Improved Conditions for Facile Overman Rearrangement

Full text of DOI:10.1021/jo9713924

188
J . Org. Chem. 1998, 63, 188-192
scribes our simple but useful solution for overcoming
problems occasionally seen in Overman rearrangements.
Im p r oved Con d ition s for F a cile Over m a n
Rea r r a n gem en t1
In our previous studies on chiral tetrodotoxin synthe-
sis, we developed a highly stereoselective introduction
of a requisite amino group by using the Overman rear-
rangement as a key step (Scheme 1).13,14 The exo-allyl
alcohol 1 was transformed into an imidate 2 with DBU
and trichloroacetonitrile in CH2Cl2 at 0 °C. The confor-
mation of the imidate 2 should be as depicted in Scheme
1 (the acetonide group occupied the pseudoaxial position)
due to A-strain between the exo-olefin and acetonide
group. Consequently, imidate 2 underwent the rear-
rangement under xylene reflux in a highly stereoselective
manner to afford the allyl trichloroacetamide 3 as a single
stereoisomer in 74% yield (two steps). In attempted
experiments to scale-up this reaction, however, we en-
countered decreasing yields (-50%), which prompted us
to reexamine the reaction conditions in order to improve
the yield and the reproducibility.
Toshio Nishikawa, Masanori Asai, Norio Ohyabu, and
Minoru Isobe*
Laboratory of Organic Chemistry, School of Bioagricultural
Sciences, Nagoya University, Chikusa,
Nagoya 464-01, J apan
Received J uly 28, 1997
The rearrangement of allyl trichloroacetimidate into
allyl trichloroacetamide (eq 1, the so-called Overman
rearrangement),2,3 has been widely used for the synthesis
Extensive examination of reaction conditions15 uncov-
ered satisfactory conditions, i.e., xylene at reflux in the
presence of K2CO3 (2 mg/ mL) as base.16 Addition of this
base would trap acids generated during thermal rear-
rangement,17 which might cause decomposition of the
imidate. This modification increased the yield of 3 to over
90% (two steps from 1), and the procedure was applicable
to 10 g scale of 1 without decreasing the yield. Another
of nitrogen-containing compounds, especially for amino
acids,4 amino sugars,5 and other complex natural prod-
ucts.6 The resulting trichloroacetamide has been directly
transformed into acylurea7 or guanidine derivative8 and
can be used as a precursor for radical cyclization.9
Furthermore, the resulting olefin can be functionalized
by neighboring group participation of the trichloroaceta-
mide to afford amino alcohol.10 Despite the usefulness
of this rearrangement, low yields and unreproducible
results have been reported in some cases (vide infra). To
solve these problems, some modifications of the Overman
rearrangement have been reported.11,12 This paper de-
important intermediate 418
in our tetrodotoxin synthesis
showed a similar improvement when the rearrangement
was conducted under these optimized conditions. In the
absence of K2CO3, Overman rearrangement (xylene,
reflux) of 4 gave a mixture of desired rearranged product
6 and aromatized byproduct 7 in 37% and 32% yields,
respectively. In contrast, addition of K2CO3 gave 6 in
62% yield (and recovered 5 in 10%) without giving any
aromatic byproducts.
(1) This study was presented at the annual meeting of J apan Society
for Bioscience, Biotechnology and Agrochemistry, Abstract. p 119,
Tokyo, J apan, April, 1997.
(2) (a) Overman, L. E. J . Am. Chem. Soc. 1974, 96, 597-599. (b)
Overman, L. E. J . Am. Chem. Soc. 1976, 98, 2901-2910. (c) Overman,
L. E. Acc. Chem. Res. 1980, 13, 218-224.
(3) For a recent review, see: Ritter, K. In Houben-Weyl. Stereose-
lective Synthesis. E 21, Vol. 9; Helmechen, G., Hoffmann, R. W., Mulzer,
J ., Schaumann, E., Eds.; Thieme: Stuttgart, 1996; pp 5677-5699.
(4) For leading references, see: (a) Takano, S.; Akiyama, M.;
Ogasawara, K. J . Chem. Soc., Chem. Commun. 1984, 770-771. (b)
Kakinuma, K.; Koudate, T.; Li, H.-Y.; Eguchi, T. Tetrahedron Lett.
1991, 32, 5801-5804. (c) Mehmandoust, M.; Petit, Y.; Larcheveˆque,
M. Tetrahedron Lett. 1992, 33, 4313-4316. (d) Imoga¨ı, H.; Petit, Y.;
Larcheveˆque, M. Tetrahedron Lett. 1996, 37, 2573-2576.
(5) For leading references, see: (a) Dyong, I.; Weigand, J .; Merten,
H. Tetrahedron Lett. 1981, 22, 2965-2968. (b) Roush, W. R.; Straub,
J . A.; Brown, R. J . J . Org. Chem. 1987, 52, 5127-5136. (c) Takeda,
K.; Kaji, E.; Konda, Y.; Sato, N.; Nakamura, H.; Miya, N.; Morizane,
A.; Yanagisawa, Y.; Akiyama, A.; Zen, S.; Harigaya, Y. Tetrahedron
Lett. 1992, 33, 7145-7148. (d) Takeda, K.; Kaji, E.; Nakamura, H.;
Akiyama, A.; Konda, Y.; Mizuno, Y.; Takayanagi, H.; Harigaya, Y.
Synthesis 1996, 341-348.
To determine the general utility of this procedure, we
applied these improved conditions to other allylic alco-
hols. The results are summarized in the Table 1.19 Some
comments follow. Rearrangement of geraniol 8 in the
absence K2CO3 gave 9 in good yield,20 which could not
be further improved by addition of the base (entry 1, 2).
(12) For trifluoroacetimidate version of Overman rearrangement,
see: (a) Savage, I.; Thomas, E. J . J . Chem. Soc., Chem. Commun. 1989,
717-719. (b) Chen, A.; Savage, I.; Thomas, E. J .; Wilson, P. D.
Tetrahedron Lett. 1993, 34, 6769-6772.
(13) Isobe, M.; Nishikawa, T.; Fukami, N.; Goto, T. Pure Appl. Chem.
1987, 59, 399-406.
(14) (a) Isobe, M.; Fukuda, Y.; Nishikawa, T.; Chabert, P.; Kawai,
T.; Goto, T. Tetrahedron Lett. 1990, 31, 3327-3330. (b) Yamamoto,
N.; Nishikawa, T.; Isobe, M. Synlett 1995, 505-506.
(15) For solvent effects in Overman rearrangement, see: (a) Vyas,
D. M.; Chiang, Y.; Doyle, T. W. J . Org. Chem. 1984, 49, 2037-2039.
(b) ref 5 (d).
(6) For example, see: (a) Danishefsky, S.; Lee, J . Y. J . Am. Chem.
Soc. 1989, 111, 4829-4837. (b) Chida, N.; Tsutsumi, N.; Ogawa, S. J .
Chem. Soc., Chem. Commun. 1995, 793-794.
(7) Atanassova, I. A.; Petrov, J . S.; Mollov, N. M. Synthesis 1987,
734-736.
(8) Yamamoto, N.; Isobe, M. Chem. Lett. 1994, 2299-2302.
(9) (a) Nagashima, H.; Wakamatsu, H.; Itoh, K. J . Chem. Soc., Chem.
Commun. 1984, 652-653. (b) Nagashima, H.; Wakamatsu, H.; Ozaki,
N.; Ishii, T.; Watanabe, M.; Tajima, T.; Itoh, K. J . Org. Chem. 1992,
57, 1682-1689, and references cited therein.
(10) (a) Cardillo, G.; Orena, M.; Sandri, S. J . Chem. Soc., Chem.
Commun. 1983, 1489-1490. (b) Cardillo, G. In Houben-Weyl. Stereo-
selective Synthesis. D.4, Vol. 8; Helmechen, G.; Hoffmann, R. W.;
Mulzer, J .; Schaumann, E., Eds.; Thieme: Stuttgart, 1996; pp 4747-
4749. (c) Nishikawa, T.; Asai, M.; Isobe, M. Unpublished results.
(11) For review of Hg(II)- and Pd(II)-catalyzed rearrangement, see:
Overman, L. E. Angew. Chem., Int. Ed. Engl. 1984, 23, 579-586.
(16) Addition of other bases such as pyridine, DBU and n-Bu3N
showed little improvement. Addition of radical inhibitors such as BHT
and 5-tert-butyl-4-hydroxy-2-methylphenyl sulfide had no effect.
(17) In fact, p-toluic acid was detected (by 1H NMR) in the crude
mixture after xylene reflux overnight.
(18) Preparation of 4 will be published elsewhere.
(19) For preparation of substrates, see: 15: Nicolaou, K. C.; Hwang,
C.-K.; Marron, B. E.; DeFees, S. A.: Couladouros, E. A.; Abe, Y.;
Carroll, P. J .; Snyder, J . P. J . Am. Chem. Soc. 1990, 112, 3040-3054.
17: ref 5 (c).
(20) Clizbe, L. A.; Overman, L. E. Organic Synthesis; Wiley: New
York, 1988; Coll. Vol. 6, pp 507-511.
S0022-3263(97)01392-3 CCC: $15.00 © 1998 American Chemical Society
Published on Web 01/09/1998

Notes
J . Org. Chem., Vol. 63, No. 1, 1998 189
Sch em e 1
rearrangements of trichloroacetimidate derivative of
3-methyl-2-cyclohexen-1-ol 19 gave 20 in low yield, even
in the presence of K2CO3 (entry 11). We found that lower
temperature (at -20 °C) during preparation of the
imidate was indispensable to avoid the elimination, and
this low temperature resulted in remarkable improve-
ment of the yield of 20 (entry 12). In this particular case,
addition of K2CO3 had only a small effect (entry 13). On
the other hand, these modifications did not improve the
rearrangement of 21 having a gem-dimethyl group (in
entry 15). The reason might be the severe 1,3-diaxal
interactions between the imidate and methyl group in
transition state, which cannot be avoided.
This study expands the range of substrates that
undergo the Overman rearrangement effectively,26 which
makes this reaction even more useful for syntheses of
complex nitrogen-containing natural products.
Exp er im en ta l Section
Gen er a l: Melting points were recorded on a Yanaco MP-
S3 melting point apparatus and are not corrected. Infrared
spectra were recorded on a J ASCO FT/IR-8300 spectrophotom-
eter and are reported in wave number (cm-1). Proton nuclear
magnetic resonance (1H NMR) spectra were recorded on Brucker
ARX-400 (400 MHz) and Varian Gemini-2000 (300 MHz) spec-
trometers. Carbon nuclear magnetic resonance (13C NMR)
spectra were recorded on J EOL EX-270 (67.9 MHz) and Varian
Gemini-2000 (75 MHz) spectrometers. Optical rotations were
Thermal rearrangement of the trifluoroacetimidate of 2,4-
hexadien-1-ol 10 was reported to give the trifluoroaceta-
mide 12 only in 35% yield, even though trifluoroacetim-
idate was considered more reactive than the corresponding
trichloroacetimidate.12 However, the trichloroacetimi-
date of 10 gave trichloroacetamide 11 in acceptable yield
even in the absence of K2CO3 (entry 3). Rearrangement
of (-)-myrtenol 13 was improved to yield 1421 in 95%
under the new conditions (entry 5 vs 6).
These conditions could be applied to unsaturated sugar
derivatives. The trichloroacetimidate of pyran 15 rear-
ranged to give 16 in good yield even in the absence of
K2CO3 (entry 7), while the corresponding ethoxy glycoside
17 was reported not to rearrange under xylene reflux.5c
Surprisingly, at elevated temperature (165 °C in o-
dichlorobenzene (DCB)) in the presence of K2CO3, the
latter rearrangement took place to afford the desired
product 1822 in 56% yield (entry 10). The higher tem-
perature might be required to invert the ground state
conformation (imidate equatorial) into the necessary
conformation (imidate group occupying axial position) for
rearrangement. In the absence of the base, the imidate
rapidly decomposed at this elevated temperature to give
18 only in low yield (entry 9).23
measured on
a J ASCO DIP-370 digital polarimeter. Low
resolution mass spectra (EI) were recorded on J EOL J MS-D 100
and J EOL J MS-700 spectrometers. High-resolution mass spec-
tra (HRMS) were recorded on a J EOL DX-705L spectrometer
and reported in m/z. Elemental analyses were performed by the
Analytical Laboratory of the School of Bioagricultural Sciences,
Nagoya University. Unless otherwise noted, nonaqueous reac-
tions were carried out under nitrogen or argon atmospheres. Dry
CH2Cl2 was distilled from CaH2 under a nitrogen atmosphere.
All other commercially available reagents were used as received.
Over m a n Rea r r a n gem en t of 1 in to Tr ich lor oa cetim i-
d a te 3 via Tr ich lor oa cetim id a te 2 in th e pr esen ce of K2CO3.
To a solution of allylic alcohol 1 (701 mg, 2.94 mmol) in dry CH2-
Cl2 (20 mL) was added DBU (0.53 mL, 3.52 mmol), and the
solution was cooled to 0 °C. To this solution was added CCl3-
CN (0.44 mL, 4.41 mmol) over 15 min. After stirring at 0 °C for
1 h, the reaction mixture was quenched with sat. NH4Cl solution.
The organic layer was washed with sat. NH4Cl solution (×2),
passed through a column packed with anhydrous Na2SO4 and
silica gel (to remove polymeric products), and evaporated under
reduced pressure to give crude trichloroacetimidate 2, which was
used for the following step without any purifications: 1H NMR
(300 MHz, CDCl3) δ 1.33 (3H, s), 1.41 (3H, s), 1.64 (3H, br s),
1.72 (1H, br d, J ) 18 Hz), 2.33 (1H, br d), 2.67 (1H, br d, J )
19 Hz), 2.94-3.10 (2H, m), 3.71 (1H, dd, J ) 8, 6.5 Hz), 4.10
(1H, dd, J ) 8, 6 Hz), 4.23 (1H, dt, J ) 10, 6.5 Hz), 4.77 (1H,
ddd, J ) 12, 6, 2 Hz), 5.00 (1H, ddd, J ) 12, 8, 2 Hz), 5.38 (1H,
br s), 5.71 (1H, ddd, J ) 8, 6, 2 Hz), 8.25 (1H, br s). To a solution
of the crude imidate 2 in p-xylene (50 mL) was added powdered
anhydrous K2CO3 (100 mg), and the mixture was heated at
reflux for 13 h with vigorous stirring. After cooling to rt, the
mixture was filtered through a pad of Super-Cel, and the
precipitate was washed with toluene. The combined filtrate was
evaporated in vacuo. The residue was purified by column
chromatography (silica 50 g, ether/hexane ) 1:10 f 1:5) to give
3 (1.02 g, 91%).
Rearrangements of cyclic γ-substituted allylic second-
ary alcohols were reported to take place in low yields and
to be unreproducible due to instability of the imidates,2b,24
which tended to eliminate trichloroacetamide.25 In fact,
(21) The product 14 was a single isomer, and its stereochemistry
was determined by NOE observed between Ha and Hb as shown in
Table 1.
(22) The stereochemistry of 18 was confirmed as follows. Reduction
of 18 with Zn-Cu gave the corresponding acetamide, which was
identical in 1H NMR and 13C NMR spectra to authentic sample given
by Dr. Y. Ichikawa. For Ichikawa’s approach, see: (a) Ichikawa, Y.;
Kobayashi, C.; Isobe, M. Synlett 1994, 919-921. (b) Ichikawa, Y.;
Kobayashi, C.; Isobe, M. J . Chem. Soc., Perkin Trans 1 1996, 377-
382.
(23) During preparation of this manuscript, the Overman rear-
rangement of a substrate similar to 17 was reported to proceed under
210 °C (in diphenyl ether) for short time to give a corresponding
trichloroacetamide. We thank Dr. Sugai for exchanging the information
prior to the publication. Okazaki, H.; Kuboki, A.; Sugai, T.; Ohta, H.
The 72th Annual Meeting of the Chemical Society of J apan, Abstract
p 1017, Tokyo, J apan, March, 1997.
(24) Overman, L. E. Tetrahedron Lett. 1975, 1149-1152.
(25) In fact, the imidates of 19 and 21 could not be detected on silica
gel TLC, but observed by 1H-NMR (see Experimental Section). In
contrast, all other imidates depicted in Table 1 could be monitored by
silica gel TLC.
(1S,6S,1′S)-Tr ich lor o-N-[1-vin yl-4-m eth yl-6-(3′,3′-dim eth yl-
2′,4′-d ioxola n yl)-cycloh ex-3-en yl]a ceta m id e (3): mp 100-
102 °C. [R]27D +70.2 (c 0.97, CHCl3). IR (KBr) 3313, 2987, 2924,
1727, 1542, 1261, 1067 cm-1 1H NMR (400 MHz, CDCl3) δ 1.39
.
(26) Recently, enantioselective Overman rearrangement by using
chiral catalyst was reported, see: Calter, M.; Hollis, T. K.; Overman,
L. E.; Ziller, J .; Zipp, G. G. J . Org. Chem. 1997, 62, 1449-1456.

190 J . Org. Chem., Vol. 63, No. 1, 1998
Ta ble 1. Over m a n Rea r r a n gem en t of Allylic Alcoh ol
Notes
a
b
All reactions were carried out using 1.00 or 2.00 mmol of starting material. Values in parentheses are yields from the literatures as
indicated. c Isolated yield.
(3H, s), 1.42 (3H, s), 1.64-1.71 (5H, m), 2.08 (1H, td, J ) 9, 7.5
Hz), 2.27 (1H, d quintet, J ) 17.5, 2.5 Hz), 3.37 (1H, ddd, J )
17.5, 6, 1.5 Hz), 3.63 (1H, dd, J ) 9, 7.5 Hz), 4.03 (1H, td, J )
9, 5.5 Hz), 4.10 (1H, dd, J ) 7.5, 5.5 Hz), 5.30 (1H, dd, J ) 17,
1 Hz), 5.32 (1H, dd, J ) 11, 1 Hz), 5.39 (1H, m), 5.82 (1H, dd, J
) 17, 11 Hz), 9.21 (1H, br s). 13C NMR (67.9 MHz, CDCl3) δ
22.7, 26.3, 26.6, 30.1, 35.9, 44.5, 60.0, 76.4, 93.9, 110.0, 116.0,
119.0, 130.8, 133.7, 160.4. Anal. Calcd for C16H23O3NCl3: C,
50.08; H, 6.04; N, 3.65. Found C, 50.25; H, 5.97; N, 3.59.
Over m a n Rea r r a n gem en t of 4 in th e a bsen ce of K2CO3.
Allylic alcohol 4 (32 mg, 0.086 mmol) was dissolved in dry CH2-
Cl2 (0.8 mL), and the solution was cooled to 0 °C. To this solution
were successively added DBU (15 µL, 0.10 mmol) and CCl3CN
(13 µL, 0.13 mmol). The mixture was stirred at 0 °C for 30 min.
The reaction was quenched with sat. NH4Cl solution. The
mixture was extracted with CH2Cl2 (×2). Combined organic
layer was dried over anhydrous Na2SO4 and evaporated under
reduced pressure. The crude product was dissolved in xylene
(3 mL). The mixture was heated at reflux temperature for 15
h. After cooling to rt, the mixture was evaporated in vacuo. The
residue was purified by silica gel TLC (ether/hexane ) 1:3) to
give the trichloroacetamide 6 (16 mg, 37%) and aromatized
product 7 (6 mg, 32%).
Over m a n Rea r r a n gem en t of 4 in th e pr esen ce of K2CO3.
To a solution of allylic alcohol 4 (76 mg, 0.21 mmol) in dry CH2-
Cl2 (5 mL) cooled at 0 °C were added DBU (49 µL, 0.32 mmol)
and CCl3CN (39 µL, 0.39 mmol) successively. The mixture was
stirred at 0 °C for 45 min. The reaction mixture was diluted
with CH2Cl2 and washed with sat. NH4Cl solution (×2), dried
over anhydrous Na2SO4, and evaporated under reduced pressure
to give crude imidate. The crude imidate was dissolved in xylene
(10 mL), and powdered K2CO3 (20 mg) was added. The mixture
was heated at a reflux temperature for 36 h. After cooling to
rt, the mixture was filtered through a pad of Super-Cel and
washed with toluene. The combined filtrate was evaporated in
vacuo. The residue was purified by column chromatography
(silica 15 g, ether/hexane ) 1:10 f 1:5) to give the trichloroac-
etamide 6 (65 mg, 62%) and unreacted imidate 4 (11 mg, 10%).

Notes
Tr ich lor oa cetim id a te of 4: 1H NMR (300 MHz, CDCl3) δ
J . Org. Chem., Vol. 63, No. 1, 1998 191
br s), 5.05 (1H, t, J ) 1 Hz), 6.71 (1H, br). 13C NMR (75 MHz,
CDCl3) δ 22.0, 25.7, 29.7, 33.7, 39.9, 40.3, 46.8, 51.1, 92.7, 112.9,
152.0, 161.0. FAB-MS (positive) m/z 296 (M + H). Anal. Calcd
for C12H16ONCl3: C, 48.59; H, 5.44; N, 4.72. Found C, 48.56;
H, 5.42; N, 4.65.
Tr ich lor oa cetim id a te of 15: 1H NMR (300 MHz, CDCl3) δ
0.06 (6H, s), 0.89 (9H, s), 3.70 (1H, ddd, J ) 8, 5.5, 2 Hz), 3.79
(1H, dd, J ) 11.5, 5.5 Hz), 3.89 (1H, dd, J ) 11.5, 2 Hz), 4.23-
4.26 (2H, m), 5.42 (1H, br d, J ) 8 Hz), 5.90-6.01 (2H, m), 8.39
(1H, br).
0.11 (3H, s), 0.13 (3H, s), 0.95 (9H, s), 1.29 (3H, s), 1.37 (3H, s),
1.66 (3H, br s), 1.72 (1H, br d, J ) 18 Hz), 2.34 (1H, br d, J ) 18
Hz), 3.08 (1H, m), 3.62 (1H, dd, J ) 8, 6 Hz), 4.05 (1H, dd, J )
8, 6 Hz), 4.14 (1H, dt, J ) 9, 6 Hz), 4.82-4.99 (3H, m), 5.36 (1H,
br s), 5.95 (1H, td, J ) 7, 2 Hz), 8.25 (1H, br s).
(1S,2S,1′S)-Tr ich lor o-N-[1-vin yl-4-m eth yl-6-(3′,3′-dim eth yl-
2′,4′-d ioxola n yl)-2-(ter t-b u t yld im et h ylsiloxy)cycloh ex-3-
en yl]a ceta m id e (6): mp 130-132 °C. [R]27 +133.7 (c 0.40,
D
CHCl3). IR (KBr) 3327, 2930, 1727, 1533, 1256 cm-1
.
1H NMR
(300 MHz, CDCl3) δ 0.05 (6H, s), 0.85 (9H, s), 1.39 (3H, s), 1.41
(3H, s), 1.51-1.62 (1H, m), 1.69 (3H, s), 1.75 (1H, dd, J ) 18.5,
6 Hz), 2.48 (1H, ddd, J ) 11.5, 9.5, 6 Hz), 3.68 (1H, m), 4.01-
4.11 (2H, m), 4.87 (1H, d, J ) 6 Hz), 5.33 (1H, dd, J ) 11, 1 Hz),
5.38 (1H, dd, J ) 17.5, 1 Hz), 5.56 (1H, dd, J ) 6, 1 Hz), 5.68
(1H, dd, J ) 17.5, 11 Hz), 8.87 (1H, br s). 13C NMR (100 MHz,
CDCl3) δ -4.5, -3.7, 18.1, 22.7, 25.9, 26.3, 26.5, 30.6, 38.6, 64.4,
66.2, 68.7, 75.6, 94.0, 109.9, 116.0, 117.5, 123.1, 132.4, 133.8,
(3R,6S)-6-[(ter t-b u t yld im et h ylsiloxy)m et h yl]-3-t r ich lo-
r oa ceta m id o-3,6-2H-p yr a n (16): mp 70-71.5 °C. [R]27D -138
(c 1.10, CHCl3). IR (KBr) 3266, 2929, 2858, 1686, 1541 cm-1
.
1H NMR (300 MHz, CDCl3) δ 0.06 (6H, s), 0.89 (9H, s), 3.60 (1H,
dd, J ) 11.5, 4.5 Hz), 3.64 (1H, dd, J ) 10.5, 5.5 Hz), 3.74 (1H,
dd, J ) 10.5, 6 Hz), 4.14 (1H, dd, J ) 11.5, 4 Hz), 4.20 (1H, m),
4.42 (1H, m), 5.93 (1H, ddd, J ) 10, 4, 2 Hz), 6.03 (1H, ddd, J )
10, 2, 1 Hz), 6.76 (1H, br d, J ) 8 Hz). 13C NMR (75 MHz, CDCl3)
δ -5.5, -5.4, 18.3, 25.8, 44.7, 64.2, 65.2, 74.1, 92.4, 124.7, 131.9,
161.7. Anal. Calcd for C14H24O4NSiCl3: C, 43.25; H, 6.22; N,
3.60. Found: C, 43.33; H, 6.33; N, 3.53.
135.4, 159.3. HRMS (FAB) for
C22H37O4NCl3Si (M + H),
512.1557, found 512.1540. Anal. Calcd for C22H38O4NCl3Si: C,
51.51; H, 7.07; N, 2.73. Found: C, 51.47; H, 7.07; N, 2.62.
(S)-5-(2′-Vin yl-5′-m et h ylp h en yl)-2,2-d im et h yl-1,3-d iox-
ola n e (7): 1H NMR (300 MHz, CDCl3) δ 1.50 (3H, s), 1.57 (3H,
s), 2.36 (3H, s), 3.60 (1H, t, J ) 8.5 Hz), 4.33 (1H, dd, J ) 8.5,
6.5 Hz,), 5.28 (1H, dd, J ) 11, 1.5 Hz), 5.35 (1H, dd, J ) 8.5, 6.5
Hz), 5.58 (1H, dd, J ) 17.5, 1.5 Hz), 6.88 (1H, dd, J ) 17.5, 11
Hz), 7.08 (1H, br d, J ) 7.5 Hz), 7.34-7.38 (2H, m). MS (FAB)
m/z 219 (M + H).
Tr ich lor oa cetim id a te of 17: 1H NMR (300 MHz, CDCl3) δ
0.06 (6H, s), 0.89 (9H, s), 1.26 (3H, t, J ) 7.5 Hz), 3.57 (1H, dq,
J ) 10, 7.5 Hz), 3.80 (1H, dd, J ) 12, 6 Hz), 3.87 (1H, dd, J )
12, 2.5 Hz), 3.91 (1H, dq, J ) 10, 7.5 Hz), 4.12 (1H, m), 5.07
(1H, m), 5.41 (1H, ddt, J ) 9.5, 1.5, 1.5 Hz), 5.87 (1H, ddd, J )
10, 3, 2 Hz), 6.07 (1H, br d, J ) 10 Hz), 8.40 (1H, br s).
Typ ica l Exp er im en ta l P r oced u r e (en tr ies 1-11 in Ta ble
1). Preparation of trichloroacetimidate: Allylic alcohol 13 (152
mg, 1.00 mmol) was dissolved in dry CH2Cl2 (5 mL), and the
solution was cooled to 0 °C. To this solution were successively
added DBU (0.22 mL, 1.50 mmol) and CCl3CN (0.18 mL, 1.80
mmol). After stirring at 0 °C for 30 min, the reaction was
quenched with sat. NH4Cl solution. The mixture was extracted
with CH2Cl2 (×2). The combined organic layer was washed with
sat. NH4Cl solution (×2), passed through a column packed with
anhydrous Na2SO4 and a thin layer of silica gel, and evaporated
under reduced pressure to give crude imidate. (a) Overman
rearrangement in the absence of K2CO3: The crude imidate was
dissolved in xylene (20 mL). The mixture was heated at reflux
temperature overnight. After cooling to rt, the mixture was
evaporated in vacuo. The residue was purified by column
chromatography (silica 30 g, ether/hexane ) 1:40) to give
trichloroacetamide 14 (212 mg, 72%). (b) Overman rearrange-
ment in the presence of K2CO3: To a solution of the crude imidate
in xylene (20 mL) was added powdered anhydrous K2CO3 (40
mg). The mixture was heated at reflux temperature overnight
with vigorous stirring. After cooling to rt, the mixture was
filtered through a pad of Super-Cel, and the precipitate was
washed with toluene. The combined filtrate was evaporated in
vacuo. The residue was purified as described above to give 14
(282 mg, 95%).
Eth yl 6-O-(ter t-bu tyldim eth ylsilyl)-2-tr ich lor oacetam ido-
2,3,4-tr id eoxy-r-D-er yth r o-h ex-3-en op yr a n osid e (18): [R]27
D
-41.7 (c 1.10, CHCl3). IR (KBr) 3423, 3345, 2930, 1720, 1506
cm-1 1H NMR (300 MHz, CDCl3) δ 0.08 (6H, s), 0.90 (9H, s),
.
1.25 (3H, t, J ) 7.5 Hz), 3.62 (1H, dq, J ) 10.5, 7.5, Hz), 3.63
(1H, dd, J ) 11, 6 Hz), 3.74 (1H, dd, J ) 11, 6 Hz), 3.88 (1H, dq,
J ) 10.5, 7.5 Hz), 4.18 (1H, m), 4.66 (1H, m), 5.03 (1H, d, J ) 5
Hz), 5.63 (1H, br d, J ) 11 Hz), 5.96 (1H, dt, J ) 11, 2.5 Hz),
7.07 (1H, br d, J ) 9 Hz). 13C NMR (75 MHz, CDCl3) δ -5.4,
15.0, 18.2, 25.8, 47.2, 64.1, 65.2, 68.8, 92.5, 94.7, 123.0, 129.3,
161.7. FAB-MS (positive) m/z 432 (M + H), 386 (M-OEt). HR-
MS (FAB) for C16H29O4NSiCl3 (M + H), calcd 432.0931, found
432.0928.
Typ ica l Exp er im en ta l P r oced u r e (en tr ies 12-15 in
Ta ble 1). To a solution of 19 (112 mg, 1.00 mmol) in dry CH2-
Cl2 (5 mL) was added DBU (0.22 mL, 1.50 mmol) and cooled to
-20 °C. To this solution was added CCl3CN (0.18 mL, 1.8 mmol)
dropwise. After stirring at -20 °C for 1 h, the reaction mixture
was quenched with cold saturated aq. NH4Cl solution. The
combined organic layer was washed with saturated NH4Cl
solution (×2), passed through a column packed with anhydrous
Na2SO4 and a thin layer of anhydrous K2CO3,27 and evaporated
under reduced pressure to give crude trichloroacetimidate which
was used for the following reaction without any purifications:
1H NMR (300 MHz, CDCl3) δ 1.60-2.10 (6H, m), 1.74 (3H, s),
5.38 (1H, m), 5.62 (1H, m), 8.22 (1H, br). The crude imidate
was dissolved in toluene (10 mL), and powdered anhydrous K2-
CO3 (20 mg) was added. The mixture was heated at reflux
temperature for 13 h with vigorous stirring. After cooling to rt,
the mixture was filtered through a pad of Super-Cel, and the
precipitate was washed with toluene. The combined filtrate was
evaporated in vacuo. The residue was purified by column
chromatography (silica 15 g, only hexane f ether/hexane ) 1:20)
to give 20 (205 mg, 80%).
Tr ich lor oa cetim id a te of 10: 1H NMR (300 MHz, CDCl3) δ
1.78 (3H, br d, J ) 7 Hz), 4.81 (2H, d, J ) 6.5 Hz), 5.68-5.85
(2H, m), 6.09 (1H, ddq, J ) 15, 10, 1.5 Hz), 6.35 (1H, dd, J )
15.5, 10.5 Hz), 8.29 (1H, br).
Tr ich lor o-N-[(4E)-1,4-h exa d ien e-3-yl]a ceta m id e (11): IR
(KBr) 3322, 1697, 1511 cm-1
.
1H NMR (300 MHz, CDCl3) δ
1.75(3H, br d, J ) 6.5 Hz), 4.94 (1H, m), 5.24 (1H, dt, J ) 10.5,
1 Hz), 5.26 (1H, dt, J ) 17.5, 1 Hz), 5.48 (1H, ddq, J ) 15.5, 6,
1.5 Hz), 5.76 (1H, dqd, J ) 15.5, 7, 1.5 Hz), 5.86 (1H, ddd, J )
17.5, 10.5, 5.5 Hz), 6.62 (1H, br). 13C NMR (75 MHz, CDCl3) δ
17.8, 54.8, 92.9, 116.6, 127.9, 129.6, 135.8, 161.1. EI-MS m/z
241 (M+), 206 (M-Cl). FAB-MS (positive) m/z 242 (M + H). HR-
MS (FAB) for C8H11ONCl3 (M + H), calcd 241.9906, found
241.9912.
Tr ich lor o-N -(1-m e t h yl-2-cycloh e xe n -1-yl)a ce t a m id e
(20): mp 50-51 °C. IR (KBr) 3426, 3348, 2934, 1717, 1499 cm-1
.
1H NMR (300 MHz, CDCl3) δ 1.52 (3H, s), 1.58-1.73 (3H, m),
1.90-2.16 (2H, m), 2.24-2.35 (1H, m), 5.75 (1H, br d, J ) 10
Hz), 5.89 (1H, dt, J ) 10, 3.5 Hz), 6.49 (1H, br). 13C NMR (75
MHz, CDCl3) δ 18.9, 24.8, 25.9, 33.4, 53.9, 93.3, 130.7, 131.0,
160.3. Anal. Calcd for C9H12ONCl3: C, 42.13; H, 4.71; N, 5.46.
Found: C, 42.12; H, 4.83; N, 5.42.
Tr ich lor oa cetim id a te of 13: 1H NMR (300 MHz, CDCl3) δ
0.86 (3H, s), 1.22 (1H, d, J ) 9 Hz, 1.29 (3H, s), 2.08-2.16 (1H,
m), 2.22 (1H, td, J ) 6, 15 Hz), 2.28-2.35 (2H, m), 2.42 (1H, dt,
J ) 6, 6 Hz), 4.67 (2H, m), 5.67 (1H, m), 8.25 (1H, br).
(1R,3S,5R)-Tr ich lor o-N-(6,6-d im e t h yl-2-m e t h yle n e b i-
Tr ich lor oa cetim id a te of 21: 1H NMR (300 MHz, CDCl3) δ
0.98 (3H, s), 1.04 (3H, s), 1.60 (1H, dd, J ) 13, 7 Hz), 1.73 (3H,
cyclo[3.1.1]h eptan -3-yl)acetam ide (14): mp 61.5-63 °C. [R]27
D
+37.3 (c 0.89, CHCl3). IR (KBr) 3430, 3336, 2936, 1706, 1508
cm-1 1H NMR (300 MHz, CDCl3) δ 0.78 (3H, s), 1.17 (1H, d, J
.
) 11 Hz), 1.29 (3H, s), 1.80 (1H, ddd, J ) 15.5, 4, 2.5 Hz), 2.07
(1H, m), 2.48-2.62 (3H, m), 4.68 (1H, br t, J ) 8 Hz), 4.93 (1H,
(27) Silica gel should not be used for removal of polymeric products
due to acid lability of the imidate.

192 J . Org. Chem., Vol. 63, No. 1, 1998
Notes
s), 1.74 (1H, br d, J ) 18 Hz), 1.86 (1H, dd, J ) 13, 6 Hz), 1.91
(1H, br d, J ) 18 Hz), 5.46 (1H, m), 5.57 (1H, m), 8.22 (1H, br
s).
Ack n ow led gm en t. We are grateful to Dr. Y. Ichika-
wa of this laboratory for fruitful discussions and his
supply of the authentic samples. Elemental analyses
and measurement of HR-MS were performed by Mr. S.
Kitamura (analytical laboratory in this school), whom
we also thank. This work was financially supported by
a Grant-in-Aid for Scientific Research from the Ministry
of Education, Science, Sports, and Culture of J apan.
Tr ich lor o-N-(1,5,5-t r im et h yl-2-cycloh exen -1-yl)a cet a -
m id e (22): IR (KBr) 3429, 3349, 2954, 1717, 1506 cm-1
.
1H
NMR (300 MHz, CDCl3) δ 0.99 (3H, s), 1.01 (3H, s), 1.48 (1H, d,
J ) 15 Hz), 1.52 (3H, s), 1.88 (2H, m), 2.21 (1H, br d, J ) 15
Hz), 5.78-5.89 (2H, m), 6.54 (1H, br). 13C NMR (75 MHz, CDCl3)
δ 27.2, 27.3, 29.1, 31.3, 38.7, 45.7, 54.2, 93.4, 128.8, 129.4, 159.8.
EI-MS m/z 268 (M-CH3), 248 (M-Cl). HR-MS (FAB) for C10H13
-
ONCl3 (M-CH3), calcd 268.0062, found 268.0060.
J O9713924