Asymmetric synthesis of cis-1,2-dialkenyl-substituted cyclopentanes via (-)-sparteine-mediated lithiation and cycloalkylation of a 9-chloro-2,7-nonadienyl carbamate

Article abstract of DOI:10.1021/jo015548i

Herein we report our comprehensive results in enantioselective cyclopentane synthesis via stereogenic allyllithium compounds. The described cycloalkylation reaction starts with a (-)-sparteine-mediated asymmetric deprotonation of the 2,7-alkadienyl carbamate 7e and leads to the enantioenriched (80% ee) and diastereomerically pure (dr = 99:1) cis-1,2-divinyl-cyclopentane 8, by a subsequent cyclization and elimination of lithium chloride. The reaction mechanism has been investigated by silylation and lithiodestannylation experiments and was found to represent a completely regioselective anti-S_N′S_E′-reaction. Trapping of the vinyllithium intermediate 12 with various electrophiles under retention of the configuration at the double bond extends the field of application for this cyclization. We also applied this reaction as the key step in the enantioselective synthesis of (+)-dihydromultifidene (17).

Full text of DOI:10.1021/jo015548i

2842
J . Org. Chem. 2001, 66, 2842-2849
Asym m etr ic Syn th esis of cis-1,2-Dia lk en yl-Su bstitu ted
Cyclop en ta n es via (-)-Sp a r tein e-Med ia ted Lith ia tion a n d
Cycloa lk yla tion of a 9-Ch lor o-2,7-n on a d ien yl Ca r ba m a te
Alexander Deiters and Dieter Hoppe*
Organisch-Chemisches Institut der Universita¨t, Corrensstrasse 40, D-48149 Mu¨nster, Germany
dhoppe@uni-muenster.de
Received J anuary 31, 2001
Herein we report our comprehensive results in enantioselective cyclopentane synthesis via
stereogenic allyllithium compounds. The described cycloalkylation reaction starts with a (-)-
sparteine-mediated asymmetric deprotonation of the 2,7-alkadienyl carbamate 7e and leads to the
enantioenriched (80% ee) and diastereomerically pure (dr ) 99:1) cis-1,2-divinyl-cyclopentane 8,
by a subsequent cyclization and elimination of lithium chloride. The reaction mechanism has been
investigated by silylation and lithiodestannylation experiments and was found to represent a
completely regioselective anti-SN′SE′-reaction. Trapping of the vinyllithium intermediate 12 with
various electrophiles under retention of the configuration at the double bond extends the field of
application for this cyclization. We also applied this reaction as the key step in the enantioselective
synthesis of (+)-dihydromultifidene (17).
In tr od u ction
nucleophile.7,8 An enantioselective cycloallylation reaction
mediated by an external ligand has not been reported so
far.9
The allylic substitution of a leaving group by a carbon
nucleophile is one of the most important reactions in
organic synthesis. In almost every allylic substitution
reaction transition metals, such as copper1 and pal-
ladium,2 are involved. Simple main-group organometal-
lics are rarely used in allylic substitutions,3 because in
intermolecular reactions the regioselectivity becomes a
major problem, giving rise to product mixtures resulting
from SN2 and SN2′ reactions.4 In intramolecular variants
these difficulties could be overcome by the different
cyclization rates in both competing mechanistic path-
ways. Due to the fast formation of five-membered rings,5
the cyclopentane synthesis6 is strongly favored in these
reactions (eq 1).
Resu lts a n d Discu ssion
Herein we report our entire efforts in cyclopentane
synthesis by carbocyclization of allyllithium compounds
(eq 2).10 Particularly challenging in this reaction is the
control of both regioselectivities, in respect of the allylic
leaving group and of the allyl anion.11 Out of the four
possible regioselective reaction pathways, eq 2 only shows
the desired γ,γ′-regioselective bond formation. Since, in
addition, we wanted to realize this cyclization in an
enantioselective fashion, by control of an external ligand,
we chose a deprotonation by a chirally modified butyl-
lithium as the initial reaction to generate the organo-
In the examples previously published, alkoxides were
used as leaving groups and a lithium alkanide 1, which
was generated by tin-lithium exchange, was utilized as
(7) Synthesis of pyrrolidines: Coldham, I.; Hufton, R.; Rathmell, R.
E. Tetrahedron Lett. 1997, 38, 7617-7620.
* To whom correspondence should be addressed. Telefax: Int +251/
8339772.
(8) Synthesis of racemic tetrahydrofurans: (a) Broka, C. A.; Shen
T. J . Am. Chem. Soc. 1989, 111, 2981-2984; (b) Broka, C. A.; Lee, W.
J .; Tong S. J . Org. Chem. 1988, 53, 1336-1338.
(1) Lipshutz, B. H.; Sengupta, S. Org. React. 1992, 41, 135.
(2) (a) Trost, B. M.; van Vranken, D. L. Chem. Rev. 1996, 96, 395.
(b) Helmchen, G.; Pfaltz, A. Acc. Chem. Res. 2000, 33, 336. (c) Reiser,
O. Angew. Chem., Int. Ed. Engl. 1993, 32, 547-550.
(3) Review: Magid, R. M. Tetrahedron 1980, 36, 1901-1930.
(4) (a) Yanagisawa, A.; Yasue, K., Yamamoto, H. Synlett 1996, 842-
844. (b) Yanagisawa, A.; Yamamoto H. In Active Metals; Fu¨rstner, A.,
Ed.; VCH: Weinheim, 1995; pp 61-84. (c) Yanagisawa, A.; Hibino,
H.; Habaue, S.; Hisada, Y.; Yamamoto, H. J . Org. Chem. 1992, 57,
6386-6387.
(5) Eliel, E. L.; Wilen, S. H. In Stereochemistry of Organic Com-
pounds; Wiley: New York, 1994; pp 675-685.
(6) Recent reviews about the synthesis of 3-eight-membered car-
bocycles: (a) Hartley, R. C.; Caldwell, S. T. J . Chem. Soc., Perkin Trans.
1 2000, 477-501; (b) Molander, G. A. Acc. Chem. Res. 1998, 31, 603-
609.
(9) (a) For an enantioselective 5-exo-tet-cyclization see: Serino, C.;
Stehle, N.; Park, Y. S.; Florio, S.; Beak, P. J . Org. Chem. 1999, 64,
1160-1165. (b) Review about enantioselective carbolithiations: Marek,
I.; J . Chem. Soc., Perkin Trans. 1 1999, 535-544.
(10) For a preliminary communication of our work, see: Deiters,
A.; Hoppe, D. Angew. Chem. 1999, 111, 529-532; Angew. Chem., Int.
Ed. Engl. 1999, 38, 546-548.
(11) We could solve this problem for intramolecular reactions, it still
exists in intermolecular variants (see ref 4). For enantioselective
cyclononadiene syntheses by an intramolecular R,R′-coupling, see: (a)
Deiters, A.; Fro¨hlich, R.; Hoppe, D. Angew. Chem. 2000, 112, 2189-
2192; Angew. Chem., Int. Ed. Engl. 2000, 39, 2105-2107. (b) Deiters,
A.; Mu¨ck-Lichtenfeld, C.; Fro¨hlich, R.; Hoppe, D. Org. Lett. 2000, 2,
2415-2418.
10.1021/jo015548i CCC: $20.00 © 2001 American Chemical Society
Published on Web 03/29/2001

cis-1,2-Dialkenyl-Substituted Cyclopentanes
J . Org. Chem., Vol. 66, No. 8, 2001 2843
Sch em e 1. Syn th esis of th e Cycliza tion
P r ecu r sor sa
Sch em e 2a
a
Reagents and conditions: (a) n-BuLi, TMEDA (9), Et2O,
-78 °C.
Sch em e 3. En a n tioselective Cycliza tion a
a
Reagents and conditions: (a) EtO2CCH2PO(OEt)2, K2CO3,
H2O, 35%; (b) DIBAH, toluene, 92%; (c) NaH, CbyCl, THF, 39%
of 6, 22% of 7b, 19% of 5; (d) LiCl, n-BuLi, CH3SO2Cl, THF, 90%.
lithium species 2.12 Due to this, the R group must acidify
the protons in R-position and has to stabilize the lithium
compound 2. We used the 2,2,4,4-tetramethyl-1,3-oxazo-
lidine-3-carbonyl group (R ) CbyO), developed in our
laboratories, because of its easy introduction and its facile
cleavage.13 As leaving group we investigated a silyloxide
(7a , X ) OTBDMS), a carbamate (7b, X ) OCby), a
phosphate (7c, X ) OPO(OEt)2),14 bromide (7d , X ) Br),
and chloride (7e, X ) Cl).15 The straightforward synthesis
of the precursor 7e is depicted in Scheme 1.
It started with commercially available glutaric dial-
dehyde (3) which was subjected to a Horner-Wads-
worth-Emmons reaction16 in aqueous solution. The
diester 417 was reduced to the diol 518 using DIBAH at
-78 °C. Carbamoylation of the sodium alkoxide of 5 with
CbyCl furnished the carbamate 6, which was subse-
quently chlorinated to yield the cyclization precursor 7e.
Complete diastereomeric purity of the cyclization precur-
sors was verified by GLC analysis; the (E)-geometry of
the double bonds was confirmed by the 1H NMR coupling
constants of the olefinic protons of the symmetrical dienes
4 (15.7 Hz) and 7b (15.2 Hz).
Cycliza tion of th e Allylic Ch lor id e 7e. The depro-
tonation of the carbamates 7a -e was carried out in
diethyl ether at -78 °C by slow addition of 1.1 equiv of
n-butyllithium/TMEDA (9). In case of 7a -d at -78 °C
no cyclization reaction took place. In the case of 7a the
substrate was completely reisolated, but analysis of the
crude reaction mixtures of 7b and 7c, in addition, showed
some unidentified minor products. Although several side-
reactions are conceivable,19 the precursor 7e was ef-
ficiently deprotonated in the R-position by means of
a
Reagents and conditions: (a) n-BuLi, (-)-sparteine (10),
solvent, temp, time (see Table 1).
Ta ble 1. (-)-Sp a r tein e-Med ia ted En a n tioselective
Cycliza tion
base
temp, time, yield,
ee,
%
entry (equiv) solvent
°C
h
%
er
1
2
3
4
5
6
7
1.1
ether
-78
-78
-88
-90
-86
-78
-78
24
7
64
50
80
90
9
76
71
75:25
83:17
88:12
90:10
50
66
76
80
1.1
toluene
toluene
toluene
toluene
toluene
ether
1.6
6
2.2
2
1.8a
2.2b
2.2c
7
80.5:19.5 61
2
83:17
80:20
66
60
2
a
b
0.1 equiv of (-)-sparteine were used. 1.2 equiv of (-)-
sparteine were used. c 2.2 equiv of LiCl were added.
n-BuLi/TMEDA (9) in the presence of the allyl chloride
moiety. The intermediate allyllithium species 2 (R )
OCby, X ) Cl) reacted smoothly, with elimination of LiCl,
to furnish the divinylcyclopentane rac-8 (68%, dr ) 99:
1), even at -78 °C (Scheme 2).20
The diastereomeric ratio of cis-8 was determined by
GLC, the relative configuration was established by NOE
measurements, and the (Z)-geometry of the enol carbam-
ate moiety is based on the small olefinic coupling constant
(6.5 Hz). By employing the chiral diamine (-)-sparteine
(10) as ligand for the butyllithium, instead of the achiral
TMEDA (9), one of the enantiotopic R-protons was
abstracted preferentially, which led to the enantioen-
riched allyllithium species (1S)-11‚10. The subsequent
cyclization at -78 °C in Et2O furnished diastereomeri-
cally pure (R,R)-8 in 64% yield (Scheme 3, Table 1, entry
(12) Reviews: (a) Hoppe, D.; Hense, T. Angew. Chem. 1997, 109,
2376-2410; Angew. Chem., Int. Ed. Engl. 1997, 36, 2282-2316. (b)
Beak, P.; Basu, A.; Gallagher, D. J .; Park, Y. S.; Thayumanavan, S.
Acc. Chem. Res. 1996, 29, 552-560.
(13) (a) Bebber, J . von; Ahrens, H.; Fro¨hlich, R.; Hoppe, D. Chem.
Eur. J . 1999, 5, 1905-1916. (b) Hintze, F.; Hoppe, D. Synthesis 1992,
1216-1218.
(14) Syntheses of allylic phosphates: S.-I. Murahashi, Y. Taniguchi,
Y. Imada, Y. Tanigawa J . Org. Chem. 1989, 54, 3292-3303.
(15) For syntheses of allylic chlorides see ref 3.
(16) Reviews about Horner-Wadsworth-Emmons reactions: (a)
Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989, 89, 863-927. (b)
Wadsworth, W. S., J r. Org. React. (N.Y.) 1977, 25, 73-253.
(17) Synthesis of 4: Villieras, J .; Raumbaud, M.; Graff, M. Synth.
Commun. 1986, 16, 149-156.
(18) For a different synthesis of 5, see: (a) Iriye, R.; Toya, T.;
Makino, J .; Aruga, R.; Doi, Y. Agric. Biol. Chem. 1988, 52, 989-996.
(b) Lennon, P.; Rosenblum, M. J . Am. Chem. Soc. 1983, 105, 1233-
1241.
(19) Possible side-reactions of the allyl chloride moiety are an
intermolecular substitution with n-BuLi, a halogen-lithium exchange
or a deprotonation in R-position to the chloro atom.
(20) Unfortunately, the application of this reaction was not possible
in the synthesis of substituted cyclohexanes (ref 35).

2844 J . Org. Chem., Vol. 66, No. 8, 2001
Deiters and Hoppe
Sch em e 4a
Sch em e 5. Syn th esis of (+)-Dih yd r om u ltifid en ea
a
Reagents and conditions: (a) n-BuLi, (-)-sparteine (10),
toluene, -90 °C, 2 h; (b) n-BuLi, TMEDA, Et2O, -78 °C, ElX.
1), in an enantiomeric ratio (er) of 75:25 (50% ee). By
using toluene as nonpolar solvent (Table 1, entry 2), the
er could be increased to 83:17 (66% ee) and through
lowering the reaction temperature to -90 °C (Table 1,
entry 4) a further enhancement up to er ) 90:10 (80%
ee) was possible. An increase of the amount of n-BuLi/
(-)-sparteine led to higher yields (Table 1, entries 2-4);
when employing 2.2 equiv of the chiral base, (R,R)-8 was
obtained in the excellent yield of 90%.
a
Reagents and conditions: (a) n-BuLi (2 equiv), TMEDA, THF,
-78 °C, 65%; (b) H2, 1 atm, Lindlar catalyst, quinoline, pentane,
76%. The lithium cation in 15 is complexed by TMEDA and/or
THF.
Sch em e 6a
The necessity for using at least 2 equiv of n-BuLi can
be explained by the formation of the vinyllithium com-
pound 12‚10. The vinylic proton at the 1-positon in 8 has
a similar acidity compared to that of the allylic R-protons
in 7e and, owing to the high cyclization rate, 7e and 8
are competing for the butyllithium. A quantitative for-
mation of 12‚10 was possible with 2 equiv of base. This
is also the reason, why the reaction could not be ac-
complished with catalytic amounts of (-)-sparteine (Table
1, entry 5), because in 12‚10 the lithium alkenide is still
chelated by the diamine. However, a smooth reaction
proceeded when using 2.2 equiv of n-BuLi and 1.2 equiv
of (-)-sparteine without loss in yield and stereoselectivity
(Table 1, entry 6).
The subsequent formation of 12‚10 from 7e provides
the opportunity to perform a multistep one-pot procedure
by trapping the intermediate 12‚10 with several electro-
philes to generate the functionalized cyclopentanes 13a-e
(Scheme 4). The substitution products 13a -e are also
accessible from 8 via 12‚9, which is equivalent to a two-
step process starting from 7e. The configurative stability
of 12 was examined by reprotonation and deuteriolysis,
as well.
a
Reagents and conditions: (a) n-BuLi, (-)-sparteine, toluene,
-78 °C; (b) H2, Pd/C, NaOAc, MeOH, 90%; (c) CbyCl, NaH, THF,
90%; (d) 1. s-BuLi, (-)-sparteine, Et2O, -78 °C; 2. TMSCl, 80%.
comparison of the sense of the optical rotation with a
previously reported value21a clearly establishes the (R,R)-
configuration of (+)-17 and hence the (R,R)-configuration
of 8.
For proposing a likely mechanism of this enantiose-
lective cycloallylation reaction, knowledge of the absolute
configurations of 8 and of the lithiated intermediate
11‚10 is required. The configuration of the latter has been
determined by transformation of 11‚10 into the allylic
silane (R)-18 and a subsequent hydrogenation of the
double bonds and simultaneous hydrogenolytic cleavage
of the chlorine atom to produce (-)-(R)-19. The enanti-
omer (+)-(S)-19 has been synthesized in a highly enan-
tioenriched form from the saturated alcohol 20 via the
alkyl carbamate 21 by using our s-BuLi/(-)-sparteine
method (Scheme 6).25 By comparison of the sense of
the optical rotations, (-)-19 and thus (+)-18 could be
assigned the (R)-configuration. Silylations of allyllithium
compounds generally proceed under inversion of the
configuration,26 hence (1S)-11‚10 was the intermediate
that led to (R,R)-8.
In vestiga tion of th e Cycliza tion Mech a n ism . To
determine the absolute configuration and to demonstrate
a synthetic application of this cycloallylation reaction,
(R,R)-8 was transformed into the natural compound
derivative (+)-dihydromultifidene (17, Scheme 5).21 The
reaction sequence starts with a vinylic lithiation of 8 to
12‚9 at -78 °C. Then, the carbenoide22 12 was allowed
to warm to room temperature, which initiated a Fritsch-
Buttenberg-Wiechell rearrangement.23 The formed alkyne
14 was lithiated by a second equiv of butyllithium and
the lithium acetylide 15 could be alkylated with EtI to
yield the alkyne 16. The synthesis was completed by a
Time-dependent silylations of (S)-11‚10 and lithio-
destannylation experiments gave deeper insights into the
Lindlar hydrogenation to the (Z)-alkene (+)-17.24
A
(24) Review on semihydrogenation of triple bonds: Marvell, E. N.;
Li, T. Synthesis 1973, 457-468.
(21) Multifidene is an attracting pheromone of the brown algae
Cutleria multifida. (a) Boland, W.; Mertes, K.; J aenicke, L.; Mu¨ller,
D. G.; Fo¨lster, E. Helv. Chim. Acta 1983, 66, 1905-1913; (b) J aenicke,
L.; Boland, W. Angew. Chem. 1982, 94, 655-724; Angew. Chem., Int.
Ed. Engl. 1982, 21, 643-712.
(25) Hoppe, D.; Paetow, M.; Hintze, F. Angew. Chem. 1993, 105,
430-432; Angew. Chem., Int. Ed. Engl. 1993, 32, 394-396. In all
known cases, deprotonation of saturated O-carbamates with s-BuLi/
10 furnished the (S)-configurated lithium species, which reacted under
retention of the configuration with the electrophile; see also ref 12a.
(26) (a) Behrens, K.; Fro¨hlich, R.; Meyer, O.; Hoppe, D. Eur. J . Org.
Chem. 1999, 2397-2403. (b) Paulsen, H.; Graeve, C.; Hoppe, D.
Synthesis 1996, 141-144.
(22) Review: Braun, M. Angew. Chem. 1998, 110, 444-465; Angew.
Chem., Int. Ed. Engl. 1998, 37, 430-451.
(23) Kocienski, P.; Dixon, N. J . Synlett 1989, 52-54; (b) Kocienski,
P.; Barber, C. Pure Appl. Chem. 1990, 62, 1933-1940.

cis-1,2-Dialkenyl-Substituted Cyclopentanes
J . Org. Chem., Vol. 66, No. 8, 2001 2845
Ta ble 2. Tim e-Dep en d en t Silyla tion
was carried out with (-)-sparteine as diamine, which
furnished (S,S)-8 (26% ee) in quantitative yield.30 These
results reveal, that the sense of stereoinformation found
in the cyclization product (R,R)-8 is, as expected, defined
in the deprotonation step.
entry
time, min
yield of (R)-18, % (% ee)
yield of 8, %
1
2
3
0
15
30
70 (56)
22 (46)
13 (34)
0
30
43
This information, together with the (1S)-configuration
of the allyllithium compound 11‚10 and the configuration
of the cyclopentane 8 (1R,2R; cis arrangement of the side
chains; (Z)-configuration of the vinyl carbamate unit)
enables us to decide for one of the three possible cycliza-
tion pathways (Scheme 8): Deprotonation of 7e leads to
the (1S)-configured allyllithium species 11‚10 in the
1-endo-conformation.31 In the previously proposed lithium
ene-mechanism10,32 11 passes through the transition state
C, in which the lithium cation is involved in the six-
membered ring. Therefore this reaction must proceed
with retention of the configuration, eventually leading
to the enantiomeric cyclopentane (S,S)-8. However, the
observed formation of (R,R)-8 suggests that the cyclo-
alkylation has to proceed in an anti-SE′ fashion in respect
of the lithium-bearing allylic moiety. Here, two different
transition states are possible: A with a chairlike confor-
mation and B with a boatlike conformation. Both of them
benefit from a favorable HOMO/LUMO-interaction of the
parallel oriented allyl moieties. A, which would furnish
the trans-substituted cyclopentane (R,S)-8, holds a more
strained trimethylene bridge than B,33 hence the reaction
pathway via transition state B has the lower activation
energy. Presumably the high charge separation in B is
compensated by coordination of “free” lithium cations,
because previous addition of LiCl to the reaction mix-
ture led to slightly higher ee’s (Table 1, entry 7).
Therefore this cyclization can be classified as a regio-,
diastereo-, and enantioselective intramolecular anti-
SE′SN′-reaction.
Sch em e 7a
a
Reagents and conditions: (a) 1. n-BuLi, (-)-sparteine, toluene,
-78 °C; 2. (CH3)3SnCl, 7%; (b) s-BuLi, TMEDA, (CH3)3SnCl,
toluene, -78 °C, 15%; (c) n-BuLi, (-)-sparteine, toluene, -78 °C,
94%; (d) 1. n-BuLi, TMEDA, toluene, -78 °C, 90%; (e) see c, 100%.
mechanism. Silylations after 15 and 30 min showed a
decrease in the enantiomeric excess of (R)-19 (Table 2).
Compared to the high ee in (R,R)-8 this, together with
the observed lithiation of 8 to 12, suggests a very fast
cyclization step. To gain more information about the
reaction mechanism, we also performed lithiodestan-
nylation experiments using the allyltin compound 22,
which has been synthesized both in racemic and in
enantioenriched form (Scheme 7). The synthesis of rac-
22 was problematic, because the injection of a hexane
solution of Me3SnCl to the reaction mixture a few
minutes after lithiation did not furnish rac-22, due to the
very high cyclization rate when TMEDA was employed
as ligand. Therefore the tin electrophile was added in situ
and s-BuLi/TMEDA27 was used as the base, which
afforded rac-22 in 15% yield. Since the cyclization is a
little slower using (-)-sparteine as diamine, addition of
Me3SnCl to the reaction mixture after 5 min yielded (R)-
22 (7%, 48% ee).28 Lithiodestannylation of rac-22 with
n-BuLi in the presence of (-)-sparteine in toluene at -78
°C furnished (R,R)-8 in nearly quantitative yield, with
an ee of 14%. This can be explained with a slight kinetic
resolution29 in the cyclization step, but it cannot count
for the high ee’s observed in 8 under deprotonation
conditions. Treatment of (R)-22 (48% ee) with n-BuLi/9
led to rac-8 in 90% yield. Probably, the stereochemical
information was lost on the stage of the TMEDA-
complexed allyllithium compound 11‚9, because TMEDA-
complexed lithium alkanides have proved to be much
more configuratively labile than the corresponding (-)-
sparteine complexes.30a,b Therefore a similar experiment
Cycliza tion of a Con figu r a tion a lly Sta ble Allyl-
lith iu m Com p ou n d . This mechanism is in contrast to
our previously proposed one,10 which includes an inver-
sion of the configuration at the lithium-bearing carbon
atom prior to the cyclization step. Therefore we wanted
to gain further evidence by the use of a allyllithium
derivative, which is definitely configurationally stable
under the reaction conditions. In our laboratories, lithi-
ated R-methyl-substituted allylic carbamates (23‚9, CH3
for Si(CH3)3) were found to be configuratively stable at
-78 °C.34 The application of an R-methyl cyclization
precursor was difficult, due to the slow deprotonation,
which led to decomposition of the allyl chloride moiety,
and the instability of the cyclization product 13b under
the basic reaction conditions.35 Therefore we employed
lithiated R-silyl allylcarbamates (like 23‚9) as new con-
figurationally stable enantioenriched allyllithium com-
(27) A strong and sterical demanding base, such as s-BuLi has the
advantage of deprotonating the allylic carbamate faster and reacting
slower with Me3SnCl compared to the use of n-BuLi.
(28) Here, no in situ trapping was applied, because the use of s-BuLi
led to a lower enantiomeric enrichment in 8 (30% ee, Et2O, -78 °C)
than n-BuLi (50% ee, Et2O, -78 °C).
(29) Review on dynamic kinetic resolution: Caddick, S.; J enkins,
K. Chem. Soc. Rev. 1996, 447-456.
(30) Other examples of inversion of the configuration by means of
stannylation (inversion) and lithiodestannylation (retention) in het-
erosubstituted allyl and benzyl compounds: (a) Weisenburger, G. A.;
Beak, P. J . Am. Chem. Soc. 1996, 118, 12218-12219. (b) Weisenburger,
G. A.; Beak, P. J . Am. Chem. Soc. 1996, 118, 3757-3758. (c) Derwing,
C.; Hoppe, D. Synthesis 1996, 149-154. (d) Carstens, A.; Hoppe, D.
Tetrahedron 1994, 50, 6097-6108.
(31) Review: Schlosser, M.; Desponds, O.; Lehmann, R.; Moret, E.;
Rauchschwalbe, G. Tetrahedron 1993, 49, 10175-10203.
(32) Review on metallo ene-reactions: Oppolzer, W. Angew. Chem.
1989, 101, 39-53; Angew. Chem., Int. Ed. Engl. 1989, 28, 38-52. (b)
Recent example of a lithium ene-reaction: Cheng, D.; Knox, K. R.;
Cohen, T. J . Am. Chem. Soc. 2000, 122, 412-413.
(33) The same reasoning was used in the explanation of cis-selective
ene-reactions: Oppolzer, W.; Snieckus, V. Angew. Chem. 1978, 90,
506-516; Angew. Chem., Int. Ed. Engl. 1978, 17, 476-486.
(34) (a) Schwark, J .-R.; Hoppe, D. Synthesis 1990, 291-294. (b)
Kra¨mer, T.; Hoppe, D. Tetrahedron Lett. 1987, 28, 5149-5152. (c)
Kra¨mer, T.; Hoppe, D. Angew. Chem. 1986, 28, 5149-5152; Angew.
Chem., Int. Ed. Engl. 1986, 25, 160-162.
(35) Deiters, A. Ph.D. Thesis, 2000, University of Mu¨nster.

2846 J . Org. Chem., Vol. 66, No. 8, 2001
Sch em e 8. P ossible Cycliza tion P a th w a ysa
Deiters and Hoppe
a
The chelate of the carbonyl group with the lithium cation is omitted for the sake of clearness.
Sch em e 9. Cycliza tion of (R)-18a
Sch em e 10a
a
Reagents and conditions: (a) n-BuLi, TMEDA (9), THF-d8
a
Reagents and conditions: (a) n-BuLi, TMEDA (9), Et2O, -78
-80 °C.
°C, 40%; (b) TBAF, THF, room temperature, 87%.
coupling of 11 to the cyclononadiene 24 and a subsequent
Cope rearrangement to 8 is also conceivable.39 To ensure
a direct formation of 8, we monitored the lithiation and
cyclization of 7e with n-BuLi/TMEDA in THF-d8 at -80
pounds.36 The cyclization precursor (R)-18 (56% ee) was
already synthesized in previous experiments and was
subjected to n-BuLi/TMEDA (2.0 equiv) at -78 °C in
Et2O. After 8.5 h (R,R)-13c was obtained in 40% yield
and 39% of 18 were reisolated (Scheme 9). The low yield
of 13c suggests a lower cyclization rate, due to the steric
hindrance of the trimethylsilyl group. The ee of 13c was
determined by GLC on a chiral stationary phase to 60%
after desilylation to 10,37 which is equivalent to 100%
chirality transfer from (R)-18 to (R,R)-13c.38 The absolute
configuration found in the cyclization product (R,R)-13c,
together with the (R)-configuration of 18, again suggests
an antarafacial coupling reaction via the transition state
D and gives another evidence for the mechanism de-
scribed in Scheme 8.
1
°C by H NMR. Here, the typical signals of 7e for H-1
(4.60 ppm) and H-9 (4.11 ppm) vanished immediately and
the characteristic signals of 8 for H-2 (4.43-4.53 ppm),
H-2′′ (4.75-4.93 ppm) and H-1′′ (5.58-5.68) appeared.
The signal for the proton at the 1-position was not visible,
indicating the fast vinylic lithiation to 11. However, after
addition of methanol, the typical doublet (J ) 4.6 Hz)
for H-1 at 7.07 ppm occurred (Scheme 10). These results
suggest that no Cope rearrangement, but the expected
direct formation of 8 from 11 takes place.
Con clu sion
NMR Exp er im en t of th e Cycliza tion Rea ction . In
contrast to the proposed cyclization mechanism, an R,R′-
In summary we developed a novel intramolecular
regio-, diastereo-, and enantioselective allylation reaction,
based on a n-BuLi/(-)-sparteine-mediated deprotonation
of an allylic carbamate, which furnished 1,2-dialkenyl-
(36) Preliminary investigations of an enantioenriched lithiated
R-silyl-cinnamyl carbamate showed a fast deprotonation and a remark-
able degree of configurative stability (see ref 35).
(37) Crowley, P. J .; Percy, J . M.; Stansfield, K. Tetrahedron Lett.
1996, 37, 8237-8240.
(38) The discrepancy of the ee values of (R)-18 and 13c is due to
the different determination methods (1H NMR shift experiment and
GLC on a chiral stationary phase).
(39) Reviews on [3,3]-sigmatropic rearrangements: (a) Bennet, G.
B. Synthesis 1977, 589-606. (b) Ziegler, F. E. Acc. Chem. Res. 1977,
10, 227-232.

cis-1,2-Dialkenyl-Substituted Cyclopentanes
J . Org. Chem., Vol. 66, No. 8, 2001 2847
in THF (10 mL) was injected and the reaction mixture was
heated to 70 °C for 48 h. Then, sat. NH4Cl (aq, 5 mL) and
water (5 mL) were added, the layers were separated, and the
aqueous phase was extracted with ether (5 × 30 mL). The
combined organic phases were dried (MgSO4), and the solvents
were removed in vacuo. The crude product was purified by
flash chromatography on silica gel (ether/pentane 1:5 f ether)
yielding the carbamate 6 (866 mg, 39%) as colorless oil, the
dicarbamate 7b (712 mg, 22%) as a highly viscous oil, and the
substrate 5 (210 mg, 19%). When only 0.25 equiv of CbyCl was
used, the formation of 7b could be successfully supressed. 6.
substituted cyclopentanes in good to excellent yields.
Further functionalization and transformation of the vinyl
carbamate moiety40 was demonstrated, and an applica-
tion of this reaction was found in the stereoselective
synthesis of (+)-dihydromultifidene. The cyclization mech-
anism was investigated to be an intramolecular anti-
SE′SN′ substitution reaction, by determination of the (1S)-
configuration of the lithiated intermediate and of the
(R,R)-configuration of the cyclization product. Silylation,
stannylation, and lithiodestannylation experiments and
employing a configurationally stable allyllithium com-
pound in the cycloallylation gave deeper insights into the
cyclization mechanism. This new concept of deprotona-
tion of an allylic carbamate in the presence of an allyl
chloride moiety gives us additional opportunities in the
development of synthetic methods using enantioenriched
lithium alkenides.11a,11b,41
1
Rf ) 0.15 (ether/pentane 1:1). H NMR (300 MHz, CDCl3): δ
1.36/1.42 (s, 6H), 1.46-1.56 (m, 8H), 1.76 (s, broad, 1H), 2.02-
2.11 (m, 4H), 3.72 (s, 2H), 4.08 (d, J ) 3.8 Hz, 2H), 4.52 (d, J
) 6.0 Hz, 2H), 5.53-5.79 (m, 4H). 13C NMR (75 MHz, CDCl3):
δ 24.1/25.2/26.5, 28.3, 59.6/60.5, 63.5, 65.0, 76.0/76.3, 94.8/95.7,
124.9, 129.4, 132.3, 135.0, 153.0. IR (neat, cm-1): 3435 (broad,
OH), 1698 (CdO). MS (EI): m/z ) 311 [3%, M+], 296 [18%,
(M - CH3)+]. Anal. Calcd for C17H29NO4 (311.42): C, 65.57;
H, 9.39; N, 4.50. Found: C, 65.55; H, 9.47; N, 4.69. 7b. tR
)
1
25.3 min (HP 1). Rf ) 0.44 (ether/pentane 1:1). H NMR (300
MHz, CDCl3): δ 1.36/1.42 (s, 12H), 1.46-1.59 (m, 14H), 2.07
(quin, J ) 6.7 Hz, J ) 7.1 Hz, 4H), 3.72 (s, 4H), 4.53 (d, J )
5.9 Hz, 4H), 5.58 (dt, J ) 5.9, J ) 15.2 Hz, 2H), 5.74 (dt, J )
15.2 Hz, J ) 6.7 Hz). 13C NMR (75 MHz, CDCl3): δ (not all
signals were visible) 24.1/25.3/26.5, 28.2, 31.4, 59.7/60.5, 65.0,
Exp er im en ta l Section
Gen er a l Meth od s. The doubling of some signals in the
NMR spectra occurs as a result of the E/Z isomerism of the
carbamate group; these signals are separated by slashes. (-)-
Sparteine (10) is commercially available (Aldrich) and was
stored under argon; TMEDA (9) was distilled from CaH2 and
kept under argon. n-BuLi was received as a 1.6 M solution in
hexane from Acros and s-BuLi as a 1.4 M solution in cyclo-
hexane/hexane (92:8) from Fluka; the latter was titrated before
use.42 Reactions with air and moisture sensitive reagents were
performed in dried glassware with dry solvents, freshly
distilled before use. The flash chromatography was performed
with an excess pressure of 1 bar on silica gel (Merck, mesh
40-63 µm).43 GLC was performed on a 25 m HP1 column at
an oven temperature of 50 °C for 1 min and then 10 °C/min to
290 °C, and the final temperature was kept for 10 min (HP1)
or on a 25 m HP1701 column at an oven temperature of 50 °C
for 1 min and then 10 °C/min to 260 °C, and the final
temperature was kept for 10 min (HP1701). For GLC on a
chiral stationary phase a 30 m BetaDex 120TM column
(Supelco) was used in an isothermic fashion; the main enan-
tiomer is marked by an asterix.
(2E,7E)-2,7-Non a d ien e-1,9-d iol (5). The diester 4 (1.50 g,
6.2 mmol, 1.0 equiv) was dissolved in THF (6 mL), cooled to
-78 °C, and was slowly treated with DIBAH (36 mL, 36.0
mmol, 5.8 equiv, 1 M solution in toluene). After 4 h stirring at
-78 °C, methanol (5 mL) and water (5 mL) were added, and
the reaction mixture was carefully warmed to room temper-
ature. Then it was stirred for further 30 min, was filtered over
MgSO4 (25 g), the precipitate was rinsed with Et2O (150 mL),
and the filtrate was concentrated in vacuo. The crude product
was purified by flash chromatography on silica gel (ether/
pentane 1:1 f ether) and 5 (887 mg, 92%) was obtained as
colorless oil. The analytical data were identical to those found
in the literature.18
76.1/76.3, 94.8/95.8, 125.0, 135.0, 151.9/152.5. IR (neat, cm-1
)
1701 (CdO). MS (EI): m/z ) 466 [3%, M+], 294 [100%, (M -
OCby)+]. Anal. Calcd for C28H42N2O6 (466.61): C, 64.35; H,
9.07; N, 6.00. Found: C, 64.29; H, 8.83; N, 6.14.
(2E,7E)-9-Ch lor o-2,7-n on a d ien yl 2,2,4,4-Tetr a m eth yl-
1,3-oxa zolid in e-3-ca r boxyla te (7e). Dry LiCl (1.09 g, 25.6
mmol, 4.0 equiv) and 6 (2.00 g, 6.4 mmol, 1.0 equiv) were
suspended in THF (50 mL) and cooled to -78 °C. After addition
of n-BuLi (5.2 mL, 8.3 mmol, 1.3 equiv, 1.6 M solution in
hexane), the reaction mixture was stirred for 10 min and
methanesulfonyl chloride (1.47 g, 12.8 mmol, 2.0 equiv) was
injected. The suspension was allowed to warm to room tem-
perature overnight, and the reaction was quenched by addition
of H2O (10 mL). After separation of the layers, the aqueous
phase was extracted with Et2O (3 × 50 mL), the combined
organic phases were dried (MgSO4), and the solvents were
evaporated. The crude product was purified by flash chroma-
tography on silica gel (ether/pentane 1:10 f 2:5), yielding 7e
(1.55 g, 73%) as a colorless liquid. tR ) 19.5 min (HP1). Rf )
0.20 (ether/pentane 1:5). 1H NMR (300 MHz, CDCl3): δ 1.40-
1.68 (m, 14H), 2.14 (q, J ) 7.1 Hz, 4H), 3.79 (s, 2H), 4.08 (dd,
J ) 6.8 Hz, J ) 0.8 Hz, 2H), 4.59 (d, J ) 5.9 Hz, 2H), 5.61-
5.74 (m, 2H), 5.75-5.87 (m, 2H). 13C NMR (75 MHz, CDCl3):
δ 24.1/25.3/26.5, 28.0, 31.2, 31.4, 45.2, 59.7/60.5, 65.0, 76.1/
76.3, 94.8/95.8, 125.1, 126.4, 134.8, 135.4, 152.5. IR (neat,
cm-1): 1696 (CdO). MS (EI): m/z 329 [1%, M+], 294 [100%,
(M - Cl)+]. Anal. Calcd for C17H28ClNO3 (329.86): C, 61.90;
H, 8.56; N, 4.25. Found: C, 61.91; H, 8.68; N, 4.38.
Typ ica l P r oced u r e for th e En a n tioselective Cycliza -
tion . [1Z,2(1R,2R)]-2-(2-Vin ylcyclop en tyl)eth en yl 2,2,4,4-
Tetr a m eth yl-1,3-oxa zolid in e-3-ca r boxyla te (8). The chlo-
ride 7e (1.70 g, 5.10 mmol, 1.0 equiv) and (-)-sparteine (2.70
g, 11.3 mmol, 2.2 equiv) were dissolved in toluene (30 mL) and
cooled to -90 °C. After slow addition of n-BuLi (7.1 mL, 11.3
mmol, 2.2 equiv, 1.6 M solution in hexane), the solution was
stirred for 2 h. CH3OH (3 mL) and NH4Cl (aq, 3 mL) were
added, and the reaction mixture was allowed to warm to room
temperature The organic layer was separated, the aqueous
phase was extracted with Et2O (3 × 100 mL), the combined
organic phases were dried over MgSO4, and the solvents were
removed in vacuo. The crude product was purified by flash
chromatography on silica (ether/pentane 1:5), yielding 1.35 g
(90%) of (R,R)-8 as a colorless oil. The ee was determinded to
80% by GLC on a BetaDex 120 column. tR ) 16.6 min (HP1).
tR ) 87.7 min, 89.8 min* (Beta-DexTM 120, 150 °C). Rf ) 0.29
(2E,7E)-9-Hyd r oxy-2,7-n on a d ien yl 2,2,4,4-Tetr a m eth yl-
1,3-oxa zolid in e-3-ca r boxyla te (6) a n d (2E,7E)-(2,7-Non a -
dien e-1,6-diyl) 1,9-Bis(2,2,4,4-tetr am eth yl-1,3-oxazolidin e-
3-ca r boxyla te) (7b). The diol 5 (1.10 g, 7.1 mmol, 1.0 equiv)
was added to a suspension of NaH (311 mg, 7.8 mmol, 1.1
equiv, 60% suspension in mineral oil) in THF (15 mL). After
stirring for 1 h, a solution of 2,2,4,4-tetramethyl-1,3-oxazoli-
dine-3-carbonyl chloride (CbyCl, 1.35 g, 7.1 mmol, 1.1 equiv)
(40) For several reactions of this masked carbonyl group see:
Peschke, B. Ph.D. Thesis, 1991, University of Kiel. See also ref 23.
(41) An application of this concept in pyrrolidine synthesis could
be accomplished recently: Deiters, A.; Wibbeling, B.; Hoppe, D. Adv.
Synth. Catal. 2001, 1, 181-183.
(42) (a) Lin, H.-S.; Paquette, L. A. Synth. Commun. 1994, 24, 2503-
2506. (b) Kofron, W. G.; Baclawski, L. M. J . Org. Chem. 1976, 41,
1871-1880.
(43) Still, W. C.; Kahn, M.; Mitra, A. J . Org. Chem. 1979, 44, 2923-
2924.
(ether/pentane 1:5). [R]20 ) +53.8 (c ) 1.00, CHCl3, 80% ee).
D
1H NMR (300 MHz, CDCl3): δ 1.21-1.65 (m, 14H), 1.76-1.85
(m, 4H), 2.52-2.68 (m, 1H), 2.97-3.15 (m, 1H), 3.77 (s, 2 H),
4.70 (dd, J ) 6.5 Hz, J ) 9.6 Hz, 1H), 4.95-5.03 (m, 2H), 5.72-

2848 J . Org. Chem., Vol. 66, No. 8, 2001
Deiters and Hoppe
5.84 (m, 1H), 6.96 (d, J ) 6.5 Hz, 1H).13C NMR (75 MHz,
CDCl3): δ 23.2/23.9/25.5, 26.7, 30.8, 32.3, 40.0, 48.0, 60.1/60.9,
76.1/76.4, 95.2/96.1, 112.7/112.8, 114.3, 133.9/134.0, 139.9,
149.3/150.1. IR (neat, cm-1): 1716 (CdO). MS (EI): m/z 293
[0.5, M+], 278 [4, (M - CH3)+]. Anal. Calcd for C17H27NO3
(293.40): C, 69.59; H, 9.28; N, 4.77. Found: C, 69.19; H, 9.21;
N, 4.79. In the other cyclization reactions, depicted in Table
1, 50-100 mg of 7e were used.
[1Z,2(1R,2R)]-1-(Tr im eth ylsilyl)-2-(2-vin ylcyclop en tyl)-
eth en yl 2,2,4,4-Tetr a m eth yl-1,3-oxa zolid in e-3-ca r boxy-
la te (13c). According to the typical procedure for the enantio-
selective cyclization-substitution sequence, 7e (100 mg, 0.30
mmol, 1.0 equiv) was treated with (-)-sparteine (316 mg, 1.35
mmol, 4.5 equiv), n-BuLi (0.75 mL, 1.20 mmol, 4.0 equiv, 1.6
M solution in hexane), and TMSCl (163 mg, 1.50 mmol, 5.0
equiv) in toluene (4 mL) at -90 °C. The described workup
procedure and a subsequent purification of the crude product
by flash chromatography on silica gel (ether/pentane 1:5)
furnished 13c in 84% yield (92 mg) as a colorless liquid. The
enantiomeric excess was determined to 80% after desilylation
pentane (4 × 20 mL), and the combined organic layers were
dried with MgSO4. After evaporation of the solvents, the crude
product was purified by flash chromatography on silica gel
(pentane). The alkyne 16 (98 mg, 65%) was obtained as a
colorless, strongly smelling liquid. tR ) 9.0 min (HP1701). Rf
) 0.29 (pentane). [R]20D ) +24.2 (c ) 1.43, pentane).44 1H NMR
(300 MHz, CDCl3): δ 1.10 (t, J ) 7.5 Hz, 3H), 1.15-1.90 (m,
6H); 2.15 (dq, J ) 7.5 Hz, J ) 2.4 Hz, 2H), 2.42-2.57 (m, 1H),
2.70-2.86 (m, 1H), 4.96-5.09 (m, 2H), 5.91-6.04 (m, 1 H).
13C NMR (75 MHz, CDCl3): δ 12.5, 14.1, 23.1, 27.7, 33.1, 36.1,
47.9, 80.6, 84.2, 114.0, 140.5. MS (EI): m/z 148 [2%, M+], 133
[25%, (M - CH3)+]. HRMS calcd for C11H16 (148.24): 148.1251
(M+). Found: 148.1214 (M+).
(+)-3,4-Dih yd r om u ltifid en e (17). Lindlar’s catalyst (5%
Pd/CaCO3/Pb, 30 mg) was placed in a 50 mL round-bottom
flask and was flushed three times with H2. Then, pentane (25
mL), quinoline (2 drops), and 16 (100 mg, 0.68 mmol, 80% ee)
were added, and the suspension was strirred under a balloon
pressurized with hydrogen. After 3 h a complete conversion
was detected by GLC. Filtration through silica gel and removal
of the solvent in vacuo furnished the crude product, which was
purified by flash chromatography on silica gel (pentane)
yielding (+)-17 (78 mg, 76%). The analytical data were
to 10. 13c. tR ) 20.3 min (HP1701). Rf ) 0.60 (ether/pentane
1
1:5). [R]20 ) +28.2 (c ) 1.85, CHCl3, 80% ee). H NMR (300
D
MHz, CDCl3): δ 0.12 (s, 9H), 1.42/1.56 (s, 12H), 1.50-1.93 (m,
6H), 2.54-2.64 (m, 1H), 2.90-3.05 (m, 1 H), 3.74 (s, 2H), 4.90-
identical with those reported in the literature.21a [R]20
)
D
+50.0, [R]20 ) +52.0 (c ) 0.39, pentane, corrected to 100%
5.01 (m, 2H), 5.27 (d, 1 H, J ) 9.3 Hz), 5.66-5.82 (m, 1H). 13
C
D
ee).44 These optical rotations agree well with the literature
NMR (75 MHz, CDCl3): δ -0.9, 23.2, 23.9/25.0/25.1/26.4, 30.6,
31.5, 40.2, 47.7, 59.6/60.5, 76.0/76.2, 94.7/95.7, 113.9, 131.5,
139.7, 151.0, 153.9. IR (neat, cm-1): 1701 (CdO). MS (EI): m/z
value: [R]20 ) +55.8 (c ) 2.56, pentane, 100% ee).21a
D
(1R,2E,7E)-9-Ch lor o-1-(t r im et h ylsilyl)-n on a -2,7-d ie-
n yl 2,2,4,4-Tetr am eth yl-1,3-oxazolidin e-3-car boxylate (18).
The chloride 7e (100 mg, 0.30 mmol, 1.0 equiv), (-)-sparteine
(106 mg, 0.45 mmol, 1.5 equiv), and TMSCl (49 mg, 0.45 mmol,
1.5 equiv) were dissolved in toluene (4 mL), cooled to -78 °C,
and treated with n-BuLi (0.29 mL. 0.45 mmol, 1.5 equiv, 1.6
M solution in hexane). After stirring for 90 min at this
temperature, CH3OH (0.5 mL) and sat. NH4Cl (aq, 0.5 mL)
were added, the reaction mixture was warmed to room
temperature and was poured into Et2O (70 mL). After drying
with MgSO4 and evaporation of the solvents, the crude product
was purified by flash chromatography on silica gel (ether/
pentane 1:5) yielding 18 as colorless liquid (85 mg, 70%). The
365 [6%, M+], 350 [30%, (M - CH3)+]. Anal. Calcd for C20H35
-
NO3Si (365.58): C, 65.71; H, 9.65; N, 3.83. Found: C, 65.64;
H, 9.96; N, 4.18.
Typ ica l P r oced u r e for th e Lith ia tion a n d Su bstitu tion
of 8. [1Z,2(1R,2R)]-1-(Tr im eth ylsta n n yl)-2-(2-vin ylcyclo-
p en t yl)et h en yl 2,2,4,4-Tet r a m et h yl-1,3-oxa zolid in e-3-
ca r boxyla te (13d ). The cyclopentane 8 (38 mg, 0.13 mmol,
1.0 equiv, 70% ee) and TMEDA (18 mg, 0.16 mmol, 1.2 equiv)
were dissolved in THF (3 mL) and cooled to -78 °C. n-BuLi
(0.09 mL, 0.14 mmol, 1.1 equiv, 1.6 M solution in hexane) was
injected slowly and after stirring for 1 h Me3SnCl (0.26 mL,
0.26 mmol, 2.0 equiv, 1 M solution in hexane) was added. The
reaction was stirred for further 90 min and was subsequently
quenched by addition of CH3OH (0.5 mL) and sat. NH4Cl (aq,
0.5 mL). After warming up the reaction mixture to room
temperature, it was poured into Et2O (70 mL) and dried
(MgSO4), and the solvents were removed in vacuo. The crude
product was purified by flash chromatography on silica gel
(ether/pentane 1:10 f 1:5) furnishing 13d (44 mg, 74%) as a
colorless oil and 7 mg (18%) of the substrate 8. tR ) 18.64 min
1
enantiomeric excess was determined to 56% by a H NMR shift
experiment with 18 (20 mg) and Eu(hfc)3 (40 mg) in CDCl3
(0.7 mL). Here, the Si(CH3)3 signal splits to two new signals
at δA 0.39 ppm* and δB 0.65 ppm. tR ) 20.9 min (HP1). Rf )
0.30 (ether/pentane 1:5). [R]20D ) +11.7 (c ) 0.73, CHCl3, 56%
ee). 1H NMR (300 MHz, CDCl3): δ 0.05 (s, 9H), 1.31-1.59 (m,
14H), 1.97-2.09 (m, 4H), 3.71 (s, 2H), 3.99 (dd, J ) 6.9 Hz, J
) 0.7 Hz, 2H), 5.03 (d, J ) 5.0 Hz, 1H), 5.42-5.78 (m, 4H).13
C
(HP1). Rf ) 0.57 (ether/pentane 2:5). [R]20 ) +7.1 (c ) 0.49,
NMR (75 MHz, CDCl3): δ -3.6, 24.1/24.3/25.4/26.6/26.9, 28.6,
31.3, 31.8, 45.3, 59.5/60.8, 70.3, 76.2/76.4, 94.7/96.0, 126.3,
127.7, 128.8, 135.7, 152.8. IR (neat, cm-1): 1697 (CdO). MS
(EI): m/z ) 366 [40%, (M - Cl)+]. Anal. Calcd for C20H36ClNO3-
Si (402.04): C, 59.75; H, 9.02; N, 3.48. Found: C, 59.65; H,
9.05; N, 3.74. 18 has also been synthesized by injection of
TMSCl 15 min (22%, 46% ee) and 30 min (13%, 34% ee) after
addition of n-BuLi.
D
CHCl3).44 1H NMR (300 MHz, CDCl3): δ 0.13 (s, 9H), 1.42/
1.56 (s, 12H), 1.50-1.93 (m, 6H), 2.54-2.67 (m, 1H), 3.08-
3.25 (m, 1H), 3.75 (s, 2H), 4.81 (d, J ) 6.4 Hz, 1H), 4.91-5.02
(m, 2H), 5.69-5.84 (m, 1H). 13C NMR (75 MHz, CDCl3): δ
-6.5, 23.3, 24.0/25.1/25.4/26.6/26.7, 30.8, 32.4, 41.0, 48.0, 59.9/
60.8, 76.2, 95.0/96.0, 114.0, 126.4/126.6, 140.2, 151.5/152.2,
154.1. IR (neat, cm-1): 1680 (CdO). MS (EI): m/z 442 [67,
(M(120Sn) - CH3)+], 440 [48, (M(118Sn) - CH3)+], 438 [27, (M(116
-
(1R)-1-(Tr im eth ylsilyl)n on yl 2,2,4,4-Tetr a m eth yl-1,3-
oxa zolid in e-3-ca r boxyla te ((R)-19). The silane 18 (47 mg,
0.12 mmol, 1.0 equiv, 56% ee), the hydrogenation catalyst (100
mg, 10% Pd on charcoal), and sodium acetate (100 mg, 1.20
mmol, 10.0 equiv) were suspended in CH3OH (10 mL). After
stirring for 6 h under a balloon pressurized with hydrogen,
the reaction mixture was filtered over silica gel. Without
Sn) - CH3)+]. Anal. Calcd for C20H35NO3Sn (456.19): C, 52.66;
H, 7.73; N, 3.07. Found: C, 52.96; H, 8.12; N, 3.32.
(1R,2R)-1-(Bu t-1-yn yl)-2-vin ylcyclop en ta n e (16). The
cyclopentane 8 (300 mg, 1.02 mmol, 1.0 equiv, 80% ee) and
TMEDA (357 mg, 3.07 mmol, 3.0 equiv) were dissolved in THF
(8 mL) and cooled to -78 °C. Then n-BuLi (1.92 mL, 3.07
mmol, 3.0 equiv, 1.6 M solution in hexane) was added, and
the reaction mixture was stirred for 90 min at -78 °C before
it was warmed to room-temperature After stirring for 2.5 h at
this temperature, the solution was cooled to 0 °C and treated
with EtI (638 mg, 4.09 mmol, 4.0 equiv). The reaction mixture
was stirred for 12 h at 40 °C and then cooled to ambient
temperature, and sat. NaHCO3 (aq, 2 mL) was injected. The
layers were separated, the aqueous phase was extracted with
purification (R)-19 was obtained in 90% yield (40 mg). [R]20
) -3.9 (c ) 0.26, CHCl3, 55% op).
D
(1S)-1-Tr im eth ylsilyl-n on yl 2,2,4,4-Tetr a m eth yl-1,3-ox-
a zolid in e-3-ca r boxyla te ((S)-19). The carbamate 21 (300
mg, 1.0 mmol, 1.0 equiv) and (-)-sparteine (469 mg, 2.0 mmol,
2.0 equiv) were dissolved in Et2O and cooled to -78 °C. After
slowly addition of s-BuLi (1.3 mL, 1.50 mmol, 1.5 equiv, 1.15
M solution in hexane/cyclohexane) and stirring for 4 h at this
temperature, TMSCl (326 mg, 3.0 mmol, 3.0 equiv) was
injected and the reaction mixture was allowed to warm to room
temperature overnight. Sat. NH4Cl (aq, 3 mL) was added, the
layers were separated, and the aqueous phase was extracted
(44) The enantiomeric excess has not been determined; since 12‚9
is configuratively stable, the enantiomeric excess in the substitution
product should be the same like in the substrate 8.

cis-1,2-Dialkenyl-Substituted Cyclopentanes
J . Org. Chem., Vol. 66, No. 8, 2001 2849
with ether (3 × 30 mL). The combined organic phases were
dried with MgSO4, and the solvents were removed in vacuo.
Purification of the crude product by flash chromatography on
silica gel (ether/pentane 1:10 f 1:5) yielded 19 (297 mg, 80%)
as a colorless liquid. tR ) 21.0 min (HP1701). Rf ) 0.47 (ether/
pentane 1:5). [R]20D ) +7.07 (c ) 2.08, CHCl3, 95% ee). 1H NMR
(300 MHz, CDCl3): δ 0.04 (s, 9H), 0.86 (t, J ) 6.8 Hz, 3 H),
1.20-1.65 (m, 26H), 3.70 (s, 2H), 4.68 (dd, J ) 10.0 Hz, 1H).
13C NMR (75 MHz, CDCl3): δ -3.3, 14.0, 22.6, 24.3/25.5/26.6,
27.1, 29.2, 29.5, 31.2, 31.8, 59.4/60.5, 68.8, 76.2, 94.6/95.9,
152.7. IR (neat, cm-1): 1693 (CdO). MS (EI): m/z ) 371 [2%,
M+], 356 [9%, (M - CH3)+]. Anal. Calcd for C20H41NO3Si
(371.63): C, 64.64; H, 11.12; N, 3.77. Found: C, 64.63; H,
11.18; N, 4.04.
(15 mg, 0.03 mmol, 1.0 equiv, 48% ee), (-)-sparteine (21 mg,
0.09 mmol, 3.0 equiv), and n-BuLi (0.04 mL, 0.06 mmol, 2.0
equiv, 1.6 M solution in hexane) were reacted in toluene (2
mL) at -78 °C for 1 h. After workup and purification of the
crude product by flash chromatography on silica gel (ether/
pentane 1:5) (S,S)-8 (9 mg, 100%. 26% ee) was obtained.
Lith ia tion a n d Cycliza tion of (R)-18. The allylsilane (R)-
18 (65 mg, 0.16 mmol, 1.0 equiv, 56% ee) and TMEDA (38 mg,
0.32 mmol, 2.0 equiv) were dissolved in Et2O (3 mL) and cooled
to -78 °C. After dropwise addition of n-BuLi (0.20 mL, 0.32
mmol, 2.0 equiv), the reaction mixture was stirred for 8.5 h.
Then CH3OH (0.5 mL) and sat. NH4Cl (0.5 mL) were added,
the reaction mixture was warmed to room temperature, and
it was poured into Et2O (70 mL) and was dried with MgSO4.
After evaporation of the solvents, the crude product was
purified by flash chromatography on silica gel (ether/pentane
1:10 f 1:6) yielding 13c (24 mg, 40%) and 7e (24 mg, 39%).
The enantiomeric excess of 13c (60% ee) was determined by
GLC on a BetaDex 120TM column after desilylation to 8. A
comparison with another sample of 8 showed the (R,R)-
configuration for 13c.
Desilyla tion of th e Su bstitu ted Cyclop en ta n e 13c. The
vinylsilane 13c (33 mg, 0.09 mmol, 1.0 equiv) was dissolved
in THF (2 mL) and TBAF (0.27 mL, 0.27 mmol, 3.0 equiv, 1
M solution in THF) was added. The reaction mixture has been
stirred for 90 min and was quenched by addition of sat. NH4-
Cl (aq, 2 mL). The layers were separated, the aqueous phase
was extracted with Et2O (3 × 10 mL), the combined organic
layers were dried with MgSO4, and the solvents were removed
in vacuo. Purification of the crude product by flash chroma-
tography on silica gel (ether/pentane 1:10) yielded 8 (23 mg,
87%).
(1R,2E,7E)-9-Ch lor o-1-(t r im et h ylst a n n yl)n on a -2,7-d i-
en yl 2,2,4,4-Tet r a m et h yl-1,3-oxa zolid in e-3-ca r b oxyla t e
((R)-22). En a n tioselective Syn th esis. 7e (200 mg, 0.61
mmol, 1.0 equiv) and (-)-sparteine (256 mg, 1.09 mmol, 1.8
equiv) were dissolved in toluene (10 mL), cooled to -78 °C,
and treated with n-BuLi (0.57 mL, 0.91 mmol, 1.5 equiv, 1.6
M solution in hexane). After 5 min (CH3)3SnCl (1.52 mL, 1.52
mmol, 2.5 equiv, 1 M solution in hexane) was injected, and
after 30 min the reaction was quenched with CH3OH (1 mL)
and sat. NH4Cl (aq, 2 mL). The layers were separated, the
aqueous phase was extracted three times with ether (20 mL),
the combined organic phases were dried (MgSO4), and the
solvents were removed in vacuo. After purification of the crude
product by flash chromatography on silica gel (ether/pentane
1:10 f 1:5), (R)-22 was obtained in 16% yield (49 mg). Other
isolated compounds were 13d (19 mg, 7%), 8 (95 mg, 53%),
and 7e (36 mg, 18%). The enantiomeric excess of 22 was
determined to 48% by an 1H NMR shift experiment with 22
(20 mg) and Eu(hfc)3 (40 mg) in CDCl3 (0.7 mL). Here, the Sn-
(CH3)3 signal splits up in two new signals at δA 0.44 ppm* and
NMR Exp er im en t of th e Cycliza tion . In a flame-dried
NMR tube, TMEDA (11 mg, 0.18 mmol, 2.3 equiv) and 7e (20
mg, 0.08 mmol, 1.0 equiv) were dissolved in THF-d8 (0.7 mL),
and cooled to -78 °C. n-BuLi (0.11 mL, 0.18 mmol, 2.3 equiv,
1.6 M solution in hexane) was added dropwise, the reaction
mixture was shaken, and the NMR tube was immediately put
into the NMR spectrometer (360 MHz), which had been cooled
to -80 °C. Identical 1H NMR spectra were measured in
intervals of 10 min, showing the typical signals of 12, as
described in the discussion part. After adding methanol (0.1
δB 0.65 ppm. [R]20 ) -9.5 (c ) 0.40, CHCl3, 48% ee).
D
Typ ica l P r oced u r e for a Cycliza tion by Lith iod esta n -
n yla tion . The carbamate rac-22 (20 mg, 0.04 mmol, 1.0 equiv)
and (-)-sparteine (19 mg, 0.08 mmol, 2.0 equiv) were dissolved
in toluene (3 mL) and cooled to -78 °C. Then, n-BuLi was
added dropwise (0.05 mL, 0.08 mmol, 2.0 equiv, 1.6 M solution
in hexane), and the reaction mixture was stirred for 90 min
at this temperature. After addition of CH3OH (0.2 mL) and
sat. NH4Cl (aq, 0.2 mL), the reaction mixture was warmed to
room temperature, diluted with Et2O (20 mL), and dried with
MgSO4. The crude product, obtained after evaporation of the
solvents, was purified by flash-chromatography on silica gel
(ether/pentane 1:5) yielding (R,R)-8 (11 mg, 94%, er ) 57:43,
14% ee).
1
mL) at -78 °C, the H NMR spectrum was identical with this
of 8.
Ack n ow led gm en t. This work was supported by the
Deutsche Forschungsgemeinschaft (Sonderforschungs-
bereich 424) and the Fonds der Chemischen Industrie.
A.D. gratefully acknowledges a fellowship of the Fonds
der Chemischen Industrie. We thank Mrs. C. Weitkamp
for her outstanding experimental assistance.
Lith iod esta n n yla tion of th e En a n tioen r ich ed Allyltin
Com p ou n d (R)-22. TMEDA a s Liga n d . According to the
typical procedure for the lithiodestannylation (R)-22 (15 mg,
0.03 mmol, 1.0 equiv, 48% ee), TMEDA (7 mg, 0.06 mmol, 2.0
equiv), and n-BuLi (0.04 mL, 0.06 mmol, 2.0 equiv, 1.6 M
solution in hexane) were reacted in toluene (2 mL) at -78 °C
for 1 h. After workup and purification of the crude product by
flash chromatography on silica gel (ether/pentane 1:5) rac-8
(8 mg, 90%) was obtained. (-)-Sp a r tein e a s Liga n d . Accord-
ing to the typical procedure for lithiodestannylation, (R)-22
Su p p or tin g In for m a tion Ava ila ble: Additional prescrip-
tions and characterizations; 1H NMR spectra of all new
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
J O015548I