Regio- and enantioselective molybdenum-catalyzed alkylations of polyenyl esters [1]

Full text of DOI:10.1021/ja992602s

10416
J. Am. Chem. Soc. 1999, 121, 10416-10417
Communications to the Editor
resultssonly the two products 9b2 and 10b2 in a 5.3:1 ratio were
formed (58% yield, 92% brsm7), and the ee of 9b was 97%.
Switching to ligand 11 led to slight improvements: 9b and 10b
were obtained in a 6.1:1 ratio (68% yield) and the ee of 9b was
>99%.
With this background, a series of polyenyl substrates as
summarized in Table 1 was examined. While the proximal double
bond must be only disubstituted, the remote double bond can bear
any number of substituents.
Regio- and Enantioselective Molybdenum-Catalyzed
Alkylations of Polyenyl Esters
Barry M. Trost,* Stefan Hildbrand, and Kalindi Dogra
Department of Chemistry, Stanford UniVersity
Stanford, California 94305-5080
ReceiVed July 22, 1999
Generally, trisubstitution on the distal double bond, notably
as in entries 3, 4, 6, and 8, gave higher ee’s than terminal
disubstitution as in entry 7 or disubstitution as in entry 5. The
use of the enol ether as in entry 8 is particularly useful for further
transformations. The trienyl substrates of entries 9 and 10 still
produce only two regioisomeric products with good regioselec-
tivity (∼10-12:1) and excellent ee (97 and 98%).
The use of polyene substrates in allylic alkylations can be
complicated by the issue of regioselectivity, as illustrated in eq
1, as well as reversibility.1,2 Thus, although much work in
asymmetric palladium-catalyzed allylic alkylations has been done,3
the utilization of polyenes has not been explored. One of the
reasons clearly stems from the anticipated selectivity for formation
of the achiral product 2.1d,e On the other hand, switching to
molybdenum should favor either 3 or 4 over 2.4,5 The recent
success in effecting an asymmetric alkylation with cinnamyl
substrates6 induced us to explore its potential with polyene
systems.
In examining the role of the linker heterocycle, we prepared
the 4-pyrimidinecarbonyl ligand 129 to decrease the σ-donation
to the molybdenum. This new ligand system gave slight improve-
ments in either ratio or ee in the two cases examined, entries 6
and 7. Further evaluation of this ligand is underway.
Our initial studies examined the reaction of 5-phenylpentadienyl
methyl carbonate, 5a (eq 2), and dimethyl sodiomalonate, 6, using
Conjugation of the allyl carbonate with an alkyne also led to
no involvement of the triple bond as shown in eq 3. In both cases,
(2)
a catalyst formed in situ from the bis-picolinylamide 7 and the
molybdenum complex 8. Only two alkylation products were
observedsthe branched one, 9a2, and the linear one, 10a1e, in
6.1:1 ratio in 95% isolated yield. None of the product derived
from attack at the benzylic position was observed. Using chiral
HPLC, the ee of 9a was established as 98% (er 99:1). Interest-
ingly, extending the conjugation as in 5b led to virtually the same
the major product (13a:14a 5.3:1, 13b:14b 7.3:1) was the
branched one with excellent ee (13a 99% ee, 13b 99% ee). In
(4) Trost, B. M.; Merlic, C. A. J. Am. Chem. Soc. 1990, 112, 9590; Trost,
B. M.; Lautens, M. Tetrahedron 1987, 43, 4817; Trost, B. M.; Lautens, M. J.
Am. Chem. Soc. 1987, 109, 1469; 1982, 104, 5543. Also see: Faller, J. W.;
Lambert, C.; Mazzieri, M. R. J. Organomet. Chem. 1990, 383, 161; Faller, J.
W.; Linebarrier, D. Organometallics 1988, 7, 1670.
(1) (a) Trost, B. M.; Bunt, R. C. J. Am. Chem. Soc. 1998, 120, 70. (b)
Nilsson, Y. I. M.; Andersson, P. G.; Backvall, J.-E. J. Am. Chem. Soc. 1993,
115, 6609. (c) Andersson, P. G.; Backvall, J.-E. J. Org. Chem. 1991, 56, 5349.
(d) Trost, B. M.; Lautens, M.; Hung, M.-H.; Carmichael, C. S. J. Am. Chem.
Soc. 1984, 106, 7641. (e) Trost, B. M.; Urch, C. J.; Hung, M.-H. Tetrahedron
Lett. 1986, 27, 4949.
(2) Trost, B. M.; Hung, M.-H. J. Am. Chem. Soc. 1984, 106, 6837.
(3) For reviews, see: Trost, B. M.; Van Vranken, D. L. Chem. ReV. 1996,
96, 395; Hayashi, T. In Catalytic Asymmetric Synthesis; Ojima, I., Ed.; VCH
Publishers: New York, 1993; pp 325-365.
(5) For work on stoichiometric π-allylmolybdenum alkylations, see:
Adams, R. D.; Chodosh, D. F.; Faller, J. W.; Rosan, A. M. J. Am. Chem. Soc.
1979, 101, 2570; McCleverty, J. A.; Murray, A. J. J. Organomet. Chem. 1978,
149, C29; Rubio, A.; Liebeskind, L. S. J. Am. Chem. Soc. 1993, 115, 891.
(6) Trost, B. M.; Hachiya, I. J. Am. Chem. Soc. 1998, 120, 1104. Also
see: Glorius, F.; Pfaltz, A. Org. Lett. 1999, 1, 141.
(7) brsm ) based upon reacted starting material.
10.1021/ja992602s CCC: $18.00 © 1999 American Chemical Society
Published on Web 10/26/1999

Communications to the Editor
J. Am. Chem. Soc., Vol. 121, No. 44, 1999 10417
Table 1. Regio- and Enantioselective Alkylations of Polyenyl Carbonatesa with Dimethyl Malonate
a All reactions performed using 10 mol % 8, 15 mol % 11, 1 equiv of allyl carbonate, 2.2 equiv of dimethyl malonate, and 2.0 equiv of sodium
hydride in 1:1 PhCH3/THF at 80-90 °C. b Isolated yields; yields in parentheses based upon recovered starting material. c Determined by 1H NMR
spectroscopy of the isolated products; also see ref 8. d Determined by chiral HPLC. e Ligand 7 employed in this run. f For this run, ligand 12 was
employed; therefore, the enantiomeric product from that obtained with ligand 11 is formed. g For this run, 20 mol % of 8 and 30 mol % of 11
employed.
the latter case, better results were obtained with 20 mol % of
catalyst than with 10 mol %.
triene substrates in entries 2, 9, and 10 may participate in
subsequent Diels-Alder reactions.1d On the other hand, the
products are also of interest in their own right. The stereochemistry
is assigned by analogy to the cinnamyl substrates6 and thus must
be considered tentative at present. Future studies are intended to
elucidate the exact nature of the active catalyst.
The lack of participation of the additional unsaturation is both
surprising and satisfying. The regioselectivity suggests that π-allyl
complex 16 is not involved in the sequence, otherwise detectable
amounts of regioisomer 4 would have been expected. This
conclusion then states that initial ionization must occur to give
15 exclusively and, furthermore, that 15 does not equilibrate to
16 to any appreciable extent. While it can be argued that (a)
complexes 15 and 16 are in dynamic equilibrium and (b) complex
15 might be the kinetically more active complex in the alkylation
step to rationalize the results, it is not obvious that complex 16
should really be significantly less reactive especially since attack
at the benzylic position in cinnamyl systems is preferred. The
types of products can be quite useful for further structural
elaboration. For example, the chiral 1,3-dienes resulting from
Acknowledgment. We thank the National Science Foundation and
the National Institutes of Health, General Medical Sciences, for the
generous support of our programs. S.H. was supported by the Swiss
National Science Foundation. K.D. is supported by a grant from
SmithKline-Beecham. Mass spectra were provided by the Mass Spec-
trometry Facility at the University of California-San Francisco supported
by the NIH Division of Research Resources.
Supporting Information Available: A sample experimental proce-
dure for the asymmetric alkylation as well as the characterization data
for all of the compounds described in the Table 1, as well as for 13a and
13b (PDF). This material is available free of charge via the Internet at
http://pubs.acs.org.
JA992602S
(8) All new compounds have been characterized spectroscopically and
elemental compositions established by combustion analysis or high-resolution
mass spectrometry.
(9) Prepared in standard fashion from the diamine and 4-pyrimidinecar-
boxylic acid [Gabriel, S.; Colman, J. Chem. Ber. 1899, 32, 1525].