Polarity matching of radical trapping: High yielding 3-exo and 4-exo cyclizations

Article abstract of DOI:10.1002/chem.200400685

A catalyzed synthesis of cyclopropanes and cyclobutanes via radical chemistry is described. The method that generally proceeds in high yields uses epoxides as radical precursors and titanocene(III) complexes as the electron transfer catalysts (see scheme)

Full text of DOI:10.1002/chem.200400685

FULL PAPER
Polarity Matching of Radical Trapping: High Yielding 3-exo and 4-exo
Cyclizations
Andreas Gansäuer,* Thorsten Lauterbach, and Daniel Geich-Gimbel[a]
Abstract: A catalyzed synthesis of cyclopropanes and cyclobutanes via radical
chemistry is described. The method that generally proceeds in high yields uses ep-
oxides as radical precursors and titanocene(iii) complexes as the electron transfer
catalysts (see scheme). The key to the success of the transformation is constituted
by the chemoselectivity of radical reduction. Electrophilic enol radicals generated
through cyclization are reduced rapidly whereas their precursors, nucleophilic
alkyl radicals, remain unaffected.
Keywords: cyclobutanes · cyclopro-
panes · epoxides · radical reactions ·
titanium
Introduction
lems. The method is complementary to the concepts used in
traditional free radical chemistry for the synthesis of small
rings. In these cases the stabilization of the carbinyl radicals
through conjugation and incorporation of some of the ring
strain of the cyclopropanes into the starting materials have
been utilized with good success.[6]
Our approach exploits the different and polarity control-
led reactivity of alkyl radicals generated from epoxides[7,8]
and enol radicals generated after cyclization towards
[Cp2TiCl], the electron transfer reagent used in this study.
This allows both formation and trapping of the unstable car-
binyl radicals as shown in Scheme 2.
Radical cyclization reactions are amongst the most powerful
and versatile methods for the construction of mono- and
polycyclic systems.[1] However, the synthesis of small rings,
that is, cyclopropanes, a highly interesting functional group
under theoretical, preparative and structural aspects,[2] and
cyclobutanes, is usually difficult. In the former case this is
because ring openings of the intermediate cyclopropyl car-
binyl radicals are amongst the fastest radical reactions
known (k~108–109 sꢀ1)[3] and in the latter case, ring closure
is one of the slowest radical reactions (k~1 sꢀ1) while ring
opening of the cyclobutylcarbinyl radical is fast,[4] as shown
in Scheme 1.
Scheme 2. Polarity matching for radical trapping.
Scheme 1. Kinetics of the 3-exo and 4-exo cyclization.
At first glance our approach may seem similar to the one
employed by Fernµndez-Mateos in his elegant stoichiomet-
ric cyclization reactions of epoxide derived radicals to alde-
hydes and ketones[7e] or to nitriles.[7f] However, both reac-
tions do not work under our catalytic conditions and must
therefore be considered as conceptually different. While a
detailed study on this discrepancy would have to be carried
out to establish the differences, we suggest hydrogen atom
abstraction from THF by the highly electrophilic and short-
lived radicals generated under Fernµndez-Mateosꢀ condi-
tions as a plausible cause.[9] Catalyst regeneration would
In this publication we wish to report our first results on
high yielding, catalytic, and tin free[5] radical syntheses of cy-
clopropanes and cyclobutanes circumventing these prob-
[a] Prof. Dr. A. Gansäuer, T. Lauterbach, D. Geich-Gimbel
KekulØ-Institut für Organische Chemie und Biochemie
der Universität Bonn
Gerhard Domagk Strasse 1, 53121 Bonn (Germany)
Fax : (+49)228-734760
E-mail: andreas.gansaeuer@uni-bonn.de
Chem. Eur. J. 2004, 10, 4983 – 4990
DOI: 10.1002/chem.200400685
ꢁ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4983

FULL PAPER
then become difficult. This is not the case under our condi-
tions.
In free radical chain reactions polarity controlled transfor-
mations have been used with excellent success, for example,
in Robertsꢀ polarity reversed catalysis.[10]
With the b-ionone derived epoxides 1, 3, and 5 good to
excellent yields of the desired cyclopropanes were achieved
through polarity controlled reduction (entries 1–3). Diaster-
eoselectivities of the cyclizations were excellent. It is impor-
tant to note the good yield of the reaction of 1 containing
an enone.[11] As this sensitive functional group is reduced
rapidly by other popular electron transfer reagents, for ex-
ample, SmI2,[12] the mildness of the radical generation from
epoxides with [Cp2TiCl] is impressively highlighted.
The alternative approach of a thermodynamic stabiliza-
tion of the cyclopropyl carbinyl radical, that has been ap-
plied with success in traditional free radical chemistry to-
gether with incorporation of some of the cyclopropaneꢀs
strain[6,13] in the starting material, was also investigated
(entry 4). With epoxide 7 cyclization should lead to a highly
stabilized benzyl radical. This intermediate is, however, re-
duced even more slowly by [Cp2TiCl] than simple alkyl radi-
cals.[8l] As none of the desired product could be isolated it is
clear that the thermodynamic promotion of the 3-exo cycli-
zation is not relevant for the other examples in table 1 also,
since radical stabilization by ketone, ester, and amide
groups (entries 1–3) is much smaller compared with
arenes,[14] especially when a tertiary radical adds to the a,b-
unsaturated carbonyl compounds (all entries except
entry 6).
Nucleophilic alkyl radicals generated through epoxide
opening are only slowly reduced by [Cp2TiCl]. Since no
other radical pathway than cyclization is available under our
reaction conditions they remain fairly stable. This results in
increased longevity that is decisive for the very slow forma-
tion of the cyclobutyl carbinyl radicals in the 4-exo cycliza-
tion. The unfavorable equilibrium for the formation of both
rings is therefore irrelevant if the radicals generated through
cyclization are reduced efficiently. The swift and exothermic
trapping of the electrophilic enol radical to yield titanium
enolates provides this desired electronic differentiation and
thus a driving force for irreversible termination of small ring
formation.
Results and Discussion
We decided to check the validity of the concept for 3-exo
cyclizations first to avoid anticipated problems of the very
slow 4-exo cyclization. The results summarized in Table 1
amply demonstrate the validity of our approach.
The other cases shown demonstrate that substitution pat-
terns difficult to access with other methods[15] can be readily
obtained in good to excellent yields. The epoxide precursors
may be mono- (11, entry 6), di- (9, 13, 15, entries 5, 7, 8),
and trisubstituted (1, 3, 5, entries 1, 2, 3). Thus tetra- (2, 4,
6, and 12, entries 1–3, 6) and even pentasubstituted cyclo-
propanes (10, 14, and 16, entries 5, 7, and 8) can be easily
prepared by our method. Diastereoselectivities are in the
usual range for radical cyclizations.
Table 1. Titanocene catalyzed 3-exo cyclizations.[10] For reasons of clarity
only the major isomer is shown.
Entry
Substrate
Product
Yield [%]
72
1
The substrates for the cyclization were prepared according
to standard procedures from known compounds as shown in
Schemes 3 and 4.
2
3
4
5
92
96
<10
95, dr 63:37
6
88, dr 81:19
7
8
72, dr 75:25
84, dr 75:25
Scheme 3. Synthesis of 3-exo cyclization precursors. See Experimental
Section for details.
4984
ꢁ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Chem. Eur. J. 2004, 10, 4983 – 4990

Radical Trapping
4983 – 4990
Scheme 6. Synthesis of precursors for the 4-exo cyclization. See Experi-
mental Section for details.
enoate is reduced before the carbonyl group.[16d] To the best
of our knowledge, our examples belong to the most efficient
4-exo cyclizations known as yet.
In summary, the concept of polarity matching of radical
trapping has provided
a highly efficient and catalytic
method for the preparation of cyclopropanes and cyclobu-
tanes through radical chemistry. It also avoids the toxicity
problems associated with tin reagents.
Experimental Section
Scheme 4. Synthesis of precursors for the 3-exo cyclization. See Experi-
mental Section for details.
General procedures: All reactions were performed in oven-dried (1008C)
glassware under Ar. THF was freshly distilled from K. Et2O was freshly
distilled from Na/K. CH2Cl2 was freshly distilled from CaH2. The prod-
ucts were purified by flash chromatography on Merck silica gel 50 (elu-
ents given in brackets, EE refers to ethyl acetate, CH to cyclohexane, PE
to petrol ether 40–608C).[17] Yields refer to analytically pure samples.
Isomer ratios were determined by suitable 1H NMR integrals of cleanly
separated signals. NMR: Bruker AMX 300, AM 400; 1H NMR, [D5]ben-
zene (7.16 ppm) and CHCl3 (7.26 ppm) in the indicated solvent as inter-
nal standard in the same solvent; 13C NMR: CDCl3 (77.16 ppm) and
C6D6 (138.06 ppm) as internal standard in the same solvent; integrals in
accord with assignments, coupling constants are measured in Hz and
We then focussed our attention to 4-exo cyclizations. It
turned out that under our conditions excellent results could
be obtained as shown in Scheme 5.
always constitutes J(H,H) coupling constants. An asterisk ( ) indicates
*
the signal of the minor diastereomer. Combustion analyses: Mr. Frank
Hambloch, Institut für Organische Chemie der Georg-August-Universität
Göttingen and Mrs. Annie Martens, KekulØ-Institut für Organische
Chemie der Rheinischen Friedrich-Wilhelms-Universität Bonn. IR spec-
tra: Perkin-Elmer 1600 series FT-IR as KBr-Pellets or neat films on KBr
plates.
The following compounds were prepared according to literature proce-
dures, or have already been described in the literature: The following
compounds were synthesized according to literature procedures: 1,[18]
17,[19] 18,[20] 23,[21] 25,[22] 27,[23] 36.[24]
Scheme 5. Titanocene catalyzed 4-exo cyclization.
General procedure 1 (GP 1)
Horner–Wadsworth–Emmons olefination: NaH (96.0 mg 4.00 mmol) was
suspended in dry Et2O (30 mL). The phosphonate (5.00 mmol) was
added dropwise to the suspension. After the reaction mixture became
clear (usually 5 min except 2 h for the tert-butyl) the aldehyde
(3.00 mmol) was added. The solution was stirred at room temperature for
the indicated time. The organic phase was washed with water (2”15 mL),
the combined aqueous layers were extracted with CH2Cl2 (10 mL). The
combined organic layers were washed with brine (5 mL) and dried
(MgSO4). The solvents were removed under reduced pressure and the
crude product purified by silica gel chromatography.
The high yields indicate that the longevity of the alkyl
radicals generated by electron transfer from titanocene(iii)
chloride is sufficient to enable the unusually slow 4-exo cyc-
lization[16] without interference of competing radical path-
ways. This results in an almost quantitative trapping of the
enol radicals obtained after cyclization to give the cyclobu-
tanes in excellent yield. The starting materials were pre-
pared as shown in Scheme 6.
General procedure 2 (GP 2)
Efficient 4-exo cyclizations via radical chain processes are
rare and require special substrates or stabilization of the
Epoxidation of olefins by mCPBA: The olefin (2.00 mmol) was dissolved
in dichloromethane (20 mL). At 08C mCPBA (518 mg, 3.00 mmol) was
added. The reaction mixture was stirred at room temperature for the in-
dicated time. After adding of Et2O (50 mL) the organic phase was
washed with 2n NaOH (2”10 mL), the combined aqueous layers were
products.[16a,b] I n SmI chemistry only cyclization of ketyl
2
radicals to enoates are known. However, at least in the case
of ketones it has been unequivocally demonstrated that the
Chem. Eur. J. 2004, 10, 4983 – 4990
www.chemeurj.org
ꢁ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4985

A. Gansäuer et al.
FULL PAPER
extracted with CH2Cl2 (10 mL). The combined organic layers were
washed with brine (5 mL) and dried (MgSO4). The solvents were re-
moved under reduced pressure and the crude product purified by silica
gel chromatography.
142.9, 123.7, 58.7, 58.2, 52.3, 36.5, 35.1, 31.3, 29.1, 28.1, 27.2, 24.1,
22.1 ppm; IR (film): n˜ =2930, 1660, 1610, 1415, 1390, 1305, 1260, 1150,
1110, 1045, 990, 895, 870, 805, 745, 715, 650, 620 cmꢀ1; HRMS (EI,
70 eV): m/z: calcd for C14H23NO2: 237.1729; found: 137.1734 [M]+.
2-(2-Hydroxy-1,5,5-trimethyl-bicyclo[4.1.0]hept-7-yl)-N,N-dimethylacet-
General procedure 3 (GP 3)
amide (6): According to GP 3
5 (237 mg, 1.00 mmol), [Cp2TiCl2]
Radical cyclization: The epoxide (1.00 mmol) was added to a suspension
of [Cp2TiCl2](24.9 mg, 100mmol), collidine hydrochloride (394 mg,
2.50 mmol) and zinc dust (131 mg, 2.00 mmol), that were heated under
vacuum until the collidine hydrochloride began to sublime slightly prior
to use, in dry THF (10 mL) and the reaction mixture stirred at room tem-
perature for the indicated time.
(24.9 mg, 100 mg), collidine hydrochloride (394 mg, 2.50 mmol) and zinc
dust (131 mg, 2.00 mmol) for 16 h. Silica gel chromatography (CH/EE
17:5) gave 6 (229 mg, 96%). Rf =0.1 (CH/EE 17:5); 1H NMR (400 MHz,
C6D6): d=4.78 (brs, 1H), 4.09 (dd, 3J=5.8, 5.8 Hz, 1H), 2.56 (s, 3H),
2.20 (dd, 2J=17.2, 3J=4.2 Hz, 1H), 2.10 (s, 3H), 1.68 (dddd, 2J=13.9,
3J=9.6, 5.8, 3.6 Hz, 1H), 1.51 (dddd, 2J=14.3, 3J=8.4, 6.0, 2.8 Hz, 1H),
1.42 (dd, 2J=17.2, 3J=11.2 Hz, 1H), 1.26 (ddd, 2J=13.6, 3J=9.7, 3.0 Hz,
After adding of Et2O (20 mL) the reaction mixture was washed with of
2n HCl (2”10 mL), in case of amides with water (2”10 mL), the com-
bined aqueous layers were extracted with CH2Cl2 (10 mL). The combined
organic layers were washed with brine (5 mL) and dried (MgSO4). The
solvents were removed under reduced pressure and the crude product
purified by silica gel chromatography.
3
1H), 1.12 (ddd, J=11.2, 6.4, 4.2 Hz, 1H), 1.09 (s, 3H), 1.03 (s, 3H), 0.96
2
3
3
(ddd, J=13.9, J=9.0, 3.4 Hz, 1H), 0.94 (s, 3H), 0.20 ppm (d, J=5.9 Hz,
1H); 13C NMR (100 MHz, C6D6): d=172.6, 71.3, 39.4, 35.7, 34.9, 33.3,
32.2, 31.3, 29.0, 28.4, 28.0, 26.9, 20.1, 18.1 ppm; IR (film): n˜ =3350, 2950,
2870, 1610, 1500, 1460, 1415, 1360, 1270, 1150, 1120, 1035, 1000, 920, 855,
795 cmꢀ1; elemental analysis calcd (%) for C14H25NO2 (239.35): C 70.25,
H 10.53, N 5.85; found: C 69.96, H 10.46, N 5.79.
1-(2-Hydroxy-1,5,5-trimethyl-bicyclo[4.1.0]hept-7-yl)-propan-2-one
(2):
According to GP 3 1 (417 mg, 2.00 mmol), [Cp2TiCl2] (48.8 mg, 200 mg),
collidine hydrochloride (788 mg, 5.00 mmol) and zinc dust (262 mg,
4.00 mmol) for 16 h. Silica gel chromatography (CH/EE 9:1) gave 2
(302 mg, 72%). Rf =0.4 (CH/EE 9:1); 1H NMR (300 MHz, CDCl3): d=
3.82 (t, 3J=6.1 Hz, 1H), 3.99 (brs, 1H), 2.80 (dd, 2J=18.9, 3J=4.2 Hz,
1H), 2.13 (s, 3H), 2.12 (dd, 2J=19.1, 3J=10.3 Hz, 1H), 1.57 (dddd, 2J=
14.1, 3J=8.7, 5.4, 3.3 Hz, 1H), 1.25–1.04 (m, 2H), 1.01 (s, 3H), 1.00 (s,
3H), 0.99–0.88 (m, 2H), 0.87 (s, 3H), 0.40 ppm (d, 3J=5, 8 Hz, 1H);
13C NMR (75 MHz, CDCl3): d=210.2, 72.2, 43.1, 39.8, 33.6, 31.6, 29.7,
28.6, 27.2, 19.9, 16.5 ppm; IR (film): n˜ =3475, 2950, 1710, 1465, 1410,
1360, 1305, 1235, 1165, 1070, 1050, 985, 895 cmꢀ1; HRMS (EI, 70 eV): m/
z: calcd for C13H22O2: 210.1620; found: 210.1631 [M]+.
1,3,3-Trimethyl-2-styryl-7-oxa-bicyclo[4.1.0]heptane (7): Benzyltriphenyl-
phosphonium bromide (3.47 g, 8.00 mmol) was suspended in THF
(60 mL). At 08C n-butyl lithium (384 mg (2.4m in hexane), 6.00 mmol)
was added dropwise (5 min). After the reaction mixture was stirred for
30 min at 08C, 17 (1.01 g, 6.00 mmol) was added dropwise (10 min). The
solution was allowed to stir at rt for 16 h. After addition of water
(30 mL) triphenylphosphine oxide was precipitated by dropwise addition
of PE. The organic layer was filtered and dried (MgSO4). The solvents
were removed under reduced pressure and the crude product purified by
silica gel chromatography (CH/EE 49:1) to yield 7 (480 mg, 33%, dr
10:1). Rf =0.4 (CH/EE 19:1); 1H NMR (400 MHz, C6D6): d=7.35–7.29
(m, 2H), 7.14–7.09 (m, 2H), 7.07–7.01 (m, 1H), 6.44 (dd, 3J=15.9,
9.3 Hz, 1H), 6.36 (d, 3J=15.8 Hz, 1H), 2.79 (dd, 3J=2.8, 1.4 Hz, 1H),
1.89 (dd, 3J=9.2, 4J=0.8 Hz, 1H), 1.84 (dddd, 2J=15.2, 3J=5.3, 4.4,
1.1 Hz, 1H), 1.57 (dddd, 2J=15.1, 3J=10.2, 5.8, 3.0 Hz, 1H), 1.43 (ddd,
3-(1,3,3-Trimethyl-7-oxa-bicyclo[4.1.0]hept-2-yl)-acrylic ethyl ester (3):
According to GP 1 17 (1.68 g, 10.0 mmol), NaH (300 mg, 12.5 mmol), the
phosphonate (3.36 g, 15.0 mmol) in THF (50 mL) for 16 h. Silica gel chro-
matography (CH/EE 9:1) to yield 3 (1.62 g, 70%). Rf =0.4 (CH/EE
17:3); 1H NMR (400 MHz, C6D6): d=7.26 (dd, 3J=15.7, 10.4 Hz, 1H),
5.97 (dd, 3J=15.7, 5J=0.6 Hz, 1H), 4.03 (qd, 3J=7.1, 5J=1.5 Hz, 2H),
2.65 (dd, 3J=2.5, 1.6 Hz, 1H), 1.76 (d, 3J=10.4 Hz, 1H), 1.69 (dddd, 2J=
15.2, 3J=5.3, 3.9, 1.4 Hz, 1H), 1.43 (dddd, 2J=15.2, 3J=10.8, 5.9, 2.7 Hz,
1H), 1.25 (ddd, 2J=13.5, 3J=10.8, 5.3 Hz, 1H), 1.02 (s, 3H), 0.97 (t, 3J=
7.1 Hz, 3H), 0.63 (s, 3H), 0.59 (s, 3H), 0.63–0.55 ppm (m, 1H); 13C NMR
(100 MHz, C6D6): d=165.6, 147.0, 124.3, 60.1, 58.8, 58.1, 52.2, 31.1, 28.7,
27.7, 27.2, 23.9, 22.0, 14.3 ppm; IR (film): n˜ =2960, 1720, 1650, 1450,
3
2
2J=13.2, J=10.1, 5.3 Hz, 1H), 1.18 (s, 3H), 0.79 (s, 3H), 0.78 (dddd, J=
3
4
13.3, J=5.6, 4.5, J=1.0 Hz, 1H), 0.66 ppm (s, 3H); 13C NMR (100 MHz,
C6D6): d=138.0, 133.0, 129.0, 128.8, 127.3, 126.7, 59.2, 59.0, 53.3, 31.6,
29.8, 28.3, 27.2, 24.1, 22.4 ppm; IR (film): n˜ =3025, 2955, 1600, 1940,
1450, 1380, 1305, 1180, 1145, 1095, 1045, 975, 895, 860, 800, 755, 725,
695 cmꢀ1; HRMS (EI, 70 eV): m/z: calcd for C17H22O: 242.1671; found:
242.1664 [M]+.
2,2-Dimethyl-3-propyl-but-3-enoic ethyl ester (19): NaH (661 mg,
28.8 mmol) was suspended in dry DMSO (30 mL) and heated at 708C for
1 h. Methyltriphenylphosphonium bromide (10.3 g, 28.8 mmol) in DMSO
(30 mL) was added. After 1 h 18 (4.66 g, 25.0 mmol) was added and the
reaction mixture was stirred at 558C for 16 h. The Reaction was stopped
by adding water (60 mL) and extracting with Et2O (3”50 mL). The com-
bined organic layer was washed with water/DMSO (1:1, 50 mL), brine
(20 mL) and dried (MgSO4). The solvents were removed under reduced
pressure and the crude product purified by silica gel chromatography
(PE/Et2O 99:1) to yield 19 (2.02 g, 44%). Rf =0.4 (PE/Et2O 19:1);
1H NMR (400 MHz, CDCl3): d=4.98 (s, 1H), 4.87 (s, 1H), 4.11 (q, 3J=
7.1 Hz, 2H), 1.93 (t, 3J=7.7 Hz, 2H), 1.48 (qt, 3J=7.7, 7.6 Hz, 2H), 1.31
(s, 6H), 1.22 (t, 3J=7.1 Hz, 3H), 0.91 ppm (t, 3J=7.3 Hz, 3H); 13C NMR
(100 MHz, CDCl3): d=176.7, 152.0, 108.3, 60.5, 48.1, 34.3, 24.8, 21.6, 14.1,
14.0 ppm; IR (film): n˜ =2960, 1730, 1640, 1465, 1380, 1255, 1135, 1030,
895 cmꢀ1; HRMS (EI, 70 eV): m/z: calcd for C11H20O2: 184.1463; found:
184.1454 [M]+.
1365, 1340, 1305, 1260, 1215, 1160, 1115, 1095, 1045, 990, 960, 905 cmꢀ1
;
HRMS (EI, 70 eV): m/z: calcd for C14H22O3: 238.1569; found: 238.1575
[M]+.
(2-Hydroxy-1,5,5-trimethyl-bicyclo[4.1.0]hept-7-yl)-acetic ethyl ester (4):
According to GP 3 3 (238 mg, 1.00 mmol), [Cp2TiCl2] (24.9 mg, 100 mg),
collidine hydrochloride (394 mg, 2.50 mmol) and zinc dust (131 mg,
2.00 mmol) for 16 h. Silica gel chromatography (CH/EE 49:1) gave 4
(222 mg, 92%). Rf =0.1 (CH/EE 19:1); 1H NMR (400 MHz, C6D6): d=
3.93–3.88 (m, 1H), 3.91 (q, 3J=7.1 Hz, 2H), 2.70 (dd, 3J=9.8, 5.0 Hz,
1H), 2.34 (dd, 2J=17.7, 3J=5.1 Hz, 1H), 1.81 (dd, 2J=17.6, 3J=10.3 Hz,
1H), 1.55 (dddd, 2J=14.1, 3J=8.8, 5.5, 3.3 Hz, 1H), 1.29 (dddd, 2J=13.9,
2
3
3J=9.5, 6.7, 2.8 Hz, 1H), 1.11 (ddd, J=13.7, J=9.0, 2.8 Hz, 1H), 1.04 (s,
3H), 1.00 (ddd, 2J=10.6, 3J=9.5, 3.3 Hz, 1H), 0.95 (t, 3J=7.2 Hz, 3H),
0.93 (s, 3H), 0.91–0.86 (m, 1H), 0.84 (s, 3H), 0.20 ppm (d, 3J=5.8 Hz,
1H); 13C NMR (100 MHz, C6D6): d=174.0, 71.8, 60.5, 39.8, 33.6, 33.6,
31.4, 28.6, 28.2, 27.6, 27.4, 19.8, 17.6, 14.1 ppm; IR (film): n˜ =3450, 2950,
1720, 1465, 1370, 1310, 1195, 1070, 1035, 930, 855 cmꢀ1; HRMS (EI,
70 eV): m/z: calcd for C14H24O3: 240.1725; found: 240.1728 [M]+.
2,2-Dimethyl-3-propyl-but-3-en-1-ol (20): Compound 19 (8.29 g,
45.0 mmol) was added dropwise to a suspension of LiAlH4 (854 mg,
22.5 mmol) in dry THF at 08C. The reaction mixture was stirred for 24 h
at room temperature. Water (1.5 mL), NaOH (1.5 mL, 15% w/v) and
water (4.5 mL) were added subsequently. The solid was filtered off and
the solvents were removed under reduced pressure to yield 20 (5.62 g,
N,N-Dimethyl-3-(1,3,3-trimethyl-7-oxa-bicyclo[4.1.0]hept-2-yl)-acrylam-
ide (5): According to GP 1 17 (466 mg, 2.77 mmol), NaH (72.0 mg,
3.00 mmol), the phosphonate (781 mg, 3.50 mmol) in THF (25 mL) for
16 h. Silica gel chromatography (CH/EE 1:1) to yield 5 (368 mg, 56%).
Rf =0.4 (EE); 1H NMR (400 MHz, C6D6): d=7.12 (d, 3J=14.5, 10.4 Hz,
1H), 6.15 (d, 3J=15.7 Hz, 1H), 2.72 (brs, 3H), 2.71 (dd, 3J=2.3, 1.1 Hz,
1H), 2.41 (brs, 3H), 1.85 (d, 3J=10.0 Hz, 1H), 1.75 (dddd, 2J=15.1, 3J=
1
88%). H NMR (400 MHz, CDCl3): d=4.94 (s, 2H), 4.38 (s, 2H), 1.97 (t,
3J=7.8 Hz, 2H), 1.27 (qt, 3J=7.6, 7.5 Hz, 2H), 1.05 (s, 6H), 0.94 ppm (t,
3J=7.3 Hz, 3H); 13C NMR (100 MHz, C6D6): d=153.4, 110.0, 69.9, 41.6,
33.5, 24.0, 22.0, 14.1 ppm; IR (film): n˜ =3390, 2960, 1633, 1465, 1040, 895,
825, 640 cmꢀ1; HRMS (EI, 70 eV): m/z: calcd for C9H18O: 142.1356;
found: 142.1356 [M]+.
2
3
5.3, 4.1, 1.2 Hz, 1H), 1.50 (dddd, J=15.1, J=10.3, 5.7, 2.8 Hz, 1H), 1.33
(ddd, 2J=13.3, 3J=10.3, 5.3 Hz, 1H), 1.13 (s, 3H), 0.73 (s, 3H), 0.69 (s,
3H), 0.70–0.61 ppm (m, 1H); 13C NMR (100 MHz, C6D6): d=165.8,
4986
ꢁ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10, 4983 – 4990

Radical Trapping
4983 – 4990
2,2-Dimethyl-3-propyl-but-3-enal (21): DMSO (6.56 g, 42.0 mmol) in
CH2Cl2 (5 mL) was added dropwise to a solution of oxalyl chloride
(5.33 g, 42.0 mmol) in CH2Cl2 (150 mL) at ꢀ608C. After 30 min 20
(4.98 g, 35.0 mmol) was added. The reaction mixture was stirred for 16 h
at ꢀ608C before NEt3 (17.0 g, 168 mmol) was added. The reaction mix-
ture was diluted with Et2O (200 mL) and washed with water (2”100 mL)
and brine (20 mL). After filtration through silica gel with Et2O (500 mL)
the solvents were removed under reduced pressure. Kugelrohr distillation
(1208C, 20 mbar) yielded 21 (3.56 g, 73%). 1H NMR (400 MHz, C6D6):
2855, 1650, 1450, 1390, 1264 cmꢀ1; HRMS (EI, 70 eV): m/z: calcd for
C13H21NO: 207.1623, found 207.1620 [M]+.
N,N-Dimethyl-3-(1-oxiranyl-cyclohexyl)-acrylamide
(11):
According
GP 2 24 (1.00 g, 4.80 mmol) and mCPBA (1.25 g (77%), 7.24 mmol) in
CH2Cl2 (40 mL) for 16 h. Silica gel chromatography (CH/EE 60:40) yield
to 11 (0.72 g, 67%). Rf =0.2 (CH/EE 60:40); 1H NMR (400 MHz,
CDCl3): d=6.62 (d, 3J=15.8 Hz, 1H), 6.26 (d, 3J=15.8 Hz, 1H), 3.04 (s,
3H), 2.96 (s, 3H), 2.76 (dd, 3J=3.9, 3J=2.9 Hz, 1H), 2.76 (dd, 2J=4.7,
3J=3.9 Hz, 1H), 2.55 (dd, 4J=4.7, 3J=3.9 Hz, 1H), 1.71–1.65 (m, 1H),
1.65–1.50 (m, 5H), 1.48–1.30 (m, 3H), 1.27–1.15 ppm (m, 1H); 13C NMR
(100 MHz, CDCl3): d=166.7, 147.8, 121.4, 58.5, 39.9, 37.5, 35.8, 33.3, 31.7,
4
3
d=9.17 (s, 1H), 4.86 (t, J=1.6 Hz, 1H), 4.81 (m, 1H), 1.75 (tdd, J=7.8,
3
4J=1.2, 1.1 Hz, 2H), 1.27 (qt, J=7.6, 7.5 Hz, 2H), 0.98 (s, 6H), 0.76 ppm
(t, 3J=7.3 Hz, 3H); 13C NMR (100 MHz, C6D6): d=201.5, 149.5, 111.7,
52.1, 46.8, 34.5, 21.8, 20.9, 13.9 ppm; IR (film): n˜ =2930, 1740, 1705, 1640,
1455, 1370, 1310, 1240, 1190, 1025 cmꢀ1; HRMS (EI, 70 eV): m/z: calcd
for C9H16O: 140.1201; found: 140.1201 [M]+.
26.0, 22.0, 21.9 ppm; IR (film): 3445, 2925, 1655, 1610, 1395, 1150 cmꢀ1
;
HRMS (EI, 70 eV): m/z: calcd for C13H21NO2: 223.1572, found 223.1575
[M]+.
2-Hydroxymethyl-spiro[2.5]octane-1-carboxylic dimethylamide (12): Ac-
cording to GP 3 11 (223 mg, 1.00 mmol), [Cp2TiCl2] (25 mg, 0.10 mmol),
collidine hydrochloride (394 mg, 2.50 mmol) and zinc dust (131 mg,
2.00 mmol) for 16 h. Silica gel chromatography (CH/EE 90:10!50:50)
gave 12 (202 mg, 90%). Rf =0.1 (CH/EE 90:10); 1H NMR (400 MHz,
CDCl3): d=6.62 (d, 3J=15.8 Hz, 1H), 6.26 (d, 3J=15.8 Hz, 1H), 3.04 (s,
3H), 2.96 (s, 3H), 2.76 (dd, 3J=3.9, 3J=2.9 Hz, 1H), 2.76 (dd, 2J=4.7,
3J=3.9 Hz, 1H), 2.55 (dd, 4J=4.7, 3J=3.9 Hz, 1H), 1.71–1.65 (m, 1H),
1.65–1.50 (m, 5H), 1.48–1.30 (m, 5H), 1.27–1.15 ppm (m, 1H); 13C NMR
(100 MHz, CDCl3): d=174.6*, 173.6, 63.9*, 62.5, 58.8, 58.6, 39.7*, 39.3*,
37.9*, 36.9, 35.9*, 35.8, 33.2, 31.9, 28.8*, 28.0, 26.9*, 26.7, 26.3*, 26.2, 26.0,
25.7*, 25.5, 23.6* ppm; IR (film): n˜ =3400, 2925, 1725, 1635, 1400, 1265,
1025 cmꢀ1; HRMS (EI, 70 eV): m/z: calcd for C13H23NO2: 225.1729,
found 225.1723 [M]+.
4,4-Dimethyl-5-propyl-hexa-2,5-dienoic dimethylamide (22): According
to GP 1 21 (701 mg, 5.00 mmol), NaH (156 mg, 6.50 mmol) and the phos-
phonate (1.79 g, 8.00 mmol) in Et2O (50 mL) for 16 h. Silica gel chroma-
tography (CH:EE 3:1) gave 22 (946 mg, 90%). Rf =0.3 (CH/EE 3:1);
1H NMR (300 MHz, C6D6): d=7.16 (d, 3J=15.4 Hz, 1H), 6.08 (d, 3J=
15.4 Hz, 1H), 4.99 (dt, 2J=0.8, 4J=0.8 Hz, 1H), 4.84 (td, 4J=1.2, 2J=
1.2 Hz, 1H), 2.73 (brs, 3H), 2.38 (brs, 3H), 1.72 (tdd, 3J=7.8, 2J=1.0,
1.1 Hz, 2H), 1.23 (qt, 3J=7.6, 7.5 Hz, 2H), 0.91 (s, 6H), 0.65 ppm (t, 3J=
7.3 Hz, 3H); 13C NMR (75 MHz, C6D6): d=166.0, 154.6, 153.5, 117.8,
108.7, 42.5, 36.3, 35.2, 34.3, 26.4, 22.4, 14.2 ppm; IR (film): n˜ =2960, 1660,
1615, 1465, 1390, 1260, 1140, 990, 895, 715, 630 cmꢀ1; HRMS (EI, 70 eV):
m/z: calcd for C13H23NO: 209.1780; found: 209.1786 [M]+.
4-Methyl-4-(2-propyl-oxiranyl)-pent-2-enoic dimethylamide (9): Accord-
ing to GP 2 22 (250 mg, 1.19 mmol) and mCPBA (77%, 535 mg,
2.39 mmol) in CH2Cl2 (29 mL) for 16 h. Silica gel chromatography (CH/
4-Methyl-1-oxa-spiro[2.5]octane-4-carbaldehyde (26): Compound 25
(4.69 g, 30.0 mmol) was added to a solution of Celite (11.0 g), 4 Š molec-
ular sieves (1.78 g) and PCC (7.54 g, 35 mmol) in CH2Cl2 (125 mL) and
stirred for 5 h at room temperature. After filtration through Florisil the
solvent was removed under reduced pressure and the crude product puri-
fied by silica gel chromatography (CH/EE 47:3) to yield 26 (2.83 g,
EE 7:3) gave
9
(246 mg, 92%). Rf =0.1 (CH/EE 1:1); 1H NMR
(400 MHz, CDCl3): d=6.84 (d, 3J=15.4 Hz, 1H), 6.20 (d, 3J=15.4 Hz,
1H), 3.05 (s, 3H), 3.29 (s, 3H), 2.67 (d, 2J=4.3 Hz, 1H), 2.56 (d, 2J=
4.3 Hz, 1H), 1.72 (ddd, 2J=14.6, 3J=10.7, 5.9 Hz, 1H), 1.58 (ddd, 2J=
14.7, 3J=10.7, 5.2 Hz, 1H), 1.25–1.11 (m, 2H), 1.09 (s, 3H), 1.04 (s, 3H),
0.83 ppm (t, 3J=7.3 Hz, 3H); 13C NMR (100 MHz, C6D6): d=165.9,
151.3, 118.9, 62.2, 47.3, 40.2, 36.4, 35.2, 32.6, 23.6, 22.8, 17.8, 14.5 ppm; IR
(film): n˜ =2965, 2875, 1660, 1620, 1470, 1395, 1280, 1145, 990, 945, 850,
1
61%). Rf =0.3 (CH/EE 9:1); H NMR (400 MHz, C6D6): d=9.50 (s, 1H),
2.27 (dd, 2J=4.2, 4J=0.6 Hz, 1H), 1.94 (d, 2J=4.2 Hz, 1H), 1.90 (ddd,
2J=13.2, 3J=8.7, 4.5 Hz, 1H), 1.52–1.42 (m, 1H), 1.34–1.26 (m, 2H),
1.25–1.14 (m, 3H), 0.94 (ddd, 2J=13.6, 3J=7.7, 4.1 Hz, 1H), 0.74 ppm (s,
3H); 13C NMR (75 MHz, C6D6): d=203.9, 60.2, 49.1, 48.5, 32.2, 31.9,
820, 715, 630 cmꢀ1
; HRMS (EI, 70 eV): m/z: calcd for C13H23NO2:
225.1729; found: 225.1731 [M]+.
24.5, 21.2, 16.9 ppm; IR (film): n˜ =2930, 1725, 1450, 1040, 775 cmꢀ1
;
2-(2-Hydroxymethyl-3,3-dimethyl-2-propyl-cyclopropyl)-N,N-dimethyl-
acetamide (10): According to GP 3 9 (169 mg, 0.75 mmol), [Cp2TiCl2]
(28.0 mg, 113 mmol), collidine hydrochloride (296 mg, 1.88 mmol) and
zinc dust (98.0 mg, 1.50 mmol) for 72 h. Silica gel chromatography (CH/
EE 1:1) gave 10 (162 mg, 95%, dr 63:37). Rf =0.4 (EE); 1H NMR
(400 MHz, CDCl3): d=3.83 (d, 2J=10.7 Hz, 1H), 3.69* (d, 2J=11.7 Hz,
1H), 3.48* (dd, 2J=12.1, 3J=1.1 Hz, 1H), 3.31 (dd, 2J=10.6, 3J=1.3 Hz,
1H), 3.31* (s, 3H), 3.27 (s, 3H), 2.94* (s, 3H), 2.93 (s, 3H), 2.81* (dd,
HRMS (EI, 70 eV): m/z: calcd for C9H14O2: 154.0994; found: 154.1001
[M]+.
N,N-Dimethyl-3-(4-methyl-1-oxa-spiro[2.5]oct-4-yl)-acrylamide (13): Ac-
cording to GP 1 26 (540 mg, 3.50 mmol), NaH (96.0 mg, 4.00 mmol) and
the phosphonate (1.00 g, 4.50 mmol) in THF (35 mL) for 2 h. Kugelrohr
distillation (2308C, 1 mbar) and silica gel chromatography (CH/EE
1
63:37) gave 13 (580 mg, 74%). Rf =0.4 (EE); H NMR (400 MHz, C6D6):
d=7.17 (d, 2J=15.7 Hz, 1H), 6.43 (d, 2J=15.7 Hz, 1H), 2.72 (brs, 3H),
2.44 (dd, 2J=4.7, 4J=1.2 Hz, 1H), 2.39 (brs, 3H), 1.99 (d, 2J=4.8 Hz,
1H), AB signal (dA1 =1.68, dB1 =1.65, JAB =13.3 Hz, additionally split by
3J=6.7, 3.9, 4J=1.2 Hz, 2H), 1.63–1.51 (m, 1H), 1.40–1.19 (m, 4H), 1.12
(ddd, 2J=13.4, 3J=9.4, 4.0 Hz, 1H), 0.83 ppm (s, 3H); 13C NMR
(100 MHz, C6D6): d=166.1, 150.2, 120.9, 62.0, 49.4, 40.3, 38.4, 36.4, 35.1,
32.0, 25.5, 22.5, 22.3 ppm; IR (film): n˜ =2935, 2860, 1660, 1620, 1495,
1395, 1265, 1145, 1035, 990, 925, 900, 835, 800, 765, 710, 620 cmꢀ1; HRMS
(EI, 70 eV): m/z: calcd for C13H21NO2: 223.1572; found: 223.1570 [M]+.
2J=15.4, J=3.5 Hz, 1H), 2.56 (dd, J=17.3, J=4.2 Hz, 1H), 2.11* (ddd,
2J=14.1, 3J=11.6, 4.9 Hz, 3H), 2.02* (d, 3J=10.9, 1H), 1.98 (dd, 2J=
15.3, 3J=11.2 Hz, 1H), 1.68 (ddd, 2J=13.9, 3J=11.5, 4.7 Hz, 1H), 1.60–
1.46* (m, 1H), 1.60–1.46* (m, 1H), 1.35–1.15* (m, 1H), 1.35–1.15 (m,
1H), 1.11 (s, 3H), 1.10* (s, 3H), 1.01 (s, 3H), 0.97* (s, 3H), 0.94 (dddd,
3
2
3
3
3
3
2J=14.1, J=11.7, 4.8, 1.0 Hz, 1H), 0.86 (t, J=7.3 Hz, 3H), 0.86* (t, J=
7.3 Hz, 3H), 0.83 (dddd, 2J=14.0, 3J=11.5, 4.8, 1.7 Hz, 1H), 0.72 (dd,
3J=10.9, 4.2 Hz, 1H), 0.41* ppm (dd, 3J=11.6, 3.5 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d=174.6*, 173.3, 65.6, 60.3*, 37.9*, 36.9, 35.8*, 35.6,
34.5, 32.1, 31.9*, 30.4*, 29.1*, 28.8, 28.1*, 27.7, 23.8*, 23.7, 22.9, 21.9*,
19.9*, 19.5, 17.8, 16.8*, 14.6, 14.5* ppm; IR (film): n˜ =3395, 2950, 1625,
1400, 1260, 1130, 1015, 795 cmꢀ1; HRMS (EI, 70 eV): m/z: calcd for
C13H25NO2: 227.1885; found: 227.1877 [M]+.
2-(1-Hydroxymethyl-6-methyl-bicyclo[4.1.0]hept-7-yl)-N,N-dimethylacet-
amide (14): According to GP 3 13 (223 mg, 1.00 mmol), [Cp2TiCl2]
(24.9 mg, 100 mmol), collidine hydrochloride (394 mg, 2.50 mmol) and
zinc dust (131 mg, 2.00 mmol) for 16 h. Silica gel chromatography (CH/
EE 1:1) gave 14 (162 mg, 72%). Rf =0.2 (EE); 1H NMR (300 MHz,
C6D6): d=4.27* (brs, 1H), 4.06 (brs, 1H), 3.90* (d, 2J=10.2 Hz, 1H),
3.76 (s, 2H), 3.61* (d, 2J=12.2 Hz, 1H), 2.58* (s, 3H), 2.56 (s, 3H), 2.36
(dd, 2J=15.4, 3J=3.6 Hz, 1H), 2.24–2.10* (m, 1H), 2.19 (s, 3H), 2.18–
N,N-Dimethyl-3-(1-vinyl-cyclohexyl)-acrylamide (24): According to GP 1
the phosphonate (2.43 g, 10.9 mmol), NaH (0.23 g, 9.10 mmol) and 23
(1.00 g, 7.25 mmol) in Et2O (40 mL) for 15 h. Silica gel chromatography
(CH/EE 98:2) gave 24 (1.08 g, 48%). Rf =0.2 (CH/EE 96:4); 1H NMR
(400 MHz, CDCl3): d=6.7 (dd, 3J=15.4, 4J=2.8 Hz, 1H), 6.11 (dd, 3J=
15.4, 5J=2.3 Hz, 1H), 5.64 (ddd, 3J=17.6, 3J=10.8, 4J=2.8, 5J=2.3 Hz,
1H), 5.05 (dddd, 3J=10.8, 5J=1.2 Hz, 1H), 4.95 (dddd, 3J=17.7, 5J=
1.3 Hz, 1H), 3.00 (s, 3H), 2.94 (s, 3H), 2.20–2.0 (m, 2H), 1.67–1.31 ppm
(m, 8H); 13C NMR (100 MHz, CDCl3): d=167.2, 152.7, 144.4, 118.2,
113.8, 43.2, 37.4, 35.8, 35.4, 26.1, 22.2 ppm; IR (neat): n˜ =3485, 2930,
3
2
3
2.12* (dm, J=4.3 Hz, 1H), 2.16* (s, 3H), 2.01 (ddd, J=14.2, J=9.3 Hz,
2
3
2
3
5.2 Hz, 1H), 1.84* (dd, J=16.9, J=11.0 Hz, 1H), 1.83 (dd, J=15.3, J=
11.5 Hz, 1H), 1.64 (dddd, 2J=13.4, 3J=4.8, 4.8, 1.5 Hz, 1H), 1.47–0.92
(m, 6H), 1.47–0.92* (m, 7H), 1.06* (s, 3H), 0.89 (s, 3H), 0.76* (dd, 3J=
10.8, 4.2 Hz, 1H), 0.69 ppm (dd, 3J=11.5, 3.6 Hz, 1H); 13C NMR
(75 MHz, C6D6): d=174.0, 172.3*, 70.0*, 64.2, 36.8, 35.2*, 35.2, 35.0*,
Chem. Eur. J. 2004, 10, 4983 – 4990
www.chemeurj.org
ꢁ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4987

A. Gansäuer et al.
FULL PAPER
33.7*, 29.7, 29.4*, 29.9, 28.8*, 28.6*, 28.4, 28.4, 27.3, 24.3*, 24.2*, 22.7*,
22.6*, 22.3, 21.8, 21.8*, 21.6, 17.2 ppm; IR (film): n˜ =3390, 2925, 1720,
1635, 1400, 1260, 1145, 1010, 615 cmꢀ1; HRMS (EI, 70 eV): m/z: calcd for
C13H23NO2: 225.1729; found: 225.1725 [M]+.
2.93 (s, 6H), 2.59 (dd, 2J=4.9, 4J=0.8 Hz, 1H), 2.58* (dd, 2J=5.2, 4J=
0.8 Hz, 1H), 2.38 (d, 3J=4.8 Hz, 1H), 2.35* (d, 2J=5.2 Hz, 1H), 1.74–
1.40 (m, 20H), 0.94 ppm (s, 6H); 13C NMR (100 MHz, CDCl3): d=
167.5*, 166.9, 150.9, 150.0*, 118.1*, 117.0, 63.8, 63.0, 52.6, 51.1*, 42.6*,
42.6, 40.0*, 39.8, 37.5*, 37.3, 37.7, 35.6*, 32.7, 32.5*, 30.5, 30.0*, 25.6,
25.2*, 23.7*, 23.1, 23.0*, 21.5 ppm; IR (film): n˜ =2925, 1660, 1615, 1460,
1390, 1270, 1140 cmꢀ1; HRMS (EI, 70 eV): m/z: calcd for C14H23NO2:
237.1729, found: 237.1725 [M]+; elemental analysis calcd (%) for
C14H23NO2: C 70.85, H 9.77, N 5.90; found: C 70.16, H 9.42, N 5.86.
1-Methyl-2-methylene-cycloheptanecarboxylic ethyl ester (28): NaH
(1.78 g, 70.5 mmol) and DMSO (40 mL) were heated for 1 h at 708C. To
the stirred solution methyltriphenylphosphonium bromide (25.5 g,
70.5 mmol) in DMSO (80 mL) was added. After 1 h 27 (13.3 g,
67.2 mmol) was added and the reaction mixture stirred for 16 h at 558C.
The reaction was interrupted by adding water (80 mL) and extracting
with cyclohexane (3”50 mL). The combined organic layers were washed
with water/DMSO (1:1, 80 mL), with brine (50 mL) and dried (MgSO4).
The solvents were removed under reduced pressure and the crude prod-
uct purified by silica gel chromatography (CH/EE 95:5) to yield 28
(9.30 g, 70%). Rf =0.2 (CH/EE 95:5); 1H NMR (400 MHz, CDCl3): d=
4.94 (s, 1H), 4.85 (s, 1H), 4.10 (t, 3J=7.1 Hz, 2H), 2.26 (m, 2H), 2.15 (d,
3J=9.2 Hz, 1H), 2.12 (d, 3J=9.3 Hz, 1H), 1.75–1.63 (m, 3H), 1.61–1.50
(m, 2H), 1.49–1.32 (m, 3H), 1.31 (s, 1H), 1.20 ppm (t, 3J=7.1 Hz, 3H);
13C NMR (100 MHz, CDCl3): d=176.9, 113.0, 60.6, 50.9, 38.4, 35.1, 31.4,
30.5, 25.0, 24.5, 14.2 ppm; IR (film): n˜ =2925, 1725, 1630, 1445, 1235,
1155, 1105 cmꢀ1; HRMS (EI, 70 eV): m/z: calcd for C17H20O2: 196.1463;
found 196.1471 [M]+.
2-(1-Hydroxymethyl-7-methyl-bicyclo[5.1.0]oct-8-yl)-N,N-dimethylacet-
amide (16): According to GP 3 15 (223 mg, 0.94 mmol), [Cp2TiCl2]
(24 mg, 0.1 mmol), collidine hydrochloride (370 mg, 2.35 mmol) and zinc
dust (123 mg, 1.88 mmol) for 16 h. Silica gel chromatography (CH/EE
85:15!0:100) yield to 16 (200 mg, 88%). Rf =0.05 (CH/EE 85:15).
1H NMR (300 MHz, CDCl3): d=3.87* (d, 2J=10.6 Hz, 1H), 3.74 (d, 2J=
2
4
2
4
12.1 Hz, 1H), 3.46 (dd, J=12.2, J=1.4 Hz, 1H), 3.28* (dd, J=10.5, J=
1.8 Hz, 1H), 3.06* (s, 3H), 2.98* (s, 3H), 2.96 (s, 3H), 2.92 (s, 3H), 2.90*
(dd, 3J=15.3, 5J=3.0 Hz, 2H), 2.65 (m, 2H), 2.19–1.55 (m, 11H), 2.19–
1.55* (m, 11H), 1.13* (s, 3H), 0.97 (s, 3H), 0.95–0.73 (m, 1H), 0.63* ppm
(dd, 3J=12.1, 5J=2.8 Hz, 1H); 13C NMR (75 MHz, CDCl3): d=174.9,
173.5*, 66.4*, 60.5, 41.2*, 38.0, 37.0*, 36.0, 35.8*, 34.7, 34.3*, 33.5*, 33.4,
32.0, 29.8*, 28.8, 26.7, 26.5*, 26.3*, 22.1*, 15.0 ppm; IR (film): n˜ =3340,
2920, 1620, 1465, 1400, 1020 cmꢀ1; HRMS (EI, 70 eV): m/z: calcd for
C14H25NO2: 239.1885, found: 239.1889 [M]+; elemental analysis calcd
(%) for C14H25NO2: C 70.25, H 10.53, N 5.85; found: C 70.09, H 10.34, N
5.68.
(1-Methyl-2-methylene-cycloheptyl)-methanol (29): Compound 28
(9.81 g, 50.0 mmol) was added dropwise to a suspension of LiAlH4
(0.95 g, 25.0 mmol) in dry diethyl ether (100 mL) at 08C. The reaction
mixture was stirred for 10 h at room temperature. Water (1.0 mL),
NaOH (1.0 mL, 15% w/v) and water (3.0 mL) were added subsequently.
The solid was filtered off and the solvents were removed under reduced
pressure. Distillation (b.p. 4.8 mbar/130–1358C) of the crude product lead
to 29 (6.32 g, 41 mmol). 1H NMR (400 MHz, CDCl3): d=4.94 (s, 1H),
4.78 (s, 1H), 3.22 (dd, 2J=10.6, 3J=3.6 Hz, 1H), 3.18 (dd, 2J=10.4, 3J=
9.4 Hz, 1H), 2.16 (dd, 2J=13.1, 3J=7.6 Hz, 1H), 1.98 (dd, 2J=13.0, 3J=
13.0 Hz, 1H), 1.83–1.77 (m, 1H), 1.70–1.53 (m, 3H), 1.42–1.37 (m, 2H),
1.29–1.18 (m, 4H), 1.03 ppm (s, 3H); 13C NMR (100 MHz, CDCl3): d=
156.1, 113.0, 70.2, 45.1, 37.3, 34.5, 32.2, 31.0, 23.7, 23.2 ppm; IR (film): n˜ =
3385, 2920, 1725, 1630, 1445, 1045 cmꢀ1; HRMS (EI, 70 eV): m/z: calcd
for C10H18O: 154.1358; found 154.1352 [M]+.
5,5,6-Trimethyl-hepta-2,6-dienoic tert-butyl ester (37): According to GP 1
the phosphonate (379 mg, 3.00 mmol), NaH (96.0 mg, 4.00 mmol) and 36
(1.26 g, 5.00 mmol) in Et2O (50 mL) for 16 h. Silica gel chromatography
(CH/EE 97:3) gave 37 (542 mg, 81%). Rf =0.4 (CH/EE 19:1); 1H NMR
(400 MHz, CDCl3): d=6.67 (dt, 3J=15.3, 3J=7.6 Hz, 1H), 5.61 (dt, 3J=
15.5, 4J=1.4 Hz, 1H), 4.67 (dq, 3J=1.4, 4J=1.4 Hz, 1H), 4.62 (dd, 3J=
4
4
1.3, J=0.5 Hz, 1H), 2.12 (dd, 3J=7.6, J=1.4 Hz, 2H), 1.63 (dd, 4J=1.3,
4J=0.5 Hz, 3H), 1.37 (s, 9H), 0.96 ppm (s, 6H); 13C NMR: d=165.9,
150.9, 145.2, 124.7, 110.2, 80.0, 43.3, 39.0, 28.2, 27.0, 19.4 ppm; IR (film):
n˜ =2970, 1715, 1650, 1455, 1367, 1335, 1160, 985, 895 cmꢀ1; HRMS: m/z:
calcd for C10H16O2: 168.1150; found: 168.1148 [MꢀC4H8]+.
1-Methyl-2-methylene-cycloheptanecarbaldehyd (30): DMSO (9.38 g,
120 mmol) in CH2Cl2 (10 mL) was added to a solution of oxalyl chloride
(7.62 g, 60.0 mmol) in CH2Cl2 (150 mL) at ꢀ608C. After 15 min 29
(7.70 g, 50.0 mmol) was added. The reaction stirred overnight before
NEt3 (34.7 mL, 250 mmol) was added. The reaction mixture was diluted
with Et2O (100 mL) and washed with water (2”100 mL) and brine
(50 mL). Drying (MgSO4), evaporation and purifying of the crude prod-
uct by silica gel chromatography (CH/EE 99:1) yield to 30 (5.16 g, 68%).
Rf =0.2 (CH/EE 98:2); 1H NMR (400 MHz, CDCl3): d=9.40 (s, 1H),
5.09 (s, 1H), 4.81 (s, 1H), 2.26 (dd, 2J=13.1, 3J=1.6 Hz, 1H), 2.24 (dd,
2J=13.1, 3J=1.6 Hz, 1H), 2.15–2.08 (m, 2H), 2.04 (d, 2J=15.1 Hz, 1H),
1.99 (d, 2J=14.7 Hz, 1H), 1.80–1.36 ppm (m, 6H), 1.20 ppm (s, 1H);
13C NMR (100 MHz, CDCl3): d=202.6, 151.6, 115.3, 55.2, 35.1, 34.4, 31.6,
24.0, 22.4 ppm; IR (film): n˜ =2925, 2855, 2695, 1725, 1630, 1445,
1370 cmꢀ1; HRMS (EI, 70 eV): m/z: calcd for C10H16O: 152.1201; found
152.1198 [M]+.
5-Methyl-5-(2-methyl-oxiranyl)-hex-2-enoic tert-butylester (32): Accord-
ing to GP 2 37 (449 mg, 2.00 mmol) and m-CPBA (672 mg (77%),
3.00 mmol) in CH2Cl2 (25 mL) for 1 h. Silica gel chromatography (CH/
1
EE 9:1) gave 32 (387 mg, 81%). Rf =0.2; H NMR (400 MHz, C6D6): d=
7.06 (dt, 3J=15.5, 3J=7, 7 Hz, 1H), 5.84 (dt, 3J=15.5, 4J=1.4 Hz, 1H),
2.39 (dq, 3J=4.6, 4J=0.8 Hz, 1H), 1.99 (d, 3J=4.5 Hz, 1H), 1.92, 1.88,
AB signal, 2J=14.1 Hz, additionally split by 3J=7.7 Hz and 4J=1.4 Hz,
2H), 1.43 (s, 9H), 0.99 (d. 4J=0.8 Hz, 3H), 0.74 (s, 3H), 0.66 ppm (s,
3H); 13C NMR (100 MHz, C6D6): d=165.4, 144.6, 125.8, 79.6, 60.3, 50.7,
41.8, 36.8, 28.2, 23.5, 22.8, 18.4 ppm; IR (film): n˜ =2975, 1715, 1650, 1455,
1370, 1340, 1285, 1165, 1075, 985, 890, 855, 825, 780 cmꢀ1; HRMS: m/z:
calcd for C14H24O3: 240.1725; found: 240.1730 [M]+.
2-(2-Hydroxymethyl-2,3,3-trimethyl-cyclobutyl)-acetic tert-butyl ester
(33): According to GP 3 32 (240 mg, 1.00 mmol), [Cp2TiCl2] (24.9 mg,
100 mg), collidine hydrochloride (394 mg, 2.50 mmol) and zinc dust
(131 mg, 2.00 mmol) for 16 h. Silica gel chromatography (CH/EE 86:14)
gave 33 (228 mg, 94%, dr 63:37). Rf =0.3 (CH/EE 3:1); 1H NMR
(400 MHz, C6D6): d=3.65* (d, 2J=10.9 Hz, 1H), 3.60 (d, 2J=10.7 Hz,
1H), 3.41* (d, 2J=11.0 Hz, 1H), 3.40 (d, 2J=10.6 Hz, 1H), 2.47–2.38 (m,
1H), 2.47–2.38* (m, 1H), 2.33 (brs, 1H), 2.21 (dd, 2J=16.3, 3J=9.9 Hz,
1H), 2.18* (dd, 2J=17.5, 3J=7.8 Hz, 1H), 2.02 (dd, 2J=16.5, 3J=5.4 Hz,
1H), 1.79* (brs, 1H), 1.63* (dd, 2J=10.8, 3J=8.0 Hz, 1H), 1.52 (dd, 2J=
10.4, 3J=8.4 Hz, 1H), 1.42–1.36* (m, 1H), 1.36* (s, 9H), 1.32 (s, 9H),
1.20 (dd, 2J=10.5, 3J=10.4 Hz, 1H), 1.22–1.15* (m, 1H), 1.04* (s, 3H),
1.02 (s, 3H), 0.96 (s, 3H), 0.94* (s, 3H), 0.81 (s, 3H), 0.78* ppm (s, 3H);
13C NMR (100 MHz, C6D6): d=173.7, 173.0*,80.1, 79.8*, 68.8, 65.2*, 45.5,
45.3*, 38.3*, 37.5*, 37.4, 37.1*, 36.6, 36.5, 36.4*, 33.6, 28.1*, 28.0, 25.7*,
24.9, 24.2, 23.7*, 19.0*, 14.8 ppm; IR (film): n˜ =3445, 2970, 1730, 1455,
1370, 1260, 1150, 1030, 950, 850, 765 cmꢀ1; HRMS (EI, 70 eV): m/z: calcd
for C14H26O3: 186.1256; found: 186.1252 [MꢀC4H8]+.
N,N-Dimethyl-3-(1-methyl-2-methylen-cycloheptyl)-acryl amide (31): Ac-
cording to GP 1 the phosphonate (3.71 g, 15.0 mmol), NaH (0.33 g,
12.5 mmol) and 30 (1.52 mmol, 10.0 mmol) in Et2O (40 mL) for 16 h.
Silica gel chromatography (CH/EE 50:50) yield to 31 (1.94 g, 93%). Rf =
1
3
0.2 (CH/EE 50:50); H NMR (400 MHz, CDCl3): d=6.86 (d, J=15.4 Hz,
1H), 6.09 (d, 3J=15.4 Hz, 1H), 4.86 (s, 1H), 4.73 (s,1H), 3.00 (s, 3H),
2.95 (s, 3H), 2.20–2.04 (m, 2H), 1.68–1.30 (m, 8H), 1.14 ppm (s, 1H);
13C NMR (100 MHz, CDCl3): d=167.3, 156.3, 153.8, 116.2, 112.9, 45.4,
37.3, 35.7, 34.1, 31.8, 30.7, 29.0, 26.9, 25.4, 23.8 ppm; IR (film): n˜ =2930,
2860, 1710, 1650, 1460, 1370, 1160 cmꢀ1; HRMS (EI, 70 eV): m/z: calcd
for C13H21NO: 221.1780; found 221.1776 [M]+.
N,N-Dimethyl-3-(4-methyl-1-oxa-spiro[2.6]-non-4-yl)-acrylamide
(15):
According GP 2 31 (1.60 g, 7.70 mmol) and mCPBA (1.98 g (77%),
11.5 mmol) in CH2Cl2 (40 mL) for 8 h. Silica gel chromatography (CH/
EE 50:50) yield to 15 (1.56 g, 86%). Rf =0.15 (CH/EE 50:50); 1H NMR
(400 MHz, CDCl3): d=6.79* (d, 3J=15.6 Hz, 1H), 6.75 (d, 3J=15.4 Hz,
1H), 6.14* (d, 3J=15.6 Hz, 1H), 6.07 (d, 3J=15.4 Hz, 1H), 3.01 (s, 6H),
5,5,6-Trimethyl-hepta-2,6-dienoic dimethylamide (38): According to GP 1
36 (505 mg, 4.00 mmol), NaH (120 mg, 5.00 mmol) and 36 (1.34 g,
6.00 mmol) in Et2O (50 mL) for 16 h. Silica gel chromatography (CH/EE
4988
ꢁ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Chem. Eur. J. 2004, 10, 4983 – 4990

Radical Trapping
4983 – 4990
4:1) gave 38 (631 mg, 81%). Rf =0.4 (CH/EE 1:1); 1H NMR (400 MHz,
CDCl3): d=6.67 (dt, 3J=15.0, 3J=7, 5 Hz, 1H), 6.16 (dt, 3J=15.1, 4J=
1.4 Hz, 1H), 4.70 (dq, 3J=1.4, 4J=1.4 Hz, 1H), 4.69 (dd, 3J=1.5, 4J=
stant of ring closure see: S.-U. Park, T. R. Varick, M. Newcomb, Tet-
rahedron Lett. 1990, 31, 2975–2978.
[5] P. A. Baguley, J. C. Walton, Angew. Chem. 1998, 110, 3272–3283;
Angew. Chem. Int. Ed. 1998, 37, 3072–3083.
4
0.7 Hz, 1H), 3.02 (brs, 3H), 2.95 (brs, 3H), 2.20 (dd, 3J=7.6, J=1.3 Hz,
2H), 1.71 (dd, 4J=1.4, 4J=0.56 Hz, 3H), 1.04 ppm (s, 6H); 13C NMR
(100 MHz, CDCl3): d=166.7, 151.0, 142.9, 122.2, 110.1, 43.8, 39.0, 37.3,
35.5, 27.0, 19.5 ppm; IR (film): n˜ =2965, 1660, 1620, 1450, 1395, 1265,
1145, 1065, 980, 890, 825, 740, 620 cmꢀ1; HRMS (EI, 70 eV): m/z: calcd
for C12H21NO2: 195.1623; found: 195.1622 [M]+.
[6] For a review and selected references see: a) A. Srikrishna in Radi-
cals in Organic Synthesis, Vol. 2 (Eds.: P. Renaud, M. Sibi), Wiley-
VCH, Weinheim, 2001, pp. 151–187; b) A. Srikrishna, G. V. R.
Sharma, P. Hemamalini, Chem. Commun. 1990, 1681–1683; c) M.
Malacria, Chem. Rev. 1996, 96, 289–306; d) M. Journet, M. Malac-
ria, J. Org. Chem. 1994, 59, 718–719; e) P. Devin, L. Fensterbank,
M. Malacria, J. Org. Chem. 1998, 63, 6764–6765.
5-Methyl-5-(2-methyl-oxiranyl)-hex-2-enoic dimethylamide (34): Accord-
ing to GP 2 38 (391 mg, 2.00 mmol) and mCPBA (77%, 672 mg,
3.00 mmol) in CH2Cl2 (25 mL) for 16 h. Silica gel chromatography (CH/
EE 1:1!0:1) gave 34 (402 mg, 95%). Rf =0.1 (CH/EE 1:1); 1H NMR
(400 MHz, C6D6): d=7.11 (dt, 3J=14.9, 3J=7, 6 Hz, 1H), 6.03 (dt, 3J=
14.9, 4J=1.5 Hz, 1H), 2.71 (brs, 3H), 2.49 (dq, 3J=4.7, 4J=0.6 Hz, 1H),
2.36 (brs, 3H), 2.06 (s, 3H), 1.99 (AB signal, 2J=13.9 Hz, additionally
split by 3J=7.7 and 4J=1.4 Hz, 2H), 1.07 (d, 4J=0.6 Hz, 1H), 0.83 (s,
3H), 0.76 ppm (s, 3H); 13C NMR (100 MHz, C6D6): d=165.8, 142.1,
123.3, 60.5, 51.0, 42.2, 36.8, 36.4, 35.2, 23.6, 22.8, 18.5 ppm; IR (film): n˜ =
[7] Stoichiometric: a) W. A Nugent, T. V. RajanBabu, J. Am. Chem.
Soc. 1988, 110, 8561–8562; b) T. V. RajanBabu, W. A. Nugent, J.
Am. Chem. Soc. 1989, 111, 4525–4527; c) T. V. RajanBabu, W. A
Nugent, M. S. Beattie, J. Am. Chem. Soc. 1990, 112, 6408–6409;
d) T. V. RajanBabu, W. A. Nugent, J. Am. Chem. Soc. 1994, 116,
986–997; e) A. Fernµndez-Mateos, E. Martin de la Nava, G. Pas-
cual Coca, A. Ramos Silva, R. Rubio Gonzµlez, Org. Lett. 1999, 1,
607; f) A. Fernµndez-Mateos, L. Mateos Burón, R. Rabanedo Cle-
mente, A. I. Ramos Silva, R. Gonzµlez, Synlett 2004, 1011–1014.
[8] Catalytic: e) A. Gansäuer, M. Pierobon, H. Bluhm, Angew. Chem.
1998, 110, 107–109; Angew. Chem. Int. Ed. 1998, 37, 101–103; f) A.
Gansäuer, H. Bluhm, M. Pierobon, J. Am. Chem. Soc. 1998, 120,
12849–12859; g) A. Gansäuer, T. Lauterbach, H. Bluhm, M. Nolte-
meyer, Angew. Chem. 1999, 111, 3112–3114; Angew. Chem. Int. Ed.
1999, 38, 2909–2910; h) A. Gansäuer, H. Bluhm, Chem. Rev. 2000,
100, 2771–2788; i) A. Gansäuer, M. Pierobon, H. Bluhm, Synthesis
2001, 2500–2520; j) A. Gansäuer, M. Pierobon, H. Bluhm, Angew.
Chem. 2002, 114, 3341–3343; Angew. Chem. Int. Ed. 2002, 41, 3206–
3208; k) A. Gansäuer, H. Bluhm, B. Rinker, S. Narayan, M. Schick,
T. Lauterbach, M. Pierobon, Chem. Eur. J. 2003, 9, 531–542; l) A.
Gansäuer, B. Rinker, M Pierobon, S. Grimme, M. Gerenkamp, C.
Mück-Lichtenfeld, Angew. Chem. 2003, 115, 3815–3818; Angew.
Chem. Int. Ed. 2003, 42, 3687–3690.
[9] Hydrogen atom abstractions from THF are very fast (k~
107 Lmolꢀ1 sꢀ1): a) V. Malatesta, K. U. Ingold, J. Am. Chem. Soc.
1981, 103, 609–614; b) V. Malatesta, J. C. Scaiano, J. Org. Chem.
1982, 47, 1455–1459; c) W. K. Busfield, I. D. Grice, I. D. Jenkins, J.
Chem. Soc. Perkin Trans. 2 1994, 1079–1086.
[10] For a review see: B. P. Roberts, Chem. Soc. Rev. 1999, 28, 25–35; for
selected examples recent see: a) Y. D. Chai, B. P. Roberts, J. Chem.
Soc. Perkin Trans. 2 2002, 1858–1868; b) Y. D. Chai, B. P. Roberts,
D. A. Tocher, J. Chem. Soc. Perkin Trans. 1 2002, 1376–1386.
[11] As opposed to SmI2, enones are only slowly reduced by [Cp2TiCl]:
L. Moisan, C. Hardouin, B. Rousseau, E. Doris, Tetrahedron Lett.
2002, 43, 2013–2015.
2970, 1660, 1615, 1495, 1395, 1265, 1150, 1060, 980, 890, 815, 775 cmꢀ1
;
HRMS: m/z: calcd for C12H20NO2: 210.1494; found: 210.1496 [MꢀH]+.
2-(2-Hydroxymethyl-2,3,3-trimethyl-cyclobutyl)-N,N-dimethylacetamide
(35): According to GP 3 34 (211 mg, 1.00 mmol), [Cp2TiCl2] (24.9 mg,
100 mg), collidine hydrochloride (394 mg, 2.50 mmol) and zinc dust
(131 mg, 2.00 mmol) for 72 h. Silica gel chromatography (EE) gave 35
(200 mg, 94%, dr 72:28). Rf =0.3 (EE); 1H NMR (400 MHz, C6D6): d=
4.63 (dd, 3J=10.0, 2.7 Hz, 1H), 4.45* (d, 3J=6.8 Hz, 1H), 4.05* (d, 2J=
2
3
2
3
11.0 Hz, 1H), 4.01 (dd, J=11.0, J=1.8 Hz, 1H), 3.56* (dd, J=10.7, J=
7.2 Hz, 1H), 3.43 (dd, 2J=10.7, 3J=10.2 Hz, 1H), 2.71 (dddd, 3J=11.1,
2
3
10.7, 8.4, 3.0 Hz, 1H), 2.55* (s, 3H), 2.50 (s, 3H), 2.37* (dd, J=14.5, J=
10.5 Hz, 1H), 2.26* (dddd, 3J=9.9, 9.9, 8.4, 4.1 Hz, 1H), 2.22* (s, 3H),
2.15 (s, 3H), 2.11* (dd, 2J=14.5, 3J=4.0 Hz, 1H), 2.03 (dd, 2J=17.3, 3J=
11.1 Hz, 1H), 1.77 (dd, 2J=17.5, 3J=2.9 Hz, 1H), 1.67* (dd, 2J=0.8, 3J=
8.3 Hz, 1H), 1.57 (dd, 2J=10.4, 3J=8.4 Hz, 1H), 1.41* (dd, 2J=10.2, 3J=
10.2 Hz, 1H), 1.28 (dd, 2J=10.6, 3J=10.6 Hz, 1H), 1.25* (s, 3H), 1.07 (s,
3H), 1.01 (s, 3H), 1.00* (s, 3H), 0.84 (s, 3H), 0.82* ppm (s, 3H);
13C NMR (100 MHz, C6D6): d=173.4*, 173.1, 68.8, 64.7*, 46.1*, 45.7,
38.6*,37.6*,37.5, 36.8*, 36.6*, 36.4, 36.1, 35.0*, 34.9*, 34.3, 34.1, 25.9*,
24.5, 24.0, 23.3*, 19.3*, 14.8 ppm; IR (film): n˜ =3265, 2935, 1610, 1505,
1560, 1410, 1260, 1160, 1045, 800, 770, 710, 690 cmꢀ1; HRMS (EI, 70 eV):
m/z: calcd for C12H23NO2: 213.1729; found: 213.1729 [M]+.
Acknowledgement
[12] For some reviews on SmI2 see: a) H. B. Kagan, J.-L. Namy, Tetrahe-
dron 1986, 42, 6573–6614; b) G. A. Molander, Chem. Rev. 1992, 92,
29–68; c) G. A. Molander, C. R. Harris, Chem. Rev. 1996, 96, 307–
338; d) T. Skrydstrup, Angew. Chem. 1997, 109, 355–357; Angew.
Chem. Int. Ed. Engl. 1997, 36, 345–347; e) A. Krief, A.-M. Laval,
Chem. Rev. 1999, 99, 745–778; f) P. G. Steel, J. Chem. Soc. Perkin
Trans. 1 2001, 2727–2751.
We are indebted to the Deutsche Forschungsgemeinschaft (SFB 624) and
the Fonds der Chemischen Industrie (Dozentenstipendium to A.G. and
Sachbeihilfen) for financial support.
[1] a) Radicals in Organic Synthesis (Eds.: P. Renaud, M. Sibi), Wiley-
VCH, Weinheim, 2001; b) A. J. McCarroll, J. C. Walton, Angew.
Chem. 2001, 113, 2282–2307; Angew. Chem. Int. Ed. 2001, 40, 2225–
2250; c) D. P. Curran, N. A. Porter, B. Giese, Stereochemistry of Rad-
ical Reactions, VCH, Weinheim, 1996; d) B. Giese, B. Kopping, T.
Göbel, J. Dickhaut, G. Thoma, K. J. Kulicke, F. Trach in Organic Re-
actions (Ed.: L. A. Paquette), Wiley, New York, 1996, pp. 301–856.
[2] For a comprehensive review see a recent issue of Chemical Reviews,
edited by A. de Meijere: A. de Meijere, Chem. Rev. 2003, 103, 931–
1648, and references therein.
[3] For the rate constant of ring opening see: a) M. Newcomb, S. Y.
Choi, J. H. Horner, J. Org. Chem. 1999, 64, 1225–1231; b) V. W.
Bowry, J. Lusztyk, K. U. Ingold, J. Am. Chem. Soc. 1991, 113, 5687–
5698; for the rate constant of ring closure see: M. Newcomb, A. G.
Glenn, W. G. Williams, J. Org. Chem. 1989, 54, 2675–2681; for an in-
sightful theoretical discussion see: D. M. Smith, A. Nicolaides, B. T.
Golding, L. Radom, J. Am. Chem. Soc. 1998, 120, 10223–10233.
[4] For the rate constants of ring opening see: J. C. Walton, J. Chem.
Soc. Perkin Trans. 2 1989, 173–177; for an estimate of the rate con-
[13] For an early report of cyclopropane formation with CrCl2 see:
D. H. R. Barton, N. K. Basu, R. H. Hesse, F. H. Morehouse, M. J. M.
Pechet, J. Am. Chem. Soc. 1966, 88, 3016–3021; for a report with
SmI2 see: H. David, C. Afonso, M. Bonin, G. Doisneau, M.-G. Guil-
lerez, F. GuibØ, Tetrahedron Lett. 1999, 40, 8557–8561.
[14] See for example a) S. Züffle, H.-D. Beckhaus, C. Rüchardt, Liebigs
Ann. 1995, 877–880; b) J. J. Brocks, F. M. Welle, H.-D. Beckhaus, C.
Rüchardt, Tetrahedron Lett. 1997, 38, 7721–7724; c) J. J. Brocks, H.-
D. Beckhaus, A. L. J. Beckwith, C. Rüchardt, J. Org. Chem. 1998,
63, 1935–1943, and references therein; for an interesting discussion
concerning radical stabilization see: M. L. Coote, A. Pross, L.
Radom, Org. Lett. 2003, 5, 4689–4692.
[15] H. Lebel, J.-F. Marcoux, C. Molinaro, A. B. Charette, Chem. Rev.
2003, 103, 977–1050.
[16] a) M. E. Jung, R. Marquez, K. N. Houk, Tetrahedron Lett. 1999, 40,
2661–2664; b) K. Ogura, N. Sumitani, A. Kayano, H. Iguchi, M.
Fujita, Chem. Lett. 1992, 1487–1488; c) D. Johnston, C. M. McCusk-
er, D. J. Procter, Tetrahedron Lett. 1999, 40, 4913–4916; d) T. K.
Hutton, K. Muir, D. J. Procter, Org. Lett. 2002, 4, 2345–2347.
Chem. Eur. J. 2004, 10, 4983 – 4990
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A. Gansäuer et al.
FULL PAPER
[17] W. C. Still, M. Kahn, A. Mitra, J. Org. Chem. 1978, 43, 2923–2925.
[18] J. He, Y. Wu, Synth. Commun. 1985, 15, 95–99.
[19] E. J. Corey, P. da Silva Jardine, J. C. Rohloff, J. Am. Chem. Soc.
1988, 110, 3672–3673.
[20] M. W. Rathke, J. Deitch, Tetrahedron Lett. 1971, 31, 2953–2956.
[21] D. Michelot, R. Lorne, C. Huynh, S. Julia, Bull. Soc. Chim. Fr. 1976,
9–10, 1482–1488.
[22] M. Kato, H. Kitahara, A. Yoshikoshi, Bull. Chem. Soc. Jpn. 1986,
59, 1647–1649.
[23] E. Hasegawa, A. Yoneoka, K. Suzuki, T. Kato, T. Kitazume, K.
Yanagi, Tetrahedron 1999, 55, 12957–12968.
[24] N. H. Andersen, S. W. Hadley. J. D. Kelly, E. R. Bacon, J. Org.
Chem. 1985, 50, 4144–4151.
Received: July 5, 2004
Published online: August 24, 2004
4990
ꢁ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10, 4983 – 4990