Ring transformations of 2,3-dihydroisoxazoles via azomethine ylides - Formation of annulated 5- and 7-membered N-heterocycles

Article abstract of DOI:10.1016/S0040-4020(01)00322-2

On thermal activation the 2,3-dihydroisoxazoles 12-14 are transformed into annulated dihydroazepines 15-17 as main products, besides minor amounts of the corresponding pyrrole derivatives 18-20. In the proposed mechanism the azomethine ylides of type III and VI are involved as intermediates which undergo 1,5- and 1,7-ring closure reactions, respectively.

Full text of DOI:10.1016/S0040-4020(01)00322-2

TETRAHEDRON
Pergamon
Tetrahedron 57 42001) 4349±4358
Ring transformations of 2,3-dihydroisoxazoles via azomethine
ylidesÐformation of annulated 5-
and 7-membered N-heterocyclesq
Wolfgang Friebolin and Wolfgang Eberbachp
Institute of Organic Chemistry and Biochemistry, University of Freiburg, Albertstrasse 21, D-79104 Freiburg, Germany
Received 24 February 2001; accepted 13 March 2001
AbstractÐOn thermal activation the 2,3-dihydroisoxazoles 12±14 are transformed into annulated dihydroazepines 15±17 as main products,
besides minor amounts of the corresponding pyrrole derivatives 18±20. In the proposed mechanism the azomethine ylides of type III and VI
are involved as intermediates which undergo 1,5- and 1,7-ring closure reactions, respectively. q 2001 Elsevier Science Ltd. All rights
reserved.
1. Introduction
also evidence for the appearance of aziridines have been
obtained 4Scheme 2).4
Among the various reduced isoxazole derivatives, the
2,3-dihydroisoxazoles belong to the less common isomers
because of their notorious chemical instability under many
conditions.2 Besides decomposition material, the mainly
isolated products are, if at all, pyrroles, 4-oxazolines, acyl
aziridines and acyclic enamines, respectively, the kind and
ratio of the products depending strongly on the substitution
pattern.3 However, as a common feature of many of these
reactions the transformations are initiated by NO-cleavage
and subsequent rebonding affording acyl aziridines which
react further by ring opening to give azomethine ylides, the
supposedly precursors of the observed variety of products
4Scheme 1).2,3
The transient formation of azomethine ylides during
reactions of those heterocycles prompted us to evaluate
the potential of 2,3-dihydroisoxazoles as precursor of
azomethine ylides. In particular, investigations were
performed that should allow 1,5- and/or 1,7-dipolar cycli-
zation reactions of the intermediate conjugated dipole
species as deactivation pathways.5
In earlier work we have shown that on photochemical acti-
vation of acyl-isoxazolines of type 1 the corresponding
doubly stabilized azomethine ylides 2 can be isolated, and
Scheme 2.
Scheme 1.
q Part 5 in the series `The pyrido[1,2-a]azepine system', for Part 4 see Ref. 1.
Keywords: 2,3-dihydroisoxazoles; azepines; azomethine ylides; dipolar cyclizations.
Corresponding author. Fax: 149-761-203-6064;
p
e-mail: eberbach@organik.chemie.uni-freiburg.de
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020401)00322-2

4350
W. Friebolin, W. Eberbach / Tetrahedron 57-2001) 4349±4358
Scheme 4.
an autoclave.11 After puri®cation of the reaction mixture by
¯ash chromatography the product analysis revealed, besides
higher molecular material, two monomeric products in each
case. On the basis of the analytical and spectroscopic data
the structure of the main products was identi®ed as the
isomeric bicyclic dihydroazepine systems 15±17, whereas
the minor components turned out to be the 1,2-annulated
pyrroles 18±20, which differ fromthe starting isoxazolines
in the formal loss of a CH4 unit; the yields are given in Table
1. For the structure elucidation of the reaction products
special NMR techniques have been applied including
HMBC spectra.12
Scheme 3. i: R±CxC±CHO, CH2Cl2 or Et2O, r.t. ii: CH2yCH±CH2±MgBr,
THF/Et2O, 08C. iii: CH3SO2Cl, NEt3, DMAP, 2788C.
2. Results and discussion
Here we present results of our studies with 2,3-dihydro-
isoxazoles bearing a butadienyl group at C-3 4Scheme 3).
The heterocyclic ring was constructed by 1,3-dipolar
cycloaddition of the known cyclic nitrones 3±5 with phenyl
and tert-butyl propiolic aldehyde, respectively. As predicted
by FMO theory and found experimentally in other cases,6,7
only the shown regioisomers 6±8 were formed. The further
functionalization included Grignard reactions with allyl
magnesium bromide affording the secondary alcohols
9±11 as diastereomeric mixtures8 which were ®nally trans-
formed into the isoxazolines 12a,b±14a,b by water elimi-
nation.9 The yields for most steps were between 70 and
90%, with the exception of 6b 455%), 12b 464%), 14a
458%) and 14b 440%).
For the transformation of 12±14 into the reaction products
15±17 and 18±20 a multi-step pathway has to be envisaged
4Scheme 5). The ®rst part of the mechanistic interpretation
is based on the general reactivity of 2,3-dihydroisoxazoles2
and includes the ring transformation of the compounds of
general type I into the bicyclic aziridines II and subsequent
C±C bond cleavage with formation of the azomethine ylide
intermediates III. The conjugated dipole systemthen under-
goes a 6p ring closure13 affording the pyrrolines IV which
under the harsh reaction conditions suffer CH3-H elimi-
nation14 to give the observed pyrroles VII. For rationalizing
the formation of the main products V a preceding isomeri-
zation of the central double bond of the conjugated dipolar
systemmust take place 4 III!VI). Analoguous 4E)N4Z)
isomerizations have been observed with diazo derivatives,15
carbonyl ylides16 and nitrones.17 In case of a deprotonated
2-azadiaryl-heptatriene the geometrical change takes place
even at 2208C.18 Finally, the syn-arranged species VI
undergoes a 1,7-dipolar electrocyclization process affording
the azepine derivatives V.1,19,20
The thermal reactions were performed with ca. 1022 molar
solutions of 12a,b±14a,b in benzene under short-time
thermolysis conditions10 at 280±3208C with a contact time
of ca. 10 s. This technique was superior to other methods
such as ¯ash-vacuumthermolysis or heating of solutions in
Table 1. Thermolysis products of 12a,b, 13a,b and 14a,b
Further evidence for the occurrence of intermediates of
type II was obtained by independent thermolysis experi-
ments with the bicyclic aziridines 21a/22a which can be
selectively obtained on photoinduced transformation of
the annulated isoxazolines 12a/13a 4Scheme 6): on
short-time thermolysis of 21a 43208C) and 22a 42808C)
the same ring expansion products 15/18 and 16/19, respec-
tively, are formed21 as have been observed with the 2,3-
dihydroisoxazoles 12a and 13a as starting materials in this
work.
Yield in %, after chromatography.
3208C/10 s.
2808C/10 s.
a
b

W. Friebolin, W. Eberbach / Tetrahedron 57-2001) 4349±4358
4351
Scheme 5.
standard; for assignments ATP, COSY, HMBC, NOESY
techniques were used. IR: Perkin Elmer PE 297 Infracord
FT±IR. UV: Perkin-Elmer Lambda 15. MS: Finnigan MAT
44 S spectrometer with Datasystem MAT SS 200 using
electron impact ionization 4EI, 70 eV) or chemical ioni-
zation 4CI, 170 eV) with isobutane. Elemental analyses:
Perkin-Elmer Elemental Analyzer 240. All reactions were
carried out in ¯ame-dried glassware under N2 atmosphere
unless otherwise stated. Analytical TLC: precoated silica
gel Merck 60 F-254 40.2 mm). Flash chromatography:
ICN-Biomedicals silica gel 4ICN Silica 32-36). Short-time
thermolysis apparatus: a vertical, externally heated Pyrex
tube 437£3 cm) packed with Raschig rings 4Pyrex,
4£4 mm); packed height 18 cm, heating zone 30 cm;
addition of the solutions through a dosing funnel 4Normag
N 8056) in a N2-steam4¯ow rate 0.75 l/h), dropping rate
13 ml/h; temperature ^108C, contact time ca. 10 s.10,11
4.2. Procedure for the preparation of the annulated
dihydroisoxazoles 6±8
Scheme 6.
6a,b: To a solution of the nitrone 3,22 4ca. 4 mmol) in 5±
10 ml dry CH2Cl2 of diethyl ether was added under argon
3-phenylpropynal23 and 3-tert-butylpropynal,17b respec-
tively, at r.t. The reaction mixture was further stirred
under argon and light exclusion at roomtemperature for
24 h. After evaporation of the solvent the oily residue was
puri®ed by ¯ash chromatography 4SiO2, cyclohexane/ethyl
acetate 20:1). The compounds 7a,b and 8a,b were likewise
prepared fromthe nitrones 424 and 5,25 respectively, follow-
ing the known protocol.4b
3. Conclusion
In summary, the experiments with various 4-isoxazolines
have shown that on thermal activation the main reaction
pathway affords azomethine ylides as key intermediates
which in the presence of appropriate p-substituents like a
butadienyl group undergo electrocyclic ring closure reac-
tions to annulated pyrrole and azepine derivatives, respec-
tively. An extension of the work with 4-isoaxazolines
bearing different side chains as well as more studies on
the photochemical reactivity of such heterocycles are in
progress.
4.2.1.
3a,6,6-Trimethyl-2-phenyl-3a,4,5,6-tetrahydro-
pyrrolo[1,2-b]isoxazol-3-carbaldehyde 36a). The reaction
of 3 4440 mg, 3.46 mmol) with 3-phenylpropynal 4455 mg,
3.5 mmol) in 5 ml dry CH2Cl2 gave 717 mg 480%) of 6a as
pale yellow oil. 1H NMR 4250 MHz): dˆ1.27 4s, 3 H, CH3),
1.34 4s, 3 H, CH3), 1.67 4s, 3 H, CH3), 1.70±1.85 4m, 2 H,
4. Experimental
4.1. General
2
3
3
CH2), 2.02 4ddd, 1 H, CH2, Jˆ13.1 Hz, Jˆ9.1 Hz, Jˆ
2
3
3
6.7 Hz), 2.43 4ddd, 1 H, CH2, Jˆ13.1 Hz, Jˆ7.0 Hz, Jˆ
4.9 Hz), 7.43±7.62 4m, 5 H, PhH), 9.64 4s, 1 H, CHO). 13C
NMR 4100 MHz): dˆ22.9 4CH3), 27.2 4CH3), 28.2 4CH3),
36.2 4CH2), 36.5 4CH2), 69.8 4Cq), 77.2 4NCq), 119.4 4yCq),
1
Melting points are uncorrected. H NMR: 250, 400 and
500 MHz; 13C NMR: 100 or 125 MHz, Brucker WM 250,
WM 400, WM 500; CDCl3 as solvent and TMS as internal

4352
W. Friebolin, W. Eberbach / Tetrahedron 57-2001) 4349±4358
126.3 4Cq,Ph), 128.6 4CPh), 128.8 4CPh), 131.4 4CPh), 169.4
4CO), 185.5 4CHO). IR: 2976 cm21, 2758, 1650 4CO),1598,
1493, 1447, 1351, 1136, 1071. UV 4CH3CN): lˆ248 nm4 e
10,800), 308 nm4 e 9200). MS 4CI): m/z 4%)ˆ258 463)
[M111], 184 43), 147 44), 123 435), 112 4100). HRMS
calcd. for C16H19NO2: 257.1416; found 257.1420.
4CPh), 129.6 4Cq,Ph), 135.1 4HCy), 151.0 4CO). IR:
3618 cm21 4OH), 3567 4OH), 3081, 2974, 1670, 1640,
1494, 1446, 1366, 1244, 1147. UV 4CH3CN): lˆ222 nm
4e 11,500), 282 nm4 e 5000). MS 4EI): m/z 4%)ˆ299 45)
[M1], 284 437), 230 425), 188 417), 105 4100), 77 451). Anal.
calcd. for C19H25NO2: C 76.22, H 8.42, N 4.68; found C
76.32, H 8.52, N 4.68. 90a: 1H NMR 4250 MHz): dˆ1.26 4s,
3 H, CH3), 1.27 4s, 3 H, CH3), 1.55 4s, 3 H, CH3), 1.68±1.93
4m, 4 H, OH, CH2), 2.27±2.56 4m, 3 H, CH2, allyl-CH2),
4.50 4m, 1 H, CHOH), 5.06±5.13 4m, 2 H, yCH2), 5.64±
5.89 4m, 1 H, HCy), 7.36 4mc, 3 H, PhH), 7.56 4mc, 2 H,
PhH). 13C NMR 4100 MHz): dˆ22.2 4CH3), 28.6 4CH3),
30.43 4CH3), 35.8 4CH2), 36.4 4CH2), 41.2 4allyl-CH2),
67.04 4CHOH), 68.9 4Cq), 78.7 4NCq), 113.6 4yCq), 118.3
4yCH2), 128.3 4CPh), 128.5 4CPh), 129.1 4CPh), 129.6 4Cq,Ph),
135.1 4HCy), 151.2 4CO). MS 4EI): m/z 4%)ˆ299 44) [M1],
284 435), 230 433), 188 424), 105 4100), 77 452). HRMS
calcd. for C19H25NO2: 299.1885; found 299.1881.
4.2.2. 2-tert-Butyl-3a,6,6-trimethyl-3a,4,5,6-tetrahydro-
pyrrolo[1,2-b]isoxazol-3-carbaldehyde 36b). The reaction
of 3 41.00 g, 7.9 mmol) with 3-tert-butylpropynal 40.87 g,
7.9 mmol) in 6 ml dry diethyl ether afforded 1.04 g 455%) of
6b as pale yellow oil. 1H NMR 4250 MHz): dˆ1.20 4s, 3 H,
CH3), 1.25 4s, 3 H, CH3), 1.38 4s, 9H, tBu), 1.55 4s, 3 H,
2
3
3
CH3), 1.59 4ddd, 1 H, CH2, Jˆ12.5 Hz, Jˆ9.2 Hz, Jˆ
2
3
3
7.3 Hz), 1.69 4ddd, 1 H, CH2, Jˆ12.5 Hz, Jˆ4.7 Hz, Jˆ
6.8 Hz), 1.94 4ddd, 1 H, CH2, 2Jˆ13.1 Hz, 3Jˆ9.2 Hz,
3Jˆ6.8 Hz), 2.32 4ddd, 1 H, CH2, Jˆ13.1 Hz, Jˆ7.3 Hz,
3Jˆ4.7 Hz), 10.01 4s, 1 H, CHO). 13C NMR 4100 MHz):
dˆ23.2 4CH3), 27.5 4CH3), 28.71 4CH3), 30.1 4tBu), 35.3
4Cq,tBu), 36.5 4CH2), 36.7 4CH2), 69.9 4NCq), 77.3 4NCq),
2
3
4.3.2. 1-32-tert-Butyl-3a,6,6-trimethyl-3a,4,5,6-tetrahydro-
pyrrolo[1,2-b]isoxazol-3-yl)-but-3-en-1-ol 39b/90b). The
reaction of 6b 4400 mg, 1.68 mmol) gave 427 mg 491%)
of 9b/90b as colorless crystals. 9b: mp 129±1308C 4diethyl
ether/pentane). 1H NMR 4250 MHz): dˆ1.18 4s, 3 H, CH3),
1.20 4s, 3 H, CH3), 1.23 4s, 9 H, tBu), 1.51 4d, 1 H, OH,
2Jˆ2.3 Hz), 1.44 4s, 3 H, CH3), 1.61±1.65 4m, 2 H, CH2,
118.5 4yCq), 178.4 4CO), 185.1 4CHO). IR: 2975 cm21
,
2869, 1643, 1602, 1461, 1367, 1339, 1275, 1178. UV
4CH3CN): lˆ295 nm4 e 9300), 225 nm4 e 5200). MS:
m/z 4%)ˆ237 412) [M1], 222 499), 168 4100), 152 451),
124 419), 84 420), 69 471). HRMS calcd. for C14H23NO2:
237.1728; found 237.1729.
3
2
3
2Jˆ15 Hz, Jˆ8.8 Hz), 1.77 4dt, 1 H, CH2, Jˆ14 Hz, Jˆ
7 Hz), 2.38±2.55 4m, 3 H, allyl-CH2, CH2), 4.84 4ddd, 1 H,
CHOH, 2Jˆ2.3 Hz, 3Jˆ4 Hz, 3Jˆ9 Hz), 5.13±5.20 4m, 2 H,
4.3. General procedure for the preparation of the
alcohols 9a,b±11a,b
3
3
3
yCH2, Jˆ10 Hz, Jˆ16 Hz), 5.86 4m, 1 H, HCy, Jˆ
10 Hz, Jˆ16 Hz). 13C NMR 4100 MHz): dˆ22.6 4CH3),
3
To stirred solutions of 6a,b±8a,b 41±2 mmol) in 5 ml of dry
THF at 08C was added slowly the suspension of freshly
prepared allylmagnesium bromide 41.2±2.5 equiv.) in
diethyl ether 45 ml). After stirring for additional 15±
120 min the reaction mixture was hydrolyzed at 08C with
saturated NH4Cl solution and then extracted with diethyl
ether 43£20 ml). The combined organic phase was washed
4saturated NaHCO3 and NaCl solution) and then dried
4MgSO4). Concentration in vacuo afforded a residue
which was puri®ed by ¯ash chromatography 4SiO2, cyclo-
hexane/ethyl acetate 10:1). In general, mixtures of the
respective diastereomers 9±11/90 ±110 were isolated.8 For
characterization, small quantities of the single isomers
were separated by repeated chromatography; however, no
con®gurational attribution has been done.
28.7 4CH3), 29.7 4tBu), 31.3 4CH3), 33.3 4Cq,tBu), 36.6
4CH2), 36.7 4CH2), 42.8 4allyl-CH2), 66.8 4CHOH), 68.5
4Cq), 78.4 4NCq), 110.0 4yCq), 118.1 4yCH2), 135.7
4HCy), 157.8 4CO). IR: 3616 cm21, 3571, 3073, 2972,
1639, 1458, 1365, 1145. MS 4EI): m/z 4%)ˆ279 46) [M1],
264 465), 210 478), 168 428), 152 427), 126 413). HRMS
calcd. for C17H29NO2: 279.2198; found 279.2200. Anal.
calcd. for C17H29NO2: C 73.07, H 10.46, N 5.01; found C
73.14, H 10.43, N 4.96. 90b: mp 125±1268C 4diethyl ether/
1
pentane) H NMR 4250 MHz): dˆ1.14 4s, 3 H, CH3), 1.23
4s, 3 H, CH3), 1.25 4s, 9 H, tBu), 1.44 4d, 1 H, OH,
2Jˆ1.6 Hz), 1.46 4s, 3 H, CH3), 1.58±1.70 4m, 2 H, CH2),
2
3
1.80 4dt, 1 H, CH2, Jˆ12,6 Hz, Jˆ7 Hz), 2.24 4dt, 1 H,
CH2, 2Jˆ12,6 Hz, 3Jˆ7 Hz), 2.42 4m, 1 H, allyl-CH2), 2.52
2
4m, 1 H, allyl-CH2), 4.85 4ddd, 1 H, CHOH, Jˆ1.6 Hz,
3Jˆ4 Hz, Jˆ9 Hz), 5.14±5.17 4m, 2 H, yCH2, Jˆ10 Hz,
3Jˆ16 Hz), 5.87 4m, 1 H, HCy, 3Jˆ10 Hz, 3Jˆ16 Hz). 13C
NMR 4100 MHz): dˆ21.8 4CH3), 28.7 4CH3), 29.8 4tBu),
32.0 4CH3), 33.3 4Cq,tBu), 36.4 4CH2), 36.8 4CH2), 41.4
4allyl-CH2), 67.0 4CHOH), 68.3 4Cq), 78.2 4NCq), 110.2
4yCq), 117.7 4yCH2), 135.7 4HCy), 158.3 4CO). IR:
3616 cm21, 3571, 3073, 2973, 1639, 1458, 1364, 1138.
MS 4EI): m/z 4%)ˆ279 46) [M1], 264 494), 210 469), 168
422), 152 420), 126 411). HRMS calcd. for C17H29NO2:
279.2198; found 279.2197.
3
3
4.3.1. 1-33a,6,6-Trimethyl-2-phenyl-3a,4,5,6-tetrahydro-
pyrrolo[1,2-b]isoxazol-3-yl)-but-3-en-1-ol 39a/90a). The
reaction of 6a 42.2 g, 8.55 mmol) yielded after ¯ash
chromatography 4SiO2, cyclohexane/ethyl acetate 20:1)
2.42 g 494%) of the mixture of 9a/90a as pale yellow
crystals. 9a: m p 95±986C 4diethyl ether/pentane). 1H
NMR 4250 MHz): dˆ1.23 4s, 3 H, CH3), 1.28 4s, 3 H,
CH3), 1.54 4s, 3 H, CH3), 1.71 4sbr, 1 H, OH), 1.74 4t, 2 H,
3
CH2, Jˆ6 Hz), 1.88 4dt, 1 H, CH2), 2.30 4dt, 1 H, CH2,
2Jˆ12,6 Hz, 3Jˆ7 Hz), 2.37±2.54 4m, 2 H, allyl-CH2),
3
3
4.50 4dd, 1 H, CHOH, Jˆ5 Hz, Jˆ9 Hz), 5.06±5.13 4m,
3
3
4.3.3. 1-32-Phenyl-3a,5,5-trimethyl-3a,4,5,6,tetrahydro-
pyrrolo[1,2-b]isoxazol-3-yl)-but-3-en-1-ol 310a/100a). The
reaction of 7a4b 41.00 g, 3.89 mmol) afforded 1.02 g 487%)
of 10a/100a as colorless crystals. 10a: mp 95±1008C
2 H, yCH2, Jˆ12 Hz, Jˆ18 Hz), 5.75±5.64 4m, 1 H,
3
3
HCy, Jˆ12 Hz, Jˆ18 Hz), 7.36 4mc, 3 H, PhH), 7.56
4mc, 2 H, PhH). 13C NMR 4100 MHz): dˆ21.9 4CH3),
28.4 4CH3), 30.7 4CH3), 36.3 4CH2), 36.5 4CH2), 40.7
4allyl-CH2), 67.2 4CHOH), 68.8 4Cq), 78.7 4NCq), 113.8
4yCq), 118.0 4yCH2), 128.3 4CPh), 128.5 4CPh), 129.0
1
4diethyl ether/ pentane). H NMR 4250 MHz): dˆ1.11 4s,
3 H, CH3), 1.19 4s, 3 H, CH3), 1.53 4s, 3 H, CH3), 1.64 4dd, 1

W. Friebolin, W. Eberbach / Tetrahedron 57-2001) 4349±4358
4353
4
2
3
H, 4-H, Jˆ1.2 Hz, Jˆ12.8 Hz), 1.86 4s, 1 H, OH), 2.40±
2.50 4d, 1 H, 4-H, 2Jˆ12.8 Hz; m, 2 H, CH2), 2.94 4d, 1 H,
6-H, 2Jˆ9.2 Hz), 3.26 4dd, 1 H, 6-H, 4Jˆ1.2 Hz, 2Jˆ
9.2 Hz), 4.53 4m, 1 H, CH4OH)), 5.05±5.15 4m, 2 H,
yCH2), 5.78 4m, 1 H, HCy), 7.37 4mc, 3 H, Ph-H), 7.55
4mc, 2 H, Ph-H). 13C NMR 4100 MHz): dˆ28.1 4CH3),
29.0 4CH3), 30.0 4CH3), 36.2 4Cq), 40.9 4CH2Cy), 49.8
4CH2), 67.0 4CHOH), 69.3 4NCH2), 78.1 4NCq), 115.2
43-C), 118.4 4yCH2), 128.3 4CPh), 128.6 4CPh), 129.2
4CPh), 129.9 4Cq,Ph), 135.1 4HCy), 149.2 4CO). IR:
3610 cm21, 3550, 3060, 2950, 2860, 1660, 1640, 1600,
1490, 1445, 1565, 1320, 1095. MS 4EI): m/z 4%)ˆ299 41)
[M1], 224 46), 202 48), 128 45), 120 461), 115 45), 105 4100),
91 418), 77 475). HRMS calcd. for C19H25NO2: 299.1885;
found 299.1886. Anal. calcd. for C19H25NO2: C 76.22, H
10 Hz, Jˆ15 Hz). 13C NMR 4100 MHz): dˆ28.3 4CH3),
28.6 4CH3), 29.2 4tBu), 31.1 4CH3), 32.8 4Cq,tBu), 36.4
4Cq), 42.3 4CH2), 51.2 4CH2), 66.7 4CHOH), 68.7 4NCH2),
77.9 4NCq), 111.7 43-C), 117.9 4yCH2), 135.4 4HCy), 155.1
4CO). IR: 3623 cm21, 3584, 3073, 2958, 1638, 1466, 1366.
MS 4EI): m/z 4%)ˆ279 45) [M1], 264 433), 222 428), 194
416), 182 430), 166 442), 152 428), 148 426), 138 422), 124
427), 107 428), 98 429). HRMS calcd. for C17H29NO2:
279.2198; found 279.2200. Anal. calcd. for C17H29NO2: C
73.07, H 10.46, N 5.01; found C 73.11, H 10.46, N 5.02.
4.3.5.
1-33a-Methyl-2-phenyl-4,5,6,7-tetrahydro-3aH-
isoxazolo[2,3-a]pyridin-3-yl)-but-3-en-1-ol 311a/110a).
The reaction of 8a4b 40.946 g, 3.89 mmol) yielded 738 mg
466%) of 11a/110a as colorless crystals. 11a: mp 104±1058C
1
1
8.42, N 4.68; found C 76.32, H 8.38 N 4.63. 100a: H
4diethyl ether/pentane). H NMR 4250 MHz): dˆ1.43 4s, 3
NMR 4250 MHz): dˆ1.13 4s, 3 H, CH3), 1.19 4s, 3 H,
H, CH3), 1.46±1.73 4m, 5 H, CH2), 1.90 4d, 1 H, 3Jˆ1.8 Hz,
OH), 2.29±2.64 4m, 3 H, CH2), 2.86 4m, 1 H, CH2), 3.31 4m,
1 H, CH2), 4.64 4m, 1 H, CHOH), 5.12, 4dd, 1 H, yCH2,
4
CH3), 1.52 4s, 3 H, CH3), 1.71 4dd, 1 H, 4-H, Jˆ1.2 Hz,
2Jˆ12.8 Hz), 1.90 4s, 1 H, OH), 2.24 4d, 1 H, 4-H, Jˆ
2
2
3
2
12.8 Hz), 2.46 4m, 2 H, CH2), 2.98 4d, 1 H, 6-H, Jˆ
2Jˆ1.5 Hz, Jˆ17 Hz), 5.18 4dd, 1 H, yCH2, Jˆ1.5 Hz,
3Jˆ11 Hz), 5.85 4m, 1 H, HCy), 7.34±7.48 4m, 5 H,
PhH). 13C NMR 4100 MHz): dˆ21.4 4CH2), 23.4 4CH2),
30.5 4CH3), 32.9 4CH2), 41.0 4CH2), 51.7 4CH2), 66.9
4CHOH), 70.34 4NCq), 115.6 4yCq), 118.2 4yCH2), 128.3,
128.8, 129.3, 130.0 4Cq,Ph), 135.2 4HCy), 151.0 4CO). IR:
3620 cm21 4OH), 3570 4OH), 3080, 2940, 2860, 1660, 1640,
1600, 1495, 1445, 1325, 1195, 920. MS 4EI): m/z 4%)ˆ285
415) [M1], 270 4100), 256 410), 244 442), 228 411), 200 412),
188 447), 180 416), 105 498), 77 445). HRMS calcd. for
C18H23NO2: 285.1729; found 285.1727. Anal. calcd. for
C18H23NO2: C 75.76, H 8.12, N 4.91; found C 75.75, H
10.1 Hz), 3.26 4dd, 1 H, 6-H, 4Jˆ1.2 Hz, 2Jˆ10.1 Hz),
4.54 4m, 1 H, CH4OH)), 5.06±5.12 4m, 1 H, yCH2), 5.14
4m, 1 H, yCH2), 5.80 4m, 1 H, HCy), 7.36 4mc, 3 H, Ph-H),
7.54 4mc, 2 H, Ph-H). 13C NMR 4100 MHz): dˆ28.2 4CH3),
28.5 4CH3), 30.1 4CH3), 36.9 4Cq), 40.9 4CH2Cy), 51.3
4CH2), 67.2 4CHOH), 69.7 4NCH2), 78.7 4NCq), 115.2
43-C), 118.2 4yCH2), 128.3 4CPh), 128.4 4CPh), 129.1
4CPh), 129.9 4Cq,Ph), 135.1 4HCy), 148.7 4CO). IR:
3610 cm21, 3550, 3060, 2950, 2860, 1660, 1640, 1600,
1490, 1445, 1565, 1320, 1095. MS 4EI): m/z 4%)ˆ299 41)
[M1], 224 45), 202 415), 196 45), 120 445), 115 44), 105
4100), 91 420), 77 470). HRMS calcd. for C19H25NO2:
299.1885; found 299.1890.
1
8.06, N 4.84. 110a: H NMR 4250 MHz): dˆ1.47 4s, 3 H,
CH3), 1.47±1.78 4m, 10 H, CH2,OH), 2.23±2.65 4m, 3 H,
CH2), 2.92 4m, 1 H, CH2), 3.28 4m, 1 H, CH2), 4.64 4m, 1 H,
CHOH), 5.12, 4dd, 1 H, yCH2, 2Jˆ1.5 Hz, 3Jˆ17 Hz), 5.18
4.3.4. 1-32-tert-Butyl-3a,5,5-trimethyl-3a,4,5,6-tetrahydro-
310b/100b).
2
3
pyrrolo[1,2-b]isoxazol-3-yl)-but-3-en-1-ol
4dd, 1 H, yCH2, Jˆ1.5 Hz, Jˆ11 Hz), 5.85 4m, 1 H,
HCy), 7.34±7.50 4m, 5 H, PhH). IR: 3620 cm21 4OH),
3570 4OH), 3080, 2940, 2860, 1660, 1640, 1600, 1495,
1445, 1325, 1195. MS 4EI): m/z 4%)ˆ285 414) [M1], 270
4100), 256 48), 244 435), 228 410), 200 410), 188 436), 180
412), 105 487), 77 438).
The reaction of 7b4b 4500 mg, 2.11 mmol) gave 517 mg
1
488%) of 10b/100b as colorless crystals. 10b: H NMR
4250 MHz): dˆ1.08 4s, 3 H, CH3), 1.15 4s, 3 H, CH3),
1.22 4s, 9 H, tBu), 1.40 4s, 3 H, CH3), 1.48 4d, 1 H, OH,
2Jˆ2 Hz), 1.55 4dd, 1 H, 4-H, 2Jˆ12.9 Hz, 4Jˆ1.3 Hz), 2.44
4m, 2 H, CH2), 2.54 4d, 1 H, 40-H, 2Jˆ12,9 Hz), 2.74 4d, 1 H,
2
2
4
6-H, Jˆ9 Hz), 3.09 4dd, 1 H, 60-H, Jˆ9 Hz, Jˆ1.3 Hz),
4.3.6. 1-[2-3tert-Butyl)-3a-methyl-4,5,6,7-tetrahydro-3aH-
isoxazolo[2,3-a]pyridin-3-yl] but-3-en-1-ol 311b/110b).
The reaction of 8b4b 4400 mg, 1.82 mmol) afforded after
¯ash chromatography 4SiO2, cyclohexane/ethyl acetate
20:1) 402 mg 483%) of 11b/110b as colorless crystals.
11b: mp 99±1008C 4diethyl ether/pentane). 1H NMR
4250 MHz): dˆ1.21 4s, 9 H, tBu), 1.31 4s, 3 H, CH3),
2
3
3
4.89 4ddd, 1 H, CHOH, Jˆ2 Hz, Jˆ4.7 Hz, Jˆ9.1 Hz),
5.14±5.20 4m, 2 H, yCH2, 3Jˆ10 Hz, 3Jˆ15 Hz), 5.82±5.89
4m, 1 H, HCy, 3Jˆ10 Hz, 3Jˆ15 Hz). 13C NMR 4100 MHz):
dˆ28.2 4CH3), 29.0 4CH3), 29.3 4tBu), 30.7 4CH3), 32.9
4Cq,tBu), 36.1 4Cq), 41.9 4CH2), 50.2 4CH2), 66.5 4CHOH),
68.5 4NCH2), 77.3 4NCq), 112.0 43-C), 118.1 4yCH2), 135.6
4HCy), 156.2 4CO). IR: 3616 cm21, 3565, 3073, 2958,
1639, 1467, 1367, 1113. MS 4EI): m/z 4%)ˆ279 47) [M1],
264 440), 238 411), 222 443), 194 420), 182 455), 166 464),
152 433), 148 430), 138 425), 124 432), 107 428), 98 430).
HRMS calcd. for C17H29NO2: 279.2198; found 279.2200.
100b: m p 97±988C 4diethyl ether/pentane). 1H NMR
4250 MHz): dˆ1.09 4s, 3 H, CH3), 1.16 4s, 3 H, CH3),
1.21 4s, 9 H, tBu), 1.45 4s, 3 H, CH3), 1.57 4d, 1 H, OH,
2
1.42±1.65 4m, 6 H, CH2), 2.30 4dbr, 1 H, Jˆ13 Hz), 2.38
2
3
4dt, 1 H, CH2, Jˆ14 Hz, Jˆ5 Hz), 2.50 4dt, 1 H, CH2,
2Jˆ14 Hz, Jˆ8 Hz), 2.69 4dt, 1 H, CH2, Jˆ11 Hz, Jˆ
3
2
3
2
3 Hz) 3.10 4m, 1 H, CH2, Jˆ11 Hz), 4.98 4ddd, 1 H,
2
3
3
CHOH, Jˆ2.2 Hz, Jˆ4 Hz, Jˆ9 Hz), 5.16±25.20 4m, 2
H, yCH2, Jˆ11 Hz, Jˆ18 Hz), 5.86 4m, 1 H, HCy). 13C
NMR 4100 MHz): dˆ21.5 4CH2), 23.3 4CH2), 29.4 4tBu),
31.0 4CH3), 33.0 4Cq,tBu), 33.1 4CH2), 41.4 4CH2), 50.9
4CH2), 66.8 4CHOH), 69.6 4NCq), 111.7 4yCq), 117.9
4yCH2), 135.6 4HCy), 158.1 4CO). IR: 3616 cm21, 3565,
3073, 2953, 1639, 1450, 1364, 1275, 1106, 1000. MS 4EI):
m/z 4%)ˆ265 47) [M1], 250 4100), 232 440), 224 427), 208
437), 190 420), 180 421), 168 441), 148 424), 93 420). HRMS
calcd. for C16H27NO2: 265.2042; found 265.2046. Anal.
3
3
2Jˆ2.6 Hz), 1.93 4dd, 1 H, 4-H, Jˆ12.9 Hz, Jˆ1.3 Hz),
2
4
2
2.17 4d, 1 H, 40-H, Jˆ12,9 Hz), 2.41 4m, 1 H, CH2), 2.52
2
4m, 1 H, CH2), 2.74 4d, 1 H, 6-H, Jˆ9 Hz), 3.11 4dd, 1 H,
2
4
2
60-H, Jˆ9 Hz, Jˆ1.3 Hz), 4.87 4ddd, 1 H, CHOH, Jˆ
3
3
2 Hz, Jˆ4 Hz, Jˆ9.7 Hz), 5.16±5.19 4m, 2 H, yCH2,
3Jˆ10 Hz, 3Jˆ15 Hz), 5.82±5.89 4m, 1 H, HCy, 3Jˆ

4354
W. Friebolin, W. Eberbach / Tetrahedron 57-2001) 4349±4358
calcd. for C16H27NO2: C 72.48, H 10.24, N 5.15; found C
72.41, H 10.26, N 5.20. 110b: m p 84±848C 4diethyl ether/
4.4.2. 3-[Buta-31E),3-dienyl]-2-3tert-butyl)-3a,6,6-trimethyl-
3a,4,5,6-tetrahydropyrrolo [1,2-b]isoxazole 312b). The
reaction of the mixture of 9b 4380 mg, 1.36 mmol), dry
NEt3 40.43 g, 4.20 mmol), DMAP 415 mg, 0.12 mmol) in
15 ml of dry CH2Cl2 with methanesulfonic acid chloride
4200 mg, 1.77 mmol) afforded 242 mg 464%) of 12b as
1
pentane). H NMR 4250 MHz): dˆ1.21 4s, 9 H, tBu), 1.36
4s, 3 H, CH3), 1.43±1.66 4m, 6H, CH23), 2.31±2.38 4m, 2 H,
2
CH2), 2.54 4dt, 1 H, CH2, Jˆ14 Hz, Jˆ8 Hz), 2.63 4m, 1
2
3
2
H, CH2, Jˆ11 Hz, Jˆ3 Hz), 3.11 4m, 1 H, CH2, Jˆ
2
3
3
1
11 Hz), 5.02 4ddd, 1 H, CHOH, Jˆ2.2 Hz, Jˆ4 Hz, Jˆ
colorless crystals; mp 41±448C 4diethyl ether/pentane). H
3
9 Hz), 5.15 4dbr, 1 H, yCH2, Jˆ10 Hz), 5.18 4dbr, 1 H,
NMR 4250 MHz): dˆ1.12 4s, 3 H, CH3), 1.25 4s, 3 H, CH3),
1.27 4s, 9 H, tBu), 1.47 4s, 3 H, CH3), 1.60±1.75 4m, 2 H,
CH2), 1.87 4ddd, 1 H, CH2, 2Jˆ12 Hz, 3Jˆ7 Hz, 3Jˆ5 Hz),
2.34 4ddd, 1 H, CH2, 2Jˆ12 Hz, 3Jˆ9 Hz, 3Jˆ7.5 Hz), 4.95
yCH2, 3Jˆ17 Hz), 5.89 4m, 1 H, HCy). 13C NMR
4100 MHz): dˆ21.6 4CH2), 23.2 4CH2), 29.3 4tBu), 31.4
4CH3), 32.2 4CH2), 33.0 4Cq,tBu), 42.5 4CH2), 51.0 4CH2),
67.0 4CHOH), 69.8 4NCq), 111.6 4yCq), 117.8 4yCH2),
135.6 4HCy), 156.6 4CO). IR: 3616 cm21, 3578, 3073,
2953, 1639, 1456, 1363, 1275, 1105, 1017. MS 4EI): m/z
4%)ˆ265 45) [M1], 250 4100), 232 421), 224 419), 208 428),
190 412), 180 416), 168 432), 148 414), 93 414). HRMS
calcd. for C16H27NO2: 265.2042; found 265.2044. Anal.
calcd. for C16H27NO2: C 72.48, H 10.24, N 5.15; found C
72.4, H 10.26, N 5.20.
2
3
4dd, 1 H, yCH2, Jˆ0.8 Hz, Jˆ10 Hz), 5.09 4dd, 1 H,
2
3
3
yCH2, Jˆ0.8 Hz, Jˆ16.9 Hz), 5.99 4dd, 1 H, HCy, Jˆ
4
3
15.8 Hz, Jˆ10.4 Hz), 6.35 4ddd, 1 H, yCH, Jˆ16.9 Hz,
3Jˆ10 Hz, Jˆ10.4 Hz), 6.54 4d, 1 H, HCy, Jˆ15.8 Hz).
13C NMR 4100 MHz): dˆ21.3 4CH3), 28.3 4CH3), 29.3
4CH3), 29.5 4tBu), 33.8 4Cq), 35.4 4CH2), 36.5 4CH2), 68.3
4Cq), 76.7 4NCq), 111.8 4yCH2), 113.8 4yCq), 124.4 4yCH),
4
3
124.8 4yCH), 138.5 4HCy), 160.2 4CO). IR: 2972 cm21
,
1615, 1572, 1460, 1365, 1166, 1000. UV 4CH3CN): lˆ
312 nm4 e 27,000), 240 nm4 e 8900). MS 4EI): m/z
4%)ˆ261 412) [M1], 246 412), 234 47), 176 420), 149
410), 134 410), 120 412), 107 411), 91 414), 57 4100).
HRMS calcd. for C17H27NO: 261.2093; found 261.2093.
Anal. calcd for C17H27NO: C 78.11, H 10.41, N 5.36;
found C 78.08, H 10.49, N 5.12.
4.4. General procedure for the preparation of 12±14
According to a method described by Overman et al.9 the
stirred solution of the alcohols 9±11 4ca. 1.5 mmol), dry
triethylamine 420 ml), 9 mol% of 4-N,N0-dimethylamino-
pyridine 4DMAP) in 15±25 ml of dry CH2Cl2 at 2788C
was treated dropwise with the solution of methanesulfonic
acid chloride 41.3 equiv.) in 1±2 ml of dry CH2Cl2. The
mixture was stirred for additional 40±60 min at 2788C
and then warmed up to room temperature. After recooling
to 2308C, hydrolysis with 20 ml of water and separation of
the the two layers, the aqueous phase was extracted with
CH2Cl2 43£50 ml). The combined organic phase was
then dried 4MgSO4) and concentrated in vacuo. Flash
chromatography of the oily residue 4SiO2, cyclohexane/
ethyl acetate 20:1 or 10:1) afforded 12±14 as pure
E-isomers.
4.4.3. 3-[Buta-31E),3-dienyl]-2-phenyl-3a,5,5-trimethyl-
3a,4,5,6-tetrahydropyrrolo[1,2-b]isoxazole 313a). The
reaction of the mixture of 10a 4620 mg, 2.09 mmol), dry
NEt3 4660 mg, 6.48 mmol), DMAP 423 mg, 0.19 mmol) in
25 ml of dry CH2Cl2 with methanesulfonic acid chloride
4310 mg, 2.71 mmol) afforded unchanged 10a 4135 mg,
1
22%) and 0.430 g 473%) of 13a as pale yellow oil. H
NMR 4250 MHz): dˆ1.09 4s, 3 H, CH3), 1.24 4s, 3 H,
2
CH3), 1.59 4s, 3 H, CH3), 1.82 4dd, 1 H, 4-H, Jˆ12.5 Hz,
2
4Jˆ1.5 Hz), 2.30 4d, 1 H, 4-H, Jˆ12.5 Hz), 2.89 4d, 1 H,
6-H, 2Jˆ8.9 Hz), 3.33 4dd, 1 H, 6-H, 2Jˆ8.9 Hz, 4Jˆ
2
3
1.5 Hz), 5.03 4ddd, 1 H, yCH2, Jˆ0.9 Hz, Jˆ10.1 Hz,
4Jˆ0.6 Hz), 5.17 4ddd, 1 H, yCH2, 2Jˆ0.9 Hz, 3Jˆ
16.8 Hz, 4Jˆ0.6 Hz), 6.13 4m, 1 H, yCH, 3Jˆ15.9,
10.4 Hz), 6.37 4m, 2 H, yCH, 3Jˆ10.4, 10.1, 15.6,
16.8 Hz), 7.40 4m, 3 H, Ph-H), 7.51 4m, 2 H, Ph-H). 13C
NMR 4100 MHz): dˆ27.8 4CH3), 28.2 4CH3), 28.2 4CH3),
37.2 4Cq), 50.1 CH2), 69.4 4NCH2), 76.8 4NCq), 115.1
4yCH2), 116.1 43-C), 124.2 4yCH), 127.3 4CPh), 128.3
4CPh), 128.4 4yCH), 129.2 4CPh), 129.7 4Cq,Ph), 138.0
4yCH), 150.0 4CO). IR: 3080 cm21, 2970, 2870, 1615,
1490, 1445, 1340, 1170, 1120, 1060, 1000, 990. UV
4CH3CN): lˆ327 nm4 e 19,400), 246 nm4 e 11,000),
235 nm4 e 11,900). MS 4EI): m/z 4%)ˆ281 433) [M1],
266 418), 224 420), 196 414), 120 495), 105 4100), 91
813). HRMS calcd. for C19H23NO: 281.1779; found
281.1780.
4.4.1. 3-[Buta-13E),3-dienyl]-3a,6,6-trimethyl-2-phenyl-
3a,4,5,6-tetrahydropyrrolo [1,2-b]isoxazole 312a). The
reaction of the mixture of 9a 42.31 g, 7.71 mmol), dry
triethylamine 42.42 g, 23.9 mmol), DMAP 485 mg,
0.5 mmol) in 45 ml of dry CH2Cl2 with methanesulfonic
acid chloride 4832 mg, 7.27 mmol) afforded 1.50 g 469%)
of 12a as yellow oil. 1H NMR 4250 MHz): dˆ1.19 4s, 3 H,
CH3), 1.32 4s, 3 H, CH3), 1.59 4s, 3 H, CH3), 1.68±1.83 4m, 2
2
3
H, CH2), 1.95 4ddd, 1 H, CH2, Jˆ12.5 Hz, Jˆ7.0 Hz,
2
3
3Jˆ4.9 Hz), 2.47 4ddd, 1 H, CH2, Jˆ12.5 Hz, Jˆ9.1 Hz,
3Jˆ7.5 Hz), 5.00 4dd, 1 H, yCH2, Jˆ1.6 Hz, Jˆ10 Hz),
2
3
2
3
5.15 4dd, 1 H, yCH2, Jˆ1.6 Hz, Jˆ16.6 Hz), 6.19 4dd, 1
3
4
H, HCy, Jˆ15.8 Hz, Jˆ10.4 Hz), 6.32±6.40 4ddd, 1 H,
3
3
4
yCH, Jˆ16.6 Hz, Jˆ10 Hz, Jˆ10.4 Hz), 6.38 4d, 1 H,
3
HCy, Jˆ15.8 Hz), 7.34±7.41 4m, 3 H, PhH), 7.52 4mc, 2
H, PhH). 13C NMR 4100 MHz): dˆ21.0 4CH3), 28.3 4CH3),
29.0 4CH3), 35.0 4CH2), 36.5 4CH2), 68.6 4Cq), 76.8 4NCq),
114.8 4yCH2), 115.5 4yCq), 124.1 4yCH), 126.8 4yCH),
128.3 4CPh), 128.4 4CPh), 129.1 4CPh), 129.2 4Cq,Ph), 138.1
4HCy), 152.2 4CO). IR: 3086 cm21, 2972, 1615, 1491,
1446, 1345, 1238, 1168, 1068, 1001. UV 4CH3CN): lˆ
250 nm4 e 12,500), 333 nm4 e 14,300). MS 4EI): m/z
4%)ˆ281 415) [M1], 266 419), 212 49), 148 410), 120
411), 105 4100), 77 436). HRMS calcd. for C19H23NO:
281.17796; found 281.17801.
4.4.4. 3-[Buta-13E),3-dienyl]-2-3tert-butyl)-3a,5,5-trimethyl-
3a,4,5,6-tetrahydropyrrolo [1,2-b]isoxazole 313b). The
reaction of the mixture of 10b 4410 mg, 1.47 mmol), dry
NEt3 4460 mg, 4.55 mmol), DMAP 416 mg, 0.13 mmol) in
15 ml of dry CH2Cl2 with methanesulfonic acid chloride
4220 mg, 1.9 mmol) afforded 263 mg 474%) of 13b as
1
pale yellow oil. H NMR 4250 MHz): dˆ1.06 4s, 3 H,
CH3), 1.19 4s, 3 H, CH3), 1.25 4s, 9 H, tBu), 1.46 4s, 3 H,

W. Friebolin, W. Eberbach / Tetrahedron 57-2001) 4349±4358
4355
CH3), 1.73 4dd, 1 H, 4-H, 2Jˆ12.6 Hz, 4Jˆ1.4 Hz), 2.20 4d,
162 48), 148 419), 134 48), 93 413), 91 413), 57 4100). HRMS
calcd. for C16H25NO: 247.1936; found 247.1937.
1 H, 4-H, 2Jˆ12.6 Hz), 2.67 4d, 1 H, 6-H, 2Jˆ8.8 Hz), 3.17
2
4
4dd, 1 H, 6-H, Jˆ8.6 Hz, Jˆ1.4 Hz), 4.98 4ddbr, 1 H,
2
yCH2, Jˆ0.6 Hz, 3Jˆ10.7 Hz), 5.11 4dtbr, 1 H, yCH2,
4.5. General procedure of the short-time thermolysis10
3
3
2Jˆ0.6 Hz, Jˆ16.8 Hz), 5.91 4dd, 1 H, yCH, Jˆ15.9,
3
1022±1023 Molar solutions of 12±14 in dry benzene were
slowly dropped through the heated thermolysis column in a
nitrogen streamat the given temperature 4the details of the
apparatus are described in Section 4.1). The reaction
mixture was collected at 08C and then concentrated in
10.5 Hz), 6.35 4ddd, 1 H, yCH, Jˆ10.5, 10.7, 16.8 Hz),
6.58 4d, 1 H, HCy, Jˆ15.9 Hz). 13C NMR 4100 MHz):
3
dˆ27.8 4CH3), 28.1 4CH3), 28.4 4CH3), 29.3 4tBu), 33.5
4Cq,tBu), 37.1 4Cq), 50.4 4CH2), 68.9 4NCH2), 76.4 4NCq),
112.8 4yCH2), 114.2 43-C), 124.6 4yCH), 125.5 4yCH),
138.4 4yCH), 158.0 4CO). IR: 2959 cm21, 1616, 1572,
1466, 1370, 1254, 1165, 1124, 1000. UV 4CH3CN): lˆ
304 nm4 e 26,600), 236 nm4 e 6600). MS 4EI): m/z
4%)ˆ263 494) [M112], 235 475), 207 499), 178 4100),
128 420), 102 416), 89 430). MS 4CI): m/z 4%)ˆ262 4100)
[M111], 204 49), 177 46), 148 46). HRMS calcd. for
C17H27NO: 261.2093; found 261.2095.
1
vacuo. After H NMR analysis of the raw material, puri®-
cation was accomplished by ¯ash chromatography 4SiO2,
cyclohexane/ethyl acetate 50:1 or 100:1). In some cases
additional puri®cation by MPLC 4SiO2, n-hexane/ethyl
acetate 50:1) was performed.
4.5.1. Thermolysis of 12a. The solution of 12a 4200 mg,
0.71 mmol) in 75 ml of dry benzene at 3208C afforded
118 mg 459%) of phenyl-43,3,9a-trimethyl-2,3,9,9a-tetra-
hydro-1H-pyrrolo[1,2-a]azepin-5-yl)-methanone 415a) as
yellow crystals and 17 mg 49%) of phenyl-45,5-dimethyl-
1-vinyl-6,7-dihydro-5H-pyrrolizin-3-yl)-methanone 418a)
as yellow oil. 15a: m p 66±678C 4diethyl ether/pentane).
1H NMR 4250 MHz): dˆ1.02 4d, 3 H, 10-CH3, 4Jˆ
4.4.5. 3-[Buta-13E),3-dienyl]-3a-methyl-2-phenyl-4,5,6,7-
tetrahydro-3aH-isoxazolo[2,3-a] pyridine 314a). The
reaction of the mixture of 11a 4700 mg, 2.48 mmol), dry
NEt3 4780 mg, 7.7 mmol), DMAP 427 mg, 0.22 mmol) in
25 ml of dry CH2Cl2 with methanesulfonic acid chloride
4370 mg, 3.23 mmol) afforded unreacted 11a 4220 mg,
1
31%) and 388 mg 458%) of 14a as orange oil. H NMR
4250 MHz): dˆ1.23±1.36 4m, 2 H, CH2), 1.45 4s, 3 H,
1.2 Hz), 1.20 4s, 3 H, CH3), 1.21 4s, 3 H, CH3), 1.65 4ddd,
2
1 H, 10-H, J1 ,1ˆ12.3 Hz, 3J1 ,2ˆ6.7 Hz, 3J1 ,2 ˆ2.7 Hz), 1.8
0
0
0
0
2
3
CH3), 1.47±1.78 4m, 3 H, CH2), 2.38 4m, 1 H, CH2), 2.90
0
4dtbr, 1 H, 1-H, Jˆ12.3 Hz, J1,2 ˆ6.7 Hz), 1.9 4dd, 1 H,
3
2
3
3
20-H, J2 ,2ˆ12.3 Hz, J2 ,1ˆ6.7 Hz, J2 ,1 ˆ2.7 Hz), 2.25
4dt, 1 H, CH2, Jˆ4 Hz, 11 Hz), 3.36 4m, 1 H, CH2), 5.03
0
0
0
0
4dd, 1 H, yCH2, 2Jˆ1.8 Hz, 3Jˆ9 Hz), 5.17 4dd, 1 H, yCH2,
2
3
0
4dtbr, 1 H, 2-H, Jˆ12.3 Hz, J2,1 ˆ6.7 Hz), 2.33 4mbr, 1 H,
3
2Jˆ1.8 Hz, Jˆ16 Hz), 6.24±6.52 4m, 3 H, yCH), 7.38±
2
3
4
4
90-H, J9 ,9ˆ15.7 Hz, J9 ,8ˆ3 Hz, J9 ,7ˆ3 Hz, J9 ,CH3
ˆ
0
0
0
0
7.53 4m, 5 H, Ph-H). 13C NMR 4100 MHz): dˆ20.0
4CH2), 23.0 4CH2), 27.6 4CH3), 31.8 4CH2), 51.4 4NCH2),
70.2 4NCq), 114.9 4yCq), 115.1 4yC), 125.0 4yC), 126.7
4yC), 128.4 4yC), 128.5 4yC), 129.3 4yC), 130.0 4yCq,Ph),
138.3 4yC), 152.7 4yCO). IR: 3090 cm21, 3030, 2940,
2860, 1615, 1490, 1445, 1340, 1170, 1060. UV 4CH3CN):
lˆ233 nm4 e 13,000), 329 nm4 e 15,400). MS 4EI): m/z
4%)ˆ267 445) [M1], 252 487), 238 410), 210 411), 162
414), 120 413), 105 4100), 77 444). HRMS calcd. for
C18H21NO: 267.1623; found 267.1623.
5
2
0
0
1.2 Hz, J9 ,6ˆ0.5 Hz), 2.5 4dd, 1 H, 9-H, J9,9 ˆ15.7 Hz,
3J9,8ˆ8.3 Hz), 5.18 4mc, 1 H, 6-H, J6,7ˆ8.3 Hz, J6,8ˆ
3
4
5
3
0
1 Hz, J6,9 ˆ0.5 Hz), 5.78 4dddd, 1 H, 8-H, J8,7ˆ10.8 Hz,
3
3
4
0
J8,9ˆ8.3 Hz, J8,9 ˆ3 Hz, J8,6ˆ1.2 Hz), 5.99 4ddd, 1 H,
3
3
3
0
7-H, J7,8ˆ10.8 Hz, J7,6ˆ8.3 Hz, J7,9 ˆ3 Hz), 7.43 4mc, 2
H, m-PhH), 7.52 4mc, 1 H, p-PhH), 8.00 4mc, 2 H, o-PhH).
13C NMR 4100 MHz): dˆ25.2 4CH3), 29.9 4CH3), 30.2
4CH3), 38.5 4CH2), 39.9 4CH2), 46.0 49-CH2), 61.1 4NCq),
65.6 4C4CH3)2), 109.5 4yCH), 125.0 4yCH), 127.7 4yCH),
128.0 4CPh), 130.4 4CPh), 132.5 4CPh), 138.3 4Cq,Ph), 142.8
4yCN), 197.1 4CO). IR: 3060 cm21, 2970, 1665, 1600,
1550, 1450, 1370, 1320, 1260, 1235, 1175, 1020. UV
4CH3CN): lˆ248 nm4 e 16,400), 303 nm4 e 7700),
393 nm4 e 2900). MS 4EI): m/z 4%)ˆ281 42) [M1], 265
448), 210 468), 132 414), 105 4100), 77 478). HRMS calcd.
for C19H23NO: 281.1780; found 281.1783. Anal. calcd. for
C19H23NO: C 81.10, H 8.24, N 4.98; found C 80.96, H 8.26,
4.4.6.
3-[Buta-13E),3-dienyl]-2-3tert-butyl)-3a-methyl-
4,5,6,7-tetrahydro-3aH-isoxazolo [2,3-a]pyridine 314b).
The reaction of the mixture of 11b 4390 mg, 1.49 mmol),
dry NEt3 4470 mg, 4.63 mmol), DMAP 416 mg, 0.13 mmol)
in 17 ml of dry CH2Cl2 with methanesulfonic acid chloride
4220 mg, 1.90 mmol) afforded unreacted 11b 460 mg, 15%)
1
1
and 147 mg 440%) of 14b as pale yellow oil. H NMR
4250 MHz): dˆ1.20±1.27 4m, 1 H, CH2), 1.24 4s, 9 H,
N 4.89. 18a: H NMR 4250 MHz): dˆ1.71 4s, 6 H, CH3),
3
3
2.44 4t, 2 H, CH2, Jˆ7.5 Hz), 2.96 4t, 2 H, CH2, Jˆ
2
3
tBu), 1.30 4s, 3 H, CH3), 1.49±1.65 4m, 4 H, CH2), 2.23
7.5 Hz), 5.00 4dd, 1 H, yCH2, Jˆ1.3 Hz, Jˆ11 Hz), 5.27
2
3
2
3
4ddt, 1 H, CH2, Jˆ14 Hz, Jˆ4 Hz, 2 Hz), 2.71 4dt, 1 H,
4dd, 1 H, yCH2, Jˆ1.3 Hz, Jˆ17.7 Hz), 6.47 4dd, 1 H,
3
2
3
3
CH2, Jˆ4 Hz, 11 Hz), 3.14 4ddt, 1 H, CH2, Jˆ11 Hz,
yCH, Jˆ11 Hz, Jˆ17.7 Hz), 6.76 4s, 1 H, pyrrole-H),
7.43 4mc, 2 H, m-PhH), 7.51 4mc, 1 H, p-PhH), 7.77 4mc, 2
H, o-PhH). 13C NMR 4100 MHz): dˆ23.3 4CH2), 27.1
42£CH3), 44.1 4Ar-CH2), 65.0 4C4CH3)2), 110.5 4yCH2),
114.8 4Cq), 124.7 4HCy), 126.7 4Cq), 128.0 4CPh), 129.0
4CHpyrrole), 129.2 4CPh), 131.0 4CPh), 140.5 4Cq), 144.4
4Cq), 184.2 4CO). IR: 3080 cm21, 2967, 1627 4CO), 1578,
1453, 1381, 1315, 1240, 1172. MS 4EI): m/z 4%)ˆ265 448)
[M1], 237 410), 210 468), 132 414), 105 4100), 77 479).
HRMS calcd. for C18H19NO: 265.1467; found 265.1468.
3Jˆ4 Hz, 1 Hz), 4.98 4dd, 1 H, yCH2, Jˆ0.6 Hz, 3Jˆ
2
10.2 Hz), 5.11 4dd, 1 H, yCH2, Jˆ0.6 Hz, 3Jˆ17 Hz),
2
3
6.06 4dd, 1 H, yCH, Jˆ10 Hz, 15.9 Hz), 6.34 4ddd, 1 H,
yCH, 3Jˆ10 Hz, 10.2 Hz, 17 Hz), 6.57 4d, 1 H, HCy,
3Jˆ15.9 Hz). 13C NMR 4100 MHz): dˆ20.0 4CH2), 23.0
4CH2), 28.2 4CH3), 29.1 4tBu), 31.6 4CH2), 33.6 4Cq,tBu),
50.9 4NCH2), 69.9 4NCq), 110.8 4yCq), 114.4 4CH), 125.5
4CH), 125.7 4CH), 138.6 4CH), 160.6 4yCO). IR:
2968 cm21, 1619, 1571, 1452, 1370, 1276, 1164, 1116,
1000. UV 4CH3CN): lˆ300 nm4 e 24,000), 239 nm4 e
7500). MS 4EI): m/z 4%)ˆ247 45) [M1], 232 413), 190 48),
4.5.2. Thermolysis of 12b. The solution of 12b 4110 mg,

4356
W. Friebolin, W. Eberbach / Tetrahedron 57-2001) 4349±4358
0.42 mmol) in 55 ml of dry benzene at 2808C afforded after
¯ash chromatography and MPLC 14 mg 413%) of phenyl-
43,3,9a-trimethyl-2,3,9,9a-tetrahydro-1H-pyrrolo[1,2-a]-
trimethyl-2,3,9,9a-tetrahydro-1H-pyrrolo[1,2-a]azepin-5-yl)-
2,2-dimethylpropan-1-one 416b) and traces 41-2 mg, ca.
1%) of 1-42,2-dimethyl-7-vinyl-2,3-dihydro-1H-pyrrolizin-
5-yl)-2,2-dimethylpropan-1-one 419b), both as yellow oils.
16b: 1H NMR 4500 MHz): dˆ1.01 4s, 3 H, CH3), 1.20 4s, 3
H, 10-CH3), 1.25 4s, 3 H, CH3), 1.27 4s, 9 H, tBu), 1.71 4d, 1
1
azepin-5-yl)-methanone 415b) as colorless solid. H NMR
4500 MHz): dˆ0.97 4s, 3 H, 10-CH3), 1.16 4s, 3 H, CH3),
1.22 4s, 3 H, CH3), 1.29 4s, 9 H, tBu), 1.70 4ddd, 1 H, 10-H,
2
3
3
2
2
J1 ,1ˆ12.4 Hz, J1 ,2ˆ6.3 Hz, J1 ,2 ˆ1.9 Hz), 1.84 4ddd, 1
H, 1-H, Jˆ12.8 Hz), 1.95 4dd, 1 H, 10-H, Jˆ12.8 Hz,
0
0
0
3
0
H, 1-H, 2Jˆ12 Hz, 3J1,2 ˆ6.9 Hz, Jˆ2 Hz), 1.88 4ddd, 1 H,
J1 ,3 ˆ0.9 Hz), 2.00 4mbr, 1 H, 9 -H, J9 ,9ˆ15.2 Hz,
4
3
2
0
0
0
0
0
20-H, J2 ,2ˆ12 Hz, 3J2 ,1ˆ6.9 Hz, 3J2 ,1 ˆ1.9 Hz), 2.15 4ddd,
J9 ,8ˆ3.6 Hz, J9 ,7ˆ3.7 Hz), 2.41 4dd, 1 H, 9-H, J9,9
ˆ
2
4
2
0
0
0
0
0
0
0
2
3
3
2
0
0
1 H, 2-H, Jˆ12 Hz, J2,1 ˆ6.9 Hz), 2.32 4m, 2 H, 9,9 -H),
15.2 Hz, J9,8ˆ8.3 Hz), 2.76 4d, 1 H, 3-H, Jˆ10.1 Hz),
3
4.96 4d, 1 H, 6-H, J6,7ˆ8 Hz), 5.67 4ddd, 1 H, 8-H,
3.00 4d, 1 H, 30-H, 2Jˆ10.1 Hz), 4.66 4d, 1 H, 6-H,
3
3
3
3
3
J8,7ˆ11 Hz, J8,9ˆ6 Hz, J8,9 ˆ4 Hz), 5.91 4ddd, 1 H, 7-
3J6,7ˆ7.6 Hz), 5.56 4ddd, 1 H, 8-H, J8,7ˆ11.5 Hz, J8,9ˆ
0
H, J7,8ˆ11 Hz, J7,6ˆ8 Hz, J7,9 ˆ2 Hz). 13C NMR
4125 MHz): dˆ24.8 4CH3), 29.9 4tBu), 29.8 4CH3), 29.8
4CH3), 38.3 4CH2), 39.6 4CH2), 44.7 49-CH2), 45.2 4Cq,tBu),
61.6 4NCq), 64.5 4C4CH3)2), 105.8 4yCH), 124.5 4yCH),
8.5 Hz, J8,9 ˆ3.6 Hz), 6.10 4ddd, 1 H, 7-H, J7,8ˆ11.5 Hz,
3
3
3
3
3
0
0
3
J7,6ˆ7.6 Hz, 3J7,9 ˆ3.7 Hz). 13C NMR 4125 MHz): dˆ25.0
0
4CH3), 27.8 4CH3), 27.9 4tBu), 28.1 4CH3), 35.9 42-Cq), 44.4
4Cq,tBu), 45.5 4CH2), 56.4 4CH2), 62.5 4NCq), 66.0 4CH2),
95.9 4yCH), 122.9 4yCH), 126.0 4yCH), 144.0 4yCN),
212.8 4CyO). IR: 2959 cm21, 1690, 1575, 1437, 1291,
1157, 1091. MS 4EI): m/z 4%)ˆ261 4100) [M1], 246 480),
204 455), 190 425), 176 454), 164 488), 162 429), 120 422),
112 439), 91 422), 80 432), 57 462). HRMS calcd. for
C17H27NO: 261.2093; found 261.2093. 19b: 1H NMR
4400 MHz): dˆ1.25 4s, 6H, CH3), 1.35 4s, 9 H, tBu), 2.68
4s, 2 H, CH2), 4.08 4s, 2 H, NCH2), 5.00 4dd, 1 H, yCH2,
2Jˆ1 Hz, 3Jˆ11 Hz), 5.28 4dd, 1 H, yCH2, 2Jˆ1 Hz,
126.3 4yCH), 143.0 4yCN), 214.6 4CO). IR: 2966 cm21
,
1684, 1570, 1460, 1431, 1391, 1366, 1246, 1153, 1097.
MS 4EI): m/z 4%)ˆ261 4100) [M1], 246 499), 192 482),
176 452), 161 438), 120 499), 80 465). HRMS calcd. for
C17H27NO: 261.2093; found 261.2091.
4.5.3. Thermolysis of 13a. The solution of 13a 4115 mg,
0.41 mmol) in 48 ml of dry benzene at 3208C afforded
56 mg 448%) of phenyl-42,2,9a-trimethyl-2,3,9,9a-tetrahy-
dro-1H-pyrrolo[1,2-a]azepine-5-yl)-methanone 416a) and
4 mg 43%) of phenyl-46,6-dimethyl-1-vinyl-6,7-dihydro-
5H-pyrrolizin-3-yl)-methanone 419a), both as orange oils.
16a: 1H NMR 4250 MHz): dˆ0.95 4s, 3 H, CH3), 0.97 4d, 3
H, 10-CH3, 4Jˆ1.1 Hz), 0.99 4s, 3 H, CH3), 1.72 4d, 1 H, 1-
3Jˆ18 Hz), 6.51 4dd, 1 H, yCH, Jˆ11 Hz, Jˆ18 Hz),
3
3
7.00 4s, 1 H, pyrrole-H).
4.5.5. Thermolysis of 14a. The solution of 14a 4150 mg,
0.56 mmol) in 70 ml of dry benzene at 2808C afforded after
¯ash chromatography 72 mg 442%) of phenyl-410a-methyl-
1,2,3,4,10,10a-hexahydro-pyrido[1,2-a]azepin-6-yl)-metha-
none 417a) and 10 mg 47%) of phenyl-41-vinyl-4,5,6,7-
tetrahydro-indolizin-3-yl)-methanone 420a), both as deep
2
2
4
H, Jˆ12.8 Hz), 1.97 4dd, 1 H, 10-H, Jˆ12.8 Hz, J1 ,3
ˆ
0
0
0.8 Hz), 2.14 4mbr, 1 H, 90-H, J9 ,9ˆ15.8 Hz, 3J9 ,8ˆ3.5 Hz,
2
0
0
4
4
2
0
0
J9 ,7ˆ3.5 Hz, JCH3ˆ1.1 Hz), 2.51 4dd, 1 H, 9-H, J9,9
ˆ
3
2
15.8 Hz, J9,8ˆ8.3 Hz), 2.63 4d, 1 H, 3-H, Jˆ10.2 Hz),
3.23 4dbr, 1 H, 30-H, 2Jˆ10.2 Hz), 5.26 4d, 1 H, 6-H,
yellow oils. 17a: H NMR 4250 MHz): dˆ1.03 4sbr, 3 H,
1
3J6,7ˆ8.0 Hz), 5.80 4ddd, 1 H, 8-H, J8,7ˆ11.5 Hz, J8,9ˆ
CH3), 1.14±1.36 4m, 4 H, CH2), 1.40±1.60 4m, 3 H, CH2),
0
3
3
3
3
2
1.70±1.75 4m, 2 H, CH2), 2.22 4dd, 1 H, 10-H, J10,10
0
8.3 Hz, J8,9 ˆ3.5 Hz), 6.10 4ddd, 1 H, 7-H, J7,8ˆ11.5 Hz,
ˆ
3
3
3
2
J7,6ˆ8.0 Hz, J7,9 ˆ3.5 Hz), 7.41 4mc, 2 H, m-PhH), 7.52
17 Hz, J10,9ˆ7.9 Hz), 2.37 4ddd, 1 H, 40-H, J4 ,4
ˆ
0
0
4mc, 1 H, p-PhH), 7.90 4mc, 2 H, o-PhH). 13C NMR
4100 MHz): dˆ25.0 4CH3), 27.4 4CH3), 27.4 4CH3), 35.8
4Cq), 46.0 4CH2), 56.5 4CH2), 60.3 4NCq), 65.3 4CH2),
105.7 4yCH), 126.0 4yCH), 126.9 4yCH), 128.1 4CPh),
129.9 4CPh), 132.7 4CPh), 137.9 4Cq,Ph), 143.6 4yCN),
196.4 4CyO). IR: 3060 cm21, 3010, 2960, 2870, 2830,
1660 4CyO), 1600, 1560, 1450, 1280, 1150. UV
4CH3CN): lˆ388 nm4 e 3000), 288 nm4 e 6500), 248 nm
4e 13,800). MS 4EI): m/z 4%)ˆ281 453) [M1], 266 428), 252
414), 184 495), 176 435), 161 417), 120 417), 105 4100), 91
412), 80 468), 77 451). HMRS calcd. for C19H23NO:
281.1780; found 281.1780. 19a: 1H NMR 4250 MHz):
dˆ1.31 4s, 6 H, CH3), 2.76 4s, 2 H, CH2), 4.18 4s, 2 H,
13.7 Hz, J4 ,3ˆ10.7 Hz, J4 ,3 ˆ3.7 Hz), 2.65 4mc, 1 H,
3
3
0
0
0
2
3
100-H, J10 ,10ˆ17 Hz, J10 ,9ˆ3 Hz), 2.88 4dt, 1 H, 4-H,
0
0
2
3
0
0
J4,4 ˆ13.7 Hz, J4,3,3 ˆ4 Hz), 5.94±6.15 4m, 3 H, 7-H,
8-H, 9-H), 7.37±7.54 4m, 3 H, PhH), 7.92 4mc, 2 H,
o-PhH). 13C NMR 4100 MHz): dˆ20.1 4CH2), 24.0 4CH3),
25.5 4CH2), 39.2 4CH2), 39.5 4CH2), 50.2 4NCH2), 55.0
4NCq), 116.1 4HCy), 125.2 4HCy), 127.8 4CPh), 129.8
4CPh), 131.9 4CPh), 132.0 4HCy), 138.8 4Cq,Ph), 146.9
4yCN), 196.8 4CO). IR: 3030 cm21, 2940, 2870, 1655
4CO), 1600, 1560, 1450, 1380, 1275, 1240, 1130. MS
4EI): m/z 4%)ˆ267 483) [M1], 252 4100), 238 421), 224
424), 210 425), 184 468), 162 432), 149 439), 132 421), 105
478). HRMS calcd. for C18H21NO: 267.1623; found
2
3
1
NCH2), 5.02 4dd, 1 H, yCH2, Jˆ1.5 Hz, Jˆ11 Hz), 5.28
267.1623. 20a: H NMR 4250 MHz): dˆ1.83±2,04 4m, 4
2
3
3
4dd, 1 H, yCH2, Jˆ1.5 Hz, Jˆ17.7 Hz), 6.48 4dd, 1 H,
H, CH2), 2.87 4t, 2 H, CH2, Jˆ6 Hz), 4.46 4t, 2 H, CH2,
3
3
yCH, Jˆ11 Hz, Jˆ17.7 Hz), 6.82 4s, 1 H, pyrrole-H),
7.41±7.57 4m, 3 H, PhH), 7.81 4mc, 2 H, o-PhH). IR:
3060 cm21, 2980, 2870, 1620 4CyO), 1600, 1460, 1390,
1275, 1260, 1160. MS 4EI): m/z 4%)ˆ265 467) [M1], 250
442), 239 415), 224 413), 210 417), 149 461), 105 479), 77
429).
3Jˆ6 Hz), 5.00 4dd, 1 H, yCH2, 2Jˆ1.2 Hz, 3Jˆ11 Hz), 5.33
4dd, 1 H, yCH2, 2Jˆ1.2 Hz, 3Jˆ17 Hz), 6.52 4dd, 1 H, HCy,
3Jˆ17 Hz, Jˆ11 Hz), 6.81 4s, 1 H, CpyrroleH), 7.41±7.54
3
4m, 3 H, PhH), 7.77 4mc, 2 H, o-PhH). IR: 3080 cm21
,
2950, 2870, 1625 4CO), 1600, 1490, 1470, 1385, 1320,
1240, 1175. MS 4EI): m/z 4%)ˆ251 499) [M1], 250 4100),
225 431), 224 436), 149 460), 105 454), 77 447). HRMS
calcd. for C17H17NO: 251.1310; found 251.1310.
4.5.4. Thermolysis of 13b. The solution of 13b 4127 mg,
0.48 mmol) in 60 ml of dry benzene at 2808C afforded after
¯ash chromatography and MPLC 48 mg 438%) of 1-42,2,9a-
4.5.6. Thermolysis of 14b. The solution of 14b 476 mg,

W. Friebolin, W. Eberbach / Tetrahedron 57-2001) 4349±4358
4357
0.31 mmol) in 40 ml of dry benzene at 2808C afforded after
¯ash chromatography and MPLC 31 mg 441%) of 1-410a-
methyl-1,2,3,4,10,10a-hexahydropyrido[1,2-a]azepin-6-yl)-
2,2-dimethylpropan-1-one 417b) as pale yellow oil and
traces 4,1%) of 2,2-dimethyl-1-41-vinyl-5,6,7,8-tetra-
hydroindolizin-3-yl)-propan-1-one 420b). 17b: 1H NMR
4250 MHz): dˆ0.99 4sbr, 3 H, CH3), 1.28 4s, 9 H, tBu),
1.53±1.66 4m, 4 H, CH2), 1.70±1.75 4m, 2 H, CH2), 2.08
13C NMR 4100 MHz): dˆ21.9 4CH3), 24.4 4CH3), 31.9
4CH3), 32.8 43-CH2), 39.6 44-CH2), 54.7 4Caziridine), 55.58
4Caziridine), 66.3 4C4CH3)2), 118.5 4yCH2), 126.9 4yCH),
128.3 4CPh), 129.6 4CPh), 132.7 4Cph), 136.0 4Cq,Ph), 136.2
4yCH), 139.1 4HCy), 196.1 4CO). IR: 3060 cm21, 2963,
1675 4CO), 1597, 1449, 1381, 1365, 1258, 1170, 1003.
MS 4EI): m/z 4%)ˆ281 431) [M1], 266 416), 212 430), 176
49), 120 471), 105 448), 800 4100), 77 449). HRMS calcd. for
C19H23NO: 281.1780; found 281.1777.
2
3
0
4dd, 1 H, 10-H, J7,7 ˆ17 Hz, J7,9ˆ8 Hz), 2.39 4ddd, 1 H,
90-H, J9 ,9ˆ14 Hz, 3J9 ,7ˆ9 Hz, 3J9 ,7 ˆ5 Hz), 2.66 4mc, 1 H,
2
0
0
3
0
0
2
70-H, J7 ,7ˆ17 Hz, J7 ,9ˆ3 Hz), 2.93 4dt, 1 H, 9-H,
0
0
4.6.2. Photolysis of 13a. A degassed solution of 13a
4200 mg, 0.71 mmol) in 230 ml of dry benzene at 208C
was irradiated for 20 min with a high pressure mercury
lamp 4Hanau TQ 150, 150 W) using a Jena ®lter
4l.290 nm). After concentration ¯ash chromatography of
the residue 4SiO2, cyclohexane/ethyl acetate 100:1) afforded
61 mg 430%) of phenyl-46-buta-1,3-dienyl-3,3,5-trimethyl-
1-aza-bicyclo[3.1.0]hex-6-yl)-methanone 422a) as orange
2
3
3
0
0
J9,9 ˆ14 Hz, J9,7 ˆ3 Hz), 5.23 4d, 1 H, 7-H, Jˆ8 Hz),
5.77 4ddd, 1 H, 9-H, J9,9ˆ11 Hz, 3Jˆ8 Hz, 4Jˆ3 Hz),
3
3
3
3
0
0
5.95 4ddd, 1 H, 9-H, J9,9 ˆ11 Hz, J9,10ˆ8 Hz, J9,10
ˆ
3 Hz). 13C NMR 4125 MHz): dˆ20.3 4CH2), 24.4 4CH3),
25.7 4CH2), 28.1 4tBu), 38.3 4CH2), 40.0 4CH2), 44.5
4Cq,tBu), 50.7 4NCH2), 54.9 4NCq), 109.9 43-CH), 125.4
45-CH), 129.1 44-CH), 149.2 4yCN), 213.5 4CO). IR:
2936 cm21, 1675, 1576, 1478, 1378, 1257, 1147, 1119,
1097. MS 4EI): m/z 4%)ˆ247 430) [M1], 232 4100), 190
416), 176 411), 164 418), 147 410). HRMS calcd. for
C16H25NO: 247.1936; found 247.1937. 20b: 1H NMR
4250 MHz): dˆ1.37 4s, 9 H, tBu), 1.78±1.94 4m, 4 H,
1
oil. H NMR 4250 MHz): dˆ1.05 4s, 3 H, CH3), 1.26 4s, 3
H, CH3), 1.28 4s, 3 H, CH3), 1.70 4dd, 1 H, 4-CH2,
2Jˆ13.6 Hz, 3Jˆ0.8 Hz), 2.05 4d, 1 H, 4-CH2, 2Jˆ
2
13.6 Hz), 2.64 4d, 1 H, 2-CH2, Jˆ12 Hz), 3.10 4dd, 1 H,
2-CH2, 2Jˆ12 Hz, 3Jˆ0.8 Hz), 5.10 4dd, 1 H, yCH2,
3
2
2Jˆ1.6 Hz, Jˆ10.7 Hz), 5.14 4dd, 1 H, yCH2, Jˆ1.6 Hz,
3
CH2), 2.82 4t, 2 H, CH2, Jˆ6 Hz), 4.30 4t, 2 H, CH2,
3Jˆ16.6 Hz), 5.69 4dbr, 1 H, 8-HCy, Jˆ15.5 Hz), 6.23±
3
3Jˆ6 Hz), 5.02 4dd, 1 H, yCH2, Jˆ1.6 Hz, Jˆ11 Hz),
2
3
2
3
6.41 4m, 2 H, 7-/9-HCy), 7.41 4mc, 2 H, m-PhH), 7.50
4mc, 1 H, p-PhH), 7.90 4mc, 2 H, o-PhH). 13C-NMR
4100 MHz): dˆ23.1 4CH3), 25.2 4CH3), 32.2 4CH3), 45.8
4Cq), 48.8, 58.8 4Caziridine), 59.8 4Caziridine), 63.1 4NCH2),
119.3 4yCH2), 125.5 4CH), 128.1 4CH), 128.4 4CH), 129.6
4CH), 130.0 4CH), 133.0 4CH), 136.0 4Cq,Ph), 136.1 4CH),
139.8 4CH), 196.7 4CO). IR: 3060 cm21, 2960, 2880, 1680
4CO), 1600, 1450, 1370, 1260, 1175, 1025. MS 4EI): m/z
4%)ˆ281 47) [M1], 266 47), 176 448), 122 411), 120 410),
105 4100), 91 412), 80 416), 77 471). HRMS calcd. for
C19H23NO: 281.1780; found 281.1778.
5.37 4dd, 1 H, yCH2, Jˆ1.6 Hz, Jˆ17.7 Hz), 6.55 4dd, 1
3
3
H, HCy, Jˆ17.7 Hz, Jˆ11 Hz), 7.12 4s, 1 H, CpyrroleH).
4.5.7. Thermolysis of 21a. The thermolysis of a solution of
20 mg 40.07 mmol) of 21a 4see Section 4.6.1) in 14 ml of
dry benzene at 2808C gave a crude material which according
1
to the H NMR analysis contained 15a and 18a, respec-
tively. Flash chromatography 4SiO2, cyclohexane/ethyl ace-
tate 20:1) of the residue afforded 5 mg 425%) of 15a and
traces of 18a.21
4.5.8. Thermolysis of 22a. The thermolysis of a solution of
33 mg 40.12 mmol) of 22a 4see Section 4.6.2) in 20 ml of
dry benzene at 3208C gave a crude material which according
Acknowledgements
1
to the H NMR analysis contained 16a and 19a, respec-
tively. Flash chromatography 4SiO2, cyclohexane/ethyl
acetate 20:1) of the residue afforded 10 mg 430%) of 16a
and traces of 19a.21
Financial support of the Fonds der Chemischen Industrie is
gratefully acknowledged.
4.6. Photolysis of 12a and 13a
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