A three-component coupling strategy for tetrahydrofuran synthesis: application of the diisopropyl tartrate modified (E)-gamma-(dimethylphenylsilyl)allylboronate as an alpha,gamma-allyl dianion equivalent.

Article abstract of DOI:10.1021/ol9913082

[reaction: see text] A highly convergent three-component coupling strategy for the stereocontrolled synthesis of 2,3,5-trisubstituted tetrahydrofurans is described. After allylboration of the first aldehyde with 1, the chiral, nonracemic allylsilanes 2 are coupled with a second aldehyde or ketone with Lewis acid catalysis to give tetrahydrofurans 3 or 4 with excellent selectivity. The 2,5-stereochemistry is controlled by operating under nonchelate (e.g., 3) or chelate (e.g., 4) conditions.

Full text of DOI:10.1021/ol9913082

ORGANIC
LETTERS
2000
Vol. 2, No. 4
461-464
A Three-Component Coupling Strategy
for Tetrahydrofuran Synthesis:
Application of the Diisopropyl Tartrate
Modified
(E)-γ-(Dimethylphenylsilyl)allylboronate
as an r,γ-Allyl Dianion Equivalent
Glenn C. Micalizio1 and William R. Roush*
Department of Chemistry, UniVersity of Michigan, Ann Arbor, Michigan 48109
roush@umich.edu
Received December 4, 1999
ABSTRACT
A highly convergent three-component coupling strategy for the stereocontrolled synthesis of 2,3,5-trisubstituted tetrahydrofurans is described.
After allylboration of the first aldehyde with 1, the chiral, nonracemic allylsilanes 2 are coupled with a second aldehyde or ketone with Lewis
acid catalysis to give tetrahydrofurans 3 or 4 with excellent selectivity. The 2,5-stereochemistry is controlled by operating under nonchelate
(e.g., 3) or chelate (e.g., 4) conditions.
The stereoselective synthesis of substituted tetrahydrofurans,
which are present in many biologically interesting natural
products, remains a topic of considerable interest.2 Studies
from several laboratories have demonstrated that the [3 +
2] annulations of allylic and allenic silanes with enone,
carbonyl, and imine electrophiles represent a powerful
method for the synthesis of both carbocyclic and heterocyclic
five-membered rings.3-5 However, widespread application
of this methodology in natural products synthesis has been
impeded by the lack of simple, general, and highly stereo-
selective methods for synthesis of chiral, nonracemic allylic
silanes, especially the parent allylsilanes.3,6,7
We have demonstrated that tartrate ester modified (E)-γ-
silylallylboronates are useful reagents for the formal R- and
γ-hydroxyallylation of aldehydes following Tamao oxidation
or epoxidation-Peterson elimination of the intermediate
allylsilanes.8,9 However, it was readily apparent that this
allylboration sequence also constituted an exceptionally
simple route to chiral, nonracemic allylsilanes of general
structure 2. Herein we demonstrate the utility of allylsilanes
2 in the highly stereocontrolled synthesis of 2,3,5-trisubsti-
(1) Holder of the 1999-2000 American Chemical Society Division of
Organic Graduate Fellowship sponsored by Eli Lilly.
(2) Elliot, M. C. J. Chem. Soc., Perkin Trans. 1 1998, 4175.
(3) Masse, C. E.; Panek, J. S. Chem. ReV. 1995, 95, 1293, and literature
cited therein.
(6) Suginome, M.; Matsumoto, A.; Ito, Y. J. Am. Chem. Soc. 1996, 118,
3061.
(7) Smitrovich, J. H.; Woerpel, K. A. J. Am. Chem. Soc. 1998, 120,
12998.
(4) (a) Danheiser, R. L.; Kwasigroch, C. A.; Tsai, Y.-M. J. Am. Chem.
Soc. 1985, 107, 7233. (b) Panek, J. S.; Yang, M. J. Am. Chem. Soc. 1991,
113, 9868. (c) Akiyama, T.; Ishikawa, K.; Ozaki, S. Chem. Lett. 1994, 627.
(5) Roberson, C. W.; Woerpel, K. A. J. Org. Chem. 1999, 64, 1434.
(8) Roush, W. R.; Grover, P. T. Tetrahedron 1992, 48, 1981.
(9) Hunt, J. A.; Roush, W. R. J. Org. Chem. 1997, 62, 1112.
(10) Roush, W. R.; Pinchuk, A., unpublished research, 1999.
(11) Brown, H. C.; Bhat, K. S. J. Am. Chem. Soc. 1986, 108, 5919.
10.1021/ol9913082 CCC: $19.00 © 2000 American Chemical Society
Published on Web 02/01/2000

tuted tetrahydrofurans via [3 + 2] annulations with alde-
hydes, R-keto esters, and 1,2-diketones (Scheme 1). We also
Treatment of allylsilane 5 with either hydrocinnamalde-
hyde or R-(benzyloxy)acetaldehyde in CH2Cl2 at -78 °C in
the presence of BF3‚OEt2 (0.5 equiv) provided the 2,5-cis-
tetrahydrofurans 8 and 9 in 54% and 68% yields, with >20:1
diastereoselectivity in each case (Scheme 3). Similarly, BF3‚
Scheme 1
Scheme 3
demonstrate that the stereoselectivity of the annulation event
can be reversed by appropriate choice of Lewis acid catalyst,
thereby providing access to both 2,5-cis- and 2,5-trans-
substituted tetrahydrofurans 3 and 4 with exceptional ste-
reoselectivity.
Allylsilanes 5-7 were synthesized in 75-99% yield by
the allylboration reactions summarized in Scheme 2.8 The
Scheme 2
OEt2-catalyzed [3 + 2] annulation of allylsilanes 6 and 7
with R-(benzyloxy)acetaldehyde furnishes the 2,5-cis-
substituted tetrahydrofurans 10 and 11 in 78% and 53%
yields, again with excellent diastereoselectivity. The stereo-
chemistry within the 2,5-cis-tetrahydrofuran rings in each
case was assigned by NOE, as summarized in Scheme 3 for
the NOE’s observed for 8.
A reversal in stereoselectivity was observed when the [3
+ 2] annulations with R-(benzyloxy)acetaldehyde were
(12) Denmark, S. E.; Almstead, N. G. J. Org. Chem. 1994, 59, 5130.
(13) Fleming, I.; Dunogues, J.; Smithers, R. Org. React. 1989, 37, 57.
(14) Panek, J. S.; Yang, M. J. Am. Chem. Soc. 1991, 113, 9868.
(15) Panek, J. S.; Beresis, R. J. Org. Chem. 1993, 58, 809.
(16) The stereochemistry of 18 has been fully assigned by NOE studies
of the tetraisopropyldisiloxane derivative prepared from diol 19 (see
Supporting Information). These data verify that inversion of the original
C-Si center occurred during the [3 + 2]-cycloaddition reaction, consistent
with previous literature documentation in refs 14 and 15.
â-hydroxylallylsilane precursor to 5 is the product of a
matched double asymmetric allylboration and was obtained
with high diastereoselectivity. The enantiomeric purity of
the â-hydroxyallylsilane corresponding to 6 was 75% ee.
However, the same intermediate can be prepared in greater
than 90% ee by using the chiral allylborating agent generated
from PhMe2SiCH2CHdCH2, KO-t-Bu, n-BuLi, and MeOB-
(Ipc)2 using the standard procedure for synthesis of allyl-
(diisopinocampheyl)boranes.10,11 Protection of the â-hydroxy-
silanes was achieved by using either TES-Cl or TBS-Cl in
the presence of Et3N and DMAP in CH2Cl2 or Cl(CH2)2Cl
(93-99% yield).
(17) Mikami, K.; Kawamoto, K.; Loh, T.-P.; Nakai, T. J. Chem. Soc.,
Chem. Commun. 1990, 1161.
(18) Panek, J. S.; Cirillo, P. F. J. Org. Chem. 1993, 58, 999.
(19) Liu, P.; Panek, J. S. Tetrahedron Lett. 1998, 39, 6143.
(20) We are also aware of one example in which the stereoselectivity of
the Mukaiyama aldol reaction of a thioketene acetal and an aldehyde is
reversed when performed under nonchelate- vs chelate-controlled condi-
tions: Gennari, C.; Bernardi, A.; Scolastico, C.; Potenza, D. Tetrahedron
Lett. 1985, 26, 4129.
462
Org. Lett., Vol. 2, No. 4, 2000

performed using SnCl4 as the Lewis acid catalyst (Scheme
4). These reactions provided the 2,5-trans-tetrahydrofurans
Scheme 5
Scheme 4
and carbonyl electrophiles may be reversed as a function of
chelation vs nonchelation control.17-20 However, all of the
previous examples have involved substituted allylsilanes (of
the methallyl, (E)-crotyl, or tiglyl types), and the interpreta-
tions provided have assumed that the olefin substituents play
a role in the reversal in stereoselectivity.17,18,21 Our results,
all of which were obtained with allylsilanes lacking substit-
uents on the double bond, indicate that the reversal of
selectivity is much more fundamental in nature.22
Keck has provided compelling arguments that the syn-
synclinal transition state (i.e., transition states A and A′ in
Figure 1, in which the carbon bearing the silicon substituent
is syn to the carbonyl oxygen) are the lowest energy
transition states available in the BF3-catalyzed reactions of
(E)-crotylstannanes and aldehydes.21,23 We consider the
quadrant of space bearing the complexed Lewis acid to be
the most sterically demanding and therefore that the BF3‚Et2O-
promoted reactions should proceed preferentially via ts A.
In the case of the chelate-controlled reactions, the syn-
12-14 in 70-85% yields and with >20:1 selectivity. Similar
results were obtained in the reactions of allylsilanes 7 with
ethyl glyoxalate (see Scheme 4). The stereochemistry in all
cases was assigned by NOE experiments, as summarized for
the specific case of 14.
The chelate-controlled [3 + 2] annulation may also be
extended to electron deficient ketones, thereby providing
access to more highly substituted tetrahydrofurans containing
a quarternary center (Scheme 5). Thus, reactions of 5 and 6
with methyl pyruvate or 2,3-butanedione promoted by SnCl4
proceed in 53-76% yield, furnishing the 2,5-trans-substi-
tuted tetrahydrofurans 16, 17, and 18, again with excellent
diastereoselectivity.
The [3 + 2] annulation reaction proceeds via stepwise anti
SE′ addition12,13 of the allylsilane to the Lewis acid-
complexed aldehyde, followed by suparafacial 1,2-silyl
migration and intramolecular ether formation, with inversion
of the original C-Si stereocenter.14-16 Our demonstration
that the stereoselectivity of the [3 + 2] annulation can be
reversed by selection of Lewis acid catalysts that support
chelate- vs nonchelate-controlled addition is striking. Several
earlier papers have demonstrated that the diastereoselectivity
of Lewis acid-catalyzed reactions of substituted allylsilanes
(21) Keck, G. E.; Savin, K. A.; Cressman, E. N. K.; Abbott, D. E. J.
Org. Chem. 1994, 59, 7889.
(22) Although Panek has demonstrated a reversal of stereoselectivity in
the [3 + 2] cycloaddition of a chiral (E)-crotylsilane and a chiral aldehyde,
it must be noted that the stereochemical outcome in this case was highly
dependent on the relative stereochemistry of the chiral crotylsilane and the
chiral aldehyde. Thus, whereas the (2S,3R)-(E)-crotysilane and (S)-2-
benzyloxypropanal exibited a reversal of selectivity in reactions performed
with BF3 vs SnCl4 as catalysts, the reaction of the enantiomeric (2R,3S)-
(E)-crotysilane and (S)-2-benzyloxypropanal gave the same product with
either BF3 or SnCl4 as catalyst. See ref 15.
(23) Denmark, S. E.; Weber, E. J.; Wilson, T.; Willson, T. M.
Tetrahedron 1989, 45, 1053.
Org. Lett., Vol. 2, No. 4, 2000
463

Scheme 6
the analogous (Ipc)2allylborane], are useful precursors for
the synthesis of highly functionalized tetrahydrofurans via
[3 + 2] annulations with a second carbonyl component. This
methodology constitutes a general and highly convergent
route to tetrahydrofurans. We have demonstrated that the
stereochemistry of this annulation process can be controlled
by selection of the appropriate Lewis acid catalyst, so as to
produce either the 2,5-cis- or 2,5-trans-substituted tetrahy-
drofurans via nonchelate- and chelate-controlled pathways,
respectively. The observed stereodivergence is consistent
with the proposition that these annulations proceed by way
of syn-synclinal ts’s. We have shown that the silyl substituent
of the products can be converted to functionality (e.g., -OH
or -H) present in a range of tetrahydrofuran-containing
natural products. Finally, this work clearly illustrates the
potential of allylboronate 1 and the derived allylsilanes 2
for use in complex fragment assembly problems in organic
synthesis, extending the scope of this chemistry beyond
conventional allyl transfer reactions. Applications of this
methodology in total synthesis will be reported in due course.
Figure 1. Synclinal transition states leading to the 2,5-cis- and
2,5-trans-tetrahydrofurans.
synclinal ts B′ is viewed as the lowest energy pathway, since
this transition structure benefits from the most favorable
HOMO-LUMO interactions (as discussed by Keck).21 We
recognize that other transition structures could in principle
contribute to the production of the minor isomers from each
reaction (e.g., antiperiplanar arrangements), but defer a more
detailed discussion of this topic to a subsequent paper.
The dimethylphenylsilyl group is a well-known surrogate
for the hydroxyl group.24 Application of the Fleming-Tamao
oxidation to substrates such as 18 proceeds smoothly
(Scheme 6). It is also possible to remove the silyl substituent
altogether, giving tetrahydrofurans that are unsubstituted at
this position. This is smootly accomplished by using a
modified version of the Hudrlik procedure25 (TBAF, 5% KO-
t-Bu, 18-c-6, DMSO, H2O), as illustrated by the conversion
of 13 and 14 to tetrahydrofurans 20 and 21 in 69-84% yields
(Scheme 6).
Acknowledgment. Support provided by the National
Institutes of Health (GM 38436) is gratefully acknowledged.
We also thank Eli Lilly for a graduate fellowship to G.C.M.
In summary, we have demonstrated that chiral allylsilanes
of general structure 2, generated by the allylboration of
aldehydes with (E)-γ-(dimethylphenylsilyl)allylboronate 1 [or
Supporting Information Available: Experimental details
for the [3 + 2] annulations and tabulated spectroscopic data
for tetrahydrofurans 12-21. This material is available free
of charge via the Internet at http://pubs.acs.org.
(24) Jones, G. R.; Landais, Y. Tetrahedron 1996, 52, 7599.
(25) (a) Hudrlik, P. F.; Holmes, P. E.; Hudrlik, A. M. Tetrahedron Lett.
1988, 29, 6395. (b) Hudrlik, P. F.; Hudrlik, A. M.; Kulkarni, A. K. J. Am.
Chem. Soc. 1982, 104, 6809.
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