The 2-(2-Azidoethyl)cycloalkanone strategy for bridged amides and medium-sized cyclic amine derivatives in the Aubé-Schmidt reaction

Article abstract of DOI:10.1055/s-0029-1219340

2-(2-Azidoethyl)cycloalkanones afford bridged lactams in the Aubé-Schmidt reaction, sometimes in excellent yield, and solvolysis yields derivatives of medium-ring amines. Attempts to divert the Schmidt reaction with an arene-mediated fragmentation of the normal Schmidt intermediate have led to an initial example. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1219340

LETTER
529
The 2-(2-Azidoethyl)cycloalkanone Strategy for Bridged Amides and
Medium-Sized Cyclic Amine Derivatives in the Aubé–Schmidt Reaction
2
-(2-Azidoeth
r
yl)cycloa
a
lkanone St
s
rategy for
e
Bridged A
m
r
ides Macleod, Stuart Lang, John A. Murphy*
WestCHEM, Dept. of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, UK
Fax +44(141)5484822; E-mail: John.Murphy@strath.ac.uk
Received 10 November 2009
Dedicated to Professor Gerry Pattenden on the occasion of his 70th birthday
come being determined by stereoelectronic effects. Nor-
mally the major product is the fused amide (as in
Scheme 1) but a recent discovery by Aubé illustrates how
to change the selectivity.6 Scheme 2 shows that when two
related substrates 7 and 10 react, the outcome can be
strongly influenced by an appropriately placed arene sub-
stituent in the substrate. The principal product from sub-
strate 7 is the fused heterocycle 8, resulting from a
reactive intermediate where the aminodiazonium group,
R2N–N2+ is equatorial (see inset in Scheme 2). Migration
of the antiperiplanar ring-junction bond leads to expulsion
of N2 and formation of 8 (the breaking and migrating
bonds are shown as bold lines in the reactive intermedi-
ates shown in Scheme 2). In substrate 10, the bridged
product 12 is the major product and arises from a reactive
intermediate with an axial aminodiazonium group. The
preference for the axial orientation arises from attractive
Abstract: 2-(2-Azidoethyl)cycloalkanones afford bridged lactams
in the Aubé–Schmidt reaction, sometimes in excellent yield, and
solvolysis yields derivatives of medium-ring amines. Attempts to
divert the Schmidt reaction with an arene-mediated fragmentation
of the normal Schmidt intermediate have led to an initial example.
Key words: Aubé, Schmidt, rearrangement, azide, heterocycle,
bridged amide, medium-ring amine, medium-ring amide
Over the past two decades, Aubé1 and Pearson2 have de-
veloped the scope of the Schmidt reaction3 remarkably
into an extremely useful reaction for synthesis.4 Aubé
concentrated largely on the reaction of alkyl azides with
ketones, for example, 1 (Scheme 1) and aldehydes,5 while
Pearson and co-workers explored the Schmidt reaction of
alkyl azides with tertiary carbocations generated from the
corresponding alcohol or alkene, for example, 4 in a pro-
cess that yields an iminium salt 6 which can then be re-
duced or deprotonated.
+
interactions between the R2N–N2 cation and the electron-
rich arene. Migration of the antiperiplanar bond leads to
the bridged amide 12 in this case. The proposals for cat-
ion-p interactions have been backed by computational
studies by Aubé.7
Aubé–Schmidt reaction
O
N2
N
H
or
HO
Very recently, this strategy has been extended beyond ar-
ene groups to sulfide groups.8 This use of electron-rich
substituents can drive these reactions towards preferential
or exclusive formation of bridged amide products.
N
Lewis acid
– N2
O
N3
3
1
2
Pearson–Schmidt reaction
H
Bridged amides have also been produced selectively in
some other special cases, notably in the preparation of
highly strained quinuclidine salt 14 by Stoltz et al.9 In this
case, the placement of the side chain b to the carbonyl
group in substrate 13 ensures that only bridged amide
products 14 and 15 could form, regardless of which bond
migrates.
R
N2
N
or
Lewis acid
R
R
N
– N2
OH
N3
6
4
5
R = alkyl, alkynyl, phenyl
We now suggest an alternative strategy for accessing
medium-ring amides, and medium-ring amine derivatives
resulting from their solvolyses. Medium-ring amines are
present in a large number of biologically important com-
pounds.10 Some of the bridged amides formed so far in
Schmidt reactions are highly strained and undergo solvo-
lysis to form medium-ring amine derivatives, while others
are less strained and need more vigorous conditions for
solvolysis.8,11
Scheme 1
The Aubé–Schmidt reaction proceeds via a cyclic inter-
mediate 2 that undergoes rearrangement with loss of nitro-
gen, N2. As shown in Scheme 2, two pathways are open
for the rearrangement involving migration of different
bonds and, when starting from a cycloalkanone, these lead
to fused amide or bridged amide, respectively, the out-
The substrates chosen for Schmidt reaction are very often
d-azidoketones, as in the examples in Schemes 1 and 2
above. It has been shown12 that when the azide group is
placed g and d to two potentially competing reactive ke-
SYNLETT 2010, No. 4, pp 0529–0534
Advanced online publication: 19.01.2010
DOI: 10.1055/s-0029-1219340; Art ID: D32209ST
© Georg Thieme Verlag Stuttgart · New York
0
1.
0
3.
2
0
1
0

530
F. Macleod et al.
LETTER
O
O
O
R
N
MeAlCl2
CH2Cl2
N
R
+
t-Bu
R
t-Bu
7, R = H
N3
t-Bu
9, 17%
12, 65%
8, 57%
11, 10%
10, R = 4-MeOC6H4
L.A.
t-Bu
t-Bu
O
H
N2
H
O
N
N
reactive intermediate from 7
8
L.A.
t-Bu
O
t-Bu
O
OMe
OMe
N
N2
N
reactive intermediate from 10
12
O
BF4
BF4
HBF4
+
N
N
Et2O, 20 °C
N3
H
H
O
O
13
14
15
76:24
Scheme 2
tones, then the d-azidocarbonyl grouping preferentially R = H, and (ii) with R = Ar. In the latter case, we wished
reacts. Aubé pointed out that g-ketoazides derived from to explore also whether in intermediates like 17 (R = Ar)
cycloalkanones fail to give the normal Schmidt product, the electronic push of the hydroxyl group that triggers the
probably due to the fact that that product would contain a migration could be diminished, perhaps through further
strained N-acylazetidine.1b Scheme 3 illustrates the point: protonation of the hydroxyl group in triflic acid or through
substrate 16 would afford reactive intermediate 17. As- association with a sufficiently strong Lewis acid. If the
suming that access to the appropriate conformation is push were sufficiently diminished, it might allow the elec-
available, migration of the ring-junction bond (shown in tron-rich arene (R = Ar) to divert the normal course of the
red) would afford an N-acylazetidine 19.
Schmidt rearrangement in favor of a fragmentation to a
macrocyclic dication 20 that could then be transformed to
a neutral amide product, for example, by tautomerism and
deprotonation.13 Dications like 20 might look like high
energy intermediates, but recent reports suggest that dica-
tions may be more prevalent in organic chemistry than
previously recognized.14
N3
N
O
OH2
Ar
R
H
H
16
20
Our search started with an examination of this last point
exclusively with substrate d-azidoketone 23, easily pre-
pared in two steps from the known indoline 21
(Scheme 4).15 This substrate bears an azidopropyl side
chain, as opposed to the azidoethyl chains in the examples
below, and was simply designed to test the relative frag-
mentation powers of the N-benzylindoline versus the tita-
nium-bound oxygen in 24 in this type of substrate. No
products resulting from fragmentation to a macrocycle 25
were seen. Instead, a combined 95% yield of the ring-
fused product 26 (78%) and the bridged lactam 27 (17%)
was formed. As with subsequent examples below, this
N2
N
O
OH
N
N
– N2
R
R
O
R
19
18
17
Scheme 3
With this information, we wondered about alternative out-
comes for the reaction of substrates like 16. Does the blue
bond migrate to form bridged amide 18? Our studies be-
low were undertaken for two types of substrate (i) with
Synlett 2010, No. 4, 529–534 © Thieme Stuttgart · New York

LETTER
2-(2-Azidoethyl)cycloalkanone Strategy for Bridged Amides
531
Cl
N3
O
O
O
H
H
KH
I(CH2)3Cl
NaN3
98%
63%
N
N
N
H
H
Bn
Bn
Bn
21
22
23
N2
N
N
OTiCln
OTiCln
TiCl4
X
N
N
H
H
Bn
Bn
24
25
– N2
O
N
N
+
N
N
O
Bn
26 78%
Bn
27 17%
Scheme 4
bridged lactam 27 gave a 13C carbonyl resonance (d = 184 ated by epoxide opening with aryl bromide 30 in the pres-
ppm) in the diagnostic 184–192 ppm region.1b
ence of a catalytic portion of CuI (Scheme 5). The
resulting alcohols 31 and 32 were oxidized with Dess–
Martin periodinane (DMP) to give ketones 33 and 34 that
were alkylated by sequential treatment with NaH and io-
doacetonitrile. The carbonyl groups in 35 and 36 were
We now proceeded to prepare 2-(2-azidoethyl)-cyclo-
alkanones to test the outcomes of their Schmidt reactions.
The synthesis of the initial substrates 41 and 42 was initi-
MgBr
OMe
30
CuI
MeO
MeO
O
OH
O
DMP
( )n
( )n
( )n
28, n = 1
29, n = 2
31, n = 1, 98%
32, n = 2, 97%
33, n = 1, 86%
34, n = 2, 88%
O
NC
NC
O
O
NaH
ICH2CN
ethylene glycol
TsOH
( )n
( )n
MeO
MeO
35, n = 1, 78%
36, n = 2, 94%
37, n = 1, 82%
38, n = 2, 81%
N3
N3
O
O
O
1. LiAlH4
2. TsN3, NaH
aq HCl (2 M)
MeOH
( )n
( )n
MeO
MeO
39, n = 1, 87%
40, n = 2, 67%
over 2 steps
41, n = 1, 97%
42, n = 2, 94%
Scheme 5
Synlett 2010, No. 4, 529–534 © Thieme Stuttgart · New York

532
F. Macleod et al.
LETTER
protected as the corresponding ketals and the nitrile some circumstances, compete with the normal Schmidt
groups reduced with LiAlH4 to give amines that were con- rearrangement.16
verted into the corresponding azides 39 and 40. Finally,
The reaction was repeated in triflic acid, thereby avoiding
deprotection of the ketals afforded the desired substrates
the need for an aqueous workup. Upon completion of ni-
41 and 42.
trogen evolution, anhydrous methanol was added to the
Treatment of ketoazide 42 with TiCl4 in CH2Cl2 afforded reaction to cleave the lactam bridge and afford an ester
bridged lactam 44 (97%) exclusively (Scheme 6). Evi- that would be easier to handle than the analogous carbox-
dently, the incorporation of an azidoethyl side chain had ylic acid. A mesylation step was also included to convert
indeed blocked formation of a fused bicyclic product. As the expected amine into a less polar sulfonamide. Pleas-
with example 23, no product resulting from fragmentation ingly, this revised protocol resulted in the isolation of
of the inter-ring bond, driven by the electron-releasing azepine 47 (22%) together with the azocinone 46 (26%).
aryl ring, was seen.
Until now, the study had involved ketones substituted
Attention was then turned towards the cyclopentanone ke- with aryl groups in the a-position. Bearing in mind the
toazide 41. In this case, the expected product 45 was not findings of Aubé on the key role of aryl groups in dictating
observed. As a water workup had been required to remove the outcome of Schmidt reactions, as discussed above,6a
the titanium byproducts, the suspicion was that any our next substrates were simple 2-(2-azidoethyl)cyclo-
bridged lactam that had formed had been easily hydro- alkanones 58 and 59 (Scheme 7); the synthesis of the de-
lyzed to the corresponding water-soluble amino acid. The sired ketoazides was completed using the same
greater strain associated with lactam 45 compared with 44 methodology as had been employed for ketoazides 41 and
would explain why 45 would undergo solvolysis more 42.
readily. However, azocinone 46 was isolated from this re-
2-(2-Azidoethyl)cyclopentanone (58) was treated with
action (37%). This corresponds to a diversion of the nor-
TfOH in CH2Cl2 at 0 °C using the same conditions used
mal Schmidt intermediate to a fragmentation pathway,
for the isolation of azepine 47. This gave sulfonamide 61
in an excellent 89% yield (Scheme 8). Similarly, 2-(2-azi-
doethyl)cyclohexanone (59) afforded sulfonamide 63
(94%). Accordingly, it seems that an aryl-ring substituent
akin to the proposed conversion of 17 into 20 (see
Scheme 6, inset). We have not yet performed a study of
the scope of such reactions, but the result clearly shows
that the fragmentation pathway driven by the arene can, in
was not needed for success in the formation of the bridged
lactams and their methanolysis products.
N2
N3
O
N
O
N
O
TiCln
TiCl4
– N2
Ar
Ar
Ar
44, 97%
42
43
Ar = 4-MeOC6H4
H
N
N3
N
O
O
O
TiCl4
+
CH2Cl2
0 °C
MeO
MeO
MeO
41
45, 0%
46, 37%
fragmentation pathway driven by arene
H
N2
N
O
N
O
N
O
TiCln
TiCln
MeO
MeO
MeO
46, 37%
Ms
N
H
N3
N
O
O
1. TfOH
2. MeOH
3. MsCl
+
O
OMe
MeO
MeO
MeO
41
47, 22%
46, 26%
Scheme 6
Synlett 2010, No. 4, 529–534 © Thieme Stuttgart · New York

LETTER
2-(2-Azidoethyl)cycloalkanone Strategy for Bridged Amides
533
ethylene glycol
O
MeCN
n-BuLi
OH
DMP
TsOH
O
CN
CN
( )n
( )n
( )n
48, n = 1
49, n = 2
50, n = 1, 49%
51, n = 2, 89%
52, n = 1, 61%
53, n = 2, 86%
O
O
O
1. LiAlH4
2. TsN3, NaH
aq. HCl (2 M)
MeOH
O
O
CN
( )n
( )n
( )n
N3
N3
54, n = 1, 71%
55, n = 2, 97%
56, n = 1, 49%
57, n = 2, 50%
58, n = 1, 99%
59, n = 2, 92%
Ts
N
N
O
1. MeOH
2. TsCl
O
TfOH
( )n
( )n
( )n
N3
O
58, n = 1
59, n = 2
60, n = 1
62, n = 2
OMe
61, n = 1, 89%
63, n = 2, 94%
Scheme 7
NaN3, DMF
complex example. Ketoazide 70 was identified as a suit-
able target. The desired substrate was readily prepared by
elaboration of trans-decalone 68 into the desired ke-
toazide using methodology developed by Vaultier and co-
workers,17 who have previously demonstrated that carb-
anions derived from N,N-dimethylhydrazones18 can be
alkylated with b-iodoazides (Scheme 8). The iodoazide
67, required for the subsequent alkylation step, was pre-
pared in three steps: the azido alcohol 65 was formed by
reaction of 2-chloroethanol (64) and NaN3 in DMF. Con-
version of 65 into tosylate 66 and treament with NaI gave
iodoazide 67. Alkylation of the N,N-dimethylhydrazone
69, derived from trans-1-decalone (68), afforded the azi-
doethyl product. Hydrolysis of the hydrazone group gave
the substrate 70 (33% over 3 steps). Reaction with triflic
acid, followed by methanolysis and tosylation provided
the expected eight-membered-ring product 71 in 79%
yield.19
Cl
Y
HO
X
65, X = OH, Y = N3, 96%
66, X = OTs, Y = N3, 65%
67, X = I, Y = N3, 81%
64
TsCl
NaI
NMe2
1. BuLi
N
O
H
H
H
2. I(CH2)2N3
3. aq HCl (2 M), MeOH
NH2NMe2, TsOH
H
68
69, 69%
Ts
O
H
1. TfOH
2. MeOH
3. TsCl
H
N
N3
O
H
H
OMe
70, 33%
over 3 steps
71, 79%
Scheme 8
Finally, we explored this methodology for the formation
of a nine-membered-ring product. Cycloheptanone hydra-
zone (73) was treated with base and alkylated with io-
doazide 67 to form ketoazide 74, following hydrolysis of
the hydrazone under mildly acidic conditions.
With this success in forming an eight-membered ring
product from a simple azidoethylcyclohexanone, we ex-
plored whether similar success could be found in a more
N3
NMe2
N
O
O
1. BuLi
2. I(CH2)2N3
NH2NMe2, TsOH
3. aq HCl (2 M), MeOH
72
73, 86%
74, 43%
Ts
N
O
N
TfOH, CH2Cl2,
0 °C, 2 h
1. TfOH, MeOH,
reflux, 64 h
2. TsCl, Et3N, DMAP,
CH2Cl2, r.t., 18 h
O
OMe
76, 83%
75, 41%
Scheme 9
Synlett 2010, No. 4, 529–534 © Thieme Stuttgart · New York

534
F. Macleod et al.
LETTER
On treatment of 74, bridged lactam 75 was isolated in
41% yield. Returning to efforts to solvolyze this bridged
amide, 75 was heated in methanol under reflux in the pres-
ence of TfOH for a period of 64 hours, followed by a to-
sylation step afforded nine-membered-ring product 76 in
83% overall yield (Scheme 9).
References and Notes
(1) (a) Aubé, J.; Milligan, G. L. J. Am. Chem. Soc. 1991, 113,
8965. (b) Milligan, G. L.; Mossman, C. J.; Aubé, J. J. Am.
Chem. Soc. 1995, 117, 10449. (c) Huh, C. W.; Somal, G. K.;
Katz, C. E.; Pei, H.; Zeng, Y.; Douglas, J. T.; Aubé, J. J. Org.
Chem. 2009, 74, 7618. (d) See also:Kumar, P. S.; Kapat, A.;
Baskaran, S. Tetrahedron Lett. 2008, 49, 1241.
(2) (a) Pearson, W. H.; Hutta, D. A.; Fang, W. K. J. Org. Chem.
2000, 65, 8326. (b) Pearson, W. H.; Schkeryantz, J. M.
Tetrahedron Lett. 1992, 33, 5291. (c) Pearson, W. H.;
Walavalkar, R.; Schkeryantz, J. M.; Fang, W. K.;
Blickensdorf, J. D. J. Am. Chem. Soc. 1993, 115, 10183.
(d) See also:Reddy, P. G.; Baskaran, S. J. Org. Chem. 2004,
69, 3093. (e) Kapat, A.; Nyfeler, E.; Giuffredi, G. T.;
Renaud, P. J. Am. Chem. Soc. 2009, 131, DOI: 10.1021/
ja908933s.
In summary, it has been demonstrated that the normal
mechanistic pathway of the Aubé–Schmidt reaction can
be diverted to selectively form bridged lactams in an effi-
cient manner when a 2-(2-azidoethyl)cycloalkanone is
used. In this case, the normal fused ring product would in-
corporate an azetidine, and the strain associated with the
formation of this small ring renders the alternative path-
way to the bridged amide product more efficient.
(3) Schmidt, K. F. Ber. Dtsch. Chem. Ges. 1924, 57, 704.
(4) For reviews, see: (a) Lang, S.; Murphy, J. A. Chem. Soc.
Rev. 2006, 35, 146. (b) Nyfeler, E.; Renaud, P. Chimia
2006, 60, 276. (c) Grecian, S.; Aubé, J. In Organic Azides:
Synthesis and Applications; Bräse, S.; Banert, K., Eds.;
Wiley-VCH: Weinheim, 2009, 191. (d) Bräse, S.; Gil, C.;
Knepper, K.; Zimmermann, V. Angew. Chem. Int. Ed. 2005,
44, 5188.
(5) Lee, H. L.; Aubé, J. Tetrahedron 2007, 63, 9007.
(6) (a) Yao, L.; Aubé, J. J. Am. Chem. Soc. 2007, 129, 2766.
(b) Ribelin, T.; Katz, C. E.; English, D. G.; Smith, S.;
Manukyan, A. K.; Day, V. W.; Neuenswander, B.; Poutsma,
J. L.; Aubé, J. Angew. Chem. Int. Ed. 2008, 47, 6233.
(c) Katz, C. E.; Aubé, J. J. Am. Chem. Soc. 2003, 125, 13948.
(7) Katz, C. E.; Ribelin, T.; Withrow, D.; Basseri, Y.;
Manukyan, A. K.; Bermudez, A.; Nuera, C. G.; Day, V. W.;
Powell, D. R.; Poutsma, J. L.; Aubé, J. J. Org. Chem. 2008,
73, 3318.
Experimental Section (see Supplementary Information file for
details of other experimental procedures and supporting data).
Typical Procedure for Schmidt Reactions
To a solution of 2-(2-azidoethyl)-2-(4-methoxy-phenyl)cyclohex-
anone (42) (0.10 g, 0.37 mmol, 1.0 equiv) in CH2Cl2 (5 mL) at 0 °C
was added dropwise TiCl4 (0.08 ml, 0.74 mmol, 2.0 equiv). This
mixture was stirred allowed to warm to r.t. and was stirred for 16 h.
The reaction was diluted by the addition of CH2Cl2 (15 mL) and
NaOH solution (2 M, 10 mL). This mixture was stirred vigorously
for 30 min. The organic phase was separated, washed with NaOH
solution (2 × 10 mL) and with sat. brine solution (2 × 20 mL). The
organic extracts were combined, dried over anhyd Na2SO4, filtered,
and concentrated at reduced pressure. The crude product was puri-
fied by column chromatography (PE and EtOAc in a 10:1 ratio and
increasing level of EtOAc during elution before changing to CH2Cl2
and MeOH in a 50:1 ratio and gradually increasing level of MeOH
during elution).
(8) Szostak, M.; Yao, L.; Aubé, J. Org. Lett. 2009, 11, 4386.
(9) Tani, K.; Stoltz, B. M. Nature (London) 2006, 441, 731.
(10) Evans, P. A.; Holmes, A. B. Tetrahedron 1991, 47, 9131.
(11) (a) Lei, Y.; Wrobleski, A. D.; Golden, J. E.; Powell, D. R.;
Aubé, J. J. Am. Chem. Soc. 2005, 127, 4552. (b) Szostak,
M.; Aubé, J. Org. Lett. 2009, 11, 3878. (c) Szostak, M.;
Yao, L.; Aubé, J. J. Org. Chem. 2009, 74, 1869.
(12) Iyengar, R.; Schildknegt, K.; Aubé, J. Org. Lett. 2000, 2,
1625.
(13) For an alternative recent fragmentation route to macrocyclic
amides, see: Murphy, J. A.; Mahesh, M.; McPheators, G.;
Anand, R. V.; McGuire, T. M.; Carling, R.; Kennedy, A. R.
Org. Lett. 2007, 9, 3233.
(14) (a) Corr, M.; Gibson, K.; Kennedy, A. R.; Murphy, J. A.
J. Am. Chem. Soc. 2009, 131, 9174. (b) Corr, M. J.;
Roydhouse, M. D.; Gibson, K. F.; Zhou, S.-Z.; Kennedy,
A. R.; Murphy, J. A. J. Am. Chem. Soc. 2009, 131, DOI:
10.1021/ja908191k.
(15) Benchekroun-Mounir, N.; Dugat, D.; Gramain, J.-C.;
Husson, H.-P. J. Org. Chem. 1993, 58, 6457.
6-(4-Methoxyphenyl)-1-azabicyclo[4.2.1]nonan-9-one (44) was
isolated as a colorless oil (0.09 g, 97%). ESI-HRMS: m/z [M + H]+
calcd for C15H20N1O2: 246.1489; found: 246.1488. IR (neat): 3040
(m), 2945 (s), 2901 (s), 2838 (m), 1705 (s), 1611 (m), 1519 (s), 1443
(s), 1380 (s), 1295 (s), 1251 (s), 1205 (m), 1185 (s), 1087 (m), 1032
(s), 890 (m), 835 (s), 761 (m) cm–1. 1H NMR (400 MHz, CDCl3):
d = 1.80–1.99 (6 H, m, CH2), 2.23–2.39 (2 H, m, CH2), 2.83 (1 H,
m, CH2), 3.30 (1 H, dt, J = 10.9, 8.8 Hz, CH2), 3.57 (1 H, ddd,
J = 10.9, 9.5, 1.8 Hz, CH2), 3.83–3.86 (4 H, m, CH2 and OCH3),
6.89 (2 H, m, ArH), 7.46 (2 H, m, ArH). 13C NMR (100 MHz,
CDCl3): d = 24.2 (CH2), 24.9 (CH2), 32.2 (CH2), 40.1 (CH2), 47.4
(CH2), 48.3 (CH2), 53.4 (C), 55.5 (CH3), 113.9 (CH), 128.2 (CH),
135.1 (C), 158.4 (C), 187.7 (C). LRMS (CI): m/z (%) = 263 (38) [M
+ NH4]+, 246 (100).
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
(16) For interception of alternative azide rearrangements by
arenes, see: Lang, S.; Kennedy, A. R.; Murphy, J. A.; Payne,
A. H. Org. Lett. 2003, 5, 3655.
(17) Khoukhi, M.; Vaultier, M.; Carrié, R. Tetrahedron Lett.
1986, 27, 1031.
Acknowledgment
We thank the EPRSC and the University of Strathclyde for funding
and the EPRSC National Mass Spectrometry Service Centre,
Swansea for mass spectra.
(18) (a) Corey, E. J.; Enders, D. Chem. Ber. 1978, 111, 1337.
(b) Corey, E. J.; Enders, D. Chem. Ber. 1978, 111, 1362.
(19) These compounds were isolated as single isomers. The most
likely stereochemistry of alkylation of the decalone enolate
would afford 70 and methanolysis would convert this into
71.
Synlett 2010, No. 4, 529–534 © Thieme Stuttgart · New York