Ring-Closing Olefin Metathesis and Radical Cyclization as Competing Pathways

Article abstract of DOI:10.1021/jo0353942

First and second generation Grubbs' catalyst mediate under otherwise identical conditions two different cyclization modes with high selectivity: a ring-closing metathesis and an atom-transfer radical addition (ATRA) pathway.

Full text of DOI:10.1021/jo0353942

Rin g-Closin g Olefin Meta th esis a n d Ra d ica l
Cycliza tion a s Com p etin g P a th w a ys
Bernd Schmidt,*,† Michael Pohler,† and
Burkhard Costisella‡
FB Chemie-Organische Chemie and FB
Chemie-Gemeinsame Einrichtungen-NMR-Spektroskopie,
Universita¨t Dortmund, Otto-Hahn-Strasse 6,
D-44227 Dortmund, Germany
bschmidt@chemie.uni-dortmund.de
Received September 24, 2003
F IGURE 1. First (A) and second (B, C) ruthenium-based
metathesis catalysts.
more active catalysts B or C lead to the formation of the
thermodynamically preferred products, whereas the less
active catalyst A gives the kinetically preferred product.
Recently, it was noted that ruthenium carbene complexes
catalyze a variety of nonmetathesis transformations.9 An
example where precatalyst A mediates an enyne meta-
thesis reaction and precatalyst B, at least to a certain
extent, an oxidative cyclization has been published by
Mori et al.10 The first nonmetathesis reactivity pattern
described for ruthenium carbene complexes was the atom
transfer radical addition reaction, often referred to as the
Kharash reaction.11 Snapper et al.12a and Demonceau et
al.12b described that olefins react with CHCl3 and CCl4,
respectively, in the presence of precatalyst A to form
addition products rather than the expected cross-meta-
thesis products.13
Abstr a ct: First and second generation Grubbs’ catalyst
mediate under otherwise identical conditions two different
cyclization modes with high selectivity: a ring-closing me-
tathesis and an atom-transfer radical addition (ATRA)
pathway.
Olefin metathesis has become one of the most impor-
tant tools in organic synthesis over the past 10 years1
due to the discovery of stable and defined precatalysts
based on molybdenum2 and ruthenium.3 Two classes of
ruthenium-based “Grubbs”-type catalysts are widely used
today: the first generation catalyst A4 and the second
generation catalysts B5a and C5b (Figure 1).
The imidazolylidene-substituted precatalysts B and C
are generally considered to be more reactive in olefin
metathesis reactions, e.g. in the conversion of electron-
poor6a or electron-rich C-C double bonds,6b which react
only slowly or not at all in the presence of the first
generation catalyst A. Only few examples have been
reported where first and second generation catalyst give
qualitatively different results. For example, the E/Z
selectivity in macro-RCM reactions may depend on the
choice of catalyst.7 An example where the ring size in an
ene-diene macro-RCM reaction depends on the catalyst
has been published by Wagner et al.8 In both cases, the
It was recently described by ourselves14 and by others15
that diallyl carbinols, derived from double addition of
allylmagnesium bromide to esters, show comparatively
low reactivity in ruthenium-catalyzed ring-closing me-
tathesis if carbene complex A is used. In contrast, smooth
conversion to the expected cyclopentenols is observed
with the second generation catalyst B.14b This observation
prompted us to investigate if the lower metathesis
activity of A can be exploited to selectively promote a
5-exo-trig cyclization via a radical pathway.16 5-Exo-trig
cyclization reactions by metal-catalyzed atom radical
transfer addition (ATRA) reactions have been described
in the literature;17 however, ruthenium-based metathesis
catalysts have, to the best of our knowledge, never been
used in this reaction.
† FB Chemie-Organische Chemie.
‡ FB Chemie-Gemeinsame Einrichtungen.
(1) Reviews: (a) Schuster, M.; Blechert, S. Angew. Chem., Int. Ed.
Engl. 1997, 36, 2036-2055. (b) Armstrong, S. K. J . Chem. Soc., Perkin
Trans. 1 1998, 371-388. (c) Fu¨rstner, A. Angew. Chem., Ind. Ed. 2000,
39, 3013-3043.
(2) Schrock, R. R.; Murdzek, J . S.; Bazan, G. C.; Robbins, J .; DiMare,
M.; O’Regan, M. J . Am. Chem. Soc. 1990, 112, 3875-3886.
(3) Fu, G. C.; Nguyen, S. T.; Grubbs, R. H.; Ziller, J . W. J . Am. Chem.
Soc. 1993, 115, 9856-9857.
(9) Alcaide, B.; Almendros, P. Chem. Eur. J . 2003, 9, 1259-1262.
(10) Mori, M.; Saito, N.; Tanaka, D.; Takimoto, M.; Sato, Y. J . Am.
Chem. Soc. 2003, 125, 5606-5607.
(4) Schwab, P.; Grubbs, R. H.; Ziller, J . W. J . Am. Chem. Soc. 1996,
118, 100-110.
(11) Kharash, M. S.; J ensen, E. V.; Urry, W. H. J . Am. Chem. Soc.
1947, 69, 1100-1105.
(5) (a) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999,
1, 953-956. (b) Huang, J .; Stevens, E. D.; Nolan, S. P.; Petersen, J . L.
J . Am. Chem. Soc. 1999, 121, 2674-2678.
(12) (a) Tallarico, J . A.; Malnick, L. M.; Snapper, M. L. J . Org. Chem.
1999, 64, 344-345. (b) Simal, F.; Demonceau, A.; Noels, A. F.
Tetrahedron Lett. 1999, 40, 5689-5693.
(6) (a) Fu¨rstner, A.; Thiel, O. R.; Ackermann, L.; Schanz, H.-J .;
Nolan, S. P. J . Org. Chem. 2000, 65, 2204-2207. (b) van Otterlo, W.
A. L.; Ngidi, E. L.; de Koning, C. B. Tetrahedron Lett. 2003, 44, 6483-
6486.
(7) (a) Fu¨rstner, A.; Thiel, O. R.; Kindler, N.; Bartkowska, B. J . Org.
Chem. 2000, 65, 7990-7995. (b) Fu¨rstner, A.; Radkowski, K.; Wirtz,
C.; Goddard, R.; Lehmann, C. W.; Mynott, R. J . Am. Chem. Soc. 2002,
124, 7061-7069. (c) Murga, J .; Falomir, E.; Garcia-Fortanet, J .; Carda,
M.; Marco, J . A. Org. Lett. 2002, 4, 3447-3449.
(8) Wagner, J .; Martin-Cabrejas, L. M.; Grossmith, C. E.; Papageor-
giou, C.; Senia, F.; Wagner, D.; France, J .; Nolan, S. P. J . Org. Chem.
2000, 65, 9255-9260.
(13) For a review on Ru-catalyzed nonmetathesis C-C bond-forming
reactions, see: (a) Trost, B. M.; Toste, F. D.; Pinkerton, A. B. Chem.
Rev. 2001, 101, 2067-2096. For other examples of atom radical
transfer addition mediated by Ru-carbene complexes, see: (b) De
Clercq, B.; Verpoort, F. Tetrahedron Lett. 2001, 42, 8959-8963. (c) De
Clercq, B.; Verpoort, F. J . Organomet. Chem. 2003, 672, 11-16.
(14) (a) Schmidt, B.; Wildemann, H. J . Chem. Soc., Perkin Trans. 1
2002, 1050-1060. (b) Schmidt, B.; Pohler, M. Org. Biomol. Chem. 2003,
1, 2512-2517.
(15) Clive, D. L. J .; Cheng, H. Chem. Commun. 2001, 605-606.
(16) (a) Brace, N. O. J . Org. Chem. 1967, 32, 2711-2718. (b) Brace,
N. O. J . Org. Chem. 1969, 34, 2441-2445.
10.1021/jo0353942 CCC: $27.50 © 2004 American Chemical Society
Published on Web 01/17/2004
J . Org. Chem. 2004, 69, 1421-1424
1421

SCHEME 1. Ra d ica l Cycliza tion a n d Rin g-Closin g
Meta th esis P a th w a y
SCHEME 2. Ch a r a cter istic NOE In ter a ction s
SCHEME 3. Mech a n istic In ter m ed ia tes a n d
Tr a n sition Sta te Geom etr ies in th e Cycliza tion
1 f 2
TABLE 1. Yield s a n d Dia ster eoselectivities of Ra d ica l
a n d Meta th esis Cycliza tion of Dia llylca r bin olsa
starting
radical cyclization RCM product
entry material
R
product (yield; dr)
(yield)
1
2
3
4
1a
1b
1c
1d
-C(CH3)3
-CH2Cl
2a (76%; >95:5)
2b (55%; 5:1)
-(CH2)3OBn 2c (72%; 4:1)
-(CH2)3OAc 2d (71%; 5:1)
3a (83%)
3b (68%)
3c (71%)
3d (71%)
a
For reagents and conditions, see Scheme 1.
We started our investigation with metathesis precursor
1a , derived from ethyl pivaloate. Treatment of 1a with a
catalytic amount (5 mol %) of first generation catalyst A
in tetrachloromethane led to no noticeable conversion at
ambient temperature. Heating the mixture to reflux,
however, induced clean conversion to a single diastere-
oisomer of a 1:1 addition product, which was identified
as the desired cyclization product 2a by elemental
analysis and by spectroscopic means. We could neither
detect any linear products resulting from single- or
double-Kharash reaction of the diene precursor 1a nor
any cyclopentene 3a resulting from ring-closing metath-
esis. Next, we checked whether the metathesis activity
of second generation catalyst B is sufficiently enhanced
to compete with the initiation of the radical cyclization
pathway. To this end, 1a was treated with B under
conditions identical with those described above for the
radical-initiated cyclization of 1a catalyzed by first
generation catalyst A. Indeed, clean ring-closing metath-
esis to 3a was observed. We were unable to detect 2a in
the 1H NMR spectrum of the crude reaction mixture. The
same experiments were conducted with other diallyl
carbinols 1b-d , and similar results were obtained in
every case, as illustrated in Scheme 1 and Table 1.
The formation of 2a is highly diastereoselective, with
the level of diastereoselectivity exceeding 95:5. For 2b-d
bearing sterically less demanding substituents R than
2a , the ratio of diastereoisomers is somewhat lower
(approximately 4:1 to 5:1). Surprisingly, a relative con-
figuration is strongly preferred where all substituents are
located on the same face of the cyclopentane ring. The
relative configuration was elucidated by one-dimensional,
gradient-selected NOE experiments; characteristic NOE
interactions are depicted in Scheme 2.
Thus, upon irradiation at the tert-butyl resonance in
2a , NOE effects were observed for the -CH2CCl3 moiety
(NOE 1) as well as for the -CH2Cl moiety (NOE 2). No
enhancement of the signals resulting from the methine
protons was observed. For 2b, upon irradiation at the
resonance for the H5 signal, enhancement of signals was
observed for both protons of the -CH2Cl moiety (NOE
1), for one proton of the other -CH2Cl moiety (NOE 3),
and for both protons of the -CH2CCl3 moiety (NOE 2).
Again, no NOE interaction with the two methine protons
was observed. The all-cis configuration observed for our
cyclization products is in accord with results reported by
Grigg et al.17a and by Tsai et al.17f and appears to be the
result of kinetic control. Addition of a CCl3 radical to one
terminal double bond of diallylcarbinol 1 results in the
formation of a secondary radical 4, which adopts a
transition state geometry where the substituent R is
located in an equatorial orientation and the hydroxy
group in an axial orientation. 5-Exo-trig cyclization gives
the radical 5, which subsequently abstracts a chlorine
from CCl4 (Scheme 3).18
In an attempt to extend the concept outlined above to
other substrates, we investigated the reactivity of dial-
lylsilanes 6. The application of first generation ruthenium
catalysts to the synthesis of silacycloalkenes has recently
been described by Undheim et al.19 Although ring-closing
metathesis products are obtained in good yields, rather
high catalyst loadings and elevated temperatures are
required to achieve complete conversion. We had previ-
ously observed that RCM of diallyldiphenylsilane 6a
using 5 mol % of Ru-based catalyst A proceeds only with
poor conversion, even in refluxing toluene.20 In contrast,
(17) (a) Grigg, R.; Devlin, J .; Ramasubbu, A.; Scott, R. M.; Stevenson,
P. J . Chem. Soc., Perkin Trans. 1 1987, 1515-1520. (b) Huther, N.;
McGrail, P. T.; Parsons, A. F. Tetrahedron Lett. 2002, 43, 2535-2538.
(c) Yang, Z.-Y.; Burton, D. J . J . Org. Chem. 1992, 57, 5144-5149. (d)
Huang, W.-Y.; Zhao, G.; Ding, Y. J . Chem. Soc., Perkin Trans. 1 1995,
1729-1730. (e) Gilbert, B. C.; Kalz, W.; Lindsay, C. I.; McGrail, P. T.;
Parsons, A. F.; Whittaker, D. T. E. J . Chem. Soc., Perkin Trans. 1 2001,
1187-1194. (f) Tsai, J . Y.; Bouhadir, K. H.; Zhou, J . L.; Webb, T. R.;
Sun, Y. H.; Shevlin, P. B. J . Org. Chem. 2003, 68, 1235-1241.
(18) For a review on stereoselective radical reactions, see: Bar, G.;
Parsons, A. F. Chem. Soc. Rev. 2003, 32, 251-263.
(19) Ahmad, I.; Falck-Pedersen, M. L.; Undheim, K. J . Organomet.
Chem. 2001, 625, 160-172.
(20) Schmidt, B. Unpublished results.
1422 J . Org. Chem., Vol. 69, No. 4, 2004

SCHEME 4. Ra d ica l Ad d ition P a th w a y a n d RCM
of Dia llylsila n es
with the terminal alkenes for the vacant coordination site
at the ruthenium. The observation that for second
generation catalysts, which have a much lower tendency
toward coordination of Lewis bases,23 ring-closing me-
tathesis reactivity is strongly preferred with these sub-
strates is in line with this assumption. To provide further
evidence for this theory, we subjected the methyl ether
of 1a to the protocol developed for radical cyclization of
diallylcarbinols (1 f 2, Scheme 1). Under these condi-
tions, ether 9 is cleanly converted to the RCM product
10. No products resulting from radical reactions could
be detected (eq 2).
with second generation catalyst B a 70% yield of silacy-
clopentene 7a is obtained under otherwise identical
conditions (eq 1). This is, to the best of our knowledge,
the first metathesis-based synthesis of 7a that has been
widely used as a synthetic building block.21
In conclusion, we describe that for RCM substrates
that are difficult to cyclize a cyclization mode involving
atom radical transfer addition can efficiently compete
with the metathesis pathway. Radical cyclization occurs
with high diastereoselectivity, and the diastereoselectiv-
ity observed is obviously the result of kinetic control.
Furthermore, we present examples where first and
second generation ruthenium catalysts give qualitatively
different results, with the less active metathesis catalyst
selectively promoting a nonmetathesis reactivity pattern.
This situation appears well-suited to apply the condi-
tions used for the transformation 1 f 2 (Scheme 1).
However, substrate 6a does not cyclize but undergoes a
double addition of CCl4 to yield a linear product 8a . We
assume that the larger silicon atom in combination with
the two sterically demanding phenyl substituents leads
to a transition state geometry that is unfavorable for
cyclization reactions, due to a larger distance between
the reacting centers. The same result was observed for
the dimethyl analogue 6b, indicating that the effect is
mainly due to the silicon, rather than the phenyl sub-
stituents. Gratifyingly, application of the protocol used
for the transformation 1 f 3 (Scheme 1) to 6a gives
silacyclopentene 7a in good yield without noticeable
formation of any radical addition product (Scheme 4).
While the reduced RCM activity of first generation
catalyst A toward diallylsilanes can be understood if the
larger atomic radius of silicon is taken into account, the
low activity toward diallylcarbinols is somewhat surpris-
ing. Numerous five-membered carba-, oxa-, or azacycles
with similar steric demand have been prepared by using
the first generation catalyst; diallylmalonate, for in-
stance, is a commonly used test substrate in ring-closing
metathesis reactions and was found to cyclize compara-
tively facile in the presence of first generation catalysts.22
Thus, it appears likely that the free hydroxy function in
diallylcarbinols 1 is responsible for the reduced metath-
esis activity of first generation catalysts toward these
substrates. We propose that the OH moiety competes
Exp er im en ta l Section
Gen er a l. General information concerning experimental tech-
niques and product characterization14b and details for NOE-
spectroscopic measurements have been published previously.24
J values are given in Hz and δ values are given in ppm. The
number in parentheses following the δC value indicates the
number of coupled protons. Whenever complete signal assign-
ment is given, this is based on H,H- or H,C-correlation spec-
troscopy.
Gen er a l P r oced u r e for th e Syn th esis of Cycliza tion
P r od u cts 2. To a solution of the corresponding precursor 1 (1.6
mmol) in tetrachloromethane (3.0 mL) was added catalyst A (60
mg, 5 mol %) under an atmosphere of argon. The mixture was
heated to reflux for 16 h; the solvent was evaporated and the
residue was purified by chromatography on silica with cyclo-
hexane-MTBE mixtures as eluent.
3-Ch lor om et h yl-1-ter t-b u t yl-4-(2,2,2-t r ich lor oet h yl)cy-
clop en ta n ol (2a ). 2a was obtained from 1a (100 mg, 0.6 mmol)
as a colorless liquid. Yield: 146 mg (76%). Chromatography:
cyclohexane/MTBE 10:1 (v/v). 1H NMR (400 MHz, CDCl3): δ 3.64
(dd, 1 H, J ) 11.0, 4.5, HCHCl), 3.49 (dd, 1 H, J ) 11.0, 7.3,
HCHCl), 3.01 (dd, 1 H, J ) 14.3, 4.9, HCHCCl3), 2.96 (m, 1 H,
CHCH2CCl3), 2.79 (m, 1 H, CHCH2Cl), 2.74 (dd, 1 H, J ) 14.3,
6.3, HCHCCl3), 1.98 (dd, 1 H, J ) 14.3, 6.3, H5), 1.83 (ddd, 1 H,
J ) 13.0, 6.5, 1.5, H2), 1.80 (dm, 1 H, J ) 13.0, H2′), 1.73 (ddd,
1 H, J ) 14.3, 8.4, 2.0, H5′), 1.39 (s, 1 H, OH), 0.96 (s, 9 H, tBu).
13C NMR (100 MHz, CDCl3): δ 99.8 (0, CCl3), 85.6 (0, COH),
54.9 (2, CH2CCl3), 47.2 (2, CH2Cl), 41.5 (2, C5), 41.2 (1, CHCH2-
Cl), 38.6 (2, C2), 38.0 (1, CHCH2CCl3), 36.5 (0, CMe3), 25.6 (3,
CH3). IR (neat, NaCl): 3480 (br w), 2964 (m), 1477 (w), 1370
(m), 1069 (w), 780 (m), 705 (m) cm-1. MS (EI, 70 eV): m/z 305
(M+ - OH, <5%), 265 (25), 227 (70), 191 (30), 127 (50), 91 (55),
(21) (a) Mignani, S.; Damour, D.; Bastart, J .-P.; Manuel, G. Synth.
Commun. 1995, 25, 3855-3861. (b) Mignani, S.; Barreau, M.; Damour,
D.; Renaudon, A.; Dejean, V.; Manuel, G. Synth. Commun. 1998, 28,
1163-1173. For reviews on silicon-carbon heterocycles, see: (c)
Hermanns, J .; Schmidt, B. J . Chem. Soc., Perkin Trans. 1 1998, 2209-
2230. (d) Hermanns, J .; Schmidt, B. J . Chem. Soc., Perkin Trans. 1
1999, 81-102.
(22) (a) Dias, E. L.; Nguyen, S. T.; Grubbs, R. H. J . Am. Chem. Soc.
1997, 119, 3887-3897. (b) Bentz, D.; Laschat, S. Synthesis 2000, 1766-
1773.
(23) (a) Sanford, M. S.; Ulman, M.; Grubbs, R. H. J . Am. Chem. Soc.
2001, 123, 749-750. (b) Sanford, M. S.; Love, J . A.; Grubbs, R. H. J .
Am. Chem. Soc. 2001, 123, 6543-6554.
(24) Schmidt, B.; Costisella, B.; Roggenbuck, R.; Westhus, M.;
Wildemann, H.; Eilbracht, P. J . Org. Chem. 2001, 66, 7658-7665.
J . Org. Chem, Vol. 69, No. 4, 2004 1423

57 (100). Anal. Calcd for C12H20OCl4: C, 44.8; H, 6.3. Found:
C, 44.9; H, 6.4.
w), 2923 (m), 2855 (w), 1458 (w), 1242 (s), 1101 (m), 695 (s) cm-1
.
MS (EI, 70 eV): m/z 414 (M+, 25), 272 (40), 229 (72), 212 (60),
91 (100), 77 (40). Anal. Calcd for C18H24O2Cl4: C, 52.2; H, 5.8.
Found: C, 52.3; H, 5.8.
1,3-Di(ch lor om et h yl)-4-(2,2,2-t r ich lor oet h yl)cyclop en -
ta n ol (2b). 2b was obtained from 1b (250 mg, 1.6 mmol) as a
colorless liquid. Yield: 269 mg (55%), 5:1 mixture of diastere-
oisomers. Chromatography: cyclohexane/MTBE 10:1 (v/v). 1H
NMR (500 MHz, CDCl3): δ 3.69 (d, 1 H, J ) 11.0, HOCCHHCl),
3.64 (d, 1 H, J ) 11.0, HOCCHHCl), 3.62 (dd, 1 H, J ) 11.3,
4.5, HCHCl), 3.56 (dd, 1 H, J ) 11.3, 7.0, HCHCl), 3.02 (dd, 1
H, J ) 14.0, 4.6, HCHCCl3), 3.01 (m, 1 H, CHCH2CCl3), 2.86
(m, 1 H, CHCH2Cl), 2.76 (dd, 1 H, J ) 14.0, 8.0, HCHCCl3), 2.26
(s, 1 H, OH), 2.14 (ddd, 1 H, J ) 13.5, 6.5, 1.7, H5), 2.06 (ddd,
1 H, J ) 14.4, 8.5, 1.8, H2), 1.90 (dd, 1 H, J ) 14.4, 6.0, H2′),
1.78 (dd, 1 H, J ) 13.5, 10.5, H5′). 13C NMR (125 MHz, CDCl3):
δ 99.5 (0, CCl3), 79.7 (0, COH), 54.7 (2, CH2CCl3), 53.8 (2,
COHCH2Cl), 46.8 (2, CHCH2Cl), 44.9 (2, C5), 41.8 (1, CHCH2-
Cl), 41.4 (2, C2), 38.3 (1, CHCH2CCl3). IR (neat, NaCl): 3439
(br w), 2927 (s), 2849 (w), 1432 (w), 757 (m) cm-1. MS (EI, 70
eV): m/z 297 (M+ - OH, 3%), 263 (34), 229 (100), 191 (38), 139
(50), 127 (83), 91 (69), 77 (44). Anal. Calcd for C9H13OCl4: C,
34.4; H, 4.2. Found: C, 34.6; H, 4.4.
1-(3-Acetoxyp r op yl)-3-ch lor om eth yl-4-(2,2,2-tr ich lor oet-
h yl)cyclop en ta n ol (2d ). 2d was obtained from 1d (300 mg,
1.4 mmol) as a colorless liquid. Yield: 366 mg (71%), 5:1 mixture
of diastereoisomers. Chromatography: cyclohexane/MTBE 20:1
1
(v/v). H NMR (400 MHz, CDCl3): δ 4.06 (t, 2 H, J ) 6.4, CH2-
OAc), 3.62 (dd, 1 H, J ) 11.3, 4.5, HCHCl), 3.53 (dd, 1 H, J )
11.3, 6.5, HCHCl), 3.02 (dd, 1 H, J ) 14.6, 4.5, HCHCCl3), 2.94
(m, 1 H, CHCH2CCl3), 2.80 (m, 1 H, CHCH2Cl), 2.74 (dd, 1 H, J
) 14.6, 7.0, HCHCCl3), 2.03 (ddd, 1 H, J ) 13.1, 6.6, 1.6, H5),
2.02 (s, 3 H, -CH3), 1.95 (ddd, 1 H, J ) 14.3, 8.3, 2.0, H2), 1.76
(3 H, H2′, CH2CH2OAc), 1.61-1.67 (4 H, H5′, CH2COH, OH).
13C NMR (100 MHz, CDCl3): δ 171.2 (0, CdO), 99.7 (0, CCl3),
79.9 (0, COH), 64.7 (2, CH2OAc), 54.9 (2, CH2CCl3), 47.1 (2, CH2-
Cl), 46.7 (2, C5), 43.2 (2, C2), 41.4 (1, CHCH2Cl), 38.0 (2, CH2-
CH2OAc), 37.9 (1, CHCH2CCl3), 24.0 (2, CH2COH), 21.0 (3, CH3).
IR (neat, NaCl): 3464 (br w), 2953 (m), 1735 (s), 1242 (s), 1033
(m). MS (EI, 70 eV): m/z 367 (M+ + 1, 5%), 288 (40), 236 (60),
163 (75), 88 (100). Anal. Calcd for C13H20O3Cl4: C, 42.7; H, 5.5.
Found: C, 43.1; H, 5.7.
1-Ben zyloxyp r op yl-3-ch lor om eth yl-4-(2,2,2-tr ich lor oet-
h yl)-cyclop en ta n ol (2c). 2c was obtained from 1c (190 mg,
0.7 mmol) as a colorless liquid. Yield: 217 mg (72%), 4:1 mixture
of diastereoisomers. Chromatography: cyclohexane/MTBE 20:1
1
(v/v). H NMR (400 MHz, CDCl3): δ 7.27-7.34 (5 H, HPh), 4.51
Ack n ow led gm en t . Generous financial support of
this work by the Deutsche Forschungsgemeinschaft, the
Fonds der Chemischen Industrie, and the department
of chemistry of the University of Dortmund is gratefully
acknowledged.
(s, 2 H, CH2Ph), 3.63 (dd, 1 H, J ) 11.1, 4.5, HCHCl), 3.53 (dd,
1 H, J ) 11.1, 6.5, HCHCl), 3.52 (t, 2 H, J ) 6.0, CH2OBn), 3.02
(dd, 1 H, J ) 14.6, 4.8, HCHCCl3), 2.95 (m, 1 H, CHCH2CCl3),
2.80 (m, 1 H, CHCH2Cl), 2.74 (dd, 1 H, J ) 14.6, 6.9, HCHCCl3),
2.66 (s, 1 H, OH), 2.06 (ddd, 1 H, J ) 13.1, 6.5, 1.8, H5), 1.98
(ddd, 1 H, J ) 14.1, 8.3, 2.0, H2), 1.71-1.77 (5 H, H2′, CH2-
COH, CH2CH2OBn), 1.62 (dd, 1 H, J ) 12.1, 12.1, H5′). 13C NMR
(100 MHz, CDCl3): δ 137.9 (0, Cipso-Ph), 128.4, 127.7 (1, CPh),
127.7 (1, Cp-Ph), 99.9 (0, CCl3), 79.6 (0, COH), 73.1 (2, CH2Ph),
70.8 (2, CH2OBn), 55.0 (2, CH2CCl3), 47.3 (2, CH2Cl), 46.8 (2,
C5), 43.6 (2, C2), 41.5 (1, CHCH2Cl), 39.4 (2, CH2CH2OBn), 38.0
(1, CHCH2CCl3), 25.4 (2, CH2COH). IR (neat, NaCl): 3415 (br
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedure and analytical data for 1a -d , 3a -d , 7a , 8a ,b, 9, and
10; NOE-spectra for 2a -c. This material is available free of
charge via the Internet at http://pubs.acs.org.
J O0353942
1424 J . Org. Chem., Vol. 69, No. 4, 2004