5
206
J . Org. Chem. 1996, 61, 5206-5207
Ster eosp ecific 1,4-Ad d ition of
Sch em e 1
Or ga n olith iu m Rea gen ts to Un pr otected 1-
a n d 2-Na p h th a len eca r boxylic Acid s. A
F a cile Rou te to 1,1,2- a n d
-
1
1,2,2-Tr isu bstitu ted
,2-Dih yd r on a p h th a len es
Barbara Plunian, J acques Mortier,* and
Michel Vaultier*
Universit e´ Rennes-I, Groupe de recherches de physicochimie
structurale, unit e´ associ e´ e au CNRS no. 704, avenue du
G e´ n e´ ral Leclerc, 35042 Rennes Cedex, France
Lo ¨ı c Toupet
Universit e´ Rennes-I, Groupe de physique cristalline, unit e´
associ e´ e au CNRS no. 15, avenue du G e´ n e´ ral Leclerc,
3
5042 Rennes Cedex, France
Received May 21, 1996
The reaction of strong nucleophiles with R,â-unsatur-
ated carbonyl compounds usually leads to products
resulting from carbonyl addition.1 Products resulting
from the alternate 1,4 or conjugate addition mode gener-
ally require the use of organocopper reagents derived
ature (-90 °C).9 We now describe a stereospecific route
to 1,1,2- and 1,2,2-trisubstituted 1,2-dihydronaphtha-
lenes 4 and 6 that involves the nucleophilic conjugate
addition of organolithium reagents to unprotected 1- and
2-naphthalenecarboxylic acids (1, 2) followed by trapping
of the intermediate carboxylic acid dilithium enolates 3
and 5 with several electrophiles (Scheme 1).1
from reactive nucleophiles.2 While a plethora of methods
have been developed and widely utilized addressing this
type of transformation, one area that has slowly devel-
oped and only recently shown promise is the conjugate
3
addition of organolithium reagents to Michael acceptors.
The conjugate addition reactions of R,â-unsaturated
carboxylic acid derivatives can be promoted by steric
interference with the 1,2-addition process. Organo-
lithium reagents undergo predominantly 1,4-addition
0,11
Treatment of a 0.1 M THF solution of naphthalenecar-
boxylic acids 1 or 2 with organolithium reagents (2.2
equiv) under the conditions depicted in Table 1, followed
by addition of an electrophile (4.0 equiv), produced the
adducts 4 and 6 in generally good yields.12 The addition
of s-butyllithium to 1 and 2 (-78 °C) followed by
quenching with methyl iodide (-78 °C) gave the adducts
reactions with unsaturated trityl ketones4,5 as well as
amide acceptors derived from highly hindered amines.6
Unsaturated esters of 2,6-di-tert-butyl-4-methoxyphenol
derivatives (BHA esters) undergo conjugate addition
reactions with a range of organolithium reagents.7
4
a ,a ′ (80%) and 6a ,a ′ (90%) as 90:10 and 70:30 mixtures
The conjugate addition to R,â-unsaturated carboxylic
of diastereoisomers (entries 1 and 6, Table 1, and Scheme
2). The trans addition was verified in each system by
acids has scarcely been achieved by using Grignard and
alkylcopper reagents.8 However, the conjugate addition
single-crystal X-ray determination of the crystalline
to R,â-ethylenic carboxylic acids has never been per-
formed by using any organolithium reagents. We have
recently demonstrated that the directed ortho-metalation
of unprotected benzoic acid can be achieved by treatment
with 2.2 equiv of s-BuLi/TMEDA in THF at low temper-
major isomers.1
3,14
Presumably, in either case the car-
boxylic acid dilithium enolates 3 and 5 are the initial
products formed, and entry of the electrophile (MeI)
proceeds from the more accessible opposite face to that
carrying the alkyl group. Furthermore, the X-ray struc-
*
To whom correspondence should be addressed. Phone: (33) 99 28
6 91. Fax: (33) 99 28 69 55. E-mail: jacques.mortier@univ-rennes1.fr.
1) Wakefield, B. J . The Chemistry of Organolithium Compounds;
Pergamon Press: New York, 1974.
2) (a) Perlmutter, P. Conjugate Addition Reactions in Organic
1
(9) (a) Mortier, J .; Moyroud, J .; Bennetau, B.; Cain, P. A. J . Org.
Chem. 1994, 59, 4042. (b) Moyroud, J .; Guesnet, J . L.; Bennetau, B.;
Mortier, J . Tetrahedron Lett. 1995, 36, 881. (c) Bennetau, B.; Mortier,
J .; Moyroud, J .; Guesnet, J . L. J . Chem. Soc., Perkin Trans. 1 1995,
1265. (d) Moyroud, J .; Guesnet, J .-L.; Bennetau, B.; Mortier, J . Bull.
Soc. Chim. Fr. 1996, 133, 133. (e) Moyroud, J .; Ch eˆ ne, A.; Guesnet,
J .-L.; Mortier, J . Heterocycles 1996, 43, 221.
(
(
Synthesis; Tetrahedron Organic Chemistry Series; Pergamon Press:
Oxford, 1992; Vol. 9. (b) Rossiter, B. E.; Swingle, N. M. Chem. Rev.
992, 92, 771.
1
(
(
3) Review: Hunt, D. A. Org. Prep. Proced. Int. 1989, 21, 705.
4) Seebach, D.; Ertas, M.; Schweizer, W. B. Helv. Chim. Acta 1985,
(10) The functionalization of chiral 1- and 2-naphthyloxazolines has
become a prominent route by which many important chiral organic
compounds are accessed: Meyers, A. I.; Lutomski, K. A.; Laucher, D.
Tetrahedron 1988, 44, 3107 and references cited therein.
6
8, 264.
5) Occasional reports of conjugate addition reactions of organo-
(
lithium reagents to unsaturated sec-butyl and tert-butyl esters have
also appeared: (a) Munch-Peterson, J . J . Org. Chem. 1957, 22, 170.
(11) For addition of organolithium to naphthalene and Grignard
addition to acylnaphthalenes, ate complexes of boranes, arene-Cr-
(CO)3 complexes, 2,6-di-tert-butyl-4-(methoxyphenyl)-1- and -2-naph-
thalenecarboxylates (BHA esters), see: (a) Tomioka, K.; Shindo, M.;
Koga, K. Tetrahedron Lett. 1993, 34, 681. (b) K u¨ ndig, E. P.; Ripa, A.;
Liu, R.; Bernardinelli, G. J . Org. Chem. 1994, 59, 4773 and references
cited therein. (c) Inoue, I.; Shindo, M.; Koga, K.; Tomioka, K.
Tetrahedron 1994, 50, 4429. Ortho-metalation appears to be the major
reaction pathway in the carboxamides when they are in the 1- and
the 2-positions of the naphthalene: (d) Mpango, G. B.; Mahalanabis,
K. K.; Madhavi, Z.; Snieckus, V. Tetrahedron Lett. 1980, 21, 4823.
(
b) Munch-Peterson, J . Org. Synth. 1961, 41, 60. (c) Cooke, M. P., J r.
Org. Synth. 1984, 49, 1144.
6) First report on the Michael-type reactivity of R,â-unsaturated
(
amides: (a) Gilbert, G.; Aycock, B. F. J . Org. Chem. 1957, 22, 1013.
Conjugate addition of organolithium reagents to unsaturated secondary
and tertiary thioamides: (b) Tamaru, Y.; Kagotani, M.; Furukawa, Y.;
Amino, Y.; Yoshida, Z. Tetrahedron Lett. 1981, 22, 3413.
(
7) Cooke, M. P., J r. J . Org. Chem. 1986, 51, 1637.
(8) (a) Klein, J .; Turkel, R. M. J . Am. Chem. Soc. 1969, 91, 6186.
1
13
(
b) Klein, J .; Zitrin, S. J . Org. Chem. 1970, 35, 666. (c) Yamamoto, Y.;
Yamamoto, S.; Yatagai, H.; Ishihara, Y.; Maruyama, K. J . Org. Chem.
982, 47, 119.
(12) All new compounds show H and C NMR and combustion
analysis in full agreement with the proposed structures. See the
supporting information.
1
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