Asymmetric addition of organolithium reagents to prochiral arene tricarbonylchromium complexes

Full text of DOI:10.1021/jo960070h

2258
J . Org. Chem. 1996, 61, 2258-2259
Sch em e 1
Asym m etr ic Ad d ition of Or ga n olith iu m
Rea gen ts to P r och ir a l Ar en e
Tr ica r bon ylch r om iu m Com p lexes
David Amurrio, Karl Khan, and E. Peter Ku¨ndig*
De´partement de Chimie Organique, Universite´ de Gene`ve,
CH-1211 Gene`ve 4, Switzerland
Received J anuary 29, 1996
The external ligand-controlled enantioselective addi-
tion of organometallic reagents to prochiral molecules is
a powerful tool in asymmetric methodology. Previous
work in this area has centered on 1,2-additions to
aldehydes and aldeheyde imines and on 1,4-additions to
R,â-unsaturated carbonyl compounds.1 Tomioka, Shindo,
and Koga have reported highly enantioselective organo-
lithium addition/protonation reactions with cyclohexyl-
imines derived from 1-naphthaldehyde and, more re-
cently, with 1-naphthyl esters.2 However, methods of
asymmetric C-C bond formation in the transformation
of benzene and substituted benzenes remain scarce3
despite the obvious synthetic potential of the transforma-
tion of an arene into a chiral nonracemic alicyclic
compound.
Ta ble 1. Sequ en tia l Asym m etr ic Ad d ition of RLi/L* a n d
P r op a r gyl Br om id e to Com p lex
The present investigation is based on our finding that
the consecutive addition of a C-nucleophile and a C-
electrophile to an arene complexed to the electrophilic
Cr(CO)3 moiety4 gives 1,2-trans-disubstituted dihydro-
arenes.5 More recently, we have shown that such trans-
formations can be combined with ortho-regioselectivtiy
for the nucleophile addition by the use of appropriate
N-containing auxiliaries σ-bound to the arene ring6
(Scheme 1). High diastereoselectivity was observed in
this sequence when enantiomerically pure tricarbonyl
phenyloxazoline chromium complexes were used.7
Here we report our initial results on the alternative
approach of regio- and enantioselective additions of
alkyl-, vinyl-, and aryllithium reagents to two prochiral
arene Cr(CO)3 complexes in the presence of chiral ligands.
Four chiral ligands figure in our investigation of the
sequential addition of phenyl-, vinyl-, and alkyllithium
reagents and propargyl bromide to the phenyloxazoline
complex 1 to give the chiral nonracemic cyclohexadiene
2 (Table 1). They are either commercially available or
readily synthesized.8,9 Racemic products were obtained
a
RLi was added to a solution of complex 1 and the chiral ligand.
Control experiments in which RLi and the chiral ligand were
mixed prior to addition to a solution of complex 1 gave very similar
b
results (yield, ee). Two equiv of chiral ligand was used. c Yield
* To whom correspondence should be addressed. Fax: (41 22) 328
7396. e-mail: Peter.Kundig@chiorg.unige.ch.
d
of isolated product after flash chromatography. The absolute
(1) For reviews see: (a) Tomioka, K. Synthesis 1990, 541. (b)
Rossiter, B. E.; Swingle, N. M. Chem. Rev. 1992, 92, 771. For recent
reports of additions to imines see: (c) Denmark, S. E.; Nakajima, N.;
Nicaise, O. J .-C. J . Am. Chem. Soc. 1994, 116, 8797. (d) Inoue, I.;
Shindo, M.; Koga, K.; Tomioka, K. Tetrahedron 1994, 50, 4429.
(2) (a) Tomioka, K.; Shindo, M.; Koga, K. J . Am. Chem. Soc. 1989,
111, 8266. (b) Tomioka, K.; Shindo, M.; Koga, K. Tetrahedron Lett.
1993, 34, 681.
(3) Birch reduction/alkylation of benzoic acid derivatives: For a
review see (a) Rabideau, P. W.; Marcinow, Z. Org. React. 1992, 42, 1.
For chiral examples see: (b) Schultz, A. G.; Macielag, M.; Sundarara-
man, P.; Taveras, A. G.; Welch, M. J . Am. Chem. Soc. 1988, 110, 7828
and references cited therein.
(4) For a review of nucleophilic additions to (arene)Cr(CO)3 com-
plexes see: Semmelhack, M. F. In Comprehensive Organometallic
Chemistry; Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford,
1995; Vol. 12, p 517.
(5) (a) Ku¨ndig, E. P.; Cunningham, A. F., J r.; Paglia, P.; Simmons,
D. P. Helv. Chim. Acta 1990, 73, 386. (b) Ku¨ndig, E. P.; Inage, M.;
Bernadinelli, G. Organometallics 1991, 10, 2921.
configuration is based on that established for 2a . This was done
after conversion to the SAMP-hydrazone derivative by comparison
of the sign of optical rotation with that of an analogously converted
compound whose configuration is known from an X-ray structure
(see ref 7). e Determined by chiral HPLC-analysis (Chiralcel OD:
e.g., 2d , hexane/i-PrOH ) 200/1, 1 mL/min, retention time;
(5R,6S)-(-)-2d , 7.8 min; (5S,6R)-(+)-2d, 9.9 min) and by optical
g
rotation. fAdded as
a
diethyl ether solution. Prepared from
tetravinyltin and MeLi in THF and used as toluene solution after
h
removal of THF in vacuo. Added as a cyclohexane/diethyl ether
i
j
(70/30) solution. Added as a hexane solution. In the absence of
HMPA 2d was obtained in a yield of 25% with an ee of 36%. k [R]20
) +479 (CHCl3, c ) 0.4).
D
when using (-)-sparteine ((-)-3) in either THF or diethyl
ether, indicating insufficient ligand complexation and/
or rapid background reaction. All subsequent reactions
were carried out in toluene. In this solvent the back-
ground reactionsaddition in the absence of added
ligandsis negligibly small at -78 °C. The results are
(6) Ku¨ndig, E. P.; Ripa, A.; Liu, R.; Bernardinelli, G. J . Org. Chem.
1994, 59, 4773.
(7) Ku¨ndig, E. P.; Ripa, A.; Bernardinelli, G. Angew. Chem., Intl.
Ed. Engl. 1992, 31, 1071.
0022-3263/96/1961-2258$12.00/0 © 1996 American Chemical Society

Communications
J . Org. Chem., Vol. 61, No. 7, 1996 2259
Sch em e 2
summarized in Table 1. The product yields achieved
using these conditions are comparable to those we obtain
for the achiral version where the reaction is carried out
in THF.6 For the second step of the sequence, the
reaction with propargyl bromide, addition of HMPA (10
equiv) is required as previously noted in the achiral
reaction. In its absence the yield was greatly reduced
(e.g., entry 4, from 65 to 25%).
In all reactions studied so far, a significant degree of
enantioselectivity has been obtained, along with the
already established regio- and stereoselectivity. An
asymmetric double addition to a benzene-based ring
system has been achieved, and the reaction exhibits a
high degree of control in the creation of the two new
stereogenic centers. The addition of the nucleophile,
under the influence of the external chiral ligand, pref-
erentially occurs at one of the enantiotopic ortho positions
of the arene.10 As expected, reactions using 4 as the
external ligand resulted in excesses of the opposite
enantiomer to that obtained when using 5 or 6.
In general, the reactions in which PhLi is the nucleo-
phile result in the highest enantioselectivities. nBuLi
consistently gives more modest results. The presence of
lithium salts in alkyllithium reagents was thought to
inhibit the reaction by their coordination to the ligand.
However, when freshly prepared vinyllithium was used,
again only modest enanantiomeric excesses were ob-
tained in most cases. That free salts were not a problem
seems to be confirmed by the absence of improvement in
enantioselectivity when using 4 equiv of external ligand.
Of the four ligands studied, the best results have
consistently been with the diethers 5 and 6. There is a
rapid fall-off in enantioslectivity when the number of
equivalents of external ligand used is reduced. A tenta-
tive interpretation of the results is that the reacting
nucleophile is oligomeric rather than monomeric, with
ligands acting as bridges rather than chelates. We are
currently attempting to isolate and characterize the
reaction intermediate. This will show ligand and nu-
cleophile arrangement and could result in a better ligand
design for a better complex match.
First results of the use of the application of this
methodology to an imine complex are shown in Scheme
2.
In the examples described with the phenyloxazoline
complex, the methodology presented here is complemen-
tary to that developed with chiral oxazolines. The
reactions with the imine complex 7 are unique in that
there are as yet no chiral imines which give both high
1,4-regio- and diastereocontrol in arene addition reac-
tions.11
In summary, we have extended the previously reported
stereo- and regioselective reactions into an asymmetric
version by the use of external chiral ligands. This
circumvents the problem of additional steps of incorpo-
rating (and removing) a chiral auxiliary in the arene and
is, therefore, potentially a more general method.12 Com-
bine this with the potential for catalysis or at least for
further optimization of the significant enantioselectivities
obtained so far, and an attractive method for asymmetric
additions across an arene double bond presents itself.
(8) (-)-Sparteine (3): Fluka. For a recent example of the catalytic
use of sparteine in asymmetric additions to aldehyde imines see ref
1c. For recent references of the use of sparteine in enantioselective
deprotonations see: (a) Beak, P.; Kerrick, S. T.; Wu, S.; Chu, J . J . Am.
Chem. Soc. 1994, 116, 3231. (b) Guarnieri, W.; Grehl, M.; Hoppe, D.
Angew. Chem., Intl. Ed. Engl. 1994, 33, 1734.
(9) Ether (1R,2R)-4, (1S,2S)-5, and (1S,2S)-6 were obtained in high
yield from the diols (1R,2R)-9, (1S,2S)-10, and (1S,2S)-11, respectively
(all >99% ee), by reaction with NaH and dimethyl sulfate. (a) Diol
(1R,2R)-9 is available commercially (Fluka). (b) Diol (1S,2S)-10 was
obtained by a literature procedure: Seemayer, R.; Schneider, M. P. J .
Chem. Soc., Chem. Commun. 1991, 49. (c) Diol (1S,2S)-11 was obtained
by a literature procedure: Sharpless, K. B.; Amberg, W.; Bennani, Y.
L.; Crispino, G. A.; Hartung, J .; J eong, K.-S.; Kwong, H.-L.; Morikawa,
K.; Wang, Z.-M.; Xu, D.; Zhang, X.-L. J . Org. Chem. 1992, 57, 2768.
(d) For previous application of 4 and 6 as chiral ligands for organo-
lithium reagent additions to naphthalenes see ref 2.
Ack n ow led gm en t. Support of this work by the
Swiss National Science foundation (Grant No. 20-
39’118.93) is gratefully acknowledged.
Su p p or tin g In for m a tion Ava ila ble: Experimental de-
tails and characterization data for ligand (1S,2S)-(+)-5. Rep-
resentative procedures for sequential additions to complexes
1 and 7. Listings of 1H- and 13C-NMR , IR, MS, and chiral
HPLC (or GC) data for cyclohexadienecarbaldehydes 8a -c (3
pages).
J O960070H
(10) For enantioselective ortho-deprotonations of prochiral arene Cr-
(CO)3 complexes by alkyl Li reagents/chiral ligands or by chiral amide
bases see: (a) Price, D. A.; Simpkins, N. S.; MacLeod, A. M.; Watt. A.
P. J . Org. Chem. 1994, 59, 1961. b) Ku¨ndig, E. P.; Quattropani, A.
Tetrahedron Lett. 1994, 35, 3497. (c) Uemura, M.; Hayashi, Y.;
Hayashi, Y. Tetrahedron Asymm. 1994, 5, 1427. (d) Schmalz, H. G.;
Schellhaas, K. Tetrahedron Lett. 1995, 36, 5515.
(11) SAMP-hydrazones can be used effectively in diastereoselective
nucleophilic additions to (arene)Cr(CO)3 complexes, but compared to
imines, hydrazones are far more resistant to nonoxidative hydrolyis.
Ku¨ndig, E. P.; Liu, R.; Ripa, A. Helv. Chim. Acta 1992, 75, 2675.
(12) Enantioselectivities need to be high though. A significant
convenience of diastereoselective reactions lies in the easy product
separation of diastereomeric products.