Stereoselective Indium-Promoted Allylation of γ-Hydroxy-γ-Lactones under Aqueous Conditions. The Neighboring Carboxyl Effect

Full text of DOI:10.1021/jo9716800

8284
J . Org. Chem. 1997, 62, 8284-8285
Ster eoselective In d iu m -P r om oted
Allyla tion of γ-Hyd r oxy-γ-La cton es u n d er
Aqu eou s Con d ition s. Th e Neigh bor in g
Ca r boxyl Effect
Patrick Bernardelli and Leo A. Paquette*
Evans Chemical Laboratories, The Ohio State University,
Columbus, Ohio 43210
Received September 9, 1997
Indium-mediated carbon-carbon bond-forming reac-
tions have commanded considerable attention recently
because of the high efficiency with which In promotes
these processes in water1 and the ability of proximal
hydroxy,2 dimethylamino,3 and keto substituents4 to
control diastereoselectivity through chelation to orga-
noindium reagents under aqueous conditions.5 No ex-
amples involving comparable intramolecular complex-
ation to a carboxylic acid residue have yet been reported.
In connection with the development of a general enan-
tioselective approach toward 3,10-epoxy-2,11-cyclized
cembranoids, the occasion to examine the stereoselectiv-
ity associated with addition of the allylindium reagent
to γ-hydroxy γ-lactones presented itself. We now report
that introduction of an allyl side chain into such systems
proceeds with a synthetically useful stereochemical bias,
a result presumably due to internal chelation to the
neighboring carboxyl group once unmasked.
F igu r e 1.
appears uniquely as an upfield triplet (see 4). A doublet
of triplets as depicted for 7 is seen for the minor isomers.
A typical set of NOE experiments is shown for 5 and 8.
The required enantiopure γ-hydroxy γ-lactones 1-3
were derived by hydrolysis of the corresponding γ-men-
thyloxy γ-lactones under acidic conditions.6 In this way,
undesired epimerization next to the hemiacetal center
was effectively skirted. Each substrate was stirred
vigorously overnight at rt with allyl bromide and indium
powder in dilute HCl (pH 3) containing 10% of ethanol
or tetrahydrofuran. The acidic environment accelerated
the rate of lactol ring opening, and the limited amount
of organic solvent guaranteed complete miscibility of the
nonmetallic reagents.7 The results are provided in Table
1.
The high diastereoselectivity observed for 1 and 3 can
be rationalized in terms of preferred coupling via a
chelated transition state in which the carboxylic acid
group coordinates to the allylindium species prior to
nucleophilic attack.8 As seen in Figure 1, this process
locks the conformation of the bicyclic ring system, thereby
causing allylation to occur via a six-membered transition
state preferentially on the Re face of the aldehyde as in
A. Under these circumstances, intramolecular delivery
from the Si face as in B is disfavored due to nonbonded
steric interactions involving the allyl group and bicyclic
framework. The higher selectivity observed for 3 can be
attributed to increased shielding of the Si face of the
aldehyde by the tert-butyldiphenylsilyl substituent.
In Table 1, entry 4, the presence of a salt such as tetra-
n-butylammonium bromide is seen to induce a significant
increase in diastereoselectivity. The phenomenon, which
The major diastereomer in each instance was easily
recognized from examination of the multiplicity and
chemical shift of its R-oxy proton, in tandem with NOE
experiments. Since an endo-oriented proton is displaced
(3) Paquette, L. A.; Mitzel, T. M.; Isaac, M. B.; Crasto, C. F.;
Schomer, W. W. J . Org. Chem. 1997, 62, 4293.
(4) Paquette, L. A.; Isaac, M. B. Heterocycles, in press.
(5) Paquette, L. A. In Green Chemistry: Frontiers in Benign Chemi-
cal Synthesis and Processing; Anastas, P., Williamson, T., Eds.; Oxford
University Press: Oxford, 1997, in press.
(6) Bernardelli, P. Ph.D. Dissertation, The Ohio State University,
1997.
(7) Direct exposure of the γ-menthyloxy γ-lactones to allyltrimeth-
ylsilane in the presence of trimethylsilyl triflate as recommended for
dimethyl acetals (Noyori, R.; Murata, S.; Suzuki, M. Tetrahedron 1981,
37, 3899) did not result in consumption of the starting material. This
lack of reactivity is attributable to the steric bulk of the menthyloxy
substituent, which impedes formation of the oxonium ion.
(8) Since the hydroxy acids are the presumed intermediates in this
reaction, the possibility exists that cyclization to the lactone with an
exo substituent may be faster than cyclization to give the lactone with
an endo-allyl group. While no guarantee can be made that both
hydroxy acids have completely cyclized, none were observed spectro-
scopically in any experiments. More importantly, the exo allyl products
were invariably isolated in yields well in excess of 50% (Table 1, entries
1, 3, and 4), even when a counterbalancing chelating substituent was
present (Table 1, entry 2). Consequently, the results are entirely
consistent with the intervention of chelated transition states as
proposed.
90° out of plane from the adjacent tertiary hydrogen, it
(1) (a) Li, C.-J . Chem. Rev. (Washington, D.C.) 1993, 93, 2023. (b)
Chan, T.-H.; Li, C.-J .; Lee, M. C.; Wei, Z. Y. Can. J . Chem. 1994, 72,
1181. (c) Lubineau, A.; Auge, J .; Queneau, Y. Synthesis 1994, 741.
(2) (a) Paquette, L. A.; Mitzel, T. M. J . Am. Chem. Soc. 1996, 118,
1931. (b) Paquette, L. A.; Lobben, P. C. J . Am. Chem. Soc. 1996, 118,
1917. (c) Isaac, M. B.; Paquette, L. A. J . Org. Chem. 1997, 62, 5333
and related references cited in these papers.
S0022-3263(97)01680-0 CCC: $14.00 © 1997 American Chemical Society

Communications
J . Org. Chem., Vol. 62, No. 24, 1997 8285
Ta ble 1. In d iu m -Med ia ted Allyla tion of 1-3 (CH2dCHCH2Br , 25 °C)a
has previously been observed with R-hydroxy aldehydes,2a
is also accompanied by considerable rate acceleration.
Interestingly, the free hydroxy derivative 2 exhibits
quite low diastereoselectivity. This increase in the
proportion of the R-allyl isomer is consistent with com-
petition between the OH and COOH groups for complex-
ation to the incoming indium reagent. Transition state
C in Figure 1 reflects the expectation that chelation to
the hydroxyl substituent can bring about favored attack
on the Si face of the aldehyde. It is particularly relevant
that the product ratio determined for 2 is not inverted.
This observation may suggest that the carboxylic acid
functionality is a more effective chelator of allylindium
than the hydroxyl group in aqueous acidic environments.
For comparison purposes, 1 was treated with allyl-
magnesium bromide in THF9 and relactonized with 10%
HCl. A 1:1.5 mixture of 4 and 7 resulted, with 4 being
the minor product. Thus, indium is a significantly better
chelating metal than magnesium for this reaction.
The methodology outlined herein constitutes a conve-
nient and reliable means for the stereoselective synthesis
of bicyclic γ-allyl lactones from γ-hydroxy precursors. For
this new application of indium-promoted Barbier allyla-
tions in aqueous media, reliance is placed on the ability
of a neighboring carboxylic acid group to guide C-C bond
formation by means of chelation to the organometallic
species.
Ack n ow led gm en t. This work was supported by the
U.S. Environmental Protection Agency (Grant No. R82-
4725-010).
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and spectral data for all new compounds (11 pages).
(9) Canonne, P.; Plamondon J .; Akssira, M. Tetrahedron 1988, 44,
2903.
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