Rearrangements of substituted 3-aza-1,2,5-hexatrienes. 3. The scope and versatility of an extremely mild 3-aza-Cope reaction

Article abstract of DOI:10.1021/jo951587g

An investigation of the [3,3]-sigmatropic reaction of substituted 3-aza-1,2,5-hexatrienes to give 4-pentenenitriles is presented. This reaction has been found to occur under a wide variety of reactions conditions (10 are reported) starting from readily av

Full text of DOI:10.1021/jo951587g

J . Org. Chem. 1996, 61, 55-62
55
Rea r r a n gem en ts of Su bstitu ted 3-Aza -1,2,5-h exa tr ien es. 3. Th e
Scop e a n d Ver sa tility of a n Extr em ely Mild 3-Aza -Cop e Rea ction
Michael A. Walters,* Andrew B. Hoem, and Colleen S. McDonough
6128 Burke Laboratory, Department of Chemistry, Dartmouth College, Hanover, New Hampshire 03755
Received August 30, 1995X
An investigation of the [3,3]-sigmatropic reaction of substituted 3-aza-1,2,5-hexatrienes to give
4-pentenenitriles is presented. This reaction has been found to occur under a wide variety of
reactions conditions (10 are reported) starting from readily available N-allylamides. In contrast
to other 3-aza-Cope reactions, this process occurs at room temperature, under essentially neutral
conditions, allowing for the facile preparation of substituted nitrile products in moderate to excellent
yields. The scope and versatility of this reaction are demonstrated by its use on a wide variety of
substrates, including nitrogen- and oxygen-substituted amides. The rearrangements of cis- and
trans-4-tert-butyl-N-allylcyclohexanecarboxamides 16a and 16b are reported and were found to
give a ratio of axial to equatorial (A:E) products consistent with A:E ratios found for other related
sigmatropic reactions. The stereochemical requirements for this reaction appear to be similar to
other [3,3]-rearrangements even though the transition state for this rearrangement is most likely
neither boat nor chairlike.
In tr od u ction
tions. The neutral 3-aza-Cope reaction occurs at tem-
peratures of 120-250 °C,2 while the positively charged
variations usually are effected at 80-120 °C.3,4 Sub-
strates for the latter family of rearrangements have been
derived from the neutral 3-amino-1,5-hexadiene frame-
work by quaternization of the nitrogen or by the use of
Lewis acids. Herein we report our investigations of a
mild 3-aza-Cope reaction which occurs at room temper-
ature under essentially neutral conditions. This reaction,
which presumably proceeds via a 3-aza-1,2,5-hexatriene
intermediate (eq 2), is the mildest neutral aza-Cope
reaction reported to date and appears to have consider-
able synthetic potential.
The stereochemical and regiochemical control of bond
formation offered by the Claisen and Cope rearrange-
ments has made these sigmatropic reactions powerful
synthetic tools in the construction of both acyclic and
cyclic molecules (eq 1).1 Many heteroatom-substituted
variations of these two fundamental reactions have been
developed, largely in efforts to produce processes with
the same useful characteristics but which might both
occur at lower temperatures (Cope, 210-260 °C; Claisen,
180-255 °C) and offer better stereochemical control in
the bond-forming step. With specific regard to nitrogen-
substituted variations of these reactions, the 3-aza-Cope
rearrangement has been especially well-investigated in
the past few years.2,3 In these studies, the potentially
tetracoordinate nature of nitrogen has proven advanta-
geous for the introduction of control elements which may
influence both the stereochemical outcome and the
catalysis of the reaction process.
Our interest in the 3-aza-Cope reaction was initiated
(2) (a) Kurth, M. J .; Brown, E. G. Synthesis 1988, 362. (b) Kurth,
M. J .; Decker, O. H. W.; Hope, H.; Yanuck, M. D. J . Am. Chem. Soc.
1985, 107, 443. (c) Kurth, M. J .; Decker, O. H. W. J . Org. Chem. 1985,
50, 5769. (d) Kurth, M. J .; Decker, O. H. W. Tetrahedron Lett. 1983,
24, 4535. (e) Ireland, R. E.; Willard, A. K. J . Org. Chem. 1974, 39,
421. (f) Hill, R. K.; Gilman, N. W. Tetrahedron Lett. 1967, 1421. (g)
Hill, R. K.; Newkome, G. R. Tetrahedron Lett. 1968, 5059. (h) Tsunoda,
T.; Tatsuki, S.; Akasaka, M.; Itoˆ, S. Tetrahedron Lett. 1993, 3297. (i)
Tsunoda, T.; Sakai, M.; Sasaki, O.; Sako, Y.; Hondo, Y.; Itoˆ, S.
Tetrahedron Lett. 1992, 33, 1651. (j) Tsunoda, T.; Sasaki, O.; Itoˆ, S.
Tetrahedron Lett. 1990, 31, 727.
(3) (a) Gilbert, J . C.; Senaratne, K. P. A. Tetrahedron Lett. 1984,
25, 2303. (b) Brannock, K. C.; Burpitt, R. D. J . Org. Chem. 1961, 20,
3576. (c) Corbier, J .; Cresson, P. C. R. Seances Acad. Sci., Ser. C 1970,
270, 2077. (d) Barta, N. S.; Cook, G. R.; Landis, M. S.; Stille, J . R. J .
Org. Chem. 1992, 57, 7188. (e) Danishefsky, S. J .; Phillips, G. B.
Tetrahedron Lett. 1984, 25, 3159. (f) Hill, R. K. Tetrahedron Lett. 1978,
4337. (g) Bailey, P. D.; Harrison, M. J . Tetrahedron Lett. 1989, 30,
5341. (h) Cook, G. R.; Barta, N. S.; Stille, J . R. J . Org. Chem. 1992,
57, 461. (i) Beholz, L. G.; Stille, J . R. J . Org. Chem. 1993, 58, 5095.
The use of a Pd(0) catalyst to effect this transformation has also been
reported. (j) Murahashi, S. I.; Makabe, Y. Tetrahedron Lett. 1985, 26,
5563. (k) Murahashi, S. I.; Makabe, Y.; Kunita, K. J . Org. Chem. 1988,
53, 4489.
The limited utility of the 3-aza-Cope for synthetic
purposes has been due, in part, to the rather harsh
conditions that are required to effect these transforma-
* Phone, 603-646-3495; FAX, 603-646-3946; e-mail, michael.a.wal-
ters@dartmouth.edu.
X Abstract published in Advance ACS Abstracts, J anuary 1, 1996.
(1) For reviews concerned with these and related [3,3]-sigmatropic
rearrangements, see the following: (a) Ziegler, F. E. Chem. Rev. 1988,
88, 1423. (b) Blechert, S. Synthesis 1989, 89, 71. (c) Lutz, R. P. Chem.
Rev. 1984, 84, 205. The ester enolate Claisen and the oxy-Cope
reactions are perhaps the best examples of research directed along
these lines. For general discussions of these processes, see: (d) Wipf,
P. In Comprehensive Organic Synthesis; Trost, B. M., Ed.; Pergamon
Press: Elmsford, NY, 1991; Vol. 5, pp 827-873, and (e) Bronson, J .
J .; Danheiser, R. L. In Comprehensive Organic Synthesis; Trost, B. M.,
Ed.; Pergamon Press: Elmsford, NY, 1991; Vol. 5, pp 999-1035.
(4) Exceptions to this temperature range have been observed. (a)
Welch, J . T.; De Corte, B.; De Kimpe, N. J . Org. Chem. 1990, 55, 4981.
Zwitterionic 3-aza-Cope examples have also been reported to occur at
lower temperatures: (b) Vedejs, E.; Gingras, M. J . Am. Chem. Soc.
1994, 116, 579. (c) Nubbemeyer, U. J . Org. Chem. 1995, 60, 3773.
0022-3263/96/1961-0055$12.00/0 © 1996 American Chemical Society

56 J . Org. Chem., Vol. 61, No. 1, 1996
Walters et al.
Ta ble 1. Rea gen t Com bin a tion s Em p loyed To Effect th e
Sch em e 1
Tr a n sfor m a tion of N-Allyla m id es to P en ten en itr iles
entry
conditionsa
yield (%)
A
B
C
D
E
F
G
H
H
I
2PPH3, 2CCl4, 3Et3N
[Ph3PBr+]Br-, 2Et3N
2PPh3, 2CBr4, 3Et3N
PPh3, I2, 2Et3N
polymeric PPh3, Br2, 2Et3N
3I2, 3P(OEt)3, 3Et3N
3I2, 3P(OMe)3, 3Et3N
Tf2O, 2(iPr)2NEt, Et2O
Tf2O, 2(iPr)2NEt, CH2Cl2
triphosgene (1/2), 3Et3N, rt
0 °C
94
55
66
56
42
86
36
67
44
78
85
40
31
39
J
K
L
M
-78 °C
(COCl)2, 2Et3N
PhCH2NEt3+Cl- (0.03%, CHCl3,
50% NaOH/H2O
a
Reference 7b.
by an infrequently cited paper by Brannock and Burpitt,5
published in 1965, which describes an extremely mild
example of this type of rearrangement. Treatment of the
readily available N-allylamides with either phosgene or
phosphorous trichloride (path a of Scheme 1) followed by
reaction of the imidoyl chloride intermediates with tri-
ethylamine (TEA) in either benzene or tetrahydrofuran
(THF) at reflux leads to the formation of the R-substi-
tuted pentenenitriles in moderate yields. The authors
hypothesized a 3-aza-1,2,5-hexatriene, an N-allylketen-
imine, as the intermediate in this reaction process.6
Remarkably, this neutral 3-aza-Cope reaction was re-
ported to occur at temperatures 120-200 °C lower than
that of the other known “neutral” version!2f
Apparently, the synthetic potential of the N-allylketen-
imine rearrangement, and the observation of its facility
relative to closely related rearrangements, lay dormant
in the literature until our investigation of the transfor-
mation began a few years ago.7 After our original report
of a mild, one-pot variation of this reaction process,
Molina8 reported the synthesis of several substituted
N-allylketenimines and their facile rearrangement to
substituted 4-pentenenitriles. In other studies, Nubbe-
meyer9 has investigated the diastereoselectivity of this
reaction in a limited number of cases and Huisgen10 has
reported the equilibration of the ketenimine and nitrile
isomers in highly-fluorinated substrates. We recently
reported ab initio calculations that confirm that the
intermediacy of a ketenimine in the transformation of
an N-allylamide to a 4-pentenenitrile is sufficient to
explain the relative facility of this reaction relative to
the neutral and charged 3-aza-Cope reactions.6 Presum-
ably, this relative facility arises from the sterically-
unencumbered nature of the ketenimine which allows it
to approach the π-system of the tethered allyl system in
an almost strain-free manner. Additionally, the almost
linear nature of the ketenimine and the length of the
CdN make the total distance the heterocumulene spans
in the transition structure almost identical to that of
counterpoised allylic system. Both of these factors
combine to make the rearrangement particularly facile
and thus particularly worthy of investigation.
Our developement of this reaction into a more versatile
process began with the investigation of the conditions
required to bring about the rearrangement in a one-pot
process. We accomplished this goal by the use of dehy-
drating conditions which had seen use in ketenimine-
forming processes subsequent to the initial work of
Brannock and Burpitt and the use of conditions for the
transformation of amides into nitriles. Our work along
these lines has demonstrated that the conversion of
N-allylamides can be effected by a wide variety of
reagents, is very general in substrate-tolerance, and
occurs under much milder conditions than were originally
reported.
Resu lts a n d Discu ssion
Rea ction Con d ition s. Our initial successful one-pot
conversion involved treatment of amide 1a with Ph3P,
CCl4, and TEA, in CH2Cl2 or CH3CN at room tempera-
ture11 (Table 1, entry A). These conditions gave the
nitrile 4a in 94% yield as the sole reaction product. The
conversion of 1a to 4a was used as a standard in the
development of other reaction conditions, and Table 1
lists the yields obtained with a variety of reagent
combinations. Although some of these reagent combina-
tions have not yet been applied to the preparation of
simple ketenimines,12 their use as activating agents in
this rearrangement suggests that they might be useful
for that purpose.
(5) Brannock, K. C.; Burpitt, R. D. J . Org. Chem. 1965, 30, 2564.
(6) Ab initio calculations confirm this as a reasonable hypothesis.
See: Walters, M. A. J . Am. Chem. Soc. 1994, 116, 11618-11619.
(7) (a) Walters, M. A.; McDonough, C. S.; Brown, P. S., J r.; Hoem,
A. B. Tetrahedron Lett. 1991, 32, 179. (b) Walters, M. A.; Hoem, A. B.;
Arcand, H. R.; Hegman, A. D.; McDonough, C. S. Tetrahedron Lett.
1993, 34, 1453. (c) Walters, M. A.; Hoem, A. B. J . Org. Chem. 1994,
59, 2645.
Further comment is required for some of these reaction
conditions. Elimination of the troublesome Ph3P-con-
taining side products was accomplished through the use
(8) (a) Molina, P.; Alajarin, M.; Lopez-Leonardo, C.; Alcantara, J .
Tetrahedron 1993, 5153. (b) Molina, P.; Alajarin, M.; Lopez-Leonardo,
C. Tetrahedron Lett. 1991, 32, 4041.
(9) Nubbemeyer, U. Synthesis 1993, 1120.
(10) Bru¨ckner, R.; Huisgen, R. Tetrahedron Lett. 1994, 35, 3281.
(11) (a) Appel, R.; Warning, K.; Ziehn, K.-D. Chem. Ber. 1973, 106,
3450. (b) Yamato, E.; Sugasawa, S. Tetrahedron Lett. 1970, 4383.
(12) For a review of the synthesis of ketenimines, see: Krow, G. R.
Angew. Chem., Int. Ed. Engl. 1971, 10, 435.

Rearrangements of 3-Aza-1,2,5-hexatrienes
J . Org. Chem., Vol. 61, No. 1, 1996 57
Ta ble 2. Exa m p les of th e 3-Aza -Cop e Rea r r a n gem en t
Sch em e 2
amide
R1
R2
method
nitrile
yield (%)
1a
1b
1c
1d
1e
1f
1g
1h
1i
Ph
CH2Ph
Ph
Ph
p-MeOC6H4
p-CF3C6H4
MeO2CCH2
CH3CH2
Br(CH2)3
PhCH2O
MeOCH2O
PthalN
H
H
Me
Ph
H
H
H
H
H
H
H
H
H
A
A
A
A
A
A
A
A
B
F
4a
4b
4c
4d
4e
4f
4g
4h
4i
94
67
60
75
85
73
69
36
30
40
59
78
66
Sch em e 3
1j
1k
1l
4j
4k
4l
F
B
F
1l
PthalN
4l
of the reagents given in entries E, F, and G of Table 1.
Non-phosphorus-based reagents were also successful in
effecting the reaction (conditions H, I, L, and M). The
conditions utilizing triphosgene/TEA appeared to be the
most vigorous of all of the reagent combinations exam-
ined,13 and under these reaction conditions the 3-aza-
Cope transformation occurred at well below room tem-
perature.
Sch em e 4
That this rearrangement is compatible with aqueous
conditions is evidenced by the use of a phase-transfer
reaction ([PhCH2NEt3]+Br-/CHCl3/NaOH/H2O, condition
M) to generate the activating species.14 This transforma-
tion presumably proceeds through the insertion of dichlo-
rocarbene into the O-H bond in the imidoyl tautomer of
the N-allylamide. Elimination of dichloromethanol leads
to the transient formation of the ketenimine intermediate
which rapidly (at least at a rate competitive with that of
attack of other nucleophiles) rearranges to the nitrile.
Although it appeared that almost any dehydrating
agent could bring about this transformation, a number
of reagents were not successful in converting the allyl-
amide to the 4-pentenenitrile. Notably, the Misunobu
conditions (DEAD, Ph3P)15 failed to facilitate the desired
rearrangement. Other reagent combinations that failed
to effect the reaction cleanly were TEA and CH3COCl,
Ac2O, CH3OCOCl, (CF3CO)2O, and 1-propylphosphonic
acid cyclic anhydride.
Scop e of th e Rea ction . The wide range of N-
allylamides that were used as ketenimine precursors for
this mild rearrangement is illustrated in Table 2. Amides
1c and 1d demonstrated that this reaction was useful
for the synthesis of quaternary nitriles. Sensitive func-
tionality that might be reactive under more vigorous
conditions survived this mild rearrangement, as is evi-
denced by the successful reactions of the ester 1g and
bromide 1i.
of [Ph3PBr+]Br- and 3 equiv of TEA, the conversion of
the primary alcohol to the bromide was accomplished
concurrently with the rearrangement, albeit in low
yield.16 Likewise, when amide 6, derived from isochro-
manone, was treated under the same conditions, the
desired bromonitrile 7 was obtained in 46% yield (Scheme
3). On the other hand, if amide 5 was treated with 1
equiv of [Ph3PBr+]Br- and TEA, the bromoamide li could
be obtained cleanly. This amide could then be induced
to rearrange, in a separate step with the usual combina-
tion of reagents, to give the bromonitrile 4i (45% yield).
Many of these same reagent combinations also proved
to be effective in the rearrangement of both R-nitrogen-
and R-oxygen-substituted N-allylamides. While the N-
phthalimide protected derivative 1l was converted quite
smoothly to the R-aminonitrile 4l (Table 2), the reactions
of the PhCH2O- and CH3OCH2O-substituted amides 1j
and 1k proceeded only sluggishly to give the protected
cyanohydrins 4j and 4k , respectively. The latter cases
seemed to be much more dependent on the reaction
conditions than were the other alkyl examples reported
in Table 2 which proceeded using a wide variety of
conditions.
One of the most intriguing results in the original
Brannock and Burpitt manuscript was their reported
conversion of N-propargylamide 8 to 3,4-pentadieneni-
trile 10 (26% yield) through what appears to be a highly-
strained 3-aza-1,2-hexadien-5-yne 9 (Scheme 4). This
transformation, however, appeared to be reasonably
facile, even under the milder conditions which we had
developed. For example, application of the standard
rearrangement conditions to amide 11 converted it to the
conjugated nitrile product 13, presumably via the initially-
As a final note on the reaction conditions, it was
possible to utilize some of the reagent combinations in a
remote functional group interconversion which took place
concomitantly with the rearrangement process (Scheme
2). For example, when amide 5 was treated with 2 equiv
(13) Eckert, H.; Forster, B. Angew. Chem., Int. Ed. Engl. 1987, 26,
894-895.
(14) Saraie, T.; Ishiguro, T.; Kawashima, K.; Morita, K. Tetrahedron
Lett. 1973, 2121.
(15) For a review of the Mitsunobu reaction, see: Mitsunobu, O.
Synthesis 1981, 1.
(16) Bestmann, H. J .; Lienert, J .; Mott, L. Liebigs Ann. Chem. 1968,
718, 24-32.

58 J . Org. Chem., Vol. 61, No. 1, 1996
Walters et al.
Ta ble 3. Com p a r ison of th e Rea r r a n gem en t of 17 to
Rela ted [3,3]-Sigm a tr op ic P r ocesses
Sch em e 5
ratio of
products ref
entry starting materiala
major product
18a
1
2
17
75:25
52:48
18
Sch em e 6
3
4
76:24
77:23
18
3a
22
formed allene 12 (Scheme 5).17 Attempts to isolate
intermediate 12 were unsuccessful. The aromatic system
in this case no doubt facilitated the isomerization from
the allene to the conjugated 1,3-diene system. Good
evidence for this contention was obtained when no
isomerization was observed subsequent to the rearrang-
ment of 15 to the allenic nitrile 14 (Scheme 6).
a
Structures 17, 21, and 23 represent intermediates.
Sch em e 7
Ster eoch em istr y. In addition to their ability to
predictably form C-C bonds, another important feature
of the Claisen and Cope rearrangements is their inherent
stereochemical control.1 This stereochemical control can
be rationalized by invoking the intermediacy of an
organized transition state which is chair- or boatlike. The
attendant gauche and 1,3-diaxial interactions between
the groups on the carbons involved in the bond-forming
process and other substituents on the cyclic assembly of
atoms can lead to marked differences between the various
diastereomeric transition states for the reaction, thus
allowing the potential for one diastereomer of the product
to be formed preferentially. For the rearrangement of
3-aza-1,2,5-hexatrienes, the transition state fits neither
the chair- nor boatlike paradigms. This situation raises
important questions concerning the stereoselectivity as-
sociated with such a transition state. To gain some
general understanding for the level of diastereocontrol
which might be present in this process relative to other
[3,3]-sigmatropic reactions, an investigation of the rear-
rangement of the conformationally-locked N-allylamides
16a -b was undertaken. The rearrangement of related
compounds has been investigated in the case of the
Claisen18 and cationic 3-aza-Cope3a reactions (Table 3,
entries 2-4). These previous studies concluded that
there was a marked preference for the bond-forming
process to occur on the equatorial face of the π-system
involved in the rearrangement process.19 An additional
impetus for determining the axial:equatorial (A:E) ratio
for the rearrangement of 16a -b was the report by
House18 that the reaction of the nitrile-stabilized anion
25 (derived from 24) with allyl bromide favored the
formation of the axial nitrile 18 in an 88:12 A:E ratio
(Scheme 7). We speculated that this reaction might,
alternatively, proceed through the 3-aza-1,2,5-hexatriene
17, given that ketenimines have been formed by the
N-alkylation of nitrile anions.12,20 This process would
lead to the same products as those formed by the direct
C-alkylation reaction, but perhaps in a different A:E
ratio. Determination of the A:E ratio in our case, wherein
the ketenimine was to be formed by an alternative
process, might allow us to rule out the exclusive inter-
mediacy of this putative species in the case reported by
House, but only if the ratio for the rearrangement of 17
turned out to be much different than 88:12.
(17) The mixture of nitrile isomers 13 was converted to one isomer
by treatment with mild acid or silica gel.
(18) House, H. O.; Lubinkowski, J .; Good, J . J . J . Org. Chem. 1975,
40, 862.
(19) [2,3]-Sigmatropic rearrangements evince a similar preference
for bond formation on the equatorial face of the cyclohexane system.
(a) Evans, D. A.; Sims, C. L.; Andrews, G. C. J . Am. Chem. Soc. 1977,
99, 5453. (b) Mander, L. N.; V., T. J . Aust. J . Chem. 1980, 33, 1559-
1568.
A mixture of the axial and equatorial amide isomers
16a and 16b (the identities of which could be character-
(20) Clarke, L. F.; Hegarty, A. F. J . Org. Chem. 1992, 57, 1940 and
references cited therein.

Rearrangements of 3-Aza-1,2,5-hexatrienes
J . Org. Chem., Vol. 61, No. 1, 1996 59
Sch em e 8
(EtO)3P/TEA led to only a trace amount of the nitrile
mixture 18a -b, even though little starting material
could be isolated from the reaction.22 When the quenched
reaction mixture was treated with 2,4-dinitrophenylhy-
drazine reagent, a small amount of the 2,4-dinitrophen-
ylhydrazone 28 was isolated (mp 169-170 °C; lit.23 mp
170-171 °C). Apparently, the slower rate of elimination
from imidoyl halide 26 (relative to the one derived from
16a ) allowed for an alternative reaction pathway, that
of the removal of the allylic proton, to occur.24 Thus, in
the case of the reaction of 16b, TEA-assisted isomeriza-
tion of the imidoyl intermediate 26 would give the
R-chloroimine 27 as the predominant product. Subse-
quent hydrolysis of this reactive species upon aqueous
workup would account for the production of aldehyde 29,
which could then be isolated as its 2,4-DNP derivative.
Con clu sion s
In conclusion, we have expanded on the pioneering
work of Brannock and Burpitt and developed what we
consider to be the mildest 3-aza-Cope reaction reported
to date. This reaction appears to be quite general, in that
it is capable of transforming a wide variety of N-allylic
amides into their corresponding substituted penteneni-
triles. Additionally, this sigmatropic process can be
effected by a wide variety of readily available reagent
combinations and occurs under surprisingly mild tem-
peratures relative to other 3-aza-Cope reactions. Finally,
this rearrangement is comparable to other [3,3]-sigma-
tropic reactions in its selectivity for reacting preferen-
tially from the equatorial face of conformationally-locked
systems like 16a and 16b. This is in spite of the fact
that this process most likely occurs via neither a chair-
nor boatlike transition state and might, therefore, be
expected to evince much lower diastereoselection. We are
continuing our investigation into the diastereofacial
selectivity of this process in both acyclic and cyclic
systems. Our results along these lines will be reported
in due course.
ized by the 1H coupling constants of He and Ha) was
readily prepared from 4-tert-butylcyclohexanecarboxylic
acid (1. SOCl2 2. CH2dCHCH2NH2). When this ∼50:50
mixture of isomers was subjected to the rearrangement
conditions, a rapid reaction of only one of the two isomers
was observed. Fortunately, the amide isomers proved
to be separable by radial chromatography, and each of
these isomers was subjected, independently, to several
of the standard rearrangement conditions which we had
developed. The axial amide 16a led to an identical 75:
25 ((3%; integration of 1H NMR resonances) mixture of
the axial and equatorial isomers of the nitrile 18,
regardless of which method (Table 1: A, 41%; F, 46%;
H, 42%; I, 27%) was employed. This ratio of isomers was
in reasonable agreement with the results reported for
comparable sigmatropic reactions (Table 3). Therefore,
even though the rearrangement of this 3-aza-1,2,5-
hexatriene proceeded via a fundamentally different tran-
sition state than in the other examples, it exhibited
relatively the same diastereofacial selectivity. Since the
A:E ratio was not drastically different from that which
House reported for the reaction of carbanion 24, we could
draw no conclusions as to the intermediacy of 17 in the
alkylation process.
In marked contrast to the smooth rearrangement of
the axial isomer 16a , the rearrangement of the equatorial
amide isomer 16b (Ph3P/CCl4/TEA) gave a very low yield
of the product nitrile 18, albeit in approximately the same
A:E ratio as had resulted from the rearrangement of
amide 16a (Scheme 8). The difference in reactivity
between 16a and 16b is most likely a manifestation of
steric acceleration or assistance.21 Both amides are
probably converted to their respective imidoyl halides at
a similar rate. Subsequent ketenimine formation from
26, however, is slower than it is from the axially-disposed,
and more sterically-encumbered, imidoyl halide derived
from 16a . Notably, the treatment of amide 16b with I2/
Exp er im en ta l Section
Gen er a l Meth od s. Unless otherwise noted, all nonaqueous
reactions were carried out under a dry argon or nitrogen
atmosphere in flame-dried glassware. Diethyl ether and
tetrahydrofuran (THF) were distilled from sodium/benzophe-
none ketyl. Dichloromethane and acetonitrile were distilled
from calcium hydride. Triethylamine (Et3N) was distilled and
stored over solid potassium hydroxide. Dimethylformamide
(DMF) was dried over activated 4 Å molecular sieves. Triph-
enylphosphine polymer bound was purchased from Fluka
Chemicka-BioChemika Analytika. Chemical shifts, for 1H
NMR spectra, are reported in δ units downfield from internal
Me4Si or from the CHCl3 solvent peak at 7.26 ppm relative to
Me4Si. 13C NMR spectra were referenced to the CDCl3 peak
at 77.2 ppm relative to Me4Si. Multiplicities are reported as
s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet),
ABq (AB quartet), app (apparent), unresolved, and br (broad).
An ABq was reported as the center of the two doublets and
the splitting distance of each doublet. An apparent (app)
(22) The crude reaction mixture showed a resonance (1H) consistent
with the presence of an aldehyde which we presumed to be 29.
Attempts to isolate this compound from the crude mixture were
unsuccessful.
(23) Cross, B.; Whitham, G. H. J . Chem. Soc. 1960, 3895.
(24) This proposed mechanism is reminiscent of a published syn-
thetic process in which the allylic deprotonation of nonenolizable
N-allyl imidoyl chlorides is found to lead to good yields of substituted
pyrroles. Engel, N.; Steglich, W. Angew. Chem., Int. Ed. Engl. 1978,
17, 676.
(21) This concept has been employed to explain the effect of
substituent conformation on a closely analogous reaction, that of the
formation of exocyclic alkenes by elimination of HBr. For example, cis-
4-tert-butylcyclohexanemethyl bromide (axial) undergoes elimination
to 1-tert-butyl-4-methylenecyclohexane at a rate nine times faster than
does the corresponding trans (equatorial) epimer. King, J . F.; Coppen,
M. J . Can. J . Chem. 1971, 49, 3714-3723. We thank a referee for
bringing this concept to our attention.

60 J . Org. Chem., Vol. 61, No. 1, 1996
Walters et al.
splitting pattern was defined as a splitting pattern that was
less complicated than predicted, usually due to coincidentally
identical splitting from chemically nonequivalent protons.
Substances for which C, H, N analyses are not reported were
purified as specified and gave spectroscopic data consistent
with being >95% of the assigned structure. Microanalysis
were performed by Spang Microanalytical Laboratory, Gal-
braith Laboratories, Inc., Schwarzkopf Microanalytical Labo-
ratory, or Atlantic Microlab, Inc.
Am id e P r ep a r a tion . All amides were produced by stan-
dard synthetic techniques. Unless otherwise noted, amides
were synthesized by the condensation of allylamine (AA) or
propargylamine with the appropriate acid chloride. Amides
1e, 1f, and 13 were produced by conversion of the appropriate
acid to the acid chloride with thionyl chloride, followed by
reaction with AA. Amides 1i and 1k were produced by the
ring-opening reaction of δ-valerolactone or isochromanone with
AA. Amide 1n was produced by condensation of the N-
phthalylglycine with pivaloyl chloride, followed by treatment
of the mixed anhydride with AA. Amide 1m was produced by
a two-step procedure from butyl glycolate. The glycolate was
protected as the methoxymethyl ether (MOMCl, Hunig’s Base),
and the resulting ester was converted to the amide by heating
with AA.
was treated with 0.122 mL of Et3N (0.879 mmol) via syringe.
The reaction was stirred for a further 45 min before purifica-
tion gave 39.5 mg of nitrile 4a (86%).
P r oced u r e G. A solution of 0.229 g of I2 (0.903 mmol) in
0.5 mL of dry CH2Cl2 was titrated via syringe with trimethyl
phosphite (0.107 mL, 0.918 mmol) until the solution was
colorless. The solution was transferred, via cannula, to a
solution of 53.8 mg of amide 1a (0.301 mmol) in 0.73 mL of
CH2Cl2. After being stirred for 15 min at rt, the solution was
treated with 0.126 mL of Et3N (0.903 mmol) via syringe. The
reaction was stirred for a further 1 h before purification gave
16.6 mg of nitrile 4a (36%).
P r oced u r e H. To a solution of 58.1 mg of amide 1a (0.332
mmol) and 0.121 mL of diisopropylethylamine (0.697 mmol)
in 1.66 mL of dry ethyl ether at room temperature was added
slowly 0.059 mL of triflic anhydride (0.347 mmol) via syringe.
This solution was stirred for 20 min before the reaction was
quenched with the addition of 3 mL of brine. Purification gave
35.0 mg of nitrile 4a (67%).
P r oced u r e I. A solution of 53.3 mg of amide 1a (0.304
mmol) dissolved in 0.5 mL of dry CH2Cl2 was transferred, via
cannula, to a solution of 46.3 mg of triphosgene (0.152 mmol)
in 0.72 mL of dry CH2Cl2. This solution was treated slowly
with 0.127 mL of Et3N (0.912 mmol) via syringe. The reaction
was stirred for 5 min before purification gave 37.0 mg of nitrile
4a (77%).
P r oced u r e J . A solution of 51.5 mg of amide 1a (0.294
mmol) dissolved in 0.5 mL of dry CH2Cl2 was transferred via
cannula to a solution of 43.6 mg of triphosgene (0.147 mmol)
in 0.7 mL of dry CH2Cl2 and cooled to 0 °C. This solution was
treated slowly with 0.123 mL of Et3N (0.882 mmol) via syringe.
This solution was stirred for 30 min before the reaction was
diluted with 3 mL of brine. Purification gave 39.1 mg of nitrile
4a (85%).
Sta n d a r d P u r ifica tion P r oced u r e. All reactions were
partitioned between water and ether when deemed complete.
The organic layer was then washed with water and brine, dried
over anhydrous MgSO4, and concentrated in vacuo. Chroma-
tography of the residue on silica gel (10% EtOAc/hexane) gave
the nitrile product.
Gen er a l P r oced u r es for th e Con ver sion of N-Allyla -
m id es to 4-P en ten en itr iles. P r ep a r a tion of 2-P h en yl-4-
p en ten en itr ile (4a ): IR (neat) 3090, 2833, 2240, 1649, 1493,
1
1451, 996, 925, 759, 701 cm-1; H NMR (300 MHz, CDCl3) δ
7.44-7.30 (m, 5H), 5.90-5.72 (m, 1H), 5.24-5.14 (m, 2H), 3.86
(t, 1H, J ) 7.7 Hz), 2.73-2.57 (m, 2H); 13C NMR (75 MHz,
CDCl3) δ 135.1, 132.5, 128.9, 128.1, 127.3, 120.2, 119.3, 39.8,
37.4; MS (EI) m/ e 157 (42), 117 (37), 116 (100), 104 (18), 92
(42), 77 (22). Anal. Calcd for C11H11N: C, 84.03; H, 7.06.
Found: C, 84.06; H, 7.09.
P r oced u r e A. To a solution of 98.3 mg of amide 1a (0.561
mmol), 0.309 g of Ph3P (1.17 mmol), and 0.235 mL of Et3N
(1.68 mmol) in 2.24 mL of dry CH2Cl2 was added 0.162 mL of
CCl4 (1.68 mmol) via syringe. After the solution was stirred
for 15 h at rt, purification gave 83.1 mg of nitrile 4a (94%).
P r oced u r e B. To a solution of 53.5 mg of amide 1a (0.305
mmol) and 0.149 g of [Ph3PBr+]Br- (0.351 mmol) in 1.22 mL
of dry CH2Cl2 at rt was added 0.106 mL of Et3N (0.763 mmol)
via syringe. After the solution was stirred for 15 h, purification
gave 26.3 mg of nitrile 4a (55%).
P r oced u r e K. A solution of 54.6 mg of amide 1a (0.312
mmol) dissolved in 0.5 mL of dry CH2Cl2 was transferred via
cannula to a solution of 46.2 mg of triphosgene (0.156 mmol)
in 0.75 mL of dry CH2Cl2 which had previously been cooled to
-78 °C. The external temperature of this solution was
maintained at <-70 °C while 0.130 mL of Et3N (0.936 mmol)
was added slowly via syringe. This solution was held at
constant temperature for 4.5 h, without being checked by TLC,
before the reaction was quenched by 3 mL of brine. Purifica-
tion gave 19.4 mg of nitrile 4a (40%).
P r oced u r e L. To a solution of 59.8 mg of amide 1a (0.341
mmol) and 0.119 mL of Et3N (0.853 mmol) in 1.37 mL of dry
CH2Cl2 at room temperature was added slowly 0.037 mL of
oxalyl chloride (0.426 mmol) via syringe. This solution was
stirred for 30 min before being quenched with 3 mL of brine.
Purification gave 16.7 mg of nitrile 4a (31%).
P r oced u r e C. To a solution of 52.5 mg of amide 1a (0.300
mmol), 0.165 g of Ph3P (0.630 mmol), and 0.129 mL of Et3N
(0.930 mmol) in 1.20 mL of dry CH2Cl2 at room temperature
was added 0.308 g of CBr4 (0.930 mmol). After the solution
was stirred for 15 h at rt, purification gave 31.1 mg of nitrile
4a (66%).
P r oced u r e D. To a solution of 82 mg of I2 (0.324 mmol) in
1.3 mL of dry CH2Cl2 was added PPh3 (0.330 mmol) until the
solution was colorless. To this solution was added 57.8 mg of
amide 1a (0.324 mmol). The solution was then stirred for 5
min at rt before the addition of 0.093 mL of Et3N (0.664 mmol)
via syringe. This solution was then stirred overnight. Puri-
fication gave 29.2 mg of nitrile 4a (56%).
P r oced u r e M. A solution of 50.9 mg of amide 1 (0.290
mmol), 1.5 mL of chloroform (0.2M), 6.6 mg of benzyltriethyl-
ammonium chloride (0.029 mmol), and 0.16 mL of 50% NaOH/
H2O was stirred overnight at room temperature. Purification
gave 17.8 mg of nitrile 2 (39%).
N-Allyl-2-p h en yla ceta m id e (1a ): IR (CH2Cl2) 3432, 3031,
1671, 1514 cm-1; 1H NMR (300 MHz, CDCl3) δ 7.38-7.22 (m,
5H), 5.83-5.60 (m, 2H), 5.10-5.00 (m, 2H), 3.83 (tt, 2H, J app
) 5.6, 1.6 Hz), 3.58 (s, 2H); 13C NMR (75 MHz, CDCl3) δ 170.9,
135.0, 134.2, 129.5, 129.1, 127.5, 116.1, 43.9, 42.0; MS (EI)
m/ e 175 (35), 118 (17), 93 (37), 91 (100), 84 (70), 65 (81). Anal.
Calcd for C11H13NO: C, 75.39; H, 7.48. Found: C, 75.43; H,
7.35.
P r oced u r e E. To a solution of 0.126 g of Ph3P-polymer
(∼3 mmol of Ph3P/g of polymer, 0.376 mmol) in 1.4 mL of CH2-
Cl2 was added slowly, via syringe, 0.018 mL of Br2 (0.351
mmol). To this solution was added 60.0 mg of amide 1a (0.342
mmol) and, after the reaction was stirred for 5 min, 0.105 mL
of Et3N (0.752 mmol). After the solution was stirred for 15 h
at rt, purification gave 22.6 mg of nitrile 4a (42%).
P r oced u r e F . A solution of 0.2230 g of I2 (0.879 mmol) in
0.5 mL of dry CH2Cl2 was titrated via syringe with triethyl
phosphite (0.153 mL, 0.894 mmol) until the solution was
colorless. This solution was transferred, via cannula, to a
solution of 51.3 mg of amide 1a (0.293 mmol) in 0.72 mL of
dry CH2Cl2. After being stirred for 5 min at rt, the solution
N-Allyl-3-p h en ylp r op a n a m id e (1b): IR (neat) 3296, 3079,
2929, 1647, 1545, 1260, 696 cm-1; 1H NMR (300 MHz, CDCl3)
δ 7.40-7.10 (m, 5H), 6.02 (br s, 1H), 5.82-6.68 (m, 1H), 5.10-
5.00 (m, 2H), 3.82 (tt, 2H, J app ) 5.7, 1.5 Hz), 2.95 (t, 2H, J )
7.8 Hz), 2.49 (t, 2H, J ) 7.8 Hz); 13C NMR (75 MHz, CDCl3) δ
172.0, 140.7, 134.0, 128.3, 128.1, 126.0, 116.0, 41.7, 38.2, 31.6;
MS (EI) m/ e 190 (9.32), 189 (44), 133 (13), 131 (23), 105 (86),
91 (93), 77 (73), 57 (100). Anal. Calcd for C12H15NO: C, 76.14;
H, 7.99. Found: C, 75.27; H, 8.01.
N-Allyl-2-p h en ylp r op a n a m id e (1c): IR (neat) 3293, 3075,
2978, 1651, 1546, 703 cm-1 1H NMR (300 MHz, CDCl3) δ
;
7.40-7.18 (m, 5H), 5.82-5.66 (m, 1H), 5.58 (br s, 1H), 5.06-
4.95 (m, 2H), 3.81 (tt, 2H, J app ) 5.6, 1.5 Hz), 3.58 (q, 1H, J )

Rearrangements of 3-Aza-1,2,5-hexatrienes
J . Org. Chem., Vol. 61, No. 1, 1996 61
7.2 Hz), 1.53 (d, 3H, J ) 7.2 Hz); 13C NMR (75 MHz, CDCl3)
δ 173.9, 141.3, 134.1, 128.8, 127.6, 127.2, 115.8, 47.0, 41.8, 18.4.
Anal. Calcd for C12H15NO: C, 76.14; H, 7.99. Found: C, 75.99;
H, 7.95.
2-Meth yl-2-p h en yl-4-p en ten en itr ile (4c). Procedure A
was used (60%): IR (neat) 2987, 2241, 1498, 1451, 927, 765,
698 cm-1; 1H NMR (300 MHz, CDCl3) δ 7.42-18 (m, 5H), 5.71-
5.55 (m, 1H), 5.12-5.01 (m, 2H), 2.65-2.46 (m, 2H), 1.64 (s,
3H); 13C NMR (75 MHz, CDCl3) δ 139.7, 131.8, 128.8, 127.8,
125.5, 123.1, 120.1, 46.26, 42.11, 26.5; MS (GC-E/I) m/ e 171
(18.68), 131 (10.06), 130 (100), 103 (40.30), 77 (13.62), 51 (4.71).
2,2-Dip h en yl-4-p en ten en itr ile (4d ). Amide 1d (158.7 mg,
0.830 mmol) was submitted to procedure A above. Purification
gave 107.4 mg of the nitrile (75%): IR (neat) 3062, 2237, 1493,
N-Allyl-2,2-d ip h en yla ceta m id e (1d ): IR (CH2Cl2) 3428,
1
3029, 1670, 1510 cm-1; H NMR (300 MHz, CDCl3) δ 7.38-
7.16 (m, 10H), 5.90-5.70 (m, 2H), 5.10-5.00 (m, 2H), 4.94 (s,
1H), 3.89 (tt, 2H, J app ) 5.6, 1.6 Hz); 13C NMR (75 MHz, CDCl3)
δ 171.8, 139.6, 134.2, 129.0, 128.9, 127.4, 116.4, 59.3, 42.2; MS
(GC-E/I) m/ e 251 (M+, 4), 168 (100), 152 (21), 41 (26). Anal.
Calcd for C17H17NO: C, 81.24; H, 6.82; N, 5.57. Found: C,
81.33; H, 6.85; N, 5.70.
1
1449, 697 cm-1; H NMR (300 MHz, CDCl3) δ 7.42-7.20 (m,
10H), 5.80-5.61 (m, 2H), 5.27-5.10 (m, 2H), 3.13 (dt, 2H, J app
) 6.8, 1.2 Hz); 13C NMR (75 MHz, CDCl3) δ 139.8, 131.9, 129.0,
128.1, 127.2, 122.1, 120.5, 51.8, 44.0; MS (GC-E/I) m/ e 233
(M+, 9), 192 (73), 165 (100). Anal. Calcd for C17H15N: C,
87.52; H, 6.48; N, 6.00. Found: C, 87.78; H, 6.46; N, 5.80.
2-(4-Meth oxyp h en yl)-4-p en ten en itr ile (4e). Amide le
(127.2 mg, 0.620 mmol) was submitted to procedure A above.
The standard pruification procedure gave 100.0 mg of the
nitrile (85%): IR (neat) 2961, 2241, 1513, 1256 cm-1; 1H NMR
(300 MHz, CDCl3) δ 7.24, 6.90 (ABq, 4H, J AB ) 8.9 Hz), 5.90-
5.69 (m, 1H), 5.24-5.11 (m, 2H), 3.80 (s, 3H), 2.66-2.53 (m,
N-Allyl-2-(4-m eth oxyp h en yl)a ceta m id e (1e): IR (CH2-
1
Cl2) 3428, 2936, 1670, 1513, 1249 cm-1; H NMR (300 MHz,
CDCl3) δ 7.18, 6.90, (app t ABq, 4H, J ) 2.6 Hz, J AB ) 8.8
Hz), 5.83-5.70 (m, 1H), 5.45 (br s, 1H), 5.09-5.00 (m, 2H),
3.87-3.80 (m, 2H), 3.81 (s, 3H), 3.55 (s, 2H); 13C NMR (75
MHz, CDCl3) δ 171.2, 158.8, 134.0, 130.5, 126.7, 115.9, 114.4,
55.2, 42.8, 41.8; MS (GC-E/I) m/ e 205 (M+, 17), 121 (100).
Anal. Calcd for C12H15NO2: C, 70.20; H, 7.37; N, 6.82.
Found: C, 70.07; H, 7.34; N, 6.52.
N-Allyl-2-(4-(tr iflu or om eth yl)p h en yl)a ceta m id e (1f): IR
(CH2Cl2) 3428, 3336, 2922, 1677, 1514, 1327, 1168, 1127 cm-1
;
2H);
13C NMR (75 MHz, CDCl3) δ 159.5, 132.8, 128.6, 127.3,
1H NMR (300 MHz, CDCl3) δ 7.61, 7.41 (ABq, 4H, J AB ) 8.2
Hz), 5.87-5.70 (m, 1H), 5.60 (br s, 1H), 5.13-5.05 (m, 2H),
3.89-3.83 (m, 2H), 3.63 (s, 2H); 13C NMR (75 MHz, CDCl3) δ
170.1, 139.3, 133.9, 129.7, 129.3, 125.7 (unresolved q, J ) 4
Hz), 124.2 (q, J ) 272 Hz), 116.4, 43.2, 42.2. Anal. Calcd for
C12H12F3NO: C, 59.26; H, 4.94; N, 5.76; MS (GC-E/I) m/ e 243
(M+, 17), 158 (70), 84 (53), 57 (35), 41 (100). Found: C, 59.03;
H, 4.93; N, 5.54.
120.7, 119.4, 114.5, 55.4, 40.0, 36.8; MS (GC-E/I) m/ e 187
(M+, 1), 158 (9), 91 (100), 65 (9).
2-(4-(Tr iflu or om et h yl)p h en yl)-4-p en t en en it r ile (4f).
Amide 1f (133.2 mg, 0.548 mmol) was submitted to procedure
A above. Purification gave 90.6 mg of the nitrile (73%): IR
(neat) 2926, 2243, 1326, 1168, 1128, 1069-1 1H NMR (300
;
MHz, CDCl3) δ 7.66, 7.47 (ABq, 4H, J AB ) 8.06 Hz), 5.90-
5.60 (m, 1H), 5.31-5.13 (m, 2H), 3.94 (t, 1H, J ) 7.08 Hz),
2.72-2.59 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 139.2, 132.0,
130.5, 128.0, 126.2 (unresolved q, J ) 3 Hz), 123.9 (q, J ) 273
Hz), 120.2, 119.8, 39.7, 37.5; MS (GC-E/I) m/ e 225 (M+, 98),
184 (100), 134 (80), 41 (99). Anal. Calcd for C12H10F3N: C,
64.00; H, 4.48; N, 6.22. Found: C, 63.96; H, 4.74; N, 6.07.
Meth yl 3-Cya n o-5-h exen oa te (4g). Procedure A was used
(69%): IR (neat) 2959, 2244, 1740, 1438, 1212, 1176 cm-1; 1H
NMR (300 MHz, CDCl3) δ 5.88-5.72 (m, 1H), 5.29-5.16 (m,
2H), 3.73 (s, 3H), 3.16-3.04 (m, 1H), 2.75-2.53 (m, 2H), 2.45-
2.36 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 170.1, 132.1, 120.5,
119.8, 52.2, 35.6, 27.1. Anal. Calcd for C8H11NO2: C, 62.71;
H, 7.24. Found: C, 62.64; H, 7.16.
Meth yl 3-(N-Allylca r ba m oyl)p r op a n oa te (1g): IR (neat)
3301, 3085, 2950, 1738, 1653, 1549, 1167 cm-1; 1H NMR (300
MHz, CDCl3) δ 6.26 (br s, 1H), 5.84-5.66 (m, 1H), 5.20-4.98
(m, 2H), 3.80 (tt, 2H, J app ) 5.7, 1.5 Hz), 3.62 (s, 3H), 2.61 (t,
2H, J ) 6.7 Hz), 2.45 (t, 2H, J ) 6.7 Hz); 13C NMR (75 MHz,
CDCl3) δ 173.3, 171.2, 134.0, 115.9, 51.6, 41.8, 30.6, 29.2; MS
(EI) m/ e 157 (17), 116 (100), 89 (23), 87 (21), 63 (18), 57 (44).
Anal. Calcd for C8H13NO3: C, 56.11; H, 7.66. Found: C, 55.04;
H, 7.86.
N-Allyl-5-br om op en ta n a m id e (1i): 1H NMR (300 MHz,
CDCl3) δ 6.15 (br s, 1H), 5.91-5.78 (m, 1H), 5.24-5.10 (m,
2H), 3.87 (tt, 2H, J app ) 5.7, 1.5 Hz), 3.43 (t, 2H, J ) 6.5 Hz),
2.26 (t, 2H, J ) 7.2 Hz), 1.97-1.74 (m, 4H); 13C NMR (75 MHz,
CDCl3) δ 172.5, 134.3, 116.4, 42.0, 35.5, 33.4, 32.2, 24.3.
N-Allyl-2-(ben zyloxy)a ceta m id e (1j): 1H NMR (300 MHz,
CDCl3) δ 7.40-7.28 (m, 5H), 6.72 (br s, 1H), 5.90-5.76 (m,
1H), 5.26-5.10 (m, 2H), 4.56 (s, 2H), 4.00 (s, 2H), 3.91 (tt, 2H,
J app ) 5.9, 1.5 Hz); 13C NMR (75 MHz, CDCl3) δ 169.4, 136.8,
134.0, 128.7, 128.3, 128.0, 116.4, 73.6. 69.5, 41.2. Anal. Calcd
for C12H15NO2: C, 70.22; H, 7.37; N, 6.82. Found: C, 69.82;
H, 7.47; N, 6.78.
N-Allyl-(2-m eth oxym eth oxy)a ceta m id e (1k ): IR (neat)
3336, 2934, 1666, 1538, 1152, 1115, 1055, 920 cm-1; 1H NMR
(300 MHz, CDCl3) δ 6.72 (br s, 1H), 5.94-5.77 (m, 1H), 5.28-
5.11 (m, 2H), 4.69 (s, 2H), 4.07 (s, 2H), 3.95 (tt, 2H, J app ) 5.7,
1.5 Hz), 3.40 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 169.2, 134.0,
116.5, 96.6, 67.1, 55.8, 41.2.
2-(3-Br om opr opyl)-4-pen ten en itr ile (4i). Amide 1i (145.9
mg, 0.663 mmol) was submitted to procedure B above. The
standard purification procedure gave 59.7 mg of the nitrile
(45%): IR (neat) 3085, 2946, 2871, 2240, 1649, 1442, 1250,
995, 922 cm-1 1H NMR (300 MHz, CDCl3) δ 5.88-5.73 (m,
;
1H), 5.23-5.15 (m, 1H), 3.43 (t, 2H, J ) 6.4 Hz), 2.69-2.57
(m, 1H), 2.36 (t, 2H, J ) 6.9 Hz), 2.20-1.88 (m, 2H), 1.88-
1.65 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 132.7, 121.1, 119.1,
36.1, 32.3, 30.7, 30.0, 29.8; MS (E/I) m/ e 203 (1.4), 202 (0.5),
201 (1.5), 122 (34), 95 (20), 94 (79), 81 (11), 80 (30), 53 (100).
Anal. Calcd for C8H12BrN: C, 47.76; H, 6.02. Found: C,
47.50; H, 5.84.
2-(Ben zyloxy)-4-p en ten en itr ile (4j). Amide 1j (59.3 mg,
0.288 mmol) was submitted to procedure F above. Purification
gave 21.8 mg of the nitrile (40%): 1H NMR (300 MHz, CDCl3)
δ 7.42-7.28 (m, 5H), 5.90-5.74 (m, 1H), 5.32-5.20 (m, 2H),
4.86, 4.54 (ABq, 2H, J AB ) 11.5 Hz, 1H), 4.19 (t, 1H, J ) 6.5
Hz), 2.61 (tt, 2H, J app ) 6.8, 1.2 Hz); 13C NMR (75 MHz, CDCl3)
δ 136.0, 130.8, 128.8, 128.7, 128.4, 120.2, 118.0, 72.4, 67.5, 37.8.
2-(Meth oxym eth oxy)-4-p en ten en itr ile (4k ) via P r oce-
d u r e F . Amide 1k (0.2570 g, 1.61 mmol) was submitted to
procedure F above. Purification gave 134.4 mg of the nitrile
(59%): 1H NMR (300 MHz, CDCl3) δ 5.92-5.76 (m, 1H), 5.34-
5.22 (m, 2H), 4.85, 4.68 (ABq, 2H, J AB ) 7.1 Hz), 4.41 (t, 1H,
N-Allyl-2-p h th a lyla ceta m id e (1l): 1H NMR (300 MHz,
DMSO-d6) δ 8.44 (br s, 1H), 7.96-7.81 (m, 4H), 5.87-5.69 (m,
1H), 5.19-5.00 (m, 2H), 4.21 (s, 2H), 3.70 (br t, 2H, J app ) 5.2
Hz); 1H NMR (300 MHz, CDCl3) δ 7.80 (m, 4H), 5.90-5.68 (m,
2H), 5.28-5.10 (m, 2H), 4.37 (s, 2H), 3.92 (tt, 2H, J app ) 5.7,
1.5 Hz); 13C NMR (75 MHz, DMSO-d6) δ 167.6, 165.9, 134.8,
134.5, 131.8, 123.2, 115.2, 40.9, 40.1. Anal. Calcd for
C13H12N2O3: C, 63.93; H, 4.95; N, 11.47. Found: C, 63.78; H,
4.95; N, 11.23.
J ) 6.6 Hz)), 3.42 (s, 3H), 2.61 (tt, 2H, J app ) 6.8, 1.2 Hz); 13
C
2-Ben zyl-4-p en ten en itr ile (4b). Procedure A was used
(67%): IR (neat) 3038, 2927, 2243, 1503, 1459, 924, 700 cm-1
;
NMR (75 MHz, CDCl3) δ 130.8, 120.4, 118.1, 95.7, 64.6, 56.4,
1H NMR (300 MHz, CDCl3) δ 7.30-7.12 (m, 5H), 5.85-5.68
(m, 1H), 5.20-5.06 (m, 2H), 2.90-2.70 (m, 3H), 2.33-2.24 (m,
2H); 13C NMR (75 MHz, CDCl3) δ 136.7, 132.5, 129.0, 128.7,
127.2, 121.2, 119.2, 37.6, 35.6, 33.5; MS (GC-E/I) m/ e 171
(2.31), 129 (4.66), 103 (2.21), 92 (13.82), 91 (100), 77 (4.34), 65
(9.44), 51 (3.91). Anal. Calcd for C12H13N: C, 84.16; H, 7.66.
Found: C, 83.81; H, 7.76.
38.0.
2-P h th alyl-4-pen ten en itr ile (4l) via P r ocedu r e B. Amide
1l (46.8 mg, 0.192 mmol) was submitted to procedure B above.
Purification gave 33.8 mg of the nitrile (78%): 1H NMR (300
MHz, CDCl3) δ 7.90-7.70 (m, 4H), 5.75-5.62 (m, 1H), 5.25-
5.10 (m, 3H), 3.00-2.80 (m, 2H); 13C NMR (75 MHz, CDCl3) δ
165.9, 134.7, 131.0, 130.2, 123.9, 121.1, 115.5, 39.1, 35.5. Anal.

62 J . Org. Chem., Vol. 61, No. 1, 1996
Walters et al.
Calcd for C13H10N2O3: C, 69.02; H, 4.46; N, 12.38. Found: C,
68.92; H, 4.52; N, 12.30.
Nitr ile 4l via P r oced u r e F . Amide 1l (56.2 mg, 0.231
mmol) was submitted to procedure F above, with the addition
of 0.002 mL of DMF. Purification gave 34.2 mg of the nitrile
(66%).
2H, J ) 5.4, 2.5 Hz), 2.95 (t, 2H, J ) 7.8 Hz), 2.49 (t, 2H, J )
7.8 Hz), 2.18 (t, 1H, J ) 2.6 Hz); 13C NMR (75 MHz, CDCl3) δ
172.2, 140.7, 128.5, 128.3, 126.2, 79.7, 71.4, 37.9, 31.5, 29.1.
Anal. Calcd for
C12H13NO: C, 76.98; H, 7.00; N, 7.48.
Found: C, 77.13; H, 7.07; N, 7.42.
2-Ben zyl-3,4-p en ta d ien en itr ile (15). Amide 14 (212.3
mg, 1.13 mmol) was submitted to procedure A above. Purifi-
cation gave 53.5 mg of the nitrile (28%): IR (neat) 3030, 2241,
N-Allyl-5-h yd r oxyp en ta n a m id e (5): IR (neat) 3294, 2936,
1642, 1551, 1421, 1263, 1065, 989, 922 cm-1 1H NMR (300
;
MHz, CDCl3) δ 6.60 (br s, 1H), 5.87-5.73 (m, 1H), 5.23-5.08
(m, 2H), 3.85 (app tt, 2H, J app ) 5.7, 1.5 Hz), 3.61 (t, 3H, J )
6.3 Hz), 2.26 (t, 2H, J ) 7.3 Hz), 1.80-1.50 (m, 4H); 13C NMR
(75 MHz, CDCl3) δ 173.6, 134.3, 116.2, 61.8, 42.0, 36.0, 32.0,
22.0.
1958, 1497, 1455, 858, 742, 701 cm-1 1H NMR (300 MHz,
;
CDCl3) δ 7.41-7.19 (m, 5H), 5.16 (app q, 1H, J app ) 6.6 Hz),
4.96 (d, 1H, J ) 6.8 Hz), 4.95 (d, 1H, J ) 7.1 Hz), 3.50-3.40
(m, 1H), 3.07-2.92 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 208.3,
136.4, 129.3, 128.9, 119.8, 87.0, 79.3, 39.2, 33.4; MS (GC-E/I)
m/ e 169 (M+, 1), 142 (44), 91 (100).
N-Allyl-2-(2-(h yd r oxym eth yl)p h en yl)a ceta m id e (6): IR
1
(CH2Cl2) 3435, 3299, 3079, 2872, 1652, 1523, 1013 cm-1; H
cis-4-ter t-Bu tyl-N-a llylcycloh exa n eca r boxa m id e (16a ):
NMR (300 MHz, CDCl3) δ 7.30-7.15 (m, 4H), 5.80-5.62 (m,
1H), 5.20 (t, 1H, J ) 5.5 Hz), 5.11-5.00 (m, 2H), 4.62 (d, 2H,
J ) 5.6 Hz), 3.81-3.72 (m, 2H), 3.62 (s, 2H); 13C NMR (75
MHz, CDCl3) δ 172.0, 139.5, 134.5, 133.8, 130.5, 130.4, 128.5,
127.7, 116.2, 63.5, 42.1, 40.6. Anal. Calcd for C12H15NO2: C,
70.22; H, 7.37; N, 6.82. Found: C, 70.49; H, 7.31; N, 7.10.
2-(2-(Br om om eth yl)ph en yl)-4-pen ten en itr ile (7). Amide
6 (44.4 mg, 0.216 mmol) was submitted to procedure B above,
with an extra equivalent of [Ph3PBr+]Br-, and gave 24.0 mg
IR (neat) 3314, 2940, 1652, 1532 cm-1 1H NMR (300 MHz,
;
CDCl3) δ 5.92-5.77 (m, 2H), 5.31-5.08 (m, 2H), 3.91 (app tt,
2H, J app ) 5.6, 1.5 Hz), 2.52-2.45 (m, 1H), 2.19-2.09 (m, 2H),
1.69-1.44 (m, 4H), 1.24 (qd, 2H, J ) 12.6, 3.5 Hz), 1.00 (tt,
1H, J ) 12.0, 3.1 Hz), 0.83 (s, 9H); 13C NMR (75 MHz, CDCl3)
δ 174.6, 134.6, 115.8, 48.0, 41.7, 39.2, 32.5, 28.5, 27.4, 23.6;
MS (GC-E/I) m/ e 223 (M+, 6), 166 (100), 57 (83), 41 (98). Anal.
Calcd for C14H25NO: C, 75.28; H, 11.28; N, 6.27. Found: C,
75.07; H, 11.49; N, 6.24.
of the nitrile (46%): IR (neat) 3062, 2237, 1493, 1449, 697 cm-1
.
Mixture of rotomers: 1H NMR (300 MHz, CDCl3) δ 7.58-7.28
(m, 4H), 5.98-5.80 (m, 1H), 5.36-5.20 (m, 2H), 4.68-4.44 (m,
2H), 4.20 (t, 1H, J ) 7.3 Hz)), 2.75-2.66 (m, 2H); 13C NMR
(75 MHz, CDCl3) δ 134.8, 134.7, 132.6, 131.3, 130.1, 128.9,
128.8, 120.4, 119.8, 43.7, 39.5, 39.2, 33.6, 30.4.
t r a n s-4-t er t -Bu t yl-N -a llylcycloh e xa n e ca r b oxa m id e
(16b): IR (CH2Cl2) 3445, 2944, 1668, 1510 cm-1; 1H NMR (300
MHz, CDCl3) δ 6.56 (br t, 1H, J ) 5.1 Hz), 5.90-5.75 (m, 1H),
5.20-5.06 (m, 2H), 3.85 (app tt, 2H, J app ) 5.7, 1.5 Hz), 2.11
(tt, 1H, J ) 12.2, 3.4 Hz), 1.99-1.80 (m, 4H), 1.56-1.39 (m,
2H), 1.06-0.96 (m, 3H), 0.84 (s, 9H); 13C NMR (75 MHz,
CDCl3) δ 176.2, 134.4, 115.5, 47.1, 45.2, 41.4, 32.2, 29.9, 27.3,
26.4; MS (GC-E/I) m/ e 223 (M+, 13), 166 (93), 57 (100), 41
(64). Anal. Calcd for C14H25NO: C, 75.28; H, 11.28; N, 6.27.
Found: C, 75.63; H, 11.52; N, 6.20.
2-P h en yl-N-(2-p r op yn yl)a ceta m id e (11): IR (CH2Cl2)
3434, 3302, 3031, 1675, 1508 cm-1; 1H NMR (300 MHz, CDCl3)
δ 7.39-7.21 (m, 5H), 6.02 (br s, 1H), 3.98 (q, 2H, J app ) 2.6
Hz), 3.56 (s, 2H), 2.18 (t, 1H, J ) 2.6 Hz); 13C NMR (75 MHz,
CDCl3) δ 170.9, 134.6, 129.5, 129.1, 127.5, 79.6, 71.6, 43.4, 29.4;
MS (GC-E/I) m/ e 173 (M+, 15), 92 (100), 65 (27), 39 (53). Anal.
Calcd for C11H11NO: C, 76.28; H, 6.40; N, 8.09. Found: C,
76.23; H, 6.44; N, 8.06.
Ack n ow led gm en t. Acknowledgement is made to
Dartmouth College and to the donors of The Petroleum
Research Fund, administered by the American Chemi-
cal Society, for the support of this work.
2-P h en yl-2,4-p en ta d ien en itr ile (13). Amide 11 (63.6 mg,
0.367 mmol) was submitted to procedure A above. Purification
gave 31.7 mg of the nitrile (56%) as a mixture of isomers: IR
(neat) 3061, 2216, 1450, 761, 692 cm-1
.
Major isomer: 1H
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra of compounds 1i, 1k , 4c, 4e, 4j, 4k , 5, 7, 13, and 15
(20 pages). This material is contained in libraries on micro-
fiche, immediately follows this article in the microfilm version
of the journal, and can be ordered from the ACS; see any
current masthead page for ordering information.
NMR (300 MHz, CDCl3) δ 7.64-7.56 (m, 2H), 7.46-7.32 (m,
3H), 7.24 (d, 1H, J ) 11.0 Hz) 7.10-6.60 (m, 1H), 5.85-5.50
(m, 2H). Mixture of isomers: 13C NMR (75 MHz, CDCl3) δ
144.1, 141.9, 133.7, 131.7, 129.6, 129.4, 129.2, 129.1, 129.0,
127.3, 126.5, 125.9; MS (GC-E/I) m/ e 155 (M+, 96), 154 (100),
140 (54), 127 (59), 115 (45).
3-P h en yl-(N-p r op yn yl)p r op a n a m id e (14): 1H NMR (300
MHz, CDCl3) δ 7.33-7.17 (m, 5H), 6.31 (br s, 1H), 3.99 (dd,
J O951587G