On the carbocyclization of ω-styrenylbenzyllithiums

Article abstract of DOI:10.1055/s-1999-5733

ω-Styrenylbenzyllithiums readily available from the corresponding ω-styrenylbenzyl selenides and butyllithiums provide after methanolysis 1-aryl-2-benzyl cyclopentanes with very high stereocontrol. The compound bearing these two groups in trans-position is produced, when the reaction is carried out in THF at -78°C or in ether at -100°C whereas its stereoisomer is generated if the reaction is performed in ether at 0°C. We proved that these reactions occur under kinetic control.

Full text of DOI:10.1055/s-1999-5733

1142
LETTER
On the Carbocyclization of w-Styrenylbenzyllithiums
Alain Krief,* Bruno Remacle, Willy Dumont
Laboratoire de Chimie Organique de Synthèse, Departement of Chemistry, Facultés Notre Dame de la Paix, 61 rue de Bruxelles,
B5000 Namur, Belgium.
Fax (0032) 8172 4536; E-mail: alain.krief@fundp.ac.be
Received 15 March 1999
Dedicated with warm affection and deep admiration to Professor L. Ghosez at the occasion of his 65th Birthday
We wanted to get an insight into the intimate mechanism
Abstract: w-Styrenylbenzyllithiums readily available from the cor-
of such reactions in order to better understand the reasons
responding w-styrenylbenzyl selenides and butyllithiums provide
for such a discrepancy between the different results cited
after methanolysis 1-aryl-2-benzyl cyclopentanes with very high
above and decided to study the reactivity of the benzylse-
stereocontrol. The compound bearing these two groups in trans-po-
sition is produced, when the reaction is carried out in THF at -78 °C lenide 1d, bearing a phenyl substituted C,C double bond
towards alkyllithiums.2,3
or in ether at -100 °C whereas its stereoisomer is generated if the re-
action is performed in ether at 0 °C. We proved that these reactions
occur under kinetic control.
Benzylselenide 1d was expected to be the precursor of
both benzyllithiums (2d and 3d resulting respectively
Key words: arylcyclopentanes, benzyllithiums, diastereoselection,
from the C-Se bond cleavage and the carbolithiation reac-
carbocyclisation
tion) which should possess carbanions of related stability
and therefore should be particularly prone to equilibrate.
2,7-Diphenyl-2-(methylseleno)-heptene 1d, prepared
A few years ago we reported that the w-alkenylbenzyllith-
4a
from 1,1-bis (methylseleno)-1-phenylethane, n-BuLi
and 5-bromo-1-phenyl-pent-1-ene, leads, on reaction with
n-BuLi in THF at -78 °C, and methanolysis at that temper-
ature, to the cyclopentane derivative 4d as a 3/97 mixture
ium 2a (R = H, Scheme 1) possesses a very high propen-
sity to rearrange to cyclopentylmethyllithium 3a which
after hydrolysis led to the corresponding 1,2-dimethyl-1-
phenyl cyclopentane 4a with almost complete stereocon-
of stereoisomers 4’d/4”d (Scheme 1, Table, entry a). The
trol depending upon the nature of the solvent and the tem-
same reaction is still effective in ether at -78 °C but it re-
perature used (3a’ and 4a’ in ether at 20 °C, 3a” and 4a”
quires the use of the more reactive s-BuLi 4b to cleave the
C,Se bond and provides the same mixture of stereoiso-
mers but with a lower stereoselectivity (Scheme 1, Table,
entry b, compare to entry a).
in THF at -78 °C).1a The reaction proved to be quite gen-
eral since related compounds whose C,C double bond
bears a thiophenyl group (R = SPh, Scheme 1) behave
similarly. 1b
Most of the reactions have been carried on a (1/1) mixture
of Z/E isomers of 1d. In few cases, we have used a starting
material highly enriched in one or the other stereoisomer
and have not observed significant change on the 4’d/4"d
ratio of stereoisomers.5
Cyclization even takes place with the w-alkenylbenzyl-
lithium 1c bearing a methyl substituent on the C,C double
bond,1c but instead leads to the cyclopent[a]indene 5c in
pentane (20 °C, 24 h; 4’/5/7 ratio 3/97/0 by GC) and to
1,2-dimethyl-1-phenyl-cyclohexane 7c soiled with some
of 4c and 5c in THF (-78 °C, 0.5 h; 46% yield; 4"/5/7 ratio
15/22/63 by GC).
We have screened, in order to control more efficiently its
stereochemical outcome, the effect of the temperature on
Table Carbocyclization of ω-stryrenyl benzyllithiums
Entry Conditions
4d yield %
(4′/4″ ratio)
a
b
c
d
e
f
(i) n-BuLi, THF, –78°C, 1h (ii) MeOH, –78°C 83 (3/97)
(i) s-BuLi, ether, –78°C, 1h (ii) MeOH, –78°C 70 (33/67
(i) s-BuLi, ether, 0°C, 1h (kk) MeOH, 0°C
72 (98/2)
(i) s-BuLi, ether, –45°C, 1h (ii) MeOH, –45°C 80 (90/10)
(i) s-BuLi, ether, –65°C, 1h (ii) MeOH, –65°C 65 (44/56)
(i) s-BuLi, ether, –100°C, 1h (ii) MeOH,
–100°C
70 (8/92)
g
h
i
(i) s-BuLi, ether, –100°C, 1h (ii) MeOH, 0°C 70 (4/96)
(i) n-BuLi, THF, 0°C, 1h (ii) MeOD 75 (27/73)
(i) n-BuLi, THF, –78°C, 1h (ii) –78°C to 0°C, 60 (26/74)
1h, (iii) MeOD, 0°C
Scheme 1
Synlett 1999, No. 07, 1142–1144 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
On the Carbocyclization of w-Styrenylbenzyllithiums
1143
the reaction performed in ether. We unexpectedly found The benzylselenide 8’d required for this study was easily
that it is possible to produce in ether either the almost pure prepared (Scheme 3) by quenching 3’d (prepared from 1d
cyclopentane stereoisomer 4’d or 4"d selectively by per- and t-butyllithium in pentane) 4c,7 with dimethyldiselenide
forming the reaction at 0 °C (Table, entry c) or at -100 °C (1 equiv. MeSeSeMe, 20 °C, 1 h, 32% yield). The newly
(Table, entry f).
formed benzylselenide 8d is a stereoisomeric mixture in
which the cis-stereoisomer at the ring junction predomi-
nates (8’d/8"d :74/26) but each stereoisomer is an epimer-
ic mixture at the benzyl site where the methylseleno
moiety has been introduced (8’d a; 77/23; 8"d a/b; 74/
26).
We also found that the ratio of stereoisomers changes con-
tinuously between 0 °C and -100 °C (Table, entries b-f)
and that the significant change occurs around -65 °C (Ta-
ble, entry e).
These reactions occur under kinetic control in the whole
range of temperature studied from -100 °C to 0 °C since
the same ratio of stereoisomers is obtained when the reac-
tion performed at -100 °C and is then quenched with deu-
teromethanol either at that temperature or at 0 °C (Table
entries f, g).
We also prepared, for control experiments the trans-
stereoisomer 8"d by performing the two consecutive re-
actions in THF ((i) 1 equiv. n-BuLi, THF, -78 °C, 0.5 h,
(ii) 1 equiv. MeSeSeMe, THF, -78 °C to 20 °C; 73%
yield, 8"d/8’d 98/2, 8"d a/b: 87/13) and have unambigu-
ously assessed the stereochemistry of the major stereoiso-
mer 8"da (Scheme 3) by X-ray crystallography.
Reactions performed in THF do not exhibit similar behav-
ior since epimerisation takes place when the reaction car-
ried out at -78 °C is heated to 0 °C prior to methanolysis
(Table, entry i).
T selenides 8’d and 8"d have been also prepared in a more
expedite way by reacting 1d with a catalytic amount of
BuLi (Scheme 4) :
Furthermore we proved that the reaction proceeds under
kinetic control in THF at -78 °C (Table, entry a). Indeed
the benzyllithium 3’d, prepared in THF at -78 °C, from
benzylselenide 8’d and n-butyllithium does not isomerize
in ether ((i) 0.2 equiv. t-BuLi, ether, 0 °C, 0.1h (ii) 0° to
20 °C, 24 h; 8d 56% yield, 8'd/8"d 72/23; 8'd a/b: 62/38;
8"d a/b: 55/45) or
to 3’’d since 4’d is obtained almost exclusively after in THF ((i) 0.2 equiv. n-BuLi, THF, -78 °C, 0.5h (ii)
methanolysis (-78 °C, 0.5h then MeOH, -78 °C, Scheme 20 °C, 24h, 8d, 80% yield, 8'd/8"d 18/82; 8'd a/b :62/
2).6
38; 8"d a/b: 52/48).
Scheme 2
Scheme 3
Synlett 1999, No. 07, 1142–1144 ISSN 0936-5214 © Thieme Stuttgart · New York

1144
A. Krief et al.
LETTER
Scheme 4
(2) Comparatively the cyclization of 2a in ether is very slow at
-78 °C. The presence of the phenyl group on the C,C double
bond enhances dramatically the rate of the reaction in that
solvent.
(3) For related reactions producing benzyllithiums after
carbocyclization (a) Wei, X.; Taylor, R.J.K. Tetrahedron Lett.
1997, 38, 6467; (b) Woltering, M.J.; Frölich, R.; Hoppe, D.
Angew. Chem. Int. Ed. Engl. 1997, 36, 1764; (c) Tomooka, K.;
Komine, N.; Sasaki, T.; Shimizu, H.; Nakai, T. Tetrahedron
Lett. 1998, 39, 9715 (d) Bailey, W.F.; Gavaskar, K.V.
Tetrahedron 1994, 50, 5957.
These results led us to assume that the newly formed pri-
mary benzylic carbanion 3d is able to cleave, in both sol-
vents used, the C-Se bond of the open chain tertiary
benzylic derivative 1d, producing simultaneously the ben-
zylic selenide 8d and the open chain tertiary-benzyllithi-
um 2d which perpetuates the cycle until 1d has
completely disappeared (Scheme 4). Related isomeriza-
tions have been recently described.8
Work is in progress to determine the behavior of related
derivatives bearing different substituent on the C,C dou-
ble bond.
(4) These reactions have been carried out with (a) 1.6 N n-BuLi in
hexanes; (b) 1.3 N s-BuLi in cyclohexane or (c) 1.7 N t-BuLi
in pentane all from the Aldrich Company.
(5) For example when the reaction is carried out with s-BuLi in
ether at -45 °C on a 50/50 or a 10/90 (Table, entry d) ratio of
Z-1d/E-1d we obtained a 88/12 or a 90/10 ratio of 4’d/4"d.
For a related result see : Hoffmann, R.W.; Koberstein, R.;
Remacle, B.; Krief, A. Chem. Commun. 1997, 2189-2190.
(6) 3"d is usually produced when the carbocyclization is
performed in THF. Using the strategy disclosed in this section
we have been able to generate instead 3’d in the same solvent.
(7) Cyclization of 2d in pentane at 20 °C leads to a
diastereoisomeric mixture of 4’d and 4"d after methanolysis.
(8) (a) Bailey, W. F.; Carson, M. W. J. Org. Chem. 1998, 63, 361;
(b) Coldham, I.; Hufton, R. Tetrahedron. 1996, 52, 12541.
Acknowledgement
Authors thanks the FRIA (Fonds de Recherche pour l’Industrie et
l’Agriculture, Belgique) for a fellowship (BR) and the FNRS (Fonds
National de la Recherche Scientifique, Belgique) for their constant
financial support (Mass Spectrometer and Polarimeter).
References and Notes
(1) (a) Krief, A.; Barbeaux, P. J. Chem. Soc. Chem. Commun.
1987, 16, 1214-1216; (b) Krief, A.; Kenda, B.; Remacle, B.
Tetrahedron 1996, 52, 7435-7463; (c) Krief, A.; Kenda, B.;
Barbeaux, P.; Guittet, E. Tetrahedron 1994, 50, 7177-7192.
Article Identifier:
1437-2096,E;1999,0,07,1142,1144,ftx,en;G09999ST.pdf
Synlett 1999, No. 07, 1142–1144 ISSN 0936-5214 © Thieme Stuttgart · New York