50-1.70 (m,
4H), 1.76 (m, 1H), 3.47 (m, 1H), 3.76 (t, 2H, J ) 5.5 Hz); 13C
NMR δ 14.10, 22.67, 26.02, 28.93, 29.34, 29.40, 29.48, 29.53,
29.61, 29.63, 29.66, 31.91, 34.56, 36.81, 59.85, 60.18. Anal.
Calcd for C16H33ON3: C, 67.80; H, 11.73; N, 14.82. Found: C,
67.78; H, 11.79; N, 14.88.
0.86 (t, 3H, J ) 7.0 Hz), 1.24-1.46 (m, 24H), 1.50 (dt, 2H, J )
14.0, 6.9 Hz), 1.71 (br s, 1H), 3.44 (m, 1H), 3.52 (dd, 1H, J )
11.2, 7.5 Hz), 3.67 (dd, 1H, J ) 11.4, 3.5 Hz); 13C NMR δ 14.10,
22.67, 26.00, 29.34, 29.41, 29.42, 29.51, 29.60, 29.64, 29.66,
30.56, 31.91, 64.49, 65.24; HRMS (FAB, MH+) calcd for m/z
C
16H34N3O 284.2702, found 284.2712.
(R)-1-Azid o-2-h exa d eca n ol: mp 45.8-46.1 °C; [R]25D -3.3°
(c 1.73, CHCl3); IR (CHCl3) 3621, 3421, 2105 cm-1; 1H NMR δ
0.86 (t, 3H, J ) 7.0 Hz), 1.24-1.48 (m, 24H), 1.70 (m, 2H),
3.22 (dd, 1H, J ) 12.8, 7.6 Hz), 3.36 (dd, 1H, J ) 12.8, 3.2
Hz), 3.74 (m, 1H); 13C NMR δ 14.10, 22.49, 25.42, 29.34, 29.49,
29.54, 29.61, 29.64, 29.66, 31.90, 34.28, 57.13, 70.85.
(S)-1-Azid o-3-h exa d eca n ol: mp 42.1-43.1 °C; [R]25D +7.5°
(c 0.5, CHCl3); IR (CHCl3) 3600, 2100 cm-1; 1H NMR δ 0.86 (t,
3H, J ) 7.0 Hz), 1.20-1.45 (m, 24H), 1.56-1.65 (m, 2H), 1.72
(m, 1H), 3.45 (m, 2H), 3.72 (m, 1H); 13C NMR δ 14.11, 22.68,
25.53, 29.35, 29.57, 29.64, 29.65, 29.68, 31.92, 35.97, 37.75,
48.62, 69.49.
(S)-2-Azid o-1-octa n ol: [R]25D +12.7° (c 2.05, CHCl3; ∼85%
1
ee); IR (CHCl3) 3616, 3427, 2125, 2105 cm-1; H NMR δ 0.86
(R)-3-Azid o-1-octa d eca n ol: mp 43.7-44.5 °C; [R]25D -23.3°
(t, 3H, J ) 7.0 Hz), 1.23-1.42 (m, 8H), 1.49 (dt, 2H, J ) 14.3,
7.2 Hz), 2.00 (br s, 1H), 3.43 (m, 1H), 3.52 (dd, 1H, J ) 11.2,
7.4 Hz), 3.66 (dd, 1H, J ) 11.2, 3.5 Hz); 13C NMR δ 64.46,
65.19. Anal. Calcd for C8H17ON3: C, 56.11; H, 10.01; N, 24.54.
Found: C, 55.91; H, 9.60; N, 24.35.
1
(c 1.59, CHCl3); IR (CHCl3) 3621, 2105 cm-1; H NMR δ 0.86
(t, 3H, J ) 7.0 Hz), 1.20-1.45 (m, 26H), 1.46-1.69 (m, 4H),
1.76 (m, 1H), 3.48 (m, 1H), 3.75 (t, 2H, J ) 5.3 Hz); 13C NMR
δ 14.10, 22.67, 26.03, 29.35, 29.40, 29.49, 29.53, 29.61, 29.64,
29.67, 31.91,34.57, 36.81, 59.83, 60.17; HRMS (FAB, MH+)
calcd for m/z C18H38N3O 312.3015, found 312.3015.
(S)-2-Azid o-4-octa d ecyn -1-ol: mp 36.8-37.7 °C; [R]25
D
+12.8° (c 1.71, CHCl3); IR (CHCl3) 3611, 3406, 2121, 2110
cm-1; 1H NMR δ 0.86 (t, 3H, J ) 7.0 Hz), 1.23-1.44 (m, 20H),
1.46 (m, 2H), 1.75 (br s, 1H), 2.12 (tt, 2H, J ) 7.1, 2.3 Hz),
2.44 (dt, 2H, J ) 6.5, 2.1 Hz), 3.61 (m, 2H), 3.76 (m, 1H); 13C
NMR δ 14.11, 18.68, 21.41, 22.67, 28.71, 28.87, 29.12, 29.34,
29.52, 29.64, 31.90, 62.50, 64.26, 74.64, 83.69. Anal. Calcd for
(S)-1-Azid o-3-octa d eca n ol: mp 49.3-50.3 °C; [R]25D +7.1°
(c 0.4, CHCl3); IR (CHCl3) 3615, 2100 cm-1; 1H NMR δ 0.86 (t,
3H, J ) 7.0 Hz), 1.20-1.47 (m, 28H), 1.50-1.71 (m, 2H), 1.74
(m, 1H), 3.44 (m, 2H), 3.71 (m, 1H); 13C NMR δ 14.11, 22.69,
25.53, 29.36, 29.57, 29.65, 29.69, 31.92, 35.97, 37.75, 48.62,
69.50.
C
18H33ON3: C, 70.31; H, 10.82; N, 13.67. Found: C, 70.24; H,
(S)-3-Azid o-1-octa d eca n ol: mp 43.5-44.5 °C; [R]25D +23.7°
10.96; N, 13.13.
1
(c 1.73, CHCl3); IR (CHCl3) 3612, 2105 cm-1; H NMR δ 0.86
(R)-1-Azido-4-octadecyn -2-ol: [R]25D -7.24° (c 1.98, CHCl3);
IR (CHCl3) 3570, 3386, 2105 cm-1; 1H NMR δ 0.86 (t, 3H, J )
7.0 Hz), 1.23-1.35 (m, 20H), 1.46 (m, 2H), 2.14 (tt, 2H, J )
7.1, 2.3 Hz), 2.41 (dt, 2H, J ) 6.1, 2.3 Hz), 3.35 (dd, 1H, J )
(t, 3H, J ) 7.0 Hz), 1.20-1.45 (m, 26H), 1.46-1.69 (m, 4H),
1.76 (m, 1H), 3.48 (m, 1H), 3.75 (t, 2H, J ) 5.3 Hz); 13C NMR
δ 14.11, 22.69, 26.04, 29.36, 29.41, 29.49, 29.54, 29.62, 29.65,
29.68, 31.92, 34.58, 36.82, 59.88, 60.20.
12.5, 6.4 Hz), 3.41 (dd, 1H, J ) 12.4, 4.2 Hz), 3.86 (m, 1H); 13
C
(R)-1-Azid o-3-octa d eca n ol: mp 49.5-50.2 °C; [R]25D -7.2°
NMR δ 14.09, 18.67, 22.66, 24.92, 28.85, 28.89, 29.11, 29.33,
1
(c 1.27, CHCl3); IR (CHCl3) 3608, 2100 cm-1; H NMR δ 0.86
29.51, 29.63, 29.66, 31.90, 55.44, 69.29, 74.41, 84.12.
(t, 3H, J ) 7.0 Hz), 1.20-1.47 (m, 28H), 1.50-1.71 (m, 2H),
1.74 (m, 1H), 3.44 (m, 2H), 3.71 (m, 1H); 13C NMR δ 14.10,
22.69, 25.52, 29.36, 29.58, 29.65, 29.69, 31.93, 35.97, 37.75,
48.62, 69.50.
1-O-(4′-Meth oxyben zyl)-2,3-O-isop r op ylid en e-6-a zid o-
6-d eoxy-D-m a n n ofu r a n ose: [R]25D +64.8° (c 2.62, CHCl3); IR
1
(CHCl3) 3507, 2097, 1513, 1249, 1079 cm-1; H NMR δ 1.30
(s, 3H), 1.44 (s, 3H), 2.59 (br s, 1H), 3.42 (dd, 1H, J ) 12.7,
6.36 Hz), 3.53 (dd, 1H, J ) 12.7, 3.1 Hz), 3.78 (s, 3H), 3.93
(dd, 1H, J ) 8.4, 3.8 Hz), 4.08 (m, 1H), 4.38 (d, 1H, J ) 11.4
Hz), 4.55 (d, 1H, J ) 11.4 Hz), 4.61 (d, 1H, J ) 5.9 Hz), 4.82
(dd, 1H, J ) 5.9, 3.9 Hz), 5.06 (s, 1H), 6.86 (d, 2H, J ) 8.6
Hz), 7.22 (d, 2H, J ) 8.6 Hz); 13C NMR δ 24.51, 25.84, 54.31,
55.23, 68.77, 69.49, 79.34, 79.74, 84.79, 104.99, 112.70, 113.84,
129.14, 129.74, 159.36. Anal. Calcd for C17H23O6N3: C, 55.88;
H, 6.35; N, 11.50. Found: C, 56.06; H, 6.50; N, 11.68.
2-Tetr a d ecyltetr a h yd r ofu r a n : IR (CHCl3) 1460, 1050
1
cm-1; H NMR δ 0.86 (t, 3H, J ) 7.0 Hz), 1.23 (m, 22H), 1.41
(m, 2H), 1.54 (m, 1H), 1.79-1.95 (m, 3H), 3.68 (dd, 1H, J )
7.3, 6.5 Hz), 3.75 (m, 1H), 3.83 (dt, 1H, J ) 7.4, 7.1 Hz); 13C
NMR δ 14.11, 22.68, 25.72, 26.41, 29.36, 29.60, 29.62, 29.67,
29.76, 31.38, 31.92, 35.75, 67.58, 79.47.
(2S,3R)-2-Azid o-(1,3-O-ben zylid en e)h exa d ec-(5E)-en e-
1,3-d iol: [R]25 +7.63° (c 2.7, CHCl3); IR (CHCl3) 2260, 1162,
D
1
735, 692 cm-1; H NMR δ 0.86 (t, 3H, J ) 7.0 Hz), 1.24 (m,
1-O-(4′-Meth oxyben zyl)-2,3-O-isop r op ylid en e-5-a zid o-
5-d eoxy-D-m a n n ofu r a n ose: [R]25D +62.2° (c 1.62, CHCl3); IR
20H), 2.02 (dt, 2H, J ) 7.0, 6.8 Hz), 2.39 (dt, 1H, J ) 14.4, 6.7
Hz), 2.55 (dt, 1H, J ) 14.9, 4.6 Hz), 3.50 (m, 1H), 3.59 (m,
1H), 3.60 (dd, 1H, J ) 10.4, 5.0 Hz), 4.34 (dd, 1H, J ) 10.8,
5.0 Hz), 5.44 (s, 1H), 5.56 (m, 2H), 7.33-7.45 (m, 5H); 13C NMR
δ 14.11, 56.35, 68.99, 80.51, 101.03, 123.93, 126.00, 128.26,
129.01, 134.66, 137.50; HRMS [FAB, MH+] calcd for C25H40N3O2
m/z 414.3120, found 414.3119 (40); [FAB, MH+ - N2] calcd
for C25H40NO2 m/z 386.3059, found 386.3055 (100).
(CHCl3) 3585, 3457, 2105, 1608, 1511, 1245, 1076 cm-1 1H
;
NMR δ 1.26 (s, 3H), 1.43 (s, 3H), 1.98 (t, 1H, J ) 6.1 Hz), 3.69
(m, 1H), 3.78 (s, 3H), 3.86 (m, 2H), 4.14 (dd, 1H, J ) 8.9, 3.4
Hz), 4.42 (d, 1H, J ) 11.3 Hz), 4.60 (d, 1H, J ) 1.1 Hz), 4.62
(d, 1H, J ) 4.0 Hz), 4.69 (dd, 1H, J ) 5.8, 3.5 Hz), 5.07 (s,
1H), 6.85 (d, 2H, J ) 8.6 Hz), 7.24 (d, 2H, J ) 8.6 Hz); 13C
NMR δ 24.69, 25.97, 55.27, 62.13, 63.29, 68.62, 79.52, 80.04,
85.32, 104.61, 112.77, 113.89, 129.02, 129.93, 159.41.
1-Azid oh exa d eca n e: IR (CHCl3) 2105 cm-1 [lit.29 IR (film)
2100 cm-1]; 1H NMR δ 0.86 (t, 3H, J ) 7.0 Hz), 1.24 (m, 26H),
1.50 (m, 2H), 3.23 (t, 2H, J ) 7.0 Hz); 13C NMR δ 14.11, 22.69,
25.83, 26.71, 28.84, 29.11, 29.28, 29.30, 29.45, 29.62, 29.68,
31.92, 51.49.
(S)-3-Azid o-4-O-h exa d ecyl-1,4-bu ta n ed iol: [R]25D +27.8°
1
(c 2.21, CHCl3); IR (CHCl3) 3580, 2095 cm-1, H NMR δ 0.86
(t, 3H, J ) 7.0 Hz), 1.23 (m, 26H), 1.55 (m, 2H), 1.71 (m, 2H),
2.29 (br s, 1H), 3.44 (m, 2H), 3.47 (dd, 1H, J ) 10.1, 6.6 Hz),
3.54 (dd, 1H, J ) 10.0, 4.1 Hz), 3.72 (m, 3H); 13C NMR δ 14.08,
22.66, 25.96, 29.34, 29.41, 29.56, 29.58, 29.63, 29.67, 31.90,
(29) Rolla, F. J . Org. Chem. 1982, 47, 4327-4329.

Azidation of 1,2- and 1,3-Diols by TMSN3, Ph3P, and DIAD
J . Org. Chem., Vol. 64, No. 16, 1999 6055
Hexa d ecyltr im eth ylsilyl eth er : IR (CHCl3) 1040 cm-1
;
edge support from the National Science Foundation
(CHE-9408535) for funds for the purchase of the 400-
MHz NMR spectrometer.
1H NMR δ 0.09 (s, 9H), 0.86 (t, 3H, J ) 7.0 Hz), 1.24 (m, 26H),
1.58 (m, 2H), 3.55 (t, 2H, J ) 6.8 Hz); 13C NMR δ -0.46, 14.11,
22.68, 25.83, 26.73, 29.15, 29.36, 29.46, 29.48, 29.54, 29.66,
19.68, 32.75, 62.76.
Su p p or tin g In for m a tion Ava ila ble: Copies of 1H and 13C
NMR spectra for compounds 1a + 1b and 2a + 2b in Tables
1 and 3. This material is available free of charge via the
Internet at http://pubs.acs.org.
Ack n ow led gm en t. This work was supported by
National Institutes of Health Grant HL 16660. We
thank the mass spectrometry facility at Michigan State
University for the HR-FAB MS. We gratefully acknowl-
J O9906375