Synthesis and aza-[2,3]-Wittig rearrangements of vinylaziridines: Scope and limitations

Article abstract of DOI:10.1021/jo9612638

cis- and trans-2,3-Trisubstituted vinylaziridines have been prepared from cis- and trans-epoxy alcohols, respectively, and used as substrates in the aza-[2,3]-Wittig rearrangement. Five different anion-stabilizing groups have been investigated for their efficiency to promote the rearrangement, and it was found that N-tert-butyl acetyl vinylaziridines were superior in this reaction, affording the corresponding cis-2,6-tetrahydropyridines (>90%) as single isomers when treated with LDA. Similarly, the corresponding (Z)-propenylaziridines gave trans,trans-2,3,6-trisubstituted tetrahydropyridines as the sole products while the (E)-propenylaziridines afforded the cis,cis-2,3,6-derivatives with equally high selectivity. The scope and limitations of the process have been investigated by varying the structure of the substrate, and the mechanism of the rearrangement has been probed to some extent; the mechanistic picture is more complex than assumed previously.

Full text of DOI:10.1021/jo9612638

8148
J . Org. Chem. 1996, 61, 8148-8159
Syn th esis a n d Aza -[2,3]-Wittig Rea r r a n gem en ts of Vin yla zir id in es:
Scop e a n d Lim ita tion s
J ens A° hman, Tomas J areva˚ng, and Peter Somfai*
Organic Chemistry 2, Center for Chemistry and Chemical Engineering, Lund Institute of Technology,
Lund University, P.O. Box 124, S-221 00 Lund, Sweden
Received J uly 3, 1996X
cis- and trans-2,3-Trisubstituted vinylaziridines have been prepared from cis- and trans-epoxy
alcohols, respectively, and used as substrates in the aza-[2,3]-Wittig rearrangement. Five different
anion-stabilizing groups have been investigated for their efficiency to promote the rearrangement,
and it was found that N-tert-butyl acetyl vinylaziridines were superior in this reaction, affording
the corresponding cis-2,6-tetrahydropyridines (>90%) as single isomers when treated with LDA.
Similarly, the corresponding (Z)-propenylaziridines gave trans,trans-2,3,6-trisubstituted tetrahy-
dropyridines as the sole products while the (E)-propenylaziridines afforded the cis,cis-2,3,6-
derivatives with equally high selectivity. The scope and limitations of the process have been
investigated by varying the structure of the substrate, and the mechanism of the rearrangement
has been probed to some extent; the mechanistic picture is more complex than assumed previously.
In tr od u ction
made which indicated that these systems tend to be
unreactive or are prone to undergo a competitive [1,2]-
rather than the desired [2,3]-rearrangement.4,5 However,
in an elegant study Durst et al. showed that N-benzyl-
4-vinyl-2-azetidinone when treated with LDA was trans-
formed into the corresponding seven-membered lactam
in high yield.6 It was also noted by these authors that
the ease with which this aza-[2,3]-Wittig rearrangement
occurred undoubtedly was associated with the consider-
able relief of ring strain in going from a four- to a seven-
membered ring. Following this key observation we
became interested in the possibility of using N-substi-
tuted vinylaziridines as substrates for this rearrange-
ment which would result in a novel entry to di- and
trisubstituted tetrahydropyridines (eq 2).7 In two pre-
liminary reports we have shown that the required vinyl-
aziridines are readily prepared in high enantiomeric
excess from epoxy alcohols and that, when deprotonated
by base, they rearrange to the corresponding tetrahy-
dropyridines. The yield and relative stereochemistry of
the products depend on the vinylaziridine geometry and
the nature of the N-activating group.8 In a parallel study
the potential of this rearrangement was demonstrated
by using it as a key step in our enantioselective synthesis
of (-)-Indolizidines 209B and 209D, two alkaloids that
have been isolated in minute quantities from Dendro-
batidae frogs.9 Herein we give a detailed account of the
preparation of various N-substituted vinylaziridines and
their subsequent rearrangement which shows the scope
and limitations of the process, both in terms of activating
groups and the structure of the substrate. In addition,
Pericyclic reactions are an important cornerstone in
organic synthesis, due mainly to their predictability and
often high selectivities. A good example is the sigma-
tropic [2,3]-Wittig rearrangement, in which an activated
allylic ether is transformed into the corresponding ho-
moallylic alcohol (eq 1, X ) O). This reaction has received
much attention from both synthetic and computational
chemists, and its potential has been demonstrated by its
use as a key step in several natural product syntheses.1
The rearrangement is generally considered to proceed by
a concerted mechanism, passing through a five-mem-
bered envelopelike transition state in which the breaking
C-O and forming C-C bonds are almost eclipsed.2,3 The
diastereoselectivities observed in this process are then a
direct consequence of the starting olefin geometry and
the preference of the activating group (G) to adopt an
endo or an exo orientation in the transition state, the
reasons for which have been shown to be of primarily
electronic origin. It has also been demonstrated that the
[2,3]-Wittig rearrangement can be performed with excel-
lent 1,3- or 1,4-chirality transfer and that high asym-
metric induction can be achieved by the use of chiral
auxiliaries.1
Somewhat surprisingly, however, the corresponding
aza-[2,3]-Wittig rearrangement (eq 1, X ) NR′′) has
received considerably less attention. At the outset of this
investigation only a few attempts in this area had been
(4) (a) Reetz, M. T.; Schinzer, D. Tetrahedron Lett. 1975, 3485-3486.
(b) Broka, C. A.; Shen, T. J . Am. Chem. Soc. 1989, 111, 2981-2984.
(c) Murata, Y.; Nakai, T. Chem. Lett. 1990, 2069-2072. (d) Coldham,
I. J . Chem. Soc., Perkin Trans. 1 1993, 1275-1276.
(5) The rearrangement described in ref 4b has been shown to proceed
by a [1,2]-mechanism, see ref 4c.
X Abstract published in Advance ACS Abstracts, November 1, 1996.
(1) (a) Nakai, T.; Mikami, K. Org. React. 1994, 46, 105-209. (b)
Marshall, J . A. In Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 3, Chapter 3.11. (c)
Mikami, K.; Nakai, T. Synthesis 1991, 594-604. (d) Nakai, T.; Mikami,
K. Chem. Rev. 1986, 86, 885-902.
(2) (a) Mikami, K.; Uchida, T.; Hirano, T.; Wu, Y.-D.; Houk, K. N.
Tetrahedron 1994, 50, 5917. (b) Wu, Y.-D.; Houk, K. N.; Marshall, J .
A. J . Org. Chem. 1990, 55, 1421-1423.
(6) Durst, T.; Elzen, R. V. D.; LeBelle, M. J . J . Am. Chem. Soc. 1972,
94, 9261-9263.
(7) The ring strain in ethylenimine has been assessed to 26.9 kcal/
mol. Dermer, O. C.; Ham, G. E. Ethylenimine and Other Aziridines;
Academic: New York, 1969; p 89.
(8) A° hman, J .; Somfai, P. J . Am. Chem. Soc. 1994, 116, 9781-9782.
A° hman, J .; Somfai, P. Tetrahedron Lett. 1996, 37, 2495-2498.
(9) A° hman, J .; Somfai, P. Tetrahedron Lett. 1995, 36, 303-306.
A° hman, J .; Somfai, P. Tetrahedron 1995, 51, 9747-9756.
(3) For a somewhat different transition state structure, see ref 1c.
S0022-3263(96)01263-7 CCC: $12.00 © 1996 American Chemical Society

Aza-[2,3]-Wittig Rearrangements of Vinylaziridines
J . Org. Chem., Vol. 61, No. 23, 1996 8149
the mechanistic aspects of this reaction have been probed
to some extent by systematically varying the structure
of the vinylaziridines.
vinylaziridines of high enantiomeric purity. However,
Wittig olefination of various N-alkylated20 or tosylated21
2-formylaziridines has been described, and since these
compounds should be readily available from Sharpless
epoxy alcohols this route was judged to be ideal for our
purposes. Thus, opening of the known epoxides 122 and
223 (ee >95%) with sodium azide24 followed by selective
protection of the primary hydroxyl group gave the cor-
responding vicinal azido alcohols (Scheme 1). These were
then subjected to Ph3P in refluxing toluene to give
aziridines 3 and 5, each as a single isomer.25 It has
previously been shown that this aziridination proceeds
via an intermediate oxazaphospholidine which decom-
poses and undergoes intramolecular SN2 displacement of
Ph3PO with concomitant formation of the aziridine, its
stereochemistry thus being inverted as compared to the
starting epoxide.26
During the course of this investigation three other
studies of the aza-[2,3]-Wittig rearrangement have ap-
peared. The Coldham group has also described the use
of vinylaziridines, prepared in racemic form by a conju-
gate addition strategy, as substrates in the rearrange-
ment and obtained results similar to our preliminary
ones.10 Anderson et al.11 recently described the successful
[2,3]-rearrangement of an allylic Boc-protected benzyl-
amine, which seems to indicate a fruitful approach for
the rearrangement of acyclic substrates, while Gawley
et al. rearranged 2-lithio-N-allylpyrrolidines and showed
that this reaction proceeds with inversion of configuration
at the lithium-bearing carbon, in analogy with the
original Wittig rearrangement.12
N-Alkylation of 3 with tert-butyl bromoacetate27 gave
aziridine 6, and subsequent removal of the silyl group
afforded alcohol 11 in good overall yield. Oxidation of
11 was best accomplished by using the Swern protocol,28
and condensation of the resultant aldehyde with the
ylides derived from methyl- and ethyltriphenylphospho-
nium bromide (KHMDS, PhMe, THF) gave vinylaziri-
dines 17 and 18, while the (E)-isomer 19 was prepared
from the same aldehyde by applying the Schlosser
modification of the Wittig olefination.29 Similarly, aziri-
dine 20 was made by the in situ condensation of the
aldehyde derived from 11 with Ph3PCHCO2Et30 while
aziridine 22 was prepared by reacting the same aldehyde
with Ph3PCHCHO to give 21a followed by reduction
(NaBH4, 90%) and silylation (99%). N-Alkylation of 3
with benzyl bromide, bromoacetonitrile, or propargyl
bromide under standard conditions gave compounds 7-9
which were converted into vinylaziridines 23-25, 27, and
29 by using the procedures described above for 17-19.
The TMS-derivatives 26, 28, and 30 were most conve-
niently prepared by deprotonation of 25, 27, and 29 with
n-BuLi at -78 °C followed by addition of TMSCl. For
the preparation of vinylaziridine 31, silyl ether 3 was
deprotected to give alcohol 4 which was alkylated with
methyl 4-bromocrotonate (83%) to give 15 which was then
oxidized and methylenated as described above. Finally,
vinylaziridines 32-34 were prepared from 5 by following
the analogous sequence of reactions as for compounds
17-19. Included in this study are also derivatives 35
and 36 the preparation of which has been previously
described.9 Since it was noted that several of these trans-
Resu lts a n d Discu ssion
Syn th esis of Vin yla zir id in es. Vinylaziridines have
received interest as precursors for a variety of nitrogen-
containing compounds and as a result several strategies
toward them have been described.13 The main thrust in
this area has been directed toward addition of azides14
or nitrene equivalents15 to 1,3-dienes, with attendant
problems with regioselectivity, while other methods such
as derivatization of vinyl epoxides,16 intramolecular SN2′
substitutions,17 reduction or alkylation of R,â-unsaturated
oximes,18 and nucleophilic additions to oximes have also
been described.19 With respect to the present investiga-
tion the main drawback with most of these methods are
the need to use a nitrogen protecting group and the fact
that they are not easily amenable to the preparation of
(10) Coldham, I.; Collis, A. J .; Mould, R. J .; Rathmell, R. E.
Tetrahedron Lett. 1995, 36, 3557-3560. Coldham, I.; Collis, A. J .;
Mould, R. J .; Rathmell, R. E. J . Chem. Soc., Perkin Trans. 1 1995,
2739-2745.
(11) Anderson, J . C.; Siddons, D. C.; Smith, S. C.; Swarbrick, M. E.
J . Chem. Soc., Chem. Commun. 1995, 1835-1836.
(12) Gawley, R. E.; Zhang, Q.; Campagna, S. J . Am. Chem. Soc.
1995, 117, 11817-11818.
(13) For a recent review on aziridine chemistry, see: Tanner, D.
Angew. Chem., Int. Ed. Engl. 1994, 33, 599-619.
(20) Borel, D.; Gelas-Mialhe, Y.; Vessie`re, R. Can. J . Chem. 1976,
54, 1582-1589.
(14) Kim, N.-S.; Kang, C. H.; Cha, J . K. Tetrahedron Lett. 1994, 35,
3489-3492. Pearson, W. H.; Bergmeier, S. C.; Williams, J . P. J . Org.
Chem. 1992, 57, 3977-3987. Hudlicky, T.; Seoane, G.; Price, J . D.;
Gadamasetti, K. G. Synlett 1990, 433-440. Pearson, W. H.; Bergmeier,
S. C.; Degan, S.; Lin, K.-C.; Poon, Y.-F.; Schkeryantz, J . M.; Williams,
J . P. J . Org. Chem. 1990, 55, 5719-5738. Hudlicky, T.; Seoane, G.;
Lovelace, T. C. J . Org. Chem. 1988, 53, 2094-2099. Schultz, A. G.;
Staib, R. R.; Eng, K. K. J . Org. Chem. 1987, 52, 2968-2972. Hudlicky,
T.; Frazier, J . O.; Seoane, G.; Tiedje, M.; Seoane, A.; Kwart, L. D.; Beal,
C. J . Am. Chem. Soc. 1986, 108, 3755-3762. Pearson, W. H.; Celebuski,
J . E.; Poon, Y.-F.; Dixon, B. R.; Glans, J . H. Tetrahedron Lett. 1986,
27, 6301-6304. Scheiner, P. J . Org. Chem. 1967, 32, 2628-2630.
(15) Knight, J . G.; Muldowney, M. P. Synlett 1995, 949-951, and
references cited therein.
(16) Wipf, P.; Fritch, P. C. J . Org. Chem. 1994, 59, 4875-4886.
Pommelet, J . C.; Chuche, J . Tetrahedron Lett. 1974, 3897-3898.
Stogryn, E. L.; Brois, S. J . J . Am. Chem. Soc. 1967, 89, 605-609.
(17) Spears, G. W.; Nakanishi, K.; Ohfune, Y. Synlett 1991, 91-92.
Hortmann, A. G.; Koo, J .-y. J . Org. Chem. 1974, 39, 3781-3783.
(18) Ricart, G. Bull. Soc. Chim. Fr. 1974, 2607-2614. Ferrero, L.;
Rouillard, M.; Decouzon, M.; Azzaro, M. Tetrahedron Lett. 1974, 131-
134. Chaabouni, R.; Laurent, A. Synthesis 1975, 464-467.
(19) Hassner, A.; D’Costa, R.; McPhail, A. T.; Butler, W. Tetrahedron
Lett. 1981, 22, 3691, 3694.
(21) Ibuka, T.; Nakai, K.; Habashita, H.; Hotta, Y.; Fujii, N.;
Mimura, N.; Miwa, Y.; Taga, T.; Yamamoto, Y. Angew. Chem., Int. Ed.
Engl. 1994, 33, 652-654. Tanner, D; Somfai, P. BioMed. Chem. Lett.
1993, 3, 2415-2418.
(22) Schweiter, M. J .; Sharpless, K. B. Tetrahedron Lett. 1985, 26,
2543-2546.
(23) Katsuki, T.; Lee, A. W. M.; Ma, P.; Martin, V. S.; Masamune,
S.; Sharpless, K. B.; Tuddenham, D.; Walker, F. J . J . Org. Chem. 1982,
47, 1373.
(24) Behrens, C. H.; Sharpless, K. B. J . Org. Chem. 1985, 50, 5696-
5704.
(25) Ittah, Y.; Sasson, Y.; Shahak, I.; Tsaroom, S.; Blum, J . J . Org.
Chem. 1978, 43, 4271-4273. Tanner, D.; Somfai, P. Tetrahedron 1988,
44, 619-624.
(26) Legters, J .; Thijs, L.; Zwanenburg, B. Recl. Trav. Chim. Pays-
Bas 1992, 111, 1-15. Po¨chlauer, P.; Mu¨ller, E. P.; Peringer, P. Helv.
Chim. Acta 1984, 67, 1238-1247.
(27) A° hman, J .; Somfai, P. Synth. Commun. 1994, 24, 1121-1127.
(28) Mancuso, A. J .; Huang, S.-L.; Swern, D. J . Org. Chem. 1978,
43, 2480-2482.
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683.
(30) Ireland, R. E.; Norbeck, D. W. J . Org. Chem. 1985, 50, 2198-
2200.

8150 J . Org. Chem., Vol. 61, No. 23, 1996
A° hman et al.
Sch em e 1a
a
Conditions: (a) NaN3, MeO(CH2)2OH, H2O, reflux; (b) t-BuMe2SiCl, Et3N, DMAP, CH2Cl2; (c) Ph3P, PhMe, reflux; (d) R′CH2Br, K2CO3,
18-crown-6, THF, rt; (e) Bu4NF, THF, 0 °C; (f) (COCl)2, DMSO, Et3N, -78 °C; (g) Ph3PCH3Br, KHMDS, THF, -15 °C (for 17, 23-25, 31,
32); Ph3PCH2CH3Br, KHMDS, THF, -15 °C (for 18, 27, 33); Ph3PCH2CH3Br, PhLi, MeOH, PhMe, -30 °C (for 19, 29, 34); Ph3PCHCO2Et,
CH2Cl2, -78 °C f rt (for 20); Ph3PCHCHO, PhMe, rt (for 21a ); (h) NaBH4, EtOH, -30 °C; (i) t-BuPh2SiCl, Et3N, DMAP, CH2Cl2; (j)
n-BuLi, TMSCl, THF, -78 °C.
2,3-trisubstituted vinylaziridines were prone to undergo
thermal [1,5]-hydrogen shifts, these compounds were
prepared and processed as quickly as possible, avoiding
any prolonged storage or handling at or above room
temperature.31
attack of PhLi on the ester moiety. The (E)-propenyl-
aziridines 19, 30, 34, and 43 are included in this study
only in order to probe the various mechanistic possibili-
ties in the aza-[2,3]-Wittig rearrangement (vide infra).
1
The H NMR spectra of aziridines 17-31 and 41-43
In a similar way the cis-2,3-trisubstituted vinylaziri-
dines 41-43 were prepared in racemic form from epoxy
alcohol 3732 by following the procedures established for
corresponding trans-derivatives 32-34 (Scheme 2). As
can be seen the present route provides (Z)-propenyl and
vinylaziridines in reasonable overall yields and with good
to excellent control over the olefin stereochemistry in the
former case (Schemes 1 and 2). However, it is notewor-
thy that in all cases studied so far the corresponding (E)-
propenyl derivatives could be obtained only in poor yields
with, at best, modest E:Z selectivity. Although varying
degrees of selectivity have previously been observed in
the Schlosser olefination, the low yields obtained were
surprising, but the cause could be traced to a competitive
all indicate the presence of a single nitrogen invertomer,
and it is reasonable to assume that the nitrogen sub-
stituent occupies the sterically less hindered position in
each case, i.e. trans to the tert-butyl substituent in
compounds 17-31 and trans to the (benzyloxy)methylene
and vinyl substituents in 41-43. This notion was also
substantiated by performing a NOESY experiment on
vinylaziridine 17 which showed an interaction between
the R-carbonyl protons and t-BuCH and CHCH2 while a
similar experiment with 42 showed an interaction be-
tween the R-carbonyl protons and both of the aziridine
methine protons. In contrast to this the spectra of
vinylaziridines 32-36 consist of two sets of lines in a
ratio of 2-4:1 at room temperature, indicating an equi-
librium of two invertomers. By performing a line-shape
1
analysis on the H NMR spectrum of 32 its barrier for
(31) Borel, D.; Gelas-Mialhe, Y.; Vessie`re, R. Can. J . Chem. 1976,
54, 1590-1598. Sauleau, J .; Sauleau, A.; Huet, J . Bull. Soc. Chim. Fr.
1978, 97-103. Hudlicky, T.; Frazier, J . O.; Seoane, G.; Tiedje, M.;
Seoane, A.; Kwart, L. D.; Beal, C. J . Am. Chem. Soc. 1986, 108, 3755-
3762. Pearson, W. H. Tetrahedron Lett. 1985, 26, 3527-3530. A° hman,
J . Somfai, P.; Tanner, D. J . Chem. Soc., Chem. Commun. 1994, 2785-
2786. Somfai, P.; A° hman, J . Tetrahedron Lett. 1995, 36, 1953-1956.
(32) For example, see: Howe, G. P.; Wang, S.; Procter, G. Tetrahe-
dron Lett. 1987, 28, 2629-2632.
inversion was calculated to be ∆Gq ) 16.5 kcal/mol (major
(33) Stephenson, D. S.; Binsch, G. QCPE 1978, 11, 365.
(34) J ennings, W. B.; Boyd, D. R. In Cyclic Organonitrogen Stereo-
dynamics; Lambert, J . B., Takeuchi, Y., Eds.; Verlag Chemie: New
York, 1992; Chapter 5. Lehn, J . M. Top. Curr. Chem. 1970, 15, 311-
377.

Aza-[2,3]-Wittig Rearrangements of Vinylaziridines
J . Org. Chem., Vol. 61, No. 23, 1996 8151
Sch em e 2a
starting vinylaziridine. Therefore nitrile derivative 24
was subjected to LDA (THF, -78 °C) but this gave,
somewhat surprisingly, only recovered starting material.
This problem was solved by using instead freshly pre-
pared KHMDS as base,36 resulting in the formation of
the corresponding tetrahydropyridines as a mixture of
diastereomers (45:46 6.6:1, 80%). Some decomposed
material, presumably the result of a facile elimination
of cyanide ion from the initially formed product, was also
obtained. Although we were pleased to observe that the
rearrangement did indeed proceed, the lower selectivity
obtained together with the instability of 45 and 46 toward
elimination discouraged further investigations with this
particular anion-stabilizing group. Instead our attention
was drawn to the fact that R-alkoxy anions derived from
allylic propargyl ethers participate in the [2,3]-rearrange-
ment to give homoallylic ethers with the opposite sense
of stereoinduction as compared to the corresponding
R-alkoxy enolates.1,37 Accordingly, N-propargyl vinyl-
aziridine 25 was selected as the next rearrangement
precursor. However, attempts to rearrange 25 by using
n-BuLi, n-BuLi/TMEDA or s-BuLi (3 equiv, THF) gave
none of the expected tetrahydropyridines and 25 was
recovered unchanged, or with complete incorporation of
deuterium at the terminal alkyne position when the
reaction was quenched with D2O. This is in contrast to
the behavior of allylic propargyl ethers which are smoothly
deprotonated by the action of n-BuLi.37,38 However,
subjecting the TMS derivative 26 to s-BuLi (THF, -78
°C) resulted in the formation of the cis-2,6- and trans-
2,6-disubstituted tetrahydropyridines 47 and 48 along
with considerable amounts of 1-pyrroline 49 (47:48:49
1.2:1.8:1, 95% total yield). The relative stereochemistry
of 47 and 48 was assigned by inspection of the relevant
a
Conditions: (a) NaN3, MeO(CH2)2OH, H2O, reflux, 97%; (b)
t-BuMe2SiCl, Et3N, DMAP, CH2Cl2, 85%; (c) Ph3P, PhMe, reflux,
59%; (d) BrCH2CO2t-Bu, K2CO3, 18-crown-6, THF, rt, 87%; (e)
Bu4NF, THF, 0 °C, 98%; (f) (COCl)2, DMSO, Et3N, -78 °C; (g)
Ph3PCH3Br, KHMDS, THF, 0 °C, 92% (for 41); Ph3PCH2CH3Br,
KHMDS, THF, -15 °C, 87% (for 42); Ph3PCH2CH3Br, PhLi,
MeOH, PhMe, -30 °C, 4% (for 43).
f minor) while the difference in free-energy between the
invertomers was found to be ∆G° ) 0.77 kcal/mol,33 which
is in agreement with literature values for similar com-
pounds.34
Rea r r a n gem en t of Vin yla zir id in es. The influence
of the activating group on the [2,3]-rearrangement, in
terms of both reaction outcome and selectivity, is sum-
marized in Table 1. Subjecting vinylaziridine 17 to LDA
in THF at -78 °C resulted in the rapid (<5 min)
formation of tetrahydropyridine 44 as a single detectable
diastereomer (1H NMR). The relative stereochemistry
of 44 was assigned by analyzing the relevant coupling
constants in its 1H NMR spectrum assuming that the
unsaturated six-membered ring adopts a half-chair con-
formation in which the tert-butyl moiety functions as a
conformational lock and occupies a pseudoequatorial
position. Support for this assignment was obtained by
hydrogenation (H2, Pd/C, EtOH) of 44 to yield the
corresponding cis-2,6-disubstituted piperidine derivative
as evident from its spectral data.35 The high selectivity
observed in the rearrangement of vinylaziridine 17 is
gratifying and presents a novel entry to cis-2,6-disubsti-
tuted piperidine alkaloids.9 It should also be noted that
tetrahydropyridine 44, as well as the other rearrange-
ment products described in this paper, are not stable to
chromatography or storage. However, the produts from
these rearrangements are normally pure (>95%), as
determined from their 1H NMR spectra, and the yields
and ratios reported refer to such crude products. It has
been shown that the activating, anion-stabilizing group
(eq 1, G) has a decisive effect on the stereochemical
outcome of the [2,3]-Wittig rearrangement of allylic
ethers, and this obviously raises the question if similar
control could be obtained for the title reaction,1 i.e. if
trans-2,6-disubstituted tetrahydropyridines could be
formed by simply changing the N-substituent in the
1
coupling constants in the H NMR spectra and verified
by NOESY experiments, while the structure elucidation
of 49 required more extensive NMR investigation (NOE-
SY, COSY, HETCOR and long-range HETCOR). As is
evident from the above results, the anion-stabilizing
group has an effect on the stereochemical outcome in the
aza-[2,3]-Wittig rearrangement of vinylaziridines, rang-
ing from a complete cis-2,6-selectivity for the tert-butyl
ester 17 to a modest trans selectivity for the anion
derived from the propargyl derivative 26. These experi-
ments also seem to indicate that the mechanistic details
of this reaction might not be as clear-cut as originally
believed, since the formation of 1-pyrroline 49 is clearly
not the result of a sigmatropic process (vide infra).8
Finally, we have also investigated the potential of the
benzyl derivative 23 and the unsaturated ester 31 as
substrates for the rearrangement. However, subjecting
23 to a variety of bases (BuLi, s-BuLi, t-BuLi) gave only
recovered starting material. The reason for this was a
facile ortho lithiation of the aromatic nuclei, as shown
by a D2O quench.39 Similarly, the enolate derived from
31 (LDA, KHMDS) also failed to react, perhaps due to
the increased thermodynamic stability of the conjugated
enolate.
Since it had been shown that a tert-butyl acetate
moiety is the most efficient activating group for the
(36) A° hman, J .; Somfai, P. Synth. Commun. 1995, 25, 2301-2303.
(37) Nakai, T.; Mikami, K.; Taya, S.; Fujita, Y. J . Am. Chem. Soc.
1981, 103, 6492-6494. Mikami, K.; Kimura, Y.; Kishi, N.; Nakai, T.
J . Org. Chem. 1983, 48, 279-281.
(38) For a discussion of nitrogen-stabilized carbanions, see: Gawley,
R. E.; Rein, K. In Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 3, Chapter 1.2.
(39) Beak, P.; Snieckus, V. Acc. Chem. Res. 1982, 15, 306-312. Beak,
P.; Meyers, A. I. Acc. Chem. Res. 1986, 19, 356-363.
(35) 1H NMR (CDCl3, 300 MHz) δ 3.17 (dd, 1H, J ) 11.2, 2.8,
t
CHCO2tBu), 2.16 (dd, 1H, J ) 11.0, 2.2, BuCH).

8152 J . Org. Chem., Vol. 61, No. 23, 1996
Ta ble 1. Th e In flu en ce of th e An ion -Sta bilizin g Gr ou p on th e [2,3]-Rea r r a n gem en t
A° hman et al.
products
trans
substrate
basea
LDA
KHMDS
d
s-BuLi
d
d
cis
pyrroline
ratiob
yield,c (%)
17, R1 ) CO2tBu
24, R1 ) CN
44
45
-
47
-
-
-
46
-
48
-
-
-
-
-
49
-
-
cis only
6.6:1
95
80
0e
25, R1 ) CtCH
26, R1 ) CtCTMS
23, R1 ) Ph
-
1.2:1.8:1
95
-
-
0e
31, R1 ) (E)-CHCHCO2Me
0e
All reactions were run in THF at -78 °C. Determined from 1H NMR. c Combined crude yields. -78 °C to rt. A variety of bases
a
b
d
were tested, see text. e The starting material was recovered.
Sch em e 3
Sch em e 4
present rearrangement, we next decided to study the
influence of the other ring substituents on the reaction
outcome. As shown in Scheme 3, the results were
gratifying, with the tetrahydropyridines being formed in
excellent yields and, in each case, as a single diastere-
omer (Scheme 3). That the high selectivity observed in
these rearrangements is the result of a kinetic formation
of the cis-2,6-tetrahydropyridines and not due to a base-
promoted equilibration of an initially formed mixture was
shown by subjecting a mixture of racemic cis- and trans-
tetrahydropyridines 52 and 58 (1.8:1) to the reaction
conditions followed by standard isolation to yield the
starting material with an unaffected isomeric ratio. Of
particular interest is the complete selectivity observed
in the rearrangements of the more highly substituted
vinylaziridines 18, 19, 33, 34, and 36. Apparently the
stereochemical information supplied by the olefin is
retained throughout the reaction, resulting in the forma-
tion of trans,trans-2,3,6-trisubstituted tetrahydropy-
ridines 50, 53, and 56 when starting from (Z)-alkenes
18, 33, and 36, respectively. Similarly, the (E)-substrates
19 and 34 upon treatment with LDA are transformed into
the corresponding cis,cis-2,3,6-trisubstituted derivatives
51 and 54 with equally impressive selectivity.40 Nor-
mally such high selectivity in these types of rearrange-
ment is associated with a concerted reaction pathway in
which the relative stereochemistry of the substrate, for
stereoelectronic or steric reasons, is effectively com-
municated to the product. An indication that the present
rearrangement might proceed by a more complicated,
stepwise, mechanism was obtained when attempting to
rearrange the unsaturated ester 20 (eq 3). When 20 was
subjected to LDA (THF, -78 °C), the â,γ-unsaturated
ester 57 was formed in high yield and as a single isomer,
although the relative stereochemistry of the imine moiety
has not yet been assigned with certainty. Apparently the
enolate derived from 20 opens the three-membered ring
to form a new enolate, which can be quenched with D2O
to yielded the R-deuterated â,γ-unsaturated ester with
complete incorporation of deuterium. Also, attempts to
rearrange silyl ether 22 gave a complicated mixture of
products containing none of the expected tetrahydropy-
ridine.
We believe that three different mechanisms are most
likely for the [2,3]-rearrangements described above
(Scheme 3). In the first of these, a concerted process
which has also been invoked in the analogous rearrange-
ments of allyl ethers,1,2 there is a requirement for the
enolate to be cis to the vinyl moiety so as to allow for
efficient orbital overlap during C-C bond formation and
opening of the three-membered ring (Scheme 4, path a).
Such a mechanism correctly accounts for the stereochem-
(40) The E:Z ratio in the starting material is, in each case, retained
as a 2,3-cis:trans ratio in the product.

Aza-[2,3]-Wittig Rearrangements of Vinylaziridines
J . Org. Chem., Vol. 61, No. 23, 1996 8153
ical outcome in the rearrangements of 17-19 and 32-
36. Alternatively, the enolate anion might dispropor-
tionate into a diradical anion followed by an intra-
molecular recombination to give the observed products
(path b). Analogous mechanistic schemes have been
proposed for the [1,2]-Wittig rearrangement of allylic
ethers1a,b and have also been invoked in the rearrange-
ment of certain allylic amines.4b-d,6 Finally, a scenario
in which the initially formed anion opens the ring to form
an allylic anion which then makes a nucleophilic attack
on the imine moiety can also be envisioned (path c). If
the second or third mechanistic alternatives are indeed
operating, involving discrete intermediates, the origin of
the observed selectivities seems less obvious to rational-
ize.
In an effort to differentiate between these mechanistic
possibilities and, hopefully, to provide some information
about the origin of the stereoselectivity in the rearrange-
ments, the following experiments were done. If a con-
certed mechanism is operating, vinylaziridines 41-43,
which exist as single N-invertomers with the ester moiety
trans to the vinyl group, should afford products with
different relative stereochemistry compared to the tet-
rahydropyridines obtained from 32-34. Accordingly,
rearrangement of 41 under standard conditions (LDA,
THF, -78 °C) gave a mixture of rac-52 and rac-58 (1.8:
1) in 93% yield (eq 4). In this reaction the trans-2,6-
The formation of 1-pyrrolines in these rearrangements
is surprising. Some information about their mode of
formation was obtained by repeating the experiment with
aziridine 28 (s-BuLi, -78 °C, THF) and quenching the
reaction with D2O. This yielded d-61a as a single
diastereomer with complete deuterium incorporation
which suggests a mechanism in which the initially
formed propargylic anion opens the aziridine ring to form
the corresponding allylic anion (eq 6). Intramolecular
addition of this anion to the alkyne moiety then gives a
vinylic anion, species known to be configurationally
stable,42 which is then quenched by D2O to give d-61a ,
thus accounting for the exclusive formation of an (E)-
vinylsilane in this process. No conclusive rationale for
the mechanism of the [2,3]-rearrangement in vinylaziri-
dines or the observed selectivities can be obtained from
these experiments. However, it is clear that the mech-
anism is more complex than we originally suggested and
that it might involve ring-opened intermediates and
concurrent reaction pathways. Further studies to clarify
these points are underway.
In conclusion, we have shown that various N-alkylated
vinylaziridines can be prepared from the corresponding
epoxy alcohols in reasonable overall yields. As for their
[2,3]-rearrangement, trans-2,3-trisubstituted vinylaziri-
dines having a tert-butyl ester moiety as an anion-
stabilizing group rearrange with complete selectivity into
the corresponding cis-2,6-disubstituted tetrahydropy-
ridines. It has also been shown that (Z)-propenylaziri-
dines afford trans,trans-2,3,6-trisubstituted tetrahydro-
pyridines upon rearrangement, while (E)-propenyl-
aziridines give the cis,cis-2,3,6-trisubstituted heterocycles
with equally impressive selectivity. Other anion-stabiliz-
ing groups, such as a nitrile or an alkyne, perform less
well in this reaction and give mixtures of products, while
a phenyl and an R,â-unsaturated ester moiety apparently
resist rearrangement. Finally, the mechanism of this
reaction has been probed to some extent and it seems to
be more complicated than originally assumed.
disubstituted derivative rac-58 could conceivably be
formed by a concerted pathway (cf. Scheme 3, path a),
but formation of rac-52 must involve a ring-opened
intermediate. Even more surprising, however, was the
finding that the (Z)-derivative 42 rearranged into rac-
53 (98%) as a single isomer while the (E)-derivative 43
under the same conditions gave rac-54 (93%) as the sole
product, neither of which would have been predicted to
be the result of a concerted process. In addition, since
vinylaziridines 33 and 42 both afford tetrahydropyridine
53 upon rearrangement while 34 and 43 give 54, it seems
reasonable to assume that these rearrangements occur
via a common ring-opened intermediate for each pair of
substrates.
Since it has been shown that cleavage-diradical
combination processes become more important at higher
temperatures,6 the rearrangement of 41 was reapeated
at 0 °C and room temperature, but no change in yield or
isomeric composition was observed. Identical results
were also obtained when 41 was rearranged in the
presence of m-dinitrobenzene, a radical trap.41
Finally, some evidence for the involvement of the allylic
anion type of intermediate has been collected (Scheme
4, path c). As discussed previously, subjecting vinylaziri-
dine 20 to LDA evidently produces such an intermediate,
as was shown by a D2O-quench. Furthermore, rear-
rangement of the propargyl derivative 28 (s-BuLi, -78
°C, THF) gives 1-pyrroline 61a as the only isolated
product in 98% yield while isomer 30 (E:Z 6:1) gave
tetrahydropyridines 59 and 60 together with 1-pyrrolines
61a and 61b (59:60:61a :61b 4.9:2.4:1.4:1) in 49% com-
bined isolated yield (eq 5).
Exp er im en ta l Section 43
(2S,3R)-3-ter t-Bu tyl-2-[[(ter t-bu tyld im eth ylsilyl)oxy]-
m eth yl]a zir id in e (3). A solution of (2R,3S)-2-azido-4,4-di-
methyl-1,3-pentanediol24 (457 mg, 2.64 mmol), tert-butyldi-
(42) J enkins, P. R.; Symons, M. C. R.; Booth, S. E.; Swain, C. J .
Tetrahedron Lett. 1992, 33, 3543.
(41) Gong, J .; Fuchs, P. L. J . Am. Chem. Soc. 1996, 118, 4486-4487.
(43) For general experimentals, see ref. 9.

8154 J . Org. Chem., Vol. 61, No. 23, 1996
A° hman et al.
methylsilyl chloride (478 mg, 3.18 mmol), triethylamine (0.58
mL, 3.70 mmol), and N,N-dimethyl-4-aminopyridine (cat.) in
dry CH2Cl2 (20 mL) was stirred for 10 h at rt. The mixture
was then poured into water (20 mL), and the organic phase
was separated and washed with sat. NH4Cl (10 mL). Drying
(MgSO4), concentration, and flash chromatography (heptane:
EtOAc 15:1) gave (2R,3S)-4-azido-2,2-dimethyl-5-[(tert-bu-
tyldimethylsilyl)oxy]-3-pentanol (489 mg) in 64% overall yield
from epoxide 1. 1H NMR (CDCl3, 300 MHz) δ 4.00 (m, 2H),
3.47 (dd, 1H, J ) 5.6, 5.0), 3.29 (m, 1H), 2.89 (d, 1H, J ) 4.9),
1.04 (s, 1H), 0.99 (s, 9H), 0.92 (s, 9H), 0.13 (s, 3H), 0.12 (s,
3H); 13C NMR (CDCl3, 75 MHz) δ 79.8, 65.1, 62.7, 34.9, 26.2,
25.9, 18.2, -5.5, -5.6; IR (neat) 3470, 2950, 2100 cm-1; HRMS
(CI+). Exact mass calcd for C13H30N3OSi (M + H): 288.2107,
found: 288.2118.
and with brine (20 mL). Drying (MgSO4), concentration, and
flash chromatography (heptane:EtOAc 10:1 f 6:1) gave 6 (542
mg, 92%). 1H NMR (CDCl3, 300 MHz) δ 3.89 (dd, 1H, J )
11.8, 3.3), 3.75, (dd, 1H, J ) 11.8, 6.7) 3.51 (d, 1H, J ) 16.2),
3.07 (d, 1H, J ) 16.2), 2.13 (dt, 1H, J ) 6.8, 3.4), 1.46 (s, 9H),
1.39 (d, 1H, J ) 3.4), 0.88 (s, 9H), 0.04 (s, 6H); 13C NMR
(CDCl3, 75 MHz) δ 170.7, 80.7, 59.8, 55.3, 53.2, 39.4, 30.2, 28.1,
27.0, 25.8, 18.1, -5.4, -5.5; IR (neat) 2970, 1750 cm-1; [R]20
D
-6.6 (c 2.28, CHCl3); HRMS (CI+). Exact mass calcd for
C19H40NO3Si (M + H): 358.2775, found: 358.2800.
(2S,3R)-N-Ben zyl-3-ter t-bu tyl-2-[[(ter t-bu tyld im eth yl-
silyl)oxy]m eth yl]a zir id in e (7). A slurry of aziridine 3 (500
mg, 2.06 mmol), benzyl bromide (0.345 mL, 3.08 mmol), K2-
CO3 (312 mg, 2.26 mmol), and 18-crown-6 (cat.) in THF (15
mL) was stirred for 3 days at rt. The white slurry was poured
into Et2O (30 mL) and washed with water (20 mL) and brine
(20 mL). Drying (MgSO4), concentration, and flash chroma-
tography (heptane:EtOAc 15:1 f 6:1) gave aziridine 7 (491
mg, 71%). 1H NMR (CDCl3, 300 MHz) δ 7.42-7.20 (m, 5H),
4.06 (d, 1H, J ) 13.2), 3.98 (dd, 1H, J ) 11.7, 3.6), 3.85, (dd,
1H, J ) 11.7, 7.5) 3.55 (d, 1H, J ) 13.2), 2.13 (dt, 1H, J ) 7.5,
3.6), 1.39 (d, 1H, J ) 3.6), 0.90 (s, 9H), 0.08 (s, 3H), 0.07 (s,
3H); 13C NMR (CDCl3, 75 MHz) δ 140.5, 128.6, 128.1, 126.7,
60.0, 56.1, 52.9, 40.5, 30.1, 27.0, 25.9, 18.2, -5.3, -5.4; IR
A solution of the azido alcohol from above (427 mg, 1.49
mmol) and triphenylphosphine (468 mg, 1.78 mmol) in toluene
(20 mL) was heated under reflux for 14 h. After cooling to rt
the mixture was concentrated, and the residue was flash
chromatographed (heptane:EtOAc 6:1 f 1:1) to give aziridine
3 (344 mg, 94%). 1H NMR (CDCl3, 300 MHz) δ 3.69 (m, 2H),
1.91 (m, 1H), 1.67 (d, 1H, J ) 3.3), 0.88 (s, 9H), 0.88 (s, 9H),
0.44 (br s, 1H), 0.05 (s, 6H); 13C NMR (CDCl3, 75 MHz) δ 34.4,
30.0, 26.8, 25.8, 18.3, -5.3, -5.4; IR (neat) 3260, 2950 cm-1
;
[R]20 +19.1 (c 2.63, CHCl3); HRMS (CI+). Exact mass calcd
(neat) 2950, 1460 cm-1; [R]20 +51.6 (c 3.05, CHCl3); HRMS
D
D
for C13H39NOSi (M + H): 244.2097, found: 244.2101.
(2S,3R)-3-ter t-Bu tyl-2-(h ydr oxym eth yl)azir idin e (4). To
a solution of 3 (520 mg, 2.13 mmol) in THF (25 mL) at 0 °C
was added tetrabutylammonium fluoride trihydrate (1.01 g,
3.20 mmol). The resultant mixture was stirred for 30 min at
0 °C. Concentration and flash chromatography (EtOAc:MeOH
1:0 f 4:1) of the residue yielded 4 (260 mg, 96%) as white
crystals (mp 77-79 °C). 1H NMR (CDCl3,400 MHz) δ 3.83 (dd,
1H, J ) 11.8, 3.3), 3.37 (dd, 1H, J ) 11.8, 6.3), 2.63 (br s, 2H),
2.10 (m, 1H), 1.78 (br s, 1H), 0.91 (s, 9H); 13C NMR (CDCl3,
100 MHz) δ 63.9, 45.2, 35.4, 30.4, 27.2; IR (neat) 3260, 2960,
1470, 1365 cm-1; [R]22D ) +22.3 (c 2.00, CHCl3); HRMS (CI+).
Exact mass calcd for C7H16NO (M + H): 130.1232, found:
130.1231.
(CI+). Exact mass calcd for C20H36NOSi (M + H): 334.2566,
found: 334.2562.
(2(2S,3R))-2-[3-ter t-Bu tyl-2-[[(ter t-bu tyld im eth ylsilyl)-
oxy]m eth yl]a zir id in -1-yl]a ceton itr ile (8). A slurry of azir-
idine 3 (1.40 g, 5.76 mmol), bromoacetonitrile (0.601 mL, 8.64
mmol), K2CO3 (875 mg, 6.30 mmol), and 18-crown-6 (cat.) in
THF (20 mL) was stirred for 2 days at rt. The white slurry
was then poured into Et2O (50 mL) and washed twice with
water (20 mL) and once with brine (20 mL). Drying (MgSO4),
concentration, and flash chromatography (heptane:EtOAc 9:1
f 4:1) gave the aziridine 8 (1.35 g, 92%). 1H NMR (CDCl3,
400 MHz) δ 4.05 (dd, 1H, J ) 12.4, 2.6), 3.80, (dd, 1H, J )
12.4, 6.8) 3.70 (d, 1H, J ) 16.6), 3.45 (d, 1H, J ) 16.6), 2.20
(ddd, 1H, J ) 6.8, 3.7, 2.6), 1.60 (d, 1H, J ) 3.7), 0.88 (s, 9H),
0.10 (s, 6H); 13C NMR (CDCl3, 100 MHz) δ 118.4, 59.7, 52.8,
41.0, 40.1, 30.6, 27.2, 26.2, 18.6, -5.0, -5.1; IR (neat) 2960,
(2S,3R)-3-[(Ben zyloxy)m eth yl]-2-[[(ter t-bu tyld im eth yl-
silyl)oxy]m eth yl]a zir id in e (5). Silylation of a mixture of
(2R,3S)-2-azido-4-(benzyloxy)-1,3-butanediol and (2S,3R)-3-
azido-4-(benzyloxy)-1,2-butanediol24 as detailed for 3 gave after
flash chromatography (heptane:EtOAc 10:1 f 4:1) (2S,3R)-3-
azido-1-(benzyloxy)-4-[(tert-butyldimethylsilyl)oxy]-2-butanol
and (2S,3R)-3-azido-4-(benzyloxy)-1-[(tert-butyldimethylsilyl)-
oxy]-2-butanol as an inseparable mixture in 90% yield. 1H
NMR (CDCl3, 400 MHz, peaks assigned from a mixture of
regioisomers) δ 7.39-7.30 (m, 5Hmaj, 5Hmin), 4.61 (s, 2Hmin),
1470 cm-1; [R]23 -1.4 (c 0.99, CHCl3); HRMS (CI+). Exact
D
mass calcd for C15H30N2O (M + H): 283.2206, found: 283.2206.
(2S,3R)-3-ter t-Bu tyl-2-[[(ter t-bu tyld im eth ylsilyl)oxy]-
m eth yl]-1-(2-p r op yn yl)a zir id in e (9). To a solution of aziri-
dine 3 (800 mg, 3.30 mmol) in THF (20 mL) were added K2-
CO3 (500 mg, 3.61 mmol), propargyl bromide (2.88 mL, 4.95
mmol, 80 wt % in toluene), and 18-crown-6 (cat.). The
resultant slurry was stirred for 2.5 days at rt. The reaction
mixture was then poured into Et2O (50 mL) and washed with
water (20 mL) and brine (20 mL). Drying (MgSO4), concentra-
tion, and flash chromatography (heptane:EtOAc 50:1 f 8:1)
gave 9 (852 mg, 86%). 1H NMR (CDCl3, 300 MHz) δ 3.96 (dd,
1H, J ) 11.9, 3.5), 3.78 (dd, 1H, J ) 11.9, 7.1), 3.54 (dd, 1H,
J ) 16.6, 2.6), 3.25 (dd, 1H, J ) 16.6, 2.6), 2.22 (t, 1H, J )
2.6), 2.14 (dt, 1H, J ) 7.2, 3.6), 1.45 (d, 1H, J ) 3.6) 1.89 (s,
9H), 1.87 (s, 9H), 0.08 (s, 6H); 13C (CDCl3, 75 MHz) δ 82.0,
71.5, 59.7, 52.7, 41.0, 40.4, 30.0, 27.0, 25.8, 18.2, -5.4, -5.5;
4.59 (s, 2Hmaj), 3.99 (dd, J ) 10.7, 3.6, 1Hmaj), 3.89 (dd, 1Hmin
J ) 10.0, 2.6), 3.86 (dd, 1Hmaj, J ) 10.6, 5.7), 3.82-3.77 (m,
1Hmin), 3.75-3.66 (m, 1Hmaj, 2Hmin), 3.65-3.59 (m, 2Hmin
,
,
2Hmaj), 3.53-3.48 (m, 1Hmaj), 2.67 (d, 1Hmaj, J ) 5.5), 2.61 (d,
1Hmin, J ) 6.1), 0.93 (s, 9Hmaj), 0.92 (s, 9Hmin), 0.11 (s, 6Hmaj),
0.10 (s, 6Hmin); 13C NMR (CDCl3, 100 MHz, from a mixture of
regioisomers) δ 138.2, 138.1, 128.9, 128.9, 128.4, 128.3, 128.2,
128.2, 128.1, 128.1, 74.0, 74.0, 71.5, 71.3, 70.9, 70.4, 64.3, 64.1,
64.0, 62.5, 26.3, 26.2, 18.7, 18.6, -5.0, -5.1; IR (neat, from a
mixture of regioisomers) 3450, 2920, 2090 cm-1; HRMS (CI+).
Exact mass calcd for C17H30N3O3Si (M + H): 352.2056,
found: 352.2062.
IR (neat): 3280, 2940, 2195 cm-1; [R]24 +9.9 (c 1.25, CHCl3);
D
HRMS(CI+). Exact mass calcd for C16H32NOSi (M + H):
278.2253, found: 278.2253.
Azir id in e 5. Flash chromatography (heptane:EtOAc 10:1
f 2:1) gave aziridine 5 in 88% yield as a colorless oil. 1H NMR
(CDCl3, 400 MHz) δ 7.37-7.29 (m, 5H), 4.57 (AB-q, 2H, J )
11.9, 7.2), 3.78 (d, 2H, J ) 3.1), 3.59 (dd, 1H, J ) 21.5, 4.6),
3.45 (dd, 1H, J ) 10.5, 6.1), 2.17 (br s, 1H), 1.98 (d, 1H, J )
2.8), 0.89 (s, 9H), 0.74 (br s, 1H), 0.06 (s, 6H); 13C NMR (CDCl3,
100 MHz) δ 138.6, 128.8, 128.8, 128.2, 128.1, 128.1, 73.5, 36.0,
26.3, 18.7, -4.9, -5.0; IR (neat) 3280, 2920 cm-1; [R]22D +22.3
ter t-Bu tyl (2(2S,3R))-2-[3-[(Ben zyloxy)m eth yl]-2-[[(ter t-
bu tyld im eth ylsilyl)oxy]m eth yl]a zir id in -1-yl]a ceta te (10).
To a solution of aziridine 5 (596 mg, 1.94 mmol) in THF (10
mL) was added 18-crown-6 (cat.), K2CO3 (295 mg, 2.13 mmol),
and tert-butyl bromoacetate (470 µL, 2.91 mmol). The result-
ant slurry was stirred at rt for 72 h. The reaction mixture
was poured into water (20 mL), and the organic layer was
separated. The aqueous phase was washed with Et2O (4 ×
15 mL), and the combined organic layers were washed with
brine (15 mL). Drying (MgSO4), concentration, and flash
chromatography (heptane:EtOAc 8:1 f 1:1) gave 10 (436 mg,
53%). 1H NMR (CDCl3, 400 MHz, peaks assigned from a
mixture of invertomers) δ 7.38-7.28 (m, 5Hmaj, 5Hmin), 4.58
(AB-q, 2Hmaj, J ) 12.0, 9.0), 4.55 (AB-q, 2Hmin, J ) 12.0, 5.8),
4.01-3.95 (m, 1Hmaj, 1Hmin), 3.87-3.78 (m, 1Hmaj, 1Hmin), 3.70-
3.61 (m, 1Hmaj, 1Hmin), 3.53-3.41 (m, 2Hmaj, 2Hmin), 3.28 (d,
(c 2.00, CHCl3); HRMS (CI+). Exact mass calcd for C17H30
NO2Si (M + H): 308.2046, found: 308.2047.
-
ter t-Bu tyl (2(2S,3R))-2-[3-ter t-Bu tyl-2-[[((ter t-bu tyld i-
m eth ylsilyl)oxy]m eth yl]a zir id in -1-yl]a ceta te (6). Aziri-
dine 3 (334 mg, 1.37 mmol), tert-butyl bromoacetate (0.333 mL,
2.06 mmol), K2CO3 (209 mg, 1.51 mmol), and 18-crown-6 (cat.)
in THF (10 mL) were stirred for 4 days at rt. The white slurry
was poured into Et2O (30 mL) and washed with water (20 mL)

Aza-[2,3]-Wittig Rearrangements of Vinylaziridines
J . Org. Chem., Vol. 61, No. 23, 1996 8155
1Hmaj, J ) 16.6), 3.15 (d, 1Hmin, J ) 16.5), 2.30-2.25 (m, 1Hmin),
2.21-2.16 (m, 1Hmaj), 1.99-1.94 (m, 1Hmaj), 1.84-1.79 (m,
1Hmin), 1.47 (s, 9Hmaj, 9Hmin), 0.90 (s, 9Hmaj, 9Hmin), 0.07 (s,
6Hmaj, 6Hmin); 13C NMR (CDCl3, 100 MHz, from a mixture of
invertomers) δ 170.9, 170.6, 138.8, 138.3, 128.8, 128.8, 128.2,
128.1, 128.1, 128.0, 81.4, 81.3, 73.5, 73.1, 72.5, 66.5, 65.7, 59.4,
54.4, 54.1, 44.4, 41.8, 41.2, 40.2, 28.5, 26.4, 26.3, 18.8, 18.6,
-4.8, -5.0; IR (neat, from a mixture of invertomers) 2850,
(CI+). Exact mass calcd for C12H22NO3 (M + H): 228.1600,
found: 228.1600.
ter t-Bu t yl (2(2S,3R))-2-[3-[(b en zyloxy)m et h yl]-2-(h y-
d r oxym eth yl)a zir id in -1-yl]a ceta te (16). Prepared from 10
in 91% yield as detailed for 11. Flash chromatography
(heptane:EtOAc 1:2 f 1:10) gave alcohol 16 as an oil. 1H NMR
(CDCl3, 400 MHz, peaks assigned from a mixture of inver-
tomers) δ 7.39-7.28 (m, 5Hmaj, 5Hmin), 4.58-4.50 (m, 2Hmaj
,
1720, 1245 cm-1; HRMS (CI+). Exact mass calcd for C23H40
NO4Si (M + H): 422.2727, found: 422.2734.
-
2Hmin), 3.97-3.89 (m, 1Hmaj, 1Hmin), 3.84-3.75 (m, 1Hmin),
3.72-3.43 (m, 3Hmaj, 3Hmin), 3.29-3.22 (m, 1Hmaj), 3.12-3.05
(m, 1Hmin), 2.93 (d, 1Hmaj, J ) 17.1), 2.41-2.28 (m, 1Hmaj,
ter t-Bu t yl (2(2S,3R))-2-[3-ter t-Bu t yl-2-(h yd r oxym et h -
yl)a zir id in -1-yl]a ceta te (11). To a solution of 6 (1.0 g, 2.79
mmol) in THF (20 mL) at 0 °C was added tetrabutylammonium
fluoride (1.32 g, 4.18 mmol), and the resultant mixture was
stirred for 30 min at 0 °C and then warmed to rt over 15 min.
The reaction mixture was poured into Et2O (30 mL) and
washed once with water (30 mL) and once with brine (20 mL).
Drying (MgSO4), concentration, and flash chromatography
(heptane:EtOAc 3:1 f 1:2) gave 11 (522 mg, 77%). 1H NMR
(CDCl3, 300 MHz) δ 3.90 (ddd, 1H, J ) 13.0, 10.1, 2.7), 3.64-
3.44 (m, 3H), 3.04 (d, 1H, J ) 16.6), 2.38 (dt, 1H, J ) 10.1,
3.0), 1.48 (s, 9H), 1.12 (d, 1H, J ) 3.0), 0.88 (s, 9H); 13C NMR
(CDCl3, 75 MHz) δ 172.0, 82.2, 58.9, 54.4, 52.1, 41.3, 30.4, 28.0,
1Hmin), 1.95-1.80 (m, 1Hmaj, 1Hmin), 1.69 (br s, 1Hmaj, 1Hmin),
1.48 (s, 9Hmaj, 9Hmin); 13C NMR (CDCl3, 100 MHz, from a
mixture of invertomers) δ 172.0, 168.5, 138.1, 128.9, 128.3,
128.2, 128.2, 128.1, 82.4, 73.8, 73.5, 73.4, 70.4, 66.5, 64.8, 63.4,
53.3, 51.2, 45.0, 39.2, 36.4, 33.7, 28.5; IR (neat, from a mixture
of invertomers) 3420, 2920, 1730 cm-1; HRMS (CI+). Exact
mass calcd for C17H26NO4 (M + H): 308.1862, found: 308.1860.
ter t-Bu tyl (2(2R,3R))-2-(3-ter t-Bu tyl-2-vin yla zir id in -1-
yl)a ceta te (17). To a stirred solution of DMSO (114 µL, 1.61
mmol) in CH2Cl2 (5 mL) at -78 °C was added oxalyl chloride
(56.3 µL, 0.664 mmol), and stirring was continued for 5 min.
Alcohol 11 (78.3 mg, 0.322 mmol) in CH2Cl2 (5 mL) was added
via cannula to the mixture, and stirring was continued for 30
min at -78 °C. Triethylamine (0.538 mL, 3.86 mmol) was then
added, and the mixture was slowly warmed to rt over 2 h. The
mixture was then poured into Et2O (20 mL) and washed twice
with water (2 × 20 mL) and once with brine (20 mL). Drying
(MgSO4) and concentration furnished the crude aldehyde
which was taken on to the next step without further purifica-
tion.
26.9; IR (neat) 3420, 2960, 1745 cm-1; [R]22 -52.4 (c 5.28,
D
CHCl3); HRMS (CI+). Exact mass calcd for C13H26NO3 (M +
H): 244.1912, found: 244.1911.
(2S,3R)-N-Ben zyl-3-ter t-bu tyl-2-(h yd r oxym eth yl)a zir i-
d in e (12). Prepared from 7 in 92% yield as detailed for 11.
Flash chromatography (heptane:EtOAc 6:1 f 1:1) furnished
12 as a white solid (mp 89-91 °C). 1H NMR (CDCl3, 300 MHz)
δ 7.48-7.20 (m, 5H), 4.02-3.88 (m, 2H), 3.78 (dd, 1H, J ) 12.2,
8.7), 3.49 (m, 1H), 2.82 (br s, 1H), 2.24 (dt, 1H, J ) 8.7, 3.6),
1.36 (d, 1H, J ) 3.6), 0.78 (s, 9H); 13C NMR (CDCl3, 75 MHz)
δ 140.0, 128.4, 128.3, 127.0, 59.8, 56.3, 53.6, 40.4, 30.3, 26.9;
IR (KBr) 3450, 2960 cm-1; [R]22D +52.4 (c 1.47, CHCl3); HRMS
(CI+). Exact mass calcd for C14H22NO (M + H): 220.1701,
found: 220.1705.
To a solution of methyltriphenylphosphonium bromide (367
mg, 0.998 mmol) in toluene (5 mL) at -15 °C was added
KHMDS (0.460 mL, 0.966 mmol, 2.1 M in THF), and the
resultant yellow slurry was stirred for 30 min at -15 °C to rt
and then recooled to -15 °C. The crude aldehyde from above
(0.322 mmol) in THF (10 mL) was then added via cannula,
and stirring was continued for 20 min at -15 °C to rt. The
yellow slurry was then poured into brine (10 mL), and the
aqueous phase was extracted with Et2O (3 × 10 mL). Drying
(MgSO4), concentration, and flash chromatography (heptane:
EtOAc 10:1 f 3:1) furnished 17 (71.4 mg, 92%). 1H NMR
(CDCl3, 300 MHz) δ 5.65 (m, 1H), 5.35 (dd, 1H, J ) 17.0, 1.8),
5.23 (dd, 1H, J ) 10.1, 1.7), 3.25 (d, 1H, J ) 16.2), 3.07 (d,
1H, J ) 16.2), 2.52 (dd, 1H, J ) 8.3, 3.4), 1.44 (s, 9H), 1.43
(m, 1H), 0.90 (s, 9H); 13C NMR (CDCl3, 75 MHz) δ 170.1, 133.2,
120.3, 80.9, 57.8, 56.4, 40.8, 30.7, 28.1, 26.8; IR (neat) 2945,
(2(2S,3R))-2-[3-ter t-Bu t yl-2-(h yd r oxym et h yl)a zir id in -
1-yl]a ceton itr ile (13). Prepared from 8 in 89% yield as
detailed for 11. Flash chromatography (heptane:EtOAc 1:1
f 1:5) gave 13 as an oil. 1H NMR (CDCl3, 300 MHz) δ 4.06
(dd, 1H, J ) 12.9, 2.7), 3.76 (dd, 1H, J ) 12.9, 7.9), 3.72 (d,
1H, J ) 16.7), 3.44 (d, 1H, J ) 16.7), 2.32 (br s 1H), 2.24 (m,
1H), 1.54 (d, 1H, J ) 3.9), 0.90 (s, 9H); 13C NMR (CDCl3, 75
MHz) δ 117.9, 58.9, 53.2, 40.5, 39.8, 30.2, 26.7; IR (neat) 3360,
2950, 2250 cm-1; [R]24 +13.1 (c 2.15, CHCl3); HRMS (CI+).
D
Exact mass calcd for C9H17N2O (M + H): 169.1341, found:
169.1350.
1745 cm-1; [R]20 +69.6 (c 4.19, CH2Cl2); HRMS (CI+). Exact
D
mass calcd for C14H26NO2 (M + H): 240.1964, found: 240.1984.
ter t-Bu tyl (2(2R,3R))-2-[3-ter t-Bu tyl-2-[(Z)-1-p r op en yl]-
a zir id in -1-yl]a ceta te (18). The aldehyde was prepared from
11 as detailed for 17. To a solution of ethyltriphenylphospho-
nium bromide (473 mg, 1.27 mmol) in toluene (5 mL) at -15
°C was added KHMDS (0.806 mL, 1.23 mmol, 1.5 M in THF),
and the resultant yellow slurry was stirred for 30 min at -15
°C to rt and then recooled to -15 °C. The crude aldehyde from
above (0.411 mmol) in THF (10 mL) was added via cannula,
and stirring was continued for 20 min at -15 °C to rt. The
yellow slurry was then poured into brine (10 mL), and the
aqueous phase was extracted with Et2O (3 × 10 mL). Drying
(MgSO4), concentration, and flash chromatography (heptane:
EtOAc 10:1 f 3:1) gave 18 (54 mg, 52%) as an inseparable
mixture of isomers (E:Z < 1:15). 1H NMR (CDCl3, 300 MHz)
δ 5.75 (ddq, 1H, J ) 10.8, 7.0, 1.8), 5.20 (m, 1H), 3.26 (d, 1H,
J ) 16.1), 3.02 (d, 1H, J ) 16.1), 2.66 (ddd, 1H, J ) 9.0, 3.5,
1.0), 1.77 (dd, 3H, J ) 7.0, 1.8), 1.43 (s, 9H), 1.37 (d, 1H, J )
3.6), 0.90 (s, 9H); 13C NMR (CDCl3, 75 MHz) δ 170.3, 131.0,
124.8, 80.8, 59.1, 56.7, 35.2, 30.7, 28.1, 26.9, 13.3; IR (neat)
(2S,3R)-3-ter t-Bu tyl-2-(h yd r oxym eth yl)-1-(2-p r op yn yl)-
a zir id in e (14). Prepared from 9 in 92% yield as detailed for
11. Flash chromatography (heptane:EtOAc 6:1 f 1:3) gave
14 as a white solid (mp 93 °C). 1H NMR (CDCl3, 300 MHz) δ
3.96 (dd, 1H, J ) 12.9, 3.2), 3.74 (dd, 1H, J ) 12.9, 9.0), 3.52
(dd, 1H, J ) 16.7, 2.5), 3.27 (dd, 1H, J ) 16.7, 2.5), 2.34 (t,
1H, J ) 2.6), 2.26 (dt, 1H, J ) 9.0, 3.6), 2.11 (br s, 1H), 1.31(d,
1H, J ) 3.9) 1.89(s, 9H); 13C NMR (CDCl3, 75 MHz) δ 81.6,
72.4, 59.5, 53.9, 41.3, 40.6, 30.2, 26.9; IR (KBr) 3180, 2940,
2130 cm-1; [R]24 -35.9 (c 1.45, CHCl3); HRMS (CI+). Exact
D
mass calcd for C10H18NO (M + H): 168.1384, found: 168.1387.
Meth yl (4(2S,3R))-4-[3-ter t-Bu tyl-2-(h yd r oxym eth yl)-
a zir id in -1-yl]-2-(E)-bu ten oa te (15). To a solution of 4 (170
mg, 1.31 mmol) in THF (20 mL) were added 18-crown-6 (cat.),
K2CO3 (200 mg, 1.45 mmol), and methyl trans-4-bromo-2-
butenoate (236 µL, 1.97 mmol). The resultant slurry was
stirred at rt for 40 h and then diluted with Et2O (50 mL). The
combined organic phases were washed with water (30 mL).
The aqueous phase was washed with Et2O (4 × 15 mL), and
the combined organic layers were washed with brine (15 mL).
Drying (MgSO4), concentration, and flash chromatography
(heptane:EtOAc 1:10 f 0:1) gave 15 (248 mg, 83%) as an off-
white solid (mp 59-63 °C). 1H NMR (CDCl3, 400 MHz) δ 7.06
(dt, 1H, J ) 15.7, 5.3), 6.12 (dt, 1H, J ) 15.7, 1.6), 3.92 (dd,
1H, J ) 12.3, 3.1), 3.75-3.68 (m, 4H), 3.50 (ddd, 1H, J ) 16.6,
4.9, 1.9), 3.19 (dd, 1H, J ) 16.6, 5.6), 2.11 (br s, 1H), 1.27 (d,
1H, J ) 3.6), 0.87 (s, 9H); 13C NMR (CDCl3, 100 MHz) δ 167.4,
147.2, 121.8, 59.9, 54.1, 53.6, 52.0, 40.5, 30.7, 27.4; IR (neat)
2950, 1745 cm-1; [R]20 +110.9 (c 2.70, CDCl3); HRMS (CI+).
D
Exact mass calcd for C15H28NO2 (M + H): 254.2120, found:
254.2118.
ter t-Bu tyl (2(2R,3R))-2-[3-ter t-Bu tyl-2-[(E)-1-p r op en yl]-
a zir id in -1-yl]a ceta te (19). The aldehyde was prepared from
11 as detailed for 17. To a stirred slurry of ethyltriphen-
ylphosphonium bromide (549 mg, 1.47 mmol) in THF (6 mL)
at 0 °C was added freshly prepared PhLi (1.48 mL, 1.47 mmol,
0.99 M in Et2O), and the resultant deep-red solution was
3190, 2960, 1720 cm-1; [R]22 +18.2 (c 2.00, CHCl3); HRMS
D

8156 J . Org. Chem., Vol. 61, No. 23, 1996
A° hman et al.
stirred at 0 °C for 20 min. After cooling to -70 °C the aldehyde
in Et2O (6 mL) was added dropwise over 10 min. After stirring
for 5 min at -70 °C the solution was warmed to -30 °C, and
an additional portion of PhLi (1.48 mL, 1.47 mmol, 0.99 M in
Et2O) was added. The mixture was stirred at -30 °C for 5
min, and then dry MeOH (0.200 mL, 5 mmol) was added
followed by phosphate buffer (2 mL, pH 7). The mixture was
warmed to rt over 2 h and then poured into brine (20 mL),
and the organic layer was separated. The aqueous phase was
extracted with Et2O (3 × 20 mL), and the combined organic
phases were washed with brine (20 mL). Drying (MgSO4),
concentration and flash chromatography (heptane: EtOAc 10:1
f 4:1) gave 19 (27 mg, 8%) as a mixture of isomers (E:Z 3.5:
1). 1H NMR (CDCl3, 300 MHz, peaks assigned from a mixture
of isomers) δ 5.76 (m, 1H), 5.20 (ddq, 1H, J ) 15.2, 8.4, 1.6),
3.23 (d, 1H, J ) 16.1), 3.04 (d, 1H, J ) 16.1), 2.49 (dd, 1H, J
) 8.3, 3.6), 1.71 (dd, 3H, J ) 6.4, 1.6), 1.43 (s, 9H); 1.39 (d,
1H, J ) 3.6), 0.92 (s, 9H); 13C NMR (CDCl3, 75 MHz, peaks
assigned from a mixture of isomers) δ 170.3, 131.9, 125.8, 80.7,
57.8, 56.4, 40.1, 30.6, 28.1, 26.9, 18.1; IR (neat) 2950, 1750
phenylsilyl chloride (31 µL, 0.122 mmol), triethylamine (19 µL,
0.138 mmol), and N,N-dimethyl-4-aminopyridine (cat.) in CH2-
Cl2 (5 mL) was stirred for 7 h at rt. The mixture was then
poured into Et2O (10 mL) and washed with water (10mL) and
brine (10 mL). The organic phase was dried (MgSO4), con-
centrated, and and flash chromatographed (heptane:EtOAc
10:1 f 6:1) to furnish silyl ether 22 (41 mg, 99%). 1H NMR
(CDCl3, 300 MHz) δ 7.75-7.65 (m, 4H), 7.48-7.34 (m, 6H),
5.89 (dt 1H, J ) 15.2, 4.6), 5.53 (ddt, 1H, J ) 15.2, 8.6, 1.5),
4.22 (dd, 2H, J ) 4.6, 1.5), 3.25 (d, 1H, J ) 16.1), 3.01 (d, 1H,
J ) 16.1), 2.54 (dd, 1H, J ) 8.6, 3.5), 1.48 (s, 9H), 1.40 (d, 1H,
J ) 3.5), 1.07 (s, 9H), 0.92 (s, 9H); 13C NMR (CDCl3, 75 MHz)
δ 170.2, 135.5, 135.1, 134.8, 133.6, 129.7, 127.7, 124.8, 80.8,
64.0, 58.1, 56.4, 39.7, 30.7, 28.1, 26.9, 26.8, 26.5, 19.2; IR (neat)
2960, 1750 cm-1; [R]20 +39.4 (c 1.55, CDCl3); HRMS (CI+).
D
Exact mass calcd for C31H46NO2Si (M + H): 508.3247, found:
508.3254.
(2R,3R)-N-Ben zyl-3-ter t-bu tyl-2-vin ylazir idin e (23). Pre-
pared from alcohol 12 in 94% yield as detailed for vinylaziri-
dine 17. Flash chromatography (heptane:EtOAc 20:1) gave
23 as an oil. 1H NMR (CDCl3, 300 MHz) δ 7.45-7.20 (m, 1H),
5.87 (ddd, 1H, J ) 17.0, 10.2, 8.8), 5.41 (dd, 1H, J ) 17.0, 1.7),
5.26 (dd, 1H, J ) 10.2, 1.7), 3.90 (d, 1H, J ) 13.2), 3.41 (d,
1H, J ) 13.2), 2.57 (dd, 1H, J ) 8.8, 3.4), 1.43 (d, 1H, J ) 3.4),
0.80 (s, 9H); 13C NMR (CDCl3, 75 MHz) δ 140.3, 134.1, 128.5,
128.1, 126.8, 119.4, 57.5, 57.3, 41.9, 30.6, 26.9; IR (neat) 2950,
1660 cm-1; [R]22D +151.2 (c 2.99, CHCl3); HRMS (CI+). Exact
mass calcd for C15H22N (M + H): 216.1752, found: 216.1762.
(2(2R,3R))-2-(3-ter t-Bu tyl-2-vin yla zir id in -1-yl)a ceton i-
tr ile (24). Prepared from 13 in 40% yield as detailed for 17.
Flash chromatography (heptane:EtOAc 4:1) gave 24 as an oil.
1H NMR (CDCl3, 300 MHz) δ 5.70 (ddd, 1H, J ) 16.9, 10.1,
8.1), 5.46 (dd, 1H, J ) 16.9, 1.5), 5.40 (dd, 1H, J ) 10.1, 1.6),
3.49 (d, 1H, J ) 16.6), 3.28 (d, 1H, J ) 16.6), 2.58 (dd, 1H, J
) 8.1, 3.7), 1.60 (d, 1H, J ) 3.7), 0.90 (s, 9H,); 13C NMR (CDCl3,
75 MHz) δ 131.2, 122.8, 177.4, 57.1, 41.8, 40.4, 30.6, 26.6; IR
cm-1
.
ter t-Bu tyl (2(2R,3R))-2-[3-ter t-Bu tyl-2-[(E)-2-(eth oxy-
ca r bon yl)vin yl]a zir id in -1-yl]a ceta te (20). To a stirred
solution of DMSO (0.455 mL, 6.41 mmol) in CH2Cl2 (20 mL)
at -78 °C was added oxalyl chloride (224 µL, 2.56 mmol), and
stirring was continued for 5 min. Alcohol 11 (312 mg, 1.28
mmol) in CH2Cl2 (10 mL) was added via cannula and stirring
was continued for 30 min at -78 °C. Triethylamine (2.13 mL,
15.3 mmol) was then added, and stirring was continued at -78
°C for 30 min before (carbethoxymethylene)triphenylphos-
phorane (1.79 g, 5.13 mmol) was added. Stirring was contin-
ued for 30 min at -78 °C, and the mixture was then slowly
warmed to 0 °C over 30 min. The mixture was poured into
brine (20 mL), and the aqueous phase was extracted with Et2O
(3 × 20 mL). Drying (MgSO4), concentration, and flash
chromatography (heptane:EtOAc 6:1 f 1:1) gave 20 (318 mg,
80%). 1H NMR (CDCl3, 300 MHz) δ 6.68 (dd, 1H, J ) 15.4,
10.1), 6.10 (d, 1H, J ) 15.4), 4.18 (q, 2H, J ) 7.2), 3.35 (d, 1H,
J ) 16.1), 3.23 (d, 1H, J ) 16.1), 2.63 (dd, 1H, J ) 10.1, 3.2),
1.63 (d, 1H, J ) 3.2), 1.44 (s, 9H), 1.27 (t, 3H, J ) 7.2), 0.89 (s,
9H); 13C NMR (CDCl3, 75 MHz) δ 169.4, 165.7, 144.1, 124.7,
81.3, 60.4, 59.8, 56.8, 39.4, 31.1, 28.0, 26.8, 14.3; IR (neat) 2960,
(neat) 2960, 2255, 1640; [R]22 +118.6 (c 1.51, CHCl3); HRMS
D
(CI+). Exact mass calcd for C10H17N2 (M + H): 165.1392,
found: 165.1389.
(2R,3R)-3-ter t-Bu tyl-1-(2-pr opyn yl)-2-vin ylazir idin e (25).
Prepared from 14 in 83% yield as detailed for 17. Flash
chromatography (heptane:EtOAc 20:1 f 6:1) gave 25 as an
oil. 1H NMR (CDCl3, 300 MHz) δ 5.76 (ddd, 1H, J ) 17.0,
10.2, 8.5), 5.39 (dd, 1H, J ) 17.0, 1.7), 5.28 (dd, 1H, J ) 10.2,
1.7), 3.36 (dd, 1H, J ) 16.5, 2.5), 3.19 (dd, 1H, J ) 16.5, 2.4),
2.52 (dd, 1H, J ) 8.5, 3.7), 2.25 (t, 1H, J ) 2.5), 1.55 (d, 1H, J
) 3.5), 0.91 (s, 9H); 13C NMR (CDCl3, 75 MHz) δ 132.9, 120.4,
81.5, 71.9, 56.8, 41.9, 41.6, 30.5, 26.8; IR (neat) 3300, 2950
cm-1; [R]22D +130.6 (c 1.61, CDCl3); HRMS (CI+). Exact mass
calcd for C10H18N (M + H): 164.1439, found: 164.1437.
(2R,3R)-3-ter t-Bu tyl-1-[3-(tr im eth ylsilyl)-2-p r op yn yl]-
2-vin yla zir id in e (26). To a solution of 25 (349 mg, 2.13
mmol) in THF (20 mL) at -78 °C was added n-BuLi (2.31 mL,
3.04 mmol, 1.6M in hexanes), and stirring was continued for
30 min at -78 °C. TMSCl (0.406 mL, 3.04 mmol) was then
added and after 1.5 h of stirring at -78 °C the reaction was
quenched by addition of pH 7 buffer (2 mL). The resultant
mixture was allowed to reach rt, poured into pH 7 buffer (10
mL), and extracted with Et2O (2 × 20 mL). The combined
organic phases were dried (MgSO4) and concentrated. Flash
chromatography of the residue (heptane:EtOAc 10:1) gave 26
(432 mg, 86%). 1H NMR(CDCl3, 300 MHz) δ 5.73 (ddd, 1H, J
) 17.0, 10.2, 8.5), 5.37 (dd, 1H, J ) 17.0, 1.7), 5.25 (dd, 1H, J
) 10.2, 1.7), 3.43 (d, 1H, J ) 16.6), 3.11 (d, 1H, J ) 16.6), 2.50
(dd, 1H, J ) 8.5, 3.7), 1.56 (d, 1H, J ) 3.7), 0.91 (s, 9H), 0.14
(s, 9H); 13C NMR (CDCl3, 75 MHz) δ 133.1, 120.3, 88.6, 71.9,
56.7, 42.8, 41.8, 30.4, 26.9, -10.8; IR (neat) 2960, 2180, 1250,
1050 cm-1; [R]24D +168.0 (c 1.39, CHCl3); HRMS (CI+). Exact
mass calcd for C14H26NSi (M + H): 236.1835, found: 236.1834.
(2R,3R)-3-ter t-Bu tyl-2-[(Z)-1-p r op en yl]-1-(2-p r op yn yl)-
a zir id in e (27). Prepared from 14 in 81% yield as detailed
for 18. Flash chromatography (heptane:EtOAc 20:1 f 6:1)
gave 27 as an inseparable mixture of isomers (E:Z 1:11). 1H
NMR (CDCl3, 300 MHz) δ 5.79 (ddq, 1H, J ) 10.7, 7.0, 1.1),
5.30 (ddd, 1H, J ) 10.7, 8.6, 1.6), 3.33 (dd, 1H, J ) 16.6, 2.5),
3.13 (dd, 1H, J ) 16.6, 2.5), 2.64 (dd, 1H, J ) 8.6, 3.5), 2.23 (t,
1H, J ) 2.5), 1.77 (dd, 3H, J ) 7.0, 1.6), 1.45 (d, 1H, J ) 3.5),
1750, 1645 cm-1; [R]22 +114.4 (c 2.67, CDCl3); HRMS (CI+).
D
Exact mass calcd for C17H30NO4 (M + H): 321.2175, found:
312.2167.
ter t-Bu tyl (2(2R,3R))-2-[3-ter t-Bu tyl-2-[(E)-3-h yd r oxy-
1-p r op en yl]-a zir id in -1-yl]a ceta te (21b). The aldehyde was
prepared from 11 as detailed for 17. To a solution of the
aldehyde (2.07 mmol) from above in benzene (20 mL) at 0 °C
was added (triphenylphosphoranylidene)acetaldehyde (3.15 g,
10.37 mmol), and the resultant mixture was stirred for 20 min
at 0 °C and then at rt for 2 days. Filtration, concentration,
and flash chromatography (heptane:EtOAc 3:1) gave 21a (104
mg, 19%). 1H NMR (CDCl3, 300 MHz) δ 9.5 (d, 1H, J ) 7.5),
6.57 (dd, 1H, J ) 15.3, 9.6), 6.39 (dd, 1H, J ) 15.3, 7.5), 3.34
(AB-q, 2H, J ) 1.0), 2.75 (dd, 1H, J ) 9.6, 3.1), 1.71 (d, 1H, J
) 3.1), 1.45 (s, 9H), 0.96 (s, 9H).
Reduction of aldehyde 21a . To a solution of the aldehyde
21a (104 mg, 0.391 mmol) in EtOH (5 mL) at -40 °C was
added NaBH4 (7 mg, 0.391 mmol), and the resultant mixture
was stirred for 20 min at -40 °C. The reaction was quenched
by the addition of acetaldehyde (44 µL, 0.782 mmol), and the
mixture was allowed to warm to rt. The mixture was then
poured into Et2O (20 mL) and washed with water (2 × 20 mL)
and brine (20 mL). Drying (MgSO4) and concentration gave
21b (95 mg, 90%) 1H NMR (CDCl3, 300 MHz) δ 6.02 (dt 1H, J
) 15.3, 5.1), 5.53 (ddt, 1H, J ) 15.3, 8.8, 1.5), 4.14 (d, 2H, J )
5.1), 3.26 (d, 1H, J ) 16.1), 3.05 (d, 1H, J ) 16.1), 2.54 (dd,
1H,, J ) 8.8 3.5), 1.84 (br s, 1H), 1.45 (s, 9H), 1.43 (d, 1H, J )
3.5), 0.90 (s, 9H); 13C NMR (CDCl3, 75 MHz) δ 170.1, 135.3,
126.4, 81.0, 63.0, 58.2, 56.5, 39.7, 30.3, 28.1, 26.8; IR (neat)
3360, 2950, 1735 cm-1; [R]22 +74.0 (c 1.47, CDCl3); HRMS
D
(CI+). Exact mass calcd for C15H28NO2 (M + H): 270.2069,
found: 270.2073.
ter t-Bu tyl (2(2R,3R))-2-[3-ter t-Bu tyl-2-((E)-3-[(ter t-bu -
tyldiph en ylsilyl)oxy]-1-pr open yl)azir idin -1-yl]acetate (22).
A solution of alcohol 21b (22 mg, 0.081 mmol), tert-butyldi-

Aza-[2,3]-Wittig Rearrangements of Vinylaziridines
J . Org. Chem., Vol. 61, No. 23, 1996 8157
0.90 (s, 9H). 13C NMR (CDCl3, 75 MHz) δ 133.1, 124.4, 81.8,
58.0, 42.1, 36.1, 30.5, 26.9, 13.4; IR (neat) 3310, 2950, 2190
cm-1; [R]24D +175.8 (c 0.609, CHCl3); HRMS (CI+). Exact mass
calcd for C12H20N (M + H): 178.1596, found: 178.1693.
(2R,3R)-3-ter t-Bu tyl-1-[3-(tr im eth ylsilyl)-2-p r op yn yl]-
2-((Z)-1-p r op en yl)a zir id in e (28). Prepared from 27 in 83%
yield as detailed for 26. Flash chromatography (heptane:
EtOAc 20:1 f 10:1) gave 28 as an inseparable mixture of
isomers (E:Z 1:11). 1H NMR (CDCl3, 300 MHz) δ 5.77 (ddq,
1H, J ) 10.8, 6.9, 1.1), 5.37 (ddq, 1H, J ) 10.4, 8.5, 1.6), 3.38
(d, 1H, J ) 16.6), 3.06 (d, 1H, J ) 16.6), 2.62 (dd, 1H, J ) 8.7,
3.8), 1.76 (dd, 3H, J ) 7.0, 1.7), 1.76 (d, 1H, J ) 3.7), 0.89 (s,
9H), 0.12 (s, 9H); 13C NMR (CDCl3, 75 MHz) δ 133.1, 124.5,
103.9, 88.3, 57.9, 43.1, 36.1, 30.4, 26.9, 13.4, -11.2; IR (neat)
1.8), 2.72 (dd, 1Hmaj, J ) 8.7, 2.7), 2.33 (d, 1Hmin, J ) 7.1),
1.92-1.87 (m, 1Hmaj, 1Hmin), 1.80 (dd, 3Hmaj, J ) 7.0, 1.7),
1.77-1.72 (m, 3Hmin), 1.46 (s, 9Hmaj, 9Hmin); 13C NMR (CDCl3,
100 MHz, from a mixture of invertomers and only major isomer
reported) δ 170.3, 138.7, 133.0, 128.8, 128.2, 128.0, 123.8, 81.4,
73.5, 72.4, 55.3, 47.2, 37.8, 28.5, 13.9; IR (neat, from a mixture
of invertomers) 2980, 1745 cm-1; HRMS (CI+). Exact mass
calcd for C19H28NO3 (M + H): 318.2069, found: 318.2069.
ter t-Bu tyl (2(2R,3R))-2-[3-[(Ben zyloxy)m eth yl]-2-[(E)-
1-p r op en yl]a zir id in -1-yl]a ceta te (34). Prepared from 16
in 5% yield as detailed for 19. Flash chromatography (hep-
tane:EtOAc 6:1 f 4:1) gave 34 as an inseparable mixture of
isomers (E:Z 1.3:1). 1H NMR (CDCl3, 400 MHz, peaks assigned
from a mixture of invertomers) δ 7.36-7.28 (m, 5Hmaj, 5Hmin),
5.91-5.81 (m, 1Hmaj), 5.80-5.73 (m, 1Hmin), 5.45-5.38 (m,
1Hmin), 5.36-5.29 (m, 1Hmaj), 4.61-4.52 (m, 2Hmaj, 2Hmin),
3.73-3.64 (m, 1Hmaj, 1Hmin), 3.55-3.45 (m, 1Hmaj, 1Hmin), 3.21
(m, 2Hmaj, 2Hmin), 2.53 (dd, 1Hmaj, J ) 8.3, 3.3), 2.10-2.05 (m,
1Hmin), 1.92-1.86 (m, 1Hmaj), 1.74 (dd, 3Hmaj, J ) 6.5, 1.5),
1.77-1.72 (m, 3Hmin), 1.46 (s, 9Hmaj, 9Hmin); 13C NMR (CDCl3,
100 MHz, from a mixture of invertomers and only major isomer
reported) δ 170.4, 138.7, 133.6, 128.8, 128.2, 128.0, 124.7, 81.4,
73.5, 72.4, 55.1, 46.0, 42.6, 28.5, 18.6; IR (neat, from a mixture
of invertomers) 2980, 1745 cm-1; HRMS (CI+). Exact mass
calcd for C19H28NO3 (M + H): 318.2069, found: 318.2067.
(2R*,3R*)-3-[(Ben zyloxy)m eth yl]-2-[[(ter t-bu tyld im eth -
ylsilyl)oxy]m eth yl]a zir id in e (38). Prepared from 37 in 87%
yield as detailed for aziridine 3. (2R*,3R*)-3-azido-1-(benzy-
loxy)-4-[(tert-butyldimethylsilyl)oxy]-2-butanol and (2R*,3R*)-
3-azido-4-(benzyloxy)-1-[(tert-butyldimethylsilyl)oxy]-2-bu-
tanol. Flash chromatography (heptane:EtOAc 6:1 f 3:1) gave
a mixture of the corresponding silyl ethers. 1H NMR (CDCl3,
400 MHz, peaks assigned from a mixture of regioisomers) δ
7.39-7.32 (m, 5Hmaj, 5Hmin), 4.62 (s, 2Hmin), 4.61 (s, 2Hmaj),
2960, 2190 cm-1; [R]24 +229.1 (c 1.63, CHCl3); HRMS (CI+).
D
Exact mass calcd for C14H26NSi (M + H): 250.1991, found:
250.1982.
(2R,3R)-3-ter t-Bu tyl-2-[(E)-1-p r op en yl]-1-(2-p r op yn yl)-
a zir id in e (29). Prepared from alcohol 14 in 32% yield as
detailed for vinylaziridine 19. Flash chromatography (hep-
tane:EtOAc 20:1 f 6:1) gave vinylaziridine 29 as an insepa-
rable mixture isomers (E:Z 3.2:1). 1H NMR(CDCl3, 300 MHz,
peaks assigned from a mixture of isomers) δ 5.81 (m, 1H), 5.37
(m, 1H), 3.34 (dd, 1H, J ) 16.6, 2.6), 3.06 (d, 1H, J ) 16.6,
2.6), 2.57 (dd, 1H, J ) 8.2, 3.7), 2.32 (m, 1H), 1.73 (dd, 3H, J
) 6.6, 1.7), 1.47 (d, 1H, J ) 3.6 Hz), 0.88 (s, 9H).
(2R,3R)-3-ter t-Bu tyl-1-[3-(tr im eth ylsilyl)-2-p r op yn yl]-
2-[(E)-1-p r op en yl]a zir id in e (30). Prepared from 29 in 70%
yield as detailed for 26. Flash chromatography (heptane:
EtOAc 20:1 f 10:1) gave 30 as an inseparable mixture of
isomers (E:Z 3.2:1). 1H NMR (CDCl3, 300 MHz, assigned from
a mixture of isomers) δ 5.79 (m, 1H), 5.36 (dd, 1H, J ) 16.8,
8.1), 3.40 (d, 1H, J ) 16.6), 3.06 (d, 1H, J ) 16.6), 2.46 (dd,
1H, J ) 8.1, 3.6), 1.73 (dd, 3H, J ) 6.6, 1.2), 1.49 (d, 1H, J )
3.6 Hz), 0.88 (s, 9H), 0.12 (s, 9H); 13C NMR (CDCl3, 75 MHz,
assigned from a mixture of isomers) δ 131.9, 125.6, 104.1, 88.3,
56.6, 42.7, 41.1, 30.3, 26.9, 18.1, -0.1; IR (neat) 2960, 2195,
3.98-3.94 (m, 1Hmaj), 3.92 (d, 1Hmin, J ) 4.4), 3.89 (d, 1Hmaj
,
J ) 6.3), 3.86 (d, 1Hmin, J ) 6.3), 3.83-3.79 (m, 1Hmin), 3.78
(d, 1Hmaj, J ) 4.4), 3.76 (d, 1Hmin, J ) 6.5), 3.70-3.67 (m,
1Hmin), 3.66 (s, 1Hmin), 3.65 (s, 1Hmin), 3.58 (s, 1Hmaj), 3.56 (s,
1Hmaj), 3.55-3.52 (m, 1Hmaj), 2.65 (br s, 1Hmaj), 2.54 (br s,
1Hmin), 0.92 (s, 9Hmaj), 0.91 (s, 9Hmin), 0.11 (s, 6Hmaj), 0.09 (s,
6Hmin); 13C NMR (CDCl3, 100 MHz, from a mixture of regio-
isomers) δ 138.1, 128.9, 128.3, 128.3, 128.2, 128.2, 74.0, 74.0,
72.3, 71.5, 71.1, 70.8, 64.7, 64.2, 64.1, 62.3, 26.3, 26.2, 26.1,
18.7, 18.6, -5.0, -5.2; IR (neat, from a mixture of regioisomers)
3450, 2920, 2100 cm-1; HRMS (CI+). Exact mass calcd for
C17H30N3O3Si (M + H): 352.2056, found: 352.2054.
Azir id in e 38. Flash chromatography (heptane:EtOAc 4:1
f 1:1) gave aziridine 38 in 59% yield as a colorless oil. 1H
NMR (CDCl3, 400 MHz) δ 7.32-7.27 (m, 5H), 4.57 (AB-q, 2H,
J ) 20.7, 11.9), 3.80-3.67 (m, 1H), 3.65-3.57 (m, 2H), 3.54-
3.43 (m, 1H), 2.40 (q, 1H, J ) 5.9), 2.33 (q, 1H, J ) 5.9), 1.68
(br s, 1H), 0.90 (s, 9H), 0.07 (s, 6H); 13C NMR (CDCl3, 100 MHz)
δ 138.6, 128.8, 128.8, 128.3, 128.1, 73.6, 70.2, 35.6, 26.4, 26.3,
18.8, -4.8, -4.9; IR (neat) 3300, 2920 cm-1; HRMS (CI+).
Exact mass calcd for C17H30NO2Si (M + H): 308.2046, found:
308.2041.
1460, 1250 cm-1; HRMS (CI+). Exact mass calcd for C15H28
NSi (M + H): 250.1991, found: 250.1979.
-
Meth yl (4(2R,3R))-4-(3-ter t-Bu tyl-2-vin yla zir id in -1-yl)-
(E)-2-bu ten oa te (31). Prepared from alcohol 15 in 17% yield
as detailed for vinylaziridine 17. Flash chromatography
(heptane:EtOAc 8:1 f 5:1) gave vinylaziridine 31 as a yellow
oil. 1H NMR (CDCl3, 400 MHz) δ 7.00 (dt, 1H, J ) 15.6, 5.2),
6.10 (dt , 1H, J ) 15.7, 3.7), 5.75-5.64 (m, 1H), 5.38 (dd, 1H,
J ) 16.9, 1.2), 5.25 (dd, 1H, J ) 10.2, 1.5), 3.74 (s, 3H), 3.38-
3.29 (m, 1H), 3.21-3.13 (m, 1H), 2.51 (dd, 1H, J ) 8.7, 3.4),
1.43 (d, 1H, J ) 3.4), 0.89 (s, 9H); 13C NMR (CDCl3, 100 MHz)
δ 167.4, 147.0, 133.6, 121.8, 120.6, 57.9, 54.6, 51.9, 41.7, 31.1,
27.3; IR (neat) 2960, 1730, 1660, 1440, 1365 cm-1; [R]22D +68.8
(c 2.00, CHCl3); HRMS (CI+). Exact mass calcd for C13H22
NO2 (M + H): 224.1651, found: 224.1674.
-
ter t-Bu t yl (2R,3R)-2-[3-[(Ben zyloxy)m et h yl]-2-vin yl-
a zir id in -1-yl]a ceta te (32). Prepared from 16 in 62% yield
as detailed for 17. Flash chromatography (heptane:EtOAc 3:1
f 3:2) gave 32 as an oil. 1H NMR (CDCl3, 300 MHz, peaks
assigned from a mixture of invertomers) δ 7.30 (m), 5.67 (m,
1Hmaj, 1Hmin), 5.42 (d, 1Hmaj, J ) 17.0), 5.33 (m 1Hmaj, 1Hmin),
5.14 (m, 1Hmin), 4.56 (m, 2Hmaj, 2Hmin), 3.79 (m, 1Hmin), 3.65
(dd, 1Hmaj, J ) 10.5, 6.0), 3.50 (dd, 1Hmaj, J ) 10.5, 5.5), 3.47
(m, 1Hmin), 3.22 (m, 2Hmaj, 2Hmin), 2.56 (dd, 1Hmaj, J ) 8.5, 3.0),
ter t-Bu t yl (2(2R*,3R*))-2-[3-[(Ben zyloxy)m et h yl]-2-
[[(ter t-bu tyld im eth ylsilyl)oxy]m eth yl]a zir id in -1-yl]a ce-
ta te (39). Prepared from aziridine 38 in 87% yield as detailed
for aziridine 6. Flash chromatography (heptane:EtOAc 8:1 f
1:1) gave 39 as an oil.
1H NMR (CDCl3, 400 MHz) δ 7.36-
2.35 (m, 1Hmin), 2.14 (m, 1Hmin), 1.95 (m, 1Hmaj), 1.47 (s, 9Hmaj
,
7.27 (m, 5H), 4.57 (AB-q, 2H, J ) 12.2, 11.8), 3.90 (dd, 1H, J
) 11.1, 5.5), 3.69 (dd, 1H, J ) 10.6, 6.1), 3.58-3.53 (m, 2H),
3.10 (AB-q, 2H, J ) 26.0, 16.2), 1.87 (q, 1H, J ) 6.3), 1.79 (q,
1H, J ) 6.7), 1.47 (s, 9H), 0.90 (s, 9H), 0.06 (d, 6H, J ) 3.0);
13C NMR (CDCl3, 100 MHz) δ 169.8, 138.7, 128.8, 128.2, 128.0,
81.6, 73.6, 69.4, 62.5, 62.2, 44.9, 43.0, 28.5, 26.3, 18.7, -4.8,
-4.9; IR (neat) 2930, 1745 cm-1; HRMS (CI+). Exact mass
calcd for C23H40NO4Si (M + H): 422.2727, found: 422.2734.
ter t-Bu tyl (2(2R*,3R*))-2-[3-[(Ben zyloxy)m eth yl]-2-(h y-
d r oxym eth yl)a zir id in -1-yl]a ceta te (40). Prepared from 39
in 98% yield as detailed for 11. Flash chromatography
(heptane:EtOAc 1:1 f 1:4) gave alcohol 40 as an oil. 1H NMR
(CDCl3,400 MHz) δ 7.37-7.30 (m, 5H), 4.53 (AB-q, 2H, J )
26.6, 11.8), 3.79-3.69 (m, 2H), 3.64 (d, 1H, J ) 16.9), 3.55-
3.46 (m, 2H), 2.61 (d, 1H, J ) 16.9), 1.98 (q, 1H, J ) 6.6), 1.88-
1.82 (m, 1H), 1.66 (s, 1H), 1.48 (s, 9H); 13C NMR (CDCl3, 100
9Hmin); 13C NMR (CDCl3, 75 MHz, peaks assigned from a
mixture of invertomers) δ 169.8, 169.7, 138.3, 137.6, 131.7,
128.4, 127.8, 127.6, 121.5, 116.6, 81.1, 73.1, 72.9, 71.7, 65.9,
54.7, 54.0, 45.5, 44.4, 42.7, 42.3, 28.1, 28.0; IR (neat, from a
mixture of invertomers) 2970, 1735 cm-1; HRMS (CI+). Exact
mass calcd for C18H26NO3 (M + H): 304.1913, found: 304.1921.
ter t-Bu tyl (2(2R,3R))-2-[3-[(Ben zyloxy)m eth yl]-2-[(Z)-
1-p r op en yl]a zir id in -1-yl]a ceta te (33). Prepared from 16
in 56% yield as detailed for 18. Flash chromatography
(heptane:EtOAc 5:1 f 2:1) gave 33 as an inseparable mixture
of isomers (E:Z 1:10). 1H NMR (CDCl3, 400 MHz, peaks
assigned from a mixture of invertomers) δ 7.36-7.28 (m, 5Hmaj
,
,
,
5Hmin), 5.90-5.81 (m, 1Hmaj, 1Hmin), 5.28-5.21 (m, 1Hmaj
1Hmin), 4.63-4.54 (m, 2Hmaj, 2Hmin), 3.73-3.64 (m, 1Hmaj
1Hmin), 3.55-3.45 (m, 1Hmaj, 1Hmin), 3.21 (d, 2Hmaj, 2Hmin, J )

8158 J . Org. Chem., Vol. 61, No. 23, 1996
A° hman et al.
MHz) δ 171.0, 138.1, 128.9, 128.9, 128.3, 82.5, 73.8, 69.4, 61.9,
60.9, 45.4, 42.3, 28.5; IR (neat) 3480, 2980, 1730 cm-1; HRMS
(CI+). Exact mass calcd for C17H26NO4 (M + H): 308.1862,
found: 308.1862.
46 6.6:1, 80%). Flash chromatography (deactivated silica,
heptane:EtOAc 20:1 f 5:1) gave 45 (9.4 mg, 41%) and 46 (2.1
mg, 9%).
(2R,6S)-6-ter t-Bu t yl-2-cya n o-1,2,3,6-t et r a h yd r op yr i-
d in e (45). 1H NMR (CDCl3, 300 MHz) δ 5.76 (m, 2H), 3.82
(dd, 1H, J ) 10.7, 3.9), 3.12 (m, 1H), 2.44 (m, 1H), 2.26 (m,
1H), 1.55 (br s, 1H), 0.92 (s, 9H,); 13C NMR (CDCl3, 75 MHz)
δ 128.2, 123.8, 120.6, 63.3, 44.2, 34.1, 29.8, 25.9; IR (neat) 3340,
ter t-Bu tyl (2(2S*,3R*))-2-[3-[(Ben zyloxy)m eth yl]-2-vi-
n yla zir id in -1-yl]a ceta te (41). Prepared from 40 in 92%
yield as detailed for 17. Flash chromatography (heptane:
EtOAc 3:1 f 3:2) gave 41 as an oil. 1H NMR (CDCl3, 300 MHz)
δ 7.30 (m, 5H), 5.66 (ddd, 1H, J ) 17.2, 10.3, 6.9), 5.39 (dd,
1H, J ) 17.2, 1.8), 5.21 (dd, 1H, J ) 10.3, 1.8), 4.56 (d, 1H, J
) 11.9), 4.48 (d, 1H, J ) 11.9), 3.70 (dd, 1H, J ) 10.5, 5.6),
3.44 (dd, 1H, J ) 10.5, 6.4), 3.20 (d, 1H, J ) 16.0), 3.02 (d,
1H, J ) 16.0), 2.15 (t, 1H, J ) 6.6), 1.95 (dd, 1H, J ) 12.2,
6.4), 1.47 (s, 9H); 13C NMR (CDCl3, 75 MHz) δ 169.1, 138.2,
133.2, 128.3, 127.8, 127.6, 118.4, 81.3, 73.1, 68.6, 61.9, 45.1,
44.5, 28.1; IR (film) 2985, 1735 cm-1; HRMS (CI+). Exact mass
calcd for C18H26NO3 (M + H): 304.1913, found: 304.1918.
ter t-Bu tyl (2(2S*,3R*))-2-[3-[(Ben zyloxy)m eth yl]-2-[(Z)-
1-p r op en yl]a zir id in -1-yl]a ceta te (42). Prepared from 40
in 87% yield as detailed for 18. Flash chromatography
(heptane:EtOAc 5:1 f 2:1) gave 42 as an inseparable mixture
of isomers (E:Z 1:17). 1H NMR (CDCl3, 400 MHz) δ 7.35-7.27
(m, 5H), 5.74-5.65 (m, 1H), 5.23 (tq, 1H, J ) 18.8, 9.6, 1.4),
4.54 (AB-q, 2H, J ) 18.9, 11.8), 3.69 (dd, 1H, J ) 10.6, 5.8),
3.46 (dd, 1H, J ) 10.6, 6.2), 3.22 (d, 1H, J ) 16.0), 3.06 (d,
1H, J ) 16.0), 2.32 (t, 1H, J ) 7.1), 1.97 (q, 1H, J ) 6.2), 1.75
(dd, 3H, J ) 6.9, 1.6), 1.47 (s, 9H); 13C NMR (CDCl3, 100 MHz)
δ 169.7, 138.7, 129.0, 128.8, 128.2, 128.0, 126.5, 81.7, 73.5, 69.7,
62.5, 45.0, 40.9, 28.5, 14.0; IR (neat) 2980, 1740 cm-1; HRMS
(CI+). Exact mass calcd for C19H28NO3 (M + H): 318.2069,
found: 318.2071.
2960, 2250, 1475 cm-1; [R]22 +41.9 (c 0.327, CHCl3); HRMS
D
(CI+). Exact mass calcd for C10H17N2 (M + H): 165.1392,
found: 165.1381.
(2S,6S)-6-ter t-Bu t yl-2-cya n o-1,2,3,6-t e t r a h yd r op yr i-
d in e (46). 1H NMR (CDCl3, 300 MHz) δ 5.79 (m, 1H), 4.21
(dd, 1H, J ) 4.6, 1.2), 3.34 (m, 1H), 2.54 (m, 1H), 2.20 (m, 1H),
1.60 (br s, 1H), 0.90 (s, 9H,); 13C NMR (CDCl3, 75 MHz) δ 127.8,
122.2, 120.3, 59.6, 43.9, 34.0, 28.7, 25.9; IR (neat) 2960, 2240,
1465 cm-1; [R]20D +10.5 (c 0.191, CHCl3); HRMS (CI+). Exact
mass calcd for C10H17N2 (M + H): 165.1392, found: 165.1401.
Rea r r a n gem en t of Vin yla zir id in e 26. To a solution of
26 (150 mg, 0.637 mmol) in THF (10 mL) at -78 °C was added
s-BuLi (0.735 mL, 0.955 mmol, 1.3 M in cyclohexane). The
red-brown solution was stirred for 15 min at -78 °C followed
by quenching the reaction with pH 7 buffer (2 mL). The
mixture was allowed to reach room temperature and was then
poured into pH 7 buffer (10 mL) and extracted with Et2O (2 ×
15 mL). Drying (MgSO4) and concentration gave the crude
product (142 mg, 95%) as a mixture of 47, 48, and 49 (47:48:
49 1.2:1.8:1). Flash chromatography (deactivated silica, hep-
tane:EtOAc 1:0 f 10:1) gave 48 (67 mg, 45%), 47 (19 mg, 13%)
and 49 (5 mg, 3%).
(2R,6S)-6-ter t-Bu tyl-2-[2-(tr im eth ylsilyl)eth yn yl]-1,2,3,6-
tetr a h yd r op yr id in e (47). 1H NMR (CDCl3, 300 MHz) δ 5.76
(m, 1H), 5.67 (m, 1H), 3.65 (dd, 1H, J ) 10.0, 4.3), 3.10 (m,
1H), 2.30-2.11 (m, 2H), 1,65 (br s, 1H), 0.93 (s, 9H), 0.18 (s,
9H); 13C NMR (CDCl3, 75 MHz) δ 127.8, 125.6, 107.8, 86.7,
64.3, 46.2, 33.8 32.8, 26.1, 0.03; IR (neat) 2980, 2160, 1540
ter t-Bu tyl (2(2S*,3R*))-2-[3-[(Ben zyloxy)m eth yl]-2-[(E)-
1-p r op en yl]a zir id in -1-yl]a ceta te (43). Prepared from 40
in 4% yield as detailed for 19. Flash chromatography (hep-
tane:EtOAc 12:1 f 6:1) gave 43 as an inseparable mixture of
isomers (E:Z 2.1:1). 1H NMR (CDCl3, 400 MHz) δ 7.36-7.28
(m, 5H), 5.87-5.78 (m, 1H), 5.27 (ddq, 1H, J ) 15.4, 7.2, 1.7),
4.60 (d, 1H, J ) 11.9), 4.50 (d, 1H, J ) 11.9), 3.71 (dd, 1H, J
) 10.5, 5.5), 3.43 (dd, 1H, J ) 10.5, 6.7), 3.17 (d, 1H, J ) 16.1),
3.03 (d, 1H, J ) 16.1), 2.11 (t, 1H, J ) 6.9), 1.89 (q, 1H, J )
6.3), 1.71 (dd, 3H, J ) 6.5, 1.6), 1.47 (s, 9H); 13C NMR (CDCl3,
100 MHz) δ 169.7, 138.7, 130.1, 128.8, 128.3, 128.0, 126.7, 81.6,
73.5, 69.1, 62.4, 45.0, 40.9, 28.5, 14.0; IR (neat) 2980, 2860,
1740 cm-1; HRMS (CI+). Exact mass calcd for C19H28NO3 (M
+ H): 318.2069, found: 318.2068.
cm-1; [R]24 +26.5 (c 0.77, CHCl3); HRMS (CI+). Exact mass
D
calcd for C14H26NSi (M + H): 236.1835, found: 236.1831.
(2S,6S)-6-ter t-Bu tyl-2-[2-(tr im eth ylsilyl)eth yn yl]-1,2,3,6-
tetr a h yd r op yr id in e (48). 1H NMR (CDCl3, 300 MHz) δ 5.73
(br s, 2H), 4.04 (dd, 1H, J ) 6.1, 2.1), 3.27 (m, 1H), 2.45 (m,
1H), 2.05 (m, 1H), 1,68 (br s, 1H), 0.93 (s, 9H), 0.15 (s, 9H);
13C NMR (CDCl3, 75 MHz) δ 127.3, 123.6, 108.2, 86.2, 58.9,
43.7, 33.7, 30.8, 26.2, 0.2; IR (neat) 2900, 2160, 1460 cm-1
;
[R]25 -77.0 (c 2.78, CHCl3); HRMS (CI+). Exact mass calcd
D
for C14H26NSi (M + H): 236.1835, found: 236.1835.
ter t-Bu tyl (2R,6S)-6-ter t-Bu tyl-1,2,3,6-tetr a h yd r op yr i-
d in e-2-ca r boxyla te (44). To a solution of diisopropylamine
(76.2 µL, 0.543 mmol) in THF (5 mL) at 0 °C was added
butyllithium (0.308 mL, 0.493 mmol, 1.6M in hexanes), and
the resultant solution was stirred for 30 min at 0 °C. The
mixture was cooled to -78 °C, and vinylaziridine 17 (59.1 mg,
0.247 mmol) in THF (5 mL) was added dropwise over 5 min.
The resultant red-brown solution was stirred for an additional
5 min and was then quenched by addition of pH 7 buffer (1
mL) and allowed to warm to rt. The phases were separated,
and the aqueous phase was extracted with Et2O (2 × 10 mL).
The combined organic phases were dried (MgSO4) and con-
centrated to give tetrahydropyridine 44 (56.1 mg, 95%) that
was pure according to 1H NMR analysis. Flash chromatog-
raphy (EtOAc:heptane 1:10 f 1:6) gave 44 (49.6 mg) which
had the same spectral data as the crude material. 1H NMR
(CDCl3, 300 Mz) δ 5.79 (m, 1H), 5.69 (m, 1H), 3.42 (dd, 1H, J
) 10.7, 4.2), 3.12 (m, 1H), 2.25 (m, 1H), 2.11 (m, 1H), 1.98 (br
s, 1H), 1.48 (s, 9H), 0.92 (s, 9H); 13C NMR (CDCl3, 75 MHz) δ
172.8, 128.4, 125.5, 80.9, 64.0, 56.4, 33.9, 29.1, 28.1, 26.1; IR
(4S,5S)-5-ter t-Bu tyl-3-[(E)-(tr im eth ylsilyl)m eth ylen e]-
4-vin yl-1-p yr r olin e (49). 1H NMR (CDCl3, 500 MHz) δ 7.60
(d, 1H, J ) 1.8), 5.99 (d, 1H, J ) 2.1), 5.69 (ddd, 1H, J ) 17.2,
10.2, 8.0), 5.02-4.96 (m, 2H), 3.76 (t, 1H, J ) 2.7), 3.19 (m,
1H), 0.92 (s, 9H), 0.13 (s, 9H); 13C NMR (CDCl3, 75 MHz) δ
167.1, 159.5, 140.8, 129.2, 114.6, 90.3, 45.2, 35.5, 26.4, -0.5;
IR(neat) 2960, 1580 cm-1; [R]24 -8.6 (c 0.67, CHCl3); HRMS
D
(CI+). Exact mass calcd for C14H26NSi (M + H): 236.1835,
found: 236.1839.
ter t-Bu tyl (2R,3R,6S)-6-ter t-Bu tyl-3-m eth yl-1,2,3,6-tet-
r a h yd r op yr id in e-2-ca r boxyla te (50). Prepared from 18 in
94% yield as detailed for 44. 1H NMR (CDCl3, 300 MHz) δ
5.66 (dt, 1H, J ) 10.2, 4.2), 5.56 (dt, 1H, J ) 10.2, 2.0), 3.03
(m, 1H), 2.96 (d, 1H, J ) 9.6), 2.28 (m, 1H), 1.98 (br s, 1H),
1.44 (s, 9H), 1.08 (d, 3H, J ) 7.0), 0.96 (s, 9H); 13C NMR
(CDCl3, 75 MHz) δ 172.8, 132.7, 127.3, 81.1, 64.0, 62.9, 33.9,
33.4, 28.1, 26.2, 18.7; IR (neat) 2950, 1745, 1455 cm-1; [R]20
D
-28.6 (c 0.39, CHCl3,); HRMS (CI+). Exact mass calcd for
C15H28NO2 (M + H): 254.2120, found: 254.2123.
(neat) 2950, 1730 cm-1; [R]20 +71.3 (c 2.14, CH2Cl2,); HRMS
D
ter t-Bu tyl (2R,3S,6S)-6-ter t-Bu tyl-3-m eth yl-1,2,3,6-tet-
r a h yd r op yr id in e-2-ca r boxyla te (51). Prepared from vinyl-
aziridine 19 (E:Z 1:1) in 92% yield as detailed for 44. The
crude product was obtained as a mixture of 51 and 50 (51:50
1:1) and flash chromatography (heptane:EtOAc 10:1 f 6:1)
gave 51 in 26% yield. 1H NMR (CDCl3, 300 MHz) δ 5.78 (ddd,
1H, J ) 10.0, 5.4, 2.1), 5.61 (dt, 1H, J ) 10.0, 1.1), 3.51 (d,
1H, J ) 3.5), 3.10 (m, 1H), 2.43 (m, 1H), 1.62 (br s, 1H), 1.44
(s, 9H), 0.97 (d, 3H, J ) 6.7), 0.93 (s, 9H); 13C NMR (CDCl3,
75 MHz) δ 178.1, 131.8, 126.4, 87.3, 68.0, 63.8, 33.8, 30.1, 28.1,
26.1, 15.1; IR (neat) 2950, 1750, 1455 cm-1; [R]22D +51.2 (c 0.26,
(CI+); calcd for C14H26NO2 (M + H): 240.1964, found: 240.1964
Rea r r a n gem en t of Vin yla zir id in e 24. To a solution of
vinylaziridine 24 (23 mg, 0.140 mmol) in THF (5 mL) at -78
°C was added KHMDS (0.215 mL, 0.280 mmol, 1.3 M in THF).
Stirring was continued for 5 min, and the reaction was then
quenched by addition of pH 7 buffer (1 mL). The mixture was
warmed to rt and was then poured into pH 7 buffer (3 mL).
The mixture was extracted with Et2O (2 × 7 mL), and the
combined organic phases were dried (MgSO4) and concentrated
to give the crude product (23 mg) as a mixture of isomers (45:

Aza-[2,3]-Wittig Rearrangements of Vinylaziridines
J . Org. Chem., Vol. 61, No. 23, 1996 8159
CHCl3); HRMS (CI+). Exact mass calcd for C15H28NO2 (M +
H): 254.2120, found: 254.2119.
cm-1; HRMS (CI+). Exact mass calcd for C18H26NO3 (M +
H): 304.1913, found: 304.1905.
ter t-Bu t yl (2R,6S)-6-[(Ben zyloxy)m et h yl]-1,2,3,6-t et -
r a h yd r op yr id in e-2-ca r boxyla te (52). Prepared from vinyl-
aziridine 32 in 98% yield as detailed for 44. Flash chroma-
tography (heptane:EtOAc 3:1 f 2:3) gave 52 (23 mg, 53%).
1H NMR (CDCl3, 300 MHz) δ 7.34 (m, 5H), 5.83 (m, 1H), 5.55
(m, 1H), 4.59 (d, 1H, J ) 11.9), 4.51 (d, 1H, J ) 11.9), 3.68 (m,
1H), 3.56 (dd, 1H, J ) 9.0, 4.0) 3.49 (dd, 1H, J ) 10.5, 4.5),
3.43 (dd, 1H, J ) 12.0, 8.5), 2.86 (br s, 1H), 2.25 (m, 2H), 1.48
(s, 9H); 13C NMR (CDCl3, 75 MHz) δ 172.1, 138.2, 128.4, 127.8,
127.6, 127.7, 126.2, 81.2, 74.0, 73.4, 55.5, 54.7, 29.1, 28.0; IR
Rea r r a n gem en t of Vin yla zir id in e 30. Vinylaziridine 30
(E:Z 3.2:1) was rearranged in 95% yield as detailed for 26 to
give 59, 60, 61a , and 61b as a mixture of isomers (59:60:61a :
61b 4.9:2.4:1.4:1). Flash chromatography (deactivated silica,
heptane:EtOAc 1:0 f 10:1) gave 59 (28%), 60 (13%), and
pyrrolines 61b and 61a as an inseparable mixture of isomers
(E:Z 1:1.4, 8%).
(2S,3S,6S)-6-ter t-Bu t yl-3-m et h yl-2-[(2-t r im et h ylsilyl)-
eth yn yl]-1,2,3,6-tetr a h yd r op yr id in e (59). 1H NMR (CDCl3,
300 MHz) δ 5.61 (s, 2H), 3.58 (d, 1H, J ) 2.7), 3.19 (m, 1H),
2.20 (m, 1H), 1.51 (br s, 1H), 1.15 (d, 3H, J ) 7.1), 0.85 (s,
9H), 0.11 (s, 9H); 13C NMR (CDCl3, 75 MHz) δ 129.8, 126.2,
108.4, 86.2, 59.4, 49.8, 35.5, 33.9, 26.4, 19.8, 0.18; IR(neat)
(neat) 3340, 2985, 1725 cm-1; [R]22 +22.9 (c 3.89, CDCl3);
D
HRMS (CI+). Exact mass calcd for C18H26NO3 (M + H):
304.1913, found: 304.1909.
3360, 2950, 2160 cm-1; [R]22 -2.4 (c 1.21, CHCl3); HRMS
ter t-Bu tyl (2R,3R,6S)-6-[(Ben zyloxy)m eth yl]-3-m eth yl-
1,2,3,6-tetr a h yd r op yr id in e-2-ca r boxyla te (53). Prepared
from vinylaziridine 33 in 95% yield as detailed for 44. 1H NMR
(CDCl3, 400 MHz) δ 7.36-7.27 (m, 5H), 5.66-5.56 (m, 2H),
4.56 (AB-q, 2H, J ) 12.0, 6.5), 3.67-3.58 (m, 1H), 3.58-3.53
(m, 1H), 3.46 (dd, 1H, J ) 8.5, 1.9), 3.06 (d, 1H, J ) 9.6), 2.49-
2.39 (m, 1H), 1.89 (br s, 1H), 1.51 (s, 9H), 1.06 (d, 3H, J )
7.0); 13C NMR (CDCl3, 100 MHz) δ 172.6, 138.6, 133.6, 128.8,
128.2, 128.1, 126.9, 81.7, 73.9, 73.8, 63.9, 54.6, 33.9, 28.5, 19.1;
IR (neat); 2970, 1730 cm-1; [R]22D +37.8 (c 2.00, CHCl3); HRMS
(CI+). Exact mass calcd for C19H28NO3 (M + H): 318.2069,
found: 318.2071.
D
(CI+). Exact mass calcd for C15H28NSi (M + H): 250.1991,
found: 250.2000.
(2R,3S,6S)-6-ter t-Bu tyl-3-m eth yl-2-[2-(tr im eth ylsilyl)-
eth yn yl)-1,2,3,6-tetr a h yd r op yr id in e (60). 1H NMR (CDCl3,
300 MHz) δ 5.79 (ddd, 1H, J ) 10.4, 5.6, 2.3), 5.57 (dd, 1H, J
) 10.4, 1.2), 3.78, (d, 1H, J ) 3.7), 3.08 (m, 1H), 2.10 (m, 1H),
1.51 (br s, 1H), 1.15 (dd, 3H, J ) 6.9, 2.3), 0.93 (s, 9H), 0.19 (s,
9H); 13C NMR (CDCl3, 75 MHz) δ 132.0, 126.4, 107.1, 88.0,
64.6, 50.2, 33.7, 33.6, 26.1, 15.4, 0.06; IR(neat) 2960, 2180 cm-1
;
[R]22D +104.3 (c 0.418, CHCl3); HRMS (CI+). Exact mass calcd
for C15H28NSi (M + H): 250.1991, found: 250.1983.
ter t-Bu tyl (2R,3S,6S)-6-[(Ben zyloxy)m eth yl]-3-m eth yl-
1,2,3,6-tetr a h yd r op yr id in e-2-ca r boxyla te (54). Prepared
from vinylaziridine 34 (E:Z 1.3:1) in 94% yield as a mixture
of isomers (54:53 1.2:1) as detailed for 44. Flash chromatog-
raphy (deactivated silica, heptane:EtOAc 1:0 f 15:1) gave pure
54 in 27% yield. 1H NMR (CDCl3, 400 MHz) δ 7.36-7.28 (m,
6H), 5.85-5.80 (m, 1H), 5.53 (dt, 1H, J ) 10.0, 1.4), 4.56 (AB-
q, 2H, J ) 23.8, 11.9), 3.68-3.62 (m, 1H), 3.60 (d, 1H, J )
4.0), 3.54 (dd, 1H, J ) 8.8, 4.3), 3.45 (dd, J ) 8.8, 7.4), 2.55-
2.48 (m, 1H), 1.50 (s, 9H), 1.40 (br s, 1H), 1.00 (d, 3H, J )
6.8); 13C NMR (CDCl3, 100 MHz) δ 172.2, 138.7, 133.0, 128.8,
128.1, 128.0, 126.9, 81.5, 74.5, 73.8, 59.7, 55.6, 32.6, 28.5, 15.7
; IR (neat) 2980, 2940, 1735 cm-1; [R]22D +39.7 (c 0.51, CHCl3);
HRMS (CI+). Exact mass calcd for C19H28NO3 (M + H):
318.2069, found: 318.2064.
(4S,5S)-5-ter t-Bu tyl-3-[(E)-(tr im eth ylsilyl)m eth ylen e]-
4-[(Z)-1-p r op en yl]-1-p yr r olin e (61a ). Prepared from 28 in
98% yield as detailed for the rearrangement of vinylaziridine
26. Flash chromatography (deactivated silica, heptane:EtOAc
1:0 f 20:1) gave 1-pyrroline 61a (11 mg, 61%). 1H NMR
(CDCl3, 500 MHz) δ 7.59 (d, 1H, J ) 2.1), 5.91 (d, 1H, J )
2.0), 5.36 (dq, 1H, J ) 10.8, 6.5), 5.18 (dt, 1H, J ) 10.8, 1.7),
3.70 (t, 1H, J ) 2.0), 3.38 (app d, 1H, J ) 10.2), 1.67 (dd, 3H,
J ) 6.5, 1.7), 0.92 (s, 9H), 0.12 (s, 9H); 13C NMR (CDCl3, 125
MHz) δ 167.2, 161.8, 133.2, 128.7, 122.2, 91.4, 39.9, 35.0, 26.7,
14.1, -0.64; IR (neat) 2970, 1595 cm-1; [R]22 +62.3 (c 0.62,
D
CHCl3); HRMS (CI+). Exact mass calcd for C14H26NSi (M +
H): 250.1991, found: 250.1992.
(4S, 5S)-5-ter t-Bu tyl-2-[(E)-(tr im eth ylsilyl)m eth ylen e]-
4-[(E)-1-p r op en yl]-1-p yr r olin e (61b). 1H NMR (CDCl3, 500
MHz, assigned from a mixture of isomers) δ 7.57 (d, 1H, J )
2.2), 5.94 (d, 1H, J ) 2.2), 5.45-5.12 (m, 2H), 3.75 (m, 1H),
3.16 (m, 1H), 1.63 (br s, 3H), 0.92 (s, 9H), 0.12 (s, 9H); 13C
NMR (CDCl3, 75 MHz, assigned from a mixture of isomers) δ
167.1, 160.9, 133.6, 128.7, 125.3, 90.5, 44.2, 35.3, 26.6, 17.8,
ter t-Bu tyl (4S,5E)-3-Aza -4-(ter t-bu tyl)-7-(eth oxyca r bo-
n yl)-2,5-h ep ta d ien eca r boxyla te (57). Prepared from vinyl-
aziridine 20 in 96% yield as detailed for the rearrangement of
aziridine 17. Flash chromatography (heptane:EtOAc 6:1) gave
57 as an oil. 1H NMR (CDCl3, 300 MHz) δ 7.55 (s, 1H), 5.80
(dd, 1H, J ) 15.5, 8.2), 5.61 (dt, 1H, J ) 15.5, 6.9), 4.18 (q,
2H, J ) 7.2), 3.37 (d, 1H, J ) 8.2), 3.06 (d, 2H, J ) 6.9), 1.53
(s, 9H), 1.25 (t, 3H, J ) 7.2), 0.91 (s, 9H); 13C NMR (CDCl3, 75
MHz) δ 171.6, 161.9, 153.8, 132.3, 124.9, 82.9, 82.2, 60.6, 37.9,
-0.57; IR (neat) 2950, 1590 cm-1
.
Ack n ow led gm en t. This work was supported finan-
cially by the Swedish Natural Science Research Council.
We are grateful to Profs. J . Sandstro¨m for calculating
the inversion barrier of 32, and D. Tanner for linguistic
improvements of the manuscript.
34.9, 28.0, 26.7, 14.2; IR (neat) 2940, 1730, 1640 cm-1; [R]22
D
+4.6 (c 1.31, CDCl3); HRMS (CI+). Exact mass calcd for
C17H30NO4 (M + H): 321.2175, found: 321.2184.
ter t-Bu tyl (2S*,6S*)-6-[(Ben zyloxy)m eth yl]-1,2,3,6-tet-
r a h yd r op yr id in e-2-ca r boxyla te (r a c-58). Prepared from
41 in 93% yield as a mixture of isomers (rac-52:rac-58 1.8:1).
Flash chromatography (heptane:EtOAc 3:1 f 2:3) gave rac-
58 in 24% yield. 1H NMR (CDCl3, 300 MHz) δ 7.34 (m, 5H),
5.83 (m, 1H), 5.58 (m, 1H), 4.59 (d, 1H, J ) 12.2), 4.53 (d, 1H,
J ) 12.2), 3.77 (m, 1H), 3.55 (t, 1H, J ) 5.9) 3.41 (m, 2H),
2.60 (brs, 1H), 2.34 (m, 2H), 1.48 (s, 9H); 13C NMR (CDCl3, 75
MHz) δ 172.7, 142.7, 138.3, 128.4, 127.6, 125.9, 125.8, 81.0,
73.0, 72.3, 51.8, 51.7, 28.1, 27.8; IR (neat) 3350, 2970, 1725
Su p p or t in g In for m a t ion Ava ila b le: Copies of the 13C
NMR spectra of compounds 3-20, 21b, 22-34, 38-54, and
57-61 (55 pages). This material is contained in libraries on
microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS;
ordering information is given on any current masthead page.
J O9612638