yield, but with diminished enantioselectivity. The minor
regioisomer, on the other hand, is obtained with higher
levels of enantiomeric purity.7
Scheme 3. Synthesis of Sapinofuranone A
Scheme 2. Combination of RRRM with Enantioselective Di-
hydroxylation
phytotoxic fungus Sphaeropsis sapinea in 1999 by Evi-
dente and co-workers.9 Our approach to sapinofuranone
A begins with ozonolytic cleavage/oxidation10 of enan-
tiomerically enriched monosilyl diol (þ)-4 to furnish
lactone 6 (Scheme 3); the resulting sensitive R-siloxy
aldehyde is used directly in a Wittig olefination. After
optimization, we were able to obtain the desired diene in
78% yield and 2.4:1 Z/E selectivity for the newly formed
olefin. Subsequent removal of the silyl group with TBAF
delivers sapinofuranone A in 94% yield.
The present regiodivergent silylation strategy can be
applied to instances where an enantiomerically enriched
mixture of substrates, such as those illustrated in Scheme
2, are used as substrates; this process is referred to as a
regiodivergent reaction on an enantioenriched mixture
(RREM).8 The nonracemic diols (þ)-2 and (ꢀ)-2 were
prepared through the use of the complementary Sharp-
less enantioselective dihydroxylation involving AD-mix-
R and AD-mix-β with 1,3-cyclohexadiene. The Os-cata-
lyzed transformations thus provide the desired ene-diol
enantiomers in high yield, albeit in low enantiomeric
purity.4 This limitation can be addressed by employing
a second catalytic, enantioselective reaction performed
sequentially such that the final product is obtained in
higher levels of enantiopurity. For example, when the
asymmetric silylation of diol (þ)-2 is carried out with
catalyst 1, monosilyl ether (þ)-4 can be isolated in 64%
yield and 97% ee. If the same transformation is per-
formed with enantiomerically enriched (ꢀ)-2, silylated
allylic alcohol (þ)-5 is generated in 64% yield and 90%
ee. It is important to note that, although the idealized
case for RRRM can provide a maximum of 50% yield of
each product, performing the two aforementioned pro-
cesses serves to increase the theoretical yield of the
products 4 or 5 (since the starting diol 2 is enantiomeri-
cally enriched).
Scheme 4. Representative Application of RREM Products
In another demonstration of utility of the method, silyl
ether (ꢀ)-5 can be converted readily into γ-siloxy-β-
methylcyclohexenone 8 (Scheme 4), which has previously
found applications in enantioselective syntheses of nat-
ural products, such as the kinamycins11 and karahana
lactone.12 Formation of enantiomerically enriched 8 is
accomplished through allylic oxidation (PCC) of mono-
silyl ether (ꢀ)-5, generating R-siloxy ketone 7. Alkylation
of 7 (MeMgBr) affords a 2:1 mixture of diastereomers
that is subjected directly to another oxidation to furnish 8
in 70% yield (ee = 90%).
In summary, the present study demonstrates the en-
antioselective catalytic silylation of racemic diols that
offers access to enantiomerically enriched monosilylated
regioisomers. We also show, through combination
with catalytic enantioselective dihydroxylation in an
RREM process, that the theoretical yield and enantio-
purity of the products can be significantly enhanced.
Finally, the utility of the method is demonstrated through
The value of the approach outlined above is high-
lighted through the utilization of (þ)-4 in the first total
synthesis of sapinofuranone A. This butanolide natural
product was first isolated from the liquid cultures of the
(7) (a) Vigneron, J. P.; Dhaenes, M.; Horeau, A. Tetrahedron 1973,
29, 1055–1059. (b) Heller, G. Angew. Chem., Int. Ed. 2000, 39, 495–499.
€
(8) For related examples, see: (a) Gansauer, A.; Fan, C.-A.; Keller,
€
F.; Keil, J. J. Am. Chem. Soc. 2007, 129, 3484–3485. (b) Gansauer, A.;
(10) Claus, R. E.; Schreiber, S. L. Org. Synth. 1986, 64, 150–156.
(11) Nicolaou, K. C.; Li, H.; Nold, A. L.; Pappo, D.; Lenzen, A. J.
Am. Chem. Soc. 2007, 129, 10356–10357.
(12) Galano, J-.M.; Audran, G.; Monti, H. Tetrahedron 2000, 56,
7477–7481.
Lei, S.; Otte, M. J. Am. Chem. Soc. 2010, 132, 11858–11859.
(9) (a) Evidente, A.; Sparapano, L.; Fierro, O.; Bruno, G.; Motta, A.
J. Nat. Prod. 1999, 62, 253–256. (b) Cimino, P.; Bifulco, G.; Evidente, A.;
Abouzeid, M.; Riccio, R.; Gomez-Paloma, L. Org. Lett. 2002, 4, 2779–
2782.
3780
Org. Lett., Vol. 13, No. 15, 2011