2-Azabicyclo[2.1.1]hexanes. 2. Substituent effects on the bromine-mediated rearrangement of 2-azabicyclo[2.2.0]hex-5-enes

Article abstract of DOI:10.1021/jo0015570

Methyl- and phenyl-substituted N-(ethoxycarbonyl)-2-azabicyclo[2.2.0]hex-5-enes 6 have been prepared by photoirradiation of appropriately substituted 1,2-dihydropyridines. Torquoselectivity is observed in the synthesis of the 3-endo-methyl- and 3-endo-phenyl-2-azabicyclo[2.2.0]hexenes 6c-e from 2-methyl- and 2-phenyl-1,2-dihydropyridines 5c-e. Products formed upon addition of bromine to 3-endo-, 4-, and 5-methyl- and 3-endo-phenyl-substituted N-(ethoxycarbonyl)-2-azabicyclo[2.2.0]hex-5-enes 6a-f were substituent dependent. For 6a,b, which lack substituents at C₃ or C₅, mixtures of unrearranged dibromides 8a,b and rearranged dibromides 9a,b were obtained. With the 3-endo-substituents in 6c-e, only rearranged dibromides 9c-e were formed; 5-methyl substitution afforded mainly unrearranged dibromide 8f and some allylic bromide 10. Both unrearranged 5-endo,6-exo-dibromo-2-azabicyclo[2.2.0]hexanes 8 and rearranged 5-anti-6-anti-dibromo-2-azabicyclo[2.1.1]hexanes 9 are formed stereoselectively. The dibromoazabicyclo[2.1.1]-hexanes 9 have been reductively debrominated to afford the first reported 2-azabicyclo[2.1.1]hexanes 11 with alkyl or aryl substituents at C-3.

Full text of DOI:10.1021/jo0015570

J . Org. Chem. 2001, 66, 1805-1810
1805
2-Aza bicyclo[2.1.1]h exa n es. 2. Su bstitu en t Effects on th e
Br om in e-Med ia ted Rea r r a n gem en t of 2-Aza bicyclo[2.2.0]h ex-5-en es
Grant R. Krow,*,† Yoon B. Lee,† Walden S. Lester,† Nian Liu,† J ing Yuan,† J ingqi Duo,†
Seth B. Herzon,† Yen Nguyen,† and David Zacharias‡
Department of Chemistry, Temple University, Philadelphia, Pennsylvania 19122, and The Institute for
Cancer Research, Fox Chase, Philadelphia, Pennsylvania 19111
grantkrow@aol.com
Received November 3, 2000
Methyl- and phenyl-substituted N-(ethoxycarbonyl)-2-azabicyclo[2.2.0]hex-5-enes 6 have been
prepared by photoirradiation of appropriately substituted 1,2-dihydropyridines. Torquoselectivity
is observed in the synthesis of the 3-endo-methyl- and 3-endo-phenyl-2-azabicyclo[2.2.0]hexenes
6c-e from 2-methyl- and 2-phenyl-1,2-dihydropyridines 5c-e. Products formed upon addition of
bromine to 3-endo-, 4-, and 5-methyl- and 3-endo-phenyl-substituted N-(ethoxycarbonyl)-2-
azabicyclo[2.2.0]hex-5-enes 6a -f were substituent dependent. For 6a ,b, which lack substituents
at C3 or C5, mixtures of unrearranged dibromides 8a ,b and rearranged dibromides 9a ,b were
obtained. With the 3-endo-substituents in 6c-e, only rearranged dibromides 9c-e were formed;
5-methyl substitution afforded mainly unrearranged dibromide 8f and some allylic bromide 10.
Both unrearranged 5-endo,6-exo-dibromo-2-azabicyclo[2.2.0]hexanes 8 and rearranged 5-anti-6-
anti-dibromo-2-azabicyclo[2.1.1]hexanes 9 are formed stereoselectively. The dibromoazabicyclo[2.1.1]-
hexanes 9 have been reductively debrominated to afford the first reported 2-azabicyclo[2.1.1]hexanes
11 with alkyl or aryl substituents at C-3.
In tr od u ction
substituent at C5 of the alkene 2 upon reaction outcomes.4
The results of these substituent effect studies are rel-
evant to projected syntheses of azabicyclic structures
related to 1, but containing multiple functional groups,
each one amenable to subsequent functionalization, for
formation of combinatorial libraries.5
The 2-azabicyclo[2.1.1]hexane ring system 1 has re-
cently been prepared by bromine-mediated rearrange-
ment of N-(alkoxycarbonyl)-2-azabicyclo[2.2.0]hex-5-ene
2.1 The latter structures 2 are conveniently prepared by
photoirradiation of N-(alkoxycarbonyl)-1,2-dihydropyr-
idines 3.2 The synthetic potential of this route to the
2-azabicyclo[2.1.1]hexane structure3 1 has prompted us
to investigate the influences of sterically demanding alkyl
substituents at C3 and C4 and a carbocation stabilizing
† Temple University.
‡ The Institute for Cancer Research.
(1) Krow, G. R.; Lee, Y. B.; Lester, W. S.; Christian, H.; Shaw, D.
A.; Yuan, J . J . Org. Chem. 1998, 63, 8558.
Resu lts a n d Discu ssion
(2) (a) Fowler, F. W. J . Org. Chem. 1972, 37, 1321. (b) Beecken, P.;
Bonfiglio, J . N.; Hasan, I.; Piwinski, J . J .; Weinstein, B.; Zollo, K. A.;
Fowler, F. W. J . Am. Chem. Soc. 1979, 101, 6677. (c) Kurita, J .; Iwata,
K.; Sakai, H.; Tsuchiya, T. Chem. Pharm. Bull. 1985, 33, 4572. (d)
Kurita, J .; Iwata, K.; Tsuchiya, T. Chem. Pharm. Bull. 1987, 35, 3166.
(e) Kurita, J .; Iwata, K.; Tsuchiya, T. J . Chem. Soc., Chem. Commun.
1986, 1188.
P r ep a r a tion of 2-Aza bicyclo[2.2.0]h ex-5-en es. Pyr-
idines 4a -c were reduced with sodium borohydride in
methanol in the presence of ethyl chloroformate according
to the procedure of Fowler2a-b to give the N-(ethoxycar-
bonyl)-1,2-dihydropyridines 5a , 5b, and 5f (Scheme 1).
Pyridines 4a ,b were admixed with MeMgBr,6a and pyri-
dine 4a was admixed with PhMgBr6b in the presence of
ethyl chloroformate to afford N-(ethoxycarbonyl)-1,2-
dihydropyridines 5c, 5d and 5e. Because of the difficulty
in purifying the 1,2-dihydropyridines 5, they were di-
(3) For routes to 2-azabicyclo[2.1.1]hexanes from substituted cy-
clobutylamines, see: (a) Stevens, C.; De Kimpe, N. J . Org. Chem. 1996,
61, 2174. (b) Gaoni, Y. Org. Prep. Proced. Int. 1995, 27, 185. (c) Park,
T. H.; Ha, Y. H.; J eong, D. Y. Patent application WO 98-KR246
19989898, Chem. Abstr. 1999, 130, 182388. For photochemical ring
closure of N-vinyl-N-allylamines to give 1-, 4-, or 5-substituted and
1,5- or 4,6-bridged 2-azabicyclo[2.1.1]hexanes, see: (d) Hughes, P.;
Clardy, J . J . Org. Chem. 1988, 53, 4793. (e) Hughes, P.; Martin, M.;
Clardy, J . Tetrahedron Lett. 1980, 21, 4579. (f) Pirrung, M. C.
Tetrahedron Lett. 1980, 21, 4577. (g) Tamura, Y.; Ishibashi, H.; Hirai,
M.; Kita, Y.; Ikeda, M. J . Org. Chem. 1975, 40, 2702. (h) Ikeda, M.;
Uchino, T.; Takahashi, M.; Ishibashi, H.; Tamura, Y.; Kido, M. Chem.
Pharm. Bull. 1985, 33, 3279. (i) Swindell, C. S.; Patel, B. P.; deSolms,
S. J .; Springer, J . P. J . Org. Chem. 1987, 52, 2346. (j) Schell, F. M.;
Cook, P. M.; Hawkinson, S. W.; Cassady, R. E.; Thiessen, W. E. J . Org.
Chem. 1979, 44, 1380. (k) Esslinger, C. S.; Koch, H. P.; Kavanaugh,
M. P.; Philips, D. P. Chamberlin, A. R.; Thompson, C. M. Bridges, R.
J . Bioorg. Med. Lett. 1998 8, 3101. (l) Piotrowski, D. W. Synlett 1999,
1091. For synthesis of 1,4-dimethyl-2-aza-3-oxobicyclo[2.1.1]hexane,
see: (m) Paquette, L. A.; Allen, G. R., J r. J . Am. Chem. Soc. 1971, 93,
4503.
(4) (a) Krow, G. R.; Lee, Y. B.; Raghavachari, R.; Szczepanski, S.
W. Tetrahedron 1991, 47, 8499. (b) Krow, G. R.; Raghavachari, R.;
Shaw, D. A.; Zacharias, D. E. Trends Heterocycl. Chem. 1990, 1, 1.
(5) (a) Lohse, A.; J ensen, K. B.; Bols, M. Tetrahedron Lett. 1999,
40, 3033. (b) Linn, J . A.; Gerritz, S. W.; Handlon, A. L.; Hyman, C. E.;
Heyer, D. Tetrahedron Lett. 1999, 40, 2227.
(6) (a) Krow, G. R.; Cannon, K. C.; Carey, J . T.; Lee, Y. B.;
Szczepanski, S. W.; Ramjit, H. G. J . Heterocycl. Chem. 1985, 22, 131.
(b) Krow, G. R.; Carey, J . T.; Zacharias, D. E.; Knaus, E. E. J . Org.
Chem. 1982, 47, 1989.
10.1021/jo0015570 CCC: $20.00 © 2001 American Chemical Society
Published on Web 02/15/2001

1806 J . Org. Chem., Vol. 66, No. 5, 2001
Krow et al.
Sch em e 1
F igu r e 1. Alternate electrocyclic ring closure pathways.
dihydropyridine 5c should have a pseudoaxial methyl
group at C2 pointed away from the ethoxycarbonyl
substituent.9 Photoexcitation of this conformation might
be followed by disrotatory twisting of vinyl protons Hb
and Hc either away from the C2 methyl group (anti) or
toward it (syn). Initially, Ha and Hb are at an angle close
to 30° in the 1,2-dihydropyridine 5c. Models indicate
these hydrogens have moved about 20° toward eclipsing
in the 3-endo-methyl cycloadduct 6c, but need to move
over 100° away from each other to form the stereoiso-
meric 3-exo-methyl stereoisomer 7. Also, models indicate
less movement of the 2-methyl group of 5c occurs as Hb
twists (about 40°) away from the pseudoaxial methyl
substituent at C2 in going to structure 6c via the anti
ring closure pathway. In the syn pathway leading to 7,
the 3-exo-methyl and Hb become nearly eclipsed, requir-
ing about 90°of twist of these groups compared to 5c.10
The structures of the 3-endo-4-dimethyl analogue 6d
(entry 4) and 3-endo-phenyl stereoisomer 6e (entry 5)
were assigned by analogy to 6c; their behavior upon
reaction with bromine is consistent with these stereo-
chemical assignments (Table 2, entries 4 and 5).
Ta ble 1. P h otocycliza tion of 1,2-Dih yd r op yr id in es 5 to
2-Aza bicyclo[2.2.0]h ex-5-en es 6
substituents
product(s)
entry
substratea
R1
R2
R3
(ratio)
yield (%)
1
2
3
4
5
6
5a
5b
5c
5d
5e
5f
H
H
H
H
H
Me
H
Me
H
Me
H
H
H
H
Me
Me
Ph
H
6a
6b
6c
6d
6e
6f
50
16
21
13
15
25
a
See ref 1.
Br om in a tion s of 2-Aza bicyclo[2.2.0]h ex-5-en es 6.
The results of the addition of bromine to the alkenes 6
at -5 °C in methylene chloride (eq 1) are shown in Table
2. The parent olefin 6a (entry 1) has previously been
shown to afford a 55:45 mixture of unrearranged 5-endo-
6-exo-dibromide 8a in addition to the rearranged 5-anti-
6-anti-dibromide 9a .1 The 1H NMR couplings for the
parent dibromides 8a and 9a are important in making
subsequent assignments of structure to the methyl
analogues. For dibromide 8a , the absence of coupling
between H1 and H6 is consistent with a nearly 90°
dihedral angle relationship for H1 and H6, which is
possible if H6 is endo oriented and the bromine is 6-exo.
The coupling of H5 with H6 (J ) 5.1 Hz) and with H4
(J ) 7.8 Hz) is consistent with a trans relationship
between H5 and H6 and a cis relationship for H5 and H4;
this requires a 5-endo bromine. For the rearranged
dibromide 9a , there is 4-bond coupling between H1 and
H4 (J ) 6.9 Hz) and an absence of coupling between H4
and its vicinal protons H3, H5, and H6. This result is
rectly irradiated in acetone to provide 2-azabicyclo[2.2.0]-
hex-5-enes 6, shown in Table 1.2a-d
Of especial interest in Table 1 is the stereochemical
assignment to the methyl group in structure 6c (entry
3), which followed from its 1H NMR spectrum. The H3
proton at δ 4.28 was a quintet (J ) 6 Hz), resulting from
its coupling with H4 and the adjacent methyl group.
Because H4 and the H3 endo proton (syn to the olefinic
bridge) have a dihedral angle near 90° and would not be
expected to show such a large coupling, H3 must be exo-
oriented (anti to the olefinic bridge); thus, the C3 methyl
group must be endo. Consistent with this assignment,
the corresponding 1H NMR couplings for the parent
structure 6a (entry 1) are J (H3 exo/H4) ) 7.2 Hz and J
(H3 endo/H4) ) 2.4 Hz.
The preference for formation of only the 3-endo-methyl
stereoisomer 6c is an example of torquoselectivity7 for
one of the possible disrotatory cyclizations of 1,2-dihy-
dropyridine 5c. In this kind of torquoselectivity (Figure
1), the alkyl group of interest is not attached directly to
the diene, but rather is one atom removed and is merely
attached to the ring tether. The stereochemical result is
explicable in terms of a least motion ring closure pathway
shown in Figure 1.8 The favored conformation of 1,2-
(8) March, J . Advanced Organic Chemistry, 4th ed.; J ohn Wiley &
Sons: New York, 1992; p 782. “Those reactions are favored which
involve the least change in atomic position and electronic configura-
tion.”
(9) Krow, G. R.; Raghavachari, Siatkowski, Chodosh, D. F. J . Org.
Chem. 1986, 51, 1916. In its crystalline form the 2-aryl substituent of
1-phenoxycarbonyl-2-p-chlorophenyl-1,2-dihydropyridine is approxi-
mately orthogonal to the plane of the diene.
(10) For an example of torquoselectivity preferences which place
allylic substituents exo in the cyclobutenes formed upon irradiation
of cyclohexa-1,3-dienes, see: Dauben, W. C.; Kellog, M. S. J . Am. Chem.
Soc. 1980, 102, 4456.
(7) Torquoselectivity refers to the twist or torsion preference in an
electrocyclic process. (a) Kirmse, Q.; Rondan, N. G.; Houk, K. N. J .
Am. Chem. Soc. 1984, 106, 7989. (b) Lopez, S.; Rey, J . G.; Rodriquez,
J .; de Lera, A. R. Tetrahedron Lett. 1995, 36, 4669. (c) Evanseck, J .
D.; Thomas IV, B. E.; Spellmeyer, D. C.; Houk, K. N. J . Org. Chem.
1995, 60, 7134.

Rearrangement of 2-Azabicyclo[2.2.0]hex-5-enes
J . Org. Chem., Vol. 66, No. 5, 2001 1807
Ta ble 2. P r od u cts F or m ed d u r in g Rea ction of
2-Aza bicyclo[2.2.0]h ex-5-en es 6 w ith Br om in e
The absence of coupling between bridgehead protons H1
or H4 and any of their vicinal hydrogens H3, H5, or H6 is
consistent with the H NMR of the parent 5-anti-6-anti-
1
dibromide 9a . Bromination of 3-endo,4-dimethyl olefin
6d (entry 4) gave a single dibromide 9d with a singlet
for H1 at δ 4.55 and a pair of doublets for H5 and H6 at
δ 4.23 and δ 3.97 (J ) 7.5 Hz). Similarly, 3-endo-phenyl
olefin 6e (entry 5) afforded the single rearranged dibro-
mide 9e, characterized by the mutually coupled doublets
for H4 and H1 at δ 3.30 and δ 4.76 (J ) 7.5 Hz).
The 5-methyl olefin 6f (entry 6) afforded mainly the
unrearranged dibromide 8f (eq 2). The exo stereochem-
istry of the methyl group at C5 was assigned on the basis
of NOE effects observed between H4 and the C5-Me
hydrogens. Allyl bromide 10 could be assigned the 6-exo-
bromo orientation on the basis of the absence of coupling
between H6 and H1, consistent with a 90° dihedral angle
for these hydrogens.
substituents
product(s)
entry
1
substratea
R1
H
R2
H
R3
H
(ratio)
yield (%)
6a
8a + 9a
(55:45)
8b + 9b
(27:73)
9c
61-78
2
6b
H
Me
H
73
3
4
5
6
6c
6d
6e
6f
H
H
H
H
Me
H
Me
Me
Ph
H
99
89
80
59
9d
9e
Me
H
8f + 10
(80:20)b
a
b
Z ) COOEt; see ref 1. 70:30 after chromatography.
Red u ctive Debr om in a tion s. Tributyltin hydride in
refluxing benzene removed the bromine atoms from
rearranged dibromides 9a -e to give azabicyclo[2.1.1]-
hexanes 11a -e in yields of 74-97% (eq 3).1 These are
the first examples of nonhalogenated 2-azabicyclo[2.1.1]-
hexanes to be alkyl or aryl substituted at C3.
consistent with dihedral angles close to 90° and anti
bromine orientations at C5 and C6.
Mech a n istic Discu ssion . An explanation for the
electrophilic bromination outcomes is depicted in Scheme
2.1 Addition of bromine to the open exo face of olefins 6
affords bromonium ions 12. Selective attack of bromide
at C5 on the endo face of 12 remote from the N-
ethoxycarbonyl group provides unrearranged dibromides
8. Competitively, neighboring group particpation by
nitrogen can lead to the formation of aziridinium ion 13.
Regioselective attack of bromide ion on intermediate 13,
at the C1 position farthest from the bromine at C5, gives
the rearranged dibromides 9.
Introduction of a methyl substituent at C4 in alkene
6b (Table 2, entry 2) results in an increase in the
rearranged 8/unrearranged 9 dibromide product ratio
relative to the unsubstituted parent alkene 6a (entry 1).
Relief of strain between the 4-methyl substituent and the
exo-bromonium ion bridge in intermediate 12 may drive
rearrangement to the aziridinium ion 13, the precursor
Bromination of 4-Me olefin 6b (entry 2) afforded a 27:
75 mixture of unrearranged dibromide 8b and rearranged
dibromide 9b. The dibromide 8b was assigned the 5-endo-
6-exo-dibromo stereochemistry because of the absence of
coupling between H1 and H6 and the coupling between
H5 and H6 (J ) 5.1 Hz), which were identical to that
1
found in the H NMR spectrum of the parent 5-endo-6-
exo-dibromide 8a . The rearranged dibromide 9b had a
singlet at δ 4.51 for H1, consistent with the absence of
coupling between H1 and H6 found in the parent 9a . The
13C NMR spectra of 9b consisted of eight lines; the single
carbon resonance at δ 56.0 for C5/C6 is consistent with
the symmetry of this isomer.
Bromination of 3-endo-methyl olefin 6c (entry 3) af-
forded dibromide 9c, which showed mutually coupled
doublets for H5 and H6 at δ 4.29 and δ 4.10 (J ) 7.5 Hz)
and also for H4 and H1 at δ 2.92 and δ 4.55 (J ) 7.2 Hz).12
(12) The structure of the 9c′ (R ) COOMe) the N-methoxycarbonyl
analogue of 9c was confirmed by X-ray structure analysis. Interest-
ingly, the nitrogen atom of 9c was found to deviate from planarity as
measured by θ ) 353.6°, where θ is the sum of the three valence angles
around nitrogen.13
(11) Tsuchiya and co-workers (refs 2c, 2d) have observed the same
torquoselectivity in the synthesis of 3-endo-phenyl-N-(benzyloxycar-
bonyl)-2-azabicyclo[2.2.0]hex-5-enes. The 3-phenyl stereochemistry was
assigned by these authors on the basis of a presumed shielding effect
on a neighboring methyl group by a 3-endo-phenyl substituent.2d The
reported coupling constants, J (H3/H4) ) 7 Hz for derived 3-aza-7-
oxatricyclo[4.1.0.02,5]heptanes and J (H3/H4) ) 8 Hz for derived 3,7-
diazatricyclo-[4.1.0.02,5]heptanes2c are consistent with an exo orienta-
tion of H3 and thus an endo orientation for the 3-phenyl groups.

1808 J . Org. Chem., Vol. 66, No. 5, 2001
Krow et al.
Sch em e 2
Yasuike have determined that the original stereochem-
ical assignments should be reversed on the basis of 400
MHz NMR coupling constants obtained at 50 °C to
remove the ambiguities of overlapping carbamate con-
formers.14 The proton H6 of the actual major isomer 15
at δ 4.14 showed only one large coupling (J ) 6.6 Hz)
consistent with an endo orientation for H6 and a 6-exo-
N-succinimidothio group. The proton H6 of the actual
minor isomer 16 at δ 4.60 appeared as a triplet (J ) 6.5
Hz) coupled to H1 and H5; this is consistent with an exo
orientation for H6 and a 6-endo-chloro substituent.
We attribute the preference for nucleophilic attack
upon bridged bromonium ion 12 and episulfonium ion 14
at C5 to the greater positive character at C5 compared to
that at C6 in these structures. The electron-withdrawing
2-aza-substituent inductively destabilizes a positive charge
at C6 with a resultant strengthening of the C6-hetereo-
atom bond.15 A steric effect due to the tetrahedral
carbamate substituent cannot be discounted, however.16
The episulfonium ion 14 is attacked to a minor extent
by chloride ion at C6, but it does not undergo intramo-
lecular nucleophilic attack by nitrogen, as does the
bromonium ion 12 to give aziridinium ion 13. This
suggests that the episulfonium ion is more stable than a
bridged aziridinium ion.
Sch em e 3
Con clu sion
A rearrangement route to 2-azabicyclo[2.1.1]hexanes
9 has provided the first examples of this ring system with
alkyl or aryl substitution at C3 and also with the
possibility of halogen functionality at C5 and C6. The
latter provide potential for further synthetic manipula-
tions.
of the rearrangement product 9b. Of greater significance
to the reaction outcome is the presence of the 3-endo-
substituents in alkenes 6c-e (Table 2, entries 3-5).
These groups block nucleophilic bromide ion attack on
the endo C5 position of intermediates 12. Bromide ion
attack from an endo direction at C6 on an exo bromonium
ion 12 is also blocked by the conformationally mobile
ethoxycarbonyl group on nitrogen. Thus, bromonium ion
12 converts to aziridinium ion 13. Attack of bromide ion
on aziridinium ion 13 occurs regioselectively at the less
hindered C1 position, which leads to the more stable
2-azabicyclo[2.1.1]hexane structures 9c-e. The prefer-
ence for rearranged product 9d from alkene 6d (entry 4)
is consistent with its provisional 3-endo-4-dimethyl ster-
eochemical assignment.
Exp er im en ta l P r oced u r es1
N-(Ethoxycarbonyl)-1,2-dihydropyridines 5a ,1 5c, and 5d ,6a
and N-(ethoxycarbonyl)-2-azabicyclo[2.2.0]hex-5-ene 6a have
been prepared previously.1 The N-(ethoxycarbonyl)-1,2-dihy-
dropyridines 5b and 5f were prepared according to the
procedure of Fowler.1 The N-(ethoxycarbonyl)-2-phenyl-1,2-
dihydropyridine 5e was prepared according to the literature
procedure for the N-benzyloxycarbonyl analogue.2c In ac-
cordance with the procedure of Tsuchiya,2c the 1,2-dihydro-
pyridines 5 were irradiated as crude mixtures because of their
ready decomposition during isolation by chromatography.
Brominations of alkenes 6 were carried out as described for
olefin 6a .1 Reductive debrominations were carried out as
described for dibromide 9a .1
A C5 methyl group (Table 2, entry 6) stabilizes positive
charge at C5 in intermediate 12, or its cationic equivalent,
and aziridinium ion 13 is not formed. Only unrearranged
dibromide 8f and allylic bromide 10 are observed. The
isomer ratios for all of the unrearranged/rearranged
dibromides 8/9 are kinetically determined, since the
purified dibromides are stable at 25 °C in CDCl3.
Tsuchiya and co-workers2c have reported that N-(meth-
oxycarbonyl)-2-azabicyclo[2.2.0]hex-5-ene (6g) reacts with
succinimide-N-sulfenyl chloride in CH2Cl2 to give two
adducts, found to have exo N-succinimidothio groups on
the basis of subsequent chemistry, in 57% and 10% yields
(Scheme 3). The minor adduct was assigned as the
5-endo-chloro-6-exo-N-succinimidothio stereoisomer 15,
and the major adduct was assigned the 6-endo-chloro-5-
exo-N-succinimidothio structure 16. Since the addition
shown in Scheme 3 presumably occurs via an episulfo-
nium ion 14 similar to the bromonium ion 12 in Scheme
2, the results of Tsuchiya were reinvestigated. Kurita and
Gen er a l P r oced u r e for P r ep a r a tion of N-(Eth oxyca r -
bon yl)-2-a za bicyclo[2.2.0]h ex-5-en es 6. Following the pro-
cedure of Fowler,2a,b a 5% solution of the 1,2-dihydropyridine
5 (3.3 mmol) in acetone (10 mL) was irradiated for 48 h in a
Rayonet photochemical reactor using RP-3000 lamps. After
(13) (a) Ohwada, T.; Achiwa, T.; Okamoto, I.; Shudo, K. Tetrahedron
Lett. 1998, 39, 865. (b) A slightly larger θ ) 356.6° has been observed
at the ring nitrogen of N-acetyl-2,4-methanoproline-N-methylamide
(proline ring numbering), which has been described as pyramidal.
See: Talluri, S.; Montelione, G. T.; van Duyne, G.; Piola, L.; Clardy,
J . Scheraga, H. A. J . Am. Chem. Soc. 1987, 109, 4473; Piela, L.;
Nemethy, G.; Scheraga, H. A. J . Am. Chem. Soc. 1987, 109, 4477.
(14) We thank J . Kurita and S. Yasuike, School of Pharmacy,
Hokuriku University, J apan, for this personal communication.
(15) The propensity for oxymercuration and PhSeCl additions to
N-(alkoxycarbonyl)-2-azabicyclo[2.2.2[oct-5-enes to add the electrophile
at C6 and the nucleophile at C5 has been noted: (a) Krow, G. R.; Fan,
D. M. J . Org. Chem. 1974, 39, 2674.
(16) The carbamate substituent of N-(methoxycarbonyl)-3-endo-(6-
chloro-3-pyridoxy)-methyl-2-azabicyclo[2.2.0]hex-5-ene has been shown
to be pyramidal by X-ray analysis: Tetrahedron 2000, 56, 9227. See
also ref 13.

Rearrangement of 2-Azabicyclo[2.2.0]hex-5-enes
J . Org. Chem., Vol. 66, No. 5, 2001 1809
removal of solvent in vacuo, chromatography of the residue
on basic alumina gave photoproducts 6.
was removed in vacuo to provide product oils, which were
chromatographed using 1:1 hexane/ether.
N-(Eth oxyca r bon yl)-2-a za bicyclo[2.2.0]h ex-5-en e (6a ).
Irradiation of 1,2-dihydropyridine 5a (500 mg, 3.3 mmol) for
24 h afforded 252 mg (50%) of photoproduct 6a (Rf ) 0.56, 1:1
hexane/ether): 1H NMR δ 1.23 (t, J ) 7.2 Hz, 3H), 3.39 (m,
1H), 3.48 (ddd, J ) 8.7, 2.4, 1.5 Hz, 1H), 3.94 (dd, J ) 8.7, 7.2
Hz, 1H), 4.11 (q, J ) 7.2 Hz, 2H), 4.81 (m, 1H), 6.49 (m, 2H);
13C NMR δ 14.5, 38,3, 49.6, 60.6, 65.5, 140.6, 142.9, 157.2;
HRMS m/z 153.0797, calcd for C8H11NO2, 153.0790.
P r ep a r a tion of N-(Eth oxyca r bon yl)-5-en d o-6-exo-d i-
b r om o-4-m et h yl-2-a za b icyclo[2.2.0]h exa n e (8b ) a n d N-
(Eth oxyca r bon yl)-5-a n ti-6-a n ti-d ibr om o-4-m eth yl-2-a za -
bicyclo[2.1.1]h exan e (9b). From 4-methyl-2-azabicyclo[2.2.0]-
hexene 6b (59 mg, 0.35 mmol) and bromine (56 mg, 0.35 mmol)
in CH2Cl2 (10 mL) there were obtained according to the general
procedure 22 mg (19%) of unrearranged dibromide 8b at Rf )
0.63 and 61 mg (54%) of rearranged dibromide 9b at Rf ) 0.55.
The dibromide 8b: 1H NMR δ 1.27 (t, J ) 7.2 Hz, 3H), 1.45
(s, 3H), 3.92 (d, J ) 9.3 Hz, 1H), 4.17 (q, J ) 7.2 Hz, 2H), 4.37
(d, J ) 5.1 Hz, 1H), 4.45 (s, 1H), 4.52 (d, J ) 9.3 Hz, 1H), 4.57
(1H, d, J ) 5.1 Hz, 1H); 13C NMR δ 14.6, 20.8, 44.1, 48.3, 57.6,
58.4, 62.2, 70.3, 155.6; HRMS m/z 325.9378, 327.9407, 329.9334,
calcd for C9H1479/79, 79/81, 81/81Br2NO2, 325.9391, 327.9371,
329.9350. The rearranged dibromide 9b: 1H NMR δ 1.27 (t,
J ) 7.2 Hz, 3H), 1.34 (s, 3H), 3.46 (s, 2H), 4.04 (s, 1H), 4.17
(q, J ) 7.2 Hz, 2H), 4.51 (s, 1H); 13C NMR δ 12.3, 14.6, 29.6,
54.5, 56.0, 61.8, 64.1, 155.0; HRMS m/z 325.9396, 327.9366,
329.9282, calcd for C9H1479/79, 79/81, 81/81Br2NO2, (M + H),
325.9391, 327.9370, 329.9350.
P r ep a r a tion of N-(Eth oxyca r bon yl)-5-a n ti-6-a n ti-d i-
br om o-3-m eth yl-2-azabicyclo-[2.1.1]h exan e (9c). From 3-en-
do-methyl-2-azabicyclo[2.2.0]hexene 6c (300 mg, 1.8 mmol)
and bromine (287 mg, 1.8 mmol) in CH2Cl2 (10 mL) there was
obtained according to the general procedure 580 mg (99%) of
rearranged dibromide 9c (Rf ) 0.49): 1H NMR δ 1.26 (t, J )
7.2 Hz, 3H), 1.41 (d, J ) 6.6 Hz, 3H), 2.92 (d, J ) 7.2 Hz, 1H),
4.10 (d, J ) 7.5 Hz, 1H), 4.15 (q, J ) 7.2 Hz, 2H), 4.29 (d, J )
7.5 Hz, 1H), 4.55 (d, J ) 7.2 Hz, 1H); 13C NMR δ 14.5, 18.0,
48.3, 52.4, 54.8, 58.1, 61.7, 66.8, 155.3; HRMS (EI) m/z
246.0124, 248.0149, calcd for C9H1379/81BrNO2 - Br, 246.0129,
248.0109.
N-(Eth oxyca r bon yl)-4-m eth yl-2-a za bicyclo[2.2.0]h ex-
5-en e (6b). According to Fowler’s procedure 3-picoline (30 g,
0.32 mmol) afforded 17.0 g (32%) of crude clear liquid 3-methyl-
1,2-dihydropyridine 5b (Rf ) 0.47, 4:1 hexane/ether): 1H NMR
δ 1.20 (t, J ) 7.2 Hz, 3H), 1.61 (s, 3H), 4.11 (m, 4H), 4.99 (m,
1H), 5.48 (m, 1H), 6.54 (m, 1H). Upon irradiation of crude 5b
(500 mg, 3.0 mmol), there was afforded 105 mg (16%) of
photoproduct 6b (Rf ) 0.51, 1:1 hexane/ether): 1H NMR δ 1.26
(t, J ) 7.2 Hz, 3H), 1.37 (s, 3H), 3.59 (d, J ) 8.4, 1.2 Hz, 1H),
3.66 (d, J ) 8.4 Hz, 1H), 4.13 (q, J ) 7.2 Hz, 2H), 4.48 (d, J )
3.3, 1.2 Hz, 1H), 6.44 (d, J ) 2.4 Hz, 1H), 6.49 (dd, J ) 3.3,
2.4 Hz, 1H); 13C NMR δ 14.6, 17.7, 46.5, 55.2, 60.6, 68.3, 137.6,
146.2, 157.1; HRMS m/z 167.0934, calcd for C9H13NO2, 167.0946.
N-(Eth oxyca r bon yl)-3-m eth yl-2-a za bicyclo[2.2.0]h ex-
5-en e (6c). Irradiation of 2-methyl-1,2-dihydropyridine 5c (500
mg, 3.0 mmol) afforded 105 mg (21%) of photoproduct 6c
(Rf ) 0.47, 1:1 hexane/ether): 1H NMR δ 1.25 (t, J ) 7.2 Hz,
3H), 1.33 (d, J ) 6.3 Hz, 3H), 3.51 (m, J ) 7.5, 7.5, 3.0, 1.8
Hz, 1H), 4.12 (q, J ) 7.2 Hz, 2H), 4.28 (qd, J ) 7.5, 6.3 Hz,
1H), 4.74 (dd, J ) 3.3, 3.0 Hz, 1H), 6.38 (dd, J ) 3.3, 2.4 Hz,
1H), 6.58 (dd, J ) 2.4, 1.8 Hz, 1H); 13C NMR δ 14.6, 16.0, 43.0,
56.1, 60.0, 63.0, 140.0, 142.7, 155.8; HRMS m/z 167.0945, calcd
for C9H13NO2, 167.0946.
N-(E t h oxyca r b on yl)-3-en d o-4-d im et h yl-2-a za b icyclo-
[2.2.0]h ex-5-en e (6d ). Irradiation of 2,3-dimethyl-1,2-dihy-
dropyridine 5d (500 mg, 2.76 mmol) afforded 65 mg (13%) of
photoproduct 6d (Rf ) 0.51, 1:1 hexane/ether): 1H NMR δ 1.26
(t, J ) 7.2 Hz, 3H), 1.29 (d, J ) 6.6 Hz, 3H), 1.34 (s, 3H), 3.94
(q, J ) 6.6 Hz, 1H), 4.13 (q, J ) 7.2 Hz, 2H), 4.39 (d, J ) 3.6
Hz, 1H), 6.36 (dd, J ) 3.6, 2.4 Hz, 1H), 6.53 (d, J ) 2.4 Hz,
1H); 13C NMR δ 14.7, 15.8, 17.7, 50.5, 60.4, 61.9, 65.6, 139.6,
144.0, CO lost; HRMS m/z 181.1104, calcd for C10H15NO2,
181.1105.
N-(Eth oxyca r bon yl)-3-en d o-p h en yl-2-a za bicyclo[2.2.0]-
h ex-5-en e (6e). Irradiation of crude 2-phenyl-1,2-dihydropyr-
idine 6e (8.79 g, 37 mmol)2c for 21 h afforded after chroma-
tography 941 mg (11%) of photoproduct 6e (Rf ) 0.43, 2:1
ether/hexane): 1H NMR δ 1.21 (t, J ) 7.0 Hz, 3H), 3.81 (d,
J ) 7.4 Hz, 1H), 4.10 (br, 2H), 4.98 (s, 1H), 5.26 (d, J ) 7.8
Hz, 1H), 6.00 (br, 1H), 6.59 (br, 1H), 7.29 (m, 5H); 13C NMR δ
44,6, 60.8, 63.1, 126.1, 127.1, 127.8, 128.5, 140.7, 141.9, 155.9;
HRMS m/z 230.1177, calcd for C14H16NO2 (M + H), 230.1181.
N-(Eth oxyca r bon yl)-5-m eth yl-2-a za bicyclo[2.2.0]h ex-
5-en e (6f). According to the general procedure, 4-picoline (30
g, 0.33 mmol) afforded 18.1 g (33%) of clear liquid 4-methyl-
1,2-dihydropyridine 5e (Rf ) 0.47, 4:1 hexane/ether): 1H NMR
δ 1.22 (t, J ) 7.2 Hz, 3H), 1.62 (s, 3H), 4.13 (s, 2H), 4.22 (s,
2H), 4.92 (m, 1H), 5.11 (m, 1H), 6.64 (m, 1H). Upon irradiation
of crude 5c (500 mg, 3.0 mmol), there was afforded 125 mg
(25%) of photoproduct 6c (Rf ) 0.40, 1:1 hexane/ether): 1H
NMR δ 1.27 (t, J ) 7.2 Hz, 3H), 1.84 (s, 3H), 3.22 (m, 1H),
3.42 (dd, J ) 8.7, 2.4 Hz, 1H), 3.85 (dd, J ) 8.7, 7.2 Hz, 1H),
4.08 (q, J ) 7.2 Hz, 2H), 4.63 (m, 1H), 6.16 (s, 1H); 13C NMR
δ 14.3, 14.9, 39.5, 48.7, 60.4, 61.8, 133.0, 153.5, 157.3; HRMS
m/z 167.0943, calcd for C9H13NO2, 167.0946.
Gen er a l P r oced u r e for Ad d ition of Br om in e to N-(Eth -
oxyca r bon yl)-2-a za bicyclo[2.2.0]h exen es 6b -f. The previ-
ously described procedure was followed1 in which a solution
of bromine (1 mmol) in CH2Cl2 (3 mL) was added dropwise to
a cold (-5 °C) solution of the alkene 6 (1 mmol) in CH2Cl2 (10
mL) under argon, and the resulting solution was stirred for 2
h and then allowed to come to room temperature and stirred
for an additional 16 h. The solution was diluted with ether
(25 mL), washed with 10% aqueous sodium bisulfite (10 mL)
and water (10 mL), dried over MgSO4, and filtered, and solvent
P r ep a r a tion of N-(Eth oxyca r bon yl)-5-a n ti-6-a n ti-d i-
br om o-3,4-d im eth yl-2-a za bicyclo[2.1.1]h exa n e (9d ). From
3-endo-4-dimethyl-2-azabicyclo[2.2.0]hexene 6d (100 mg, 0.55
mmol) and bromine (88 mg, 0.55 mmol) in CH2Cl2 (10 mL)
there was obtained according to the general procedure 168 mg
(89%) of rearranged dibromide 9d (Rf ) 0.66): 1H NMR δ 1.24
(s, 3H), 1.28 (t, J ) 7.2 Hz, 3H), 1.35 (d, J ) 6.3 Hz, 3H), 3.79
(q, J ) 6.3 Hz, 3H), 3.97 (d, J ) 7.5 Hz, 1H), 4.18 (q, J ) 7.2
Hz, 2H), 4.23 (d, J ) 7.5 Hz, 1H), 4.55 (s, 1H); 13C NMR δ
11.5, 14.5, 15.8, 52.8, 55.7, 57.5, 60.6, 61.6, 64.1, 155.4; HRMS
(EI) m/z 260.0284, 262.0251, calcd for C10H1579/81BrNO2 - Br,
260.0286, 262.0266.
P r ep a r a tion of N-(Eth oxyca r bon yl)-5-a n ti-6-a n ti-d i-
br om o-3-ph en yl-2-azabicyclo[2.1.1]h exan e (9e). From 3-en-
do-phenyl-2-azabicyclo[2.2.0]hexene 6e (114 mg, 0.50 mmol)
and bromine (80 mg, 0.50 mmol) in CH2Cl2 (13 mL) there was
obtained according to the general procedure 165 mg (85%) of
rearranged dibromide 9e (Rf ) 0.55, 2:1 ether/hexane): 1H
NMR δ 1.28 (br, 3H), 3.30 (d, J ) 7.5 Hz, 1H), 4.23 (m, 4H),
4.76 (d, J ) 7.5 Hz, 1H), 5.17 (s, 1H), 7.44 (m, 5H); 13C NMR
δ 1.5, 47.1, 51.5, 55.4, 62.2, 64.4, 66.9, 126.2, 127.8, 128.7,
137.4, 156.3; mp 187.5-189.0 °C (ether). HRMS (FAB) m/z
387.9572, calcd for C14H1679/79Br2NO2 (M + H), 387.9548.
P r ep a r a tion of N-(Eth oxyca r bon yl)-5-en d o-6-exo-d i-
br om o-5-exo-m eth yl-2-a za bicyclo[2.2.0]h exa n e (8f) a n d
N-(Eth oxyca r bon yl)-6-exo-br om o-5-m eth ylen e-2-a za bicy-
clo[2.2.0]h exan e (10). (Meth od A). From 5-methyl-azabicyclo-
[2.2.0]hexene 6f (221 mg, 1.32 mmol) and bromine (211 mg,
1.32 mmol) in CH2Cl2 (25 mL) there was obtained according
to the general procedure 172 mg of an oil with a minor
component 10 inseparable by column chromatography. Reflux
of the mixture in benzene (3 h) decomposed the minor
component, and chromatography gave 82 mg (43%) of unre-
arranged dibromide 8f at Rf ) 0.50: 1H NMR (70 °C) δ 1.27
(t, J ) 7.2 Hz, 3H), 2.00 (s, 3H), 3.07 (ddd, J ) 7.2, 4.5, 2.7
Hz, 1H), 4.15 (q, J ) 7.2 Hz, 2H), 4.28 (dd, J ) 9.6, 7.2 Hz,
1H), 4.46 (dd, J ) 9.6, 2.7 Hz, 1H), 4.54 (d, J ) 4.5 Hz, 1H),
4.93 (s, 1H); an NOE of 11% was observed for the peak at δ
3.07 (H4) upon irradiation of the methyl group at δ 3.00; 13C
NMR δ 14.6, 32.3, 44.6, 54.8, 55.6, 59.6, 61.5, 66.2, 155.3;
79/79,
HRMS m/z 325.9379, 327.9370, 329.9359, calcd for C9H14

1810 J . Org. Chem., Vol. 66, No. 5, 2001
Krow et al.
79/81,
81/81Br2NO2, (M + H), 325.9391, 327.9371, 329.9350.
1.32 (dd, J ) 10.5, 7.5 Hz, 1H), 1.57 (dd, J ) 10.2, 7.8 Hz,
1H), 1.76 (m, 1H), 1.88 (m, 1H), 2.51 (m, 1H), 3.80 (q, J ) 6.0
Hz, 1H), 4.18 (q, J ) 7.2 Hz, 2H), 4.39 (br, 1H); 13C NMR δ
14.6, 17.9, 36.4, 42.2, 43.8, 55.5, 60.4, 61.1, 156.7; HRMS (EI)
m/z 169.1105, calcd for C9H15NO2, 169.1093.
P r ep a r a t ion of N-(E t h oxyca r b on yl)-3,4-d im et h yl-2-
a za bicyclo[2.1.1]h exa n e (11d ). From dibromide 9d (252 mg,
0.74 mmol), AIBN (17 mg, 0.11 mmol), and tributyltin hydride
(596 µL, 2.22 mmol) there was obtained according to the
general procedure 115 mg (85%) of a clear oil 11d (Rf ) 0.60):
1H NMR δ 1.13 (s, 3H), 1.21 (t, J ) 7.2 Hz, 3H), 1.20 (bs, 3H),
1.37 (dd, J ) 10.2, 7.2 Hz, 1H), 1.47 (m, 1H), 1.57 (m, 1H),
1.61 (m, 1H), 3.42 (m, 1H), 4.08 (q, J ) 7.2 Hz, 2H), 4.25 (br,
1H); 13C NMR δ 14.7, 15.1, 16.0, 40.1, 46.7, 49.7, 57.9, 58.8,
60.4, 156.3; HRMS (EI) m/z 183.1273, calcd for C10H17NO2,
183.1260.
P r ep a r a tion of N-(Eth oxyca r bon yl)-3-p h en yl-2-a za bi-
cyclo[2.1.1]h exa n e (11e). From dibromide 9e (130 mg, 0.33
mmol), AIBN (6 mg, 0.04 mmol), and tributyltin hydride (250
µL, 270 mg, 0.93 mmol) there was obtained according to the
general procedure, after washing with concentrated aqueous
KF solution (5 mL), 57 mg (74%) of a clear oil 11e (Rf ) 0.40,
1:1 hexane/ether: 1H NMR δ 7.32 (m, 5H), 4.88 (s, 1H), 4.30
(d, J ) 6.6 Hz, 1H), 4.16 (d, J ) 5.7 Hz, 1H), 4.12 (br, 2H),
3.77 (br, 1H), 2.72 (d, J ) 6.6 Hz, 1H), 2.71 (d, J ) 7.5 Hz,
1H), 1.77 (dd, J ) 5.7, 7.5 Hz, 1H), 1.20 (m, 3H); 13C NMR δ
157.6, 140.7, 128.0, 126.7, 126.4, 62.8, 61.3, 61.0, 45.3, 42.5,
35.6, 14.7; HRMS m/z 232.1345, calcd for C14H18NO2 (M + 1)
232.1338.
(Meth od B). From 5-methylazabicyclo[2.2.0]hexene 6f (173
mg, 1.03 mmol) and bromine (160 mg, 1.0 mmol) in CH2Cl2
(15 mL) there was obtained according to the general procedure
310 mg of a 3.2-5.4:1 oily mixture of dibromide 6f and allylic
bromide 10. Column chromatography on silica gel (hexane:
ether 3:1) afforded 180 mg (59%) of a 2.1-2.7 mixture of 8f
and 10. (Meth od C). From alkene 6f (221 mg, 1.32 mmol) and
bromine (211 mg, 1.32 mmol) in THF (25 mL) after 14 h at 25
°C there was obtained after the usual workup and chroma-
tography 81 mg (25%) of a 1:7 mixture of dibromide 8f and
allylic bromide 10: 1H NMR (70 °C) δ 1.26 (t, J ) 7.2 Hz, 3H),
3.62 (dd, J ) 6.3, 4.2 Hz, 1H), 3.91 (d, J ) 8.1 Hz, 1H), 4.14
(q, J ) 7.2 Hz, 2H), 4.30 (dd, J ) 8.1, 6.3 Hz, 1H), 4.67 (d,
J ) 4.2 Hz, 1H), 4.97 (s, 1H), 5.27 (d, J ) 1.2 Hz, 1H), 5.40 (d,
J ) 1.2 Hz, H); 13C NMR δ 14.6, 39.2, 47.8, 54.9, 61.2, 67.4,
113.6, 116.2, 155.4; HRMS m/z 246.0130, calcd for C9H13
-
79BrNO2, (M + H), 246.0147.
Gen er a l P r oced u r e for Debr om in a tion s of 5,6-Di-
br om o-2-a za bicyclo[2.1.1]h exa n es 9. P r ep a r a tion of N-
(Eth oxycar bon yl)-4-m eth yl-2-azabicyclo[2.1.1]h exan es 11.
The previously described procedure1 was followed in which the
dibromide 9 (176 mg, 0.56 mmol) and 2,2′-azobis(2-methyl-
propionitrile) (AIBN) (90 mg, 0.54 mmol) were dissolved in
benzene (10 mL), the system was purged with argon for 15
min, tributyltin hydride (454 µL, 491 mg, 1.69 mmol) was
added through a rubber septum, and the resulting solution
was heated to 80 °C for 2 h. The reaction mixture was cooled
to room temperature, and the benzene was removed in vacuo
to give a residue that upon chromatography (10:1 hexane/
ether) gave compounds 11, Rf (1:1 hexane/ether).
Ack n ow led gm en t. We thank Temple University
and the National Institutes of Health grants CA-10925
and CA-06927 for support of this work and George
Kemmerer, Dan Hu, Askia Sheik, Alex Pak, and Vernon
Alford for assistance.
P r ep a r a tion of N-(Eth oxyca r bon yl)-4-m eth yl-2-a za bi-
cyclo[2.1.1]h exa n e (11b). From dibromide 9b (76 mg, 0.23
mmol), AIBN (3 mg, 0.02 mmol), and tributyltin hydride (213
mg, 0.73 mmol) there was obtained according to the general
procedure 36 mg (92%) of a clear oil 11b (Rf ) 0.40): 1H NMR
δ 1.22 (t, J ) 7.2 Hz, 3H), 1.26 (s, 3H), 1.41 (m, 2H), 1.62 (m,
2H), 3.12, (s, 2H), 4.10 (q, J ) 7.2 Hz, 2H), 4.31 (bs, 1H); 13C
NMR δ 14.7, 17.0, 45.1, 46.7, 53.9, 58.5, 60.7, 155.8; HRMS
(EI) m/z 169.1103, calcd for C9H15NO2, 169.1092.
P r ep a r a tion of N-(Eth oxyca r bon yl)-3-m eth yl-2-a za bi-
cyclo[2.1.1]h exa n e (11c). From dibromide 9c (415 mg, 1.27
mmol), AIBN (30 mg, 0.18 mmol), and tributyltin hydride
(1024 µL, 3.80 mmol) there was obtained according to the
general procedure 209 mg (97%) of a clear oil 11c (Rf ) 0.49):
1H NMR δ 1.22 (t, J ) 7.2 Hz, 3H), 1.28 (d, J ) 6 Hz, 3H),
Su p p or tin g In for m a tion Ava ila ble: The experimental
procedure, tables of the crystal data, bond lengths and angles,
atomic coordinates, and anisotropic thermal parameters ac-
company the ORTEP drawing for the N-(methoxycarbonyl)-
3-methyl-2-azabicyclo[2.1.1]hexane dibromide 9c′; 1H spectra
for the crude dihydropyridines 5 and 1H and 13C spectra for
other new structures. This material is available free of charge
via the Internet at http://pubs.acs.org.
J O0015570