Abstract
Titanium (IV) fluoride catalysts, prepared by the combination
of (R )-2,2′-binaphthol and TiF4 ,
are effective for promoting the homoaldol addition of 1-ethoxy-1-(trimethylsilyloxy)cyclopropane
to aldehydes. The reactions proceed with ee’s of up to
72% and are effective with a range of aldehyde substrates.
The reactions show greatly improved enantioselectivity when compared
to those catalyzed by titanium(IV) triflates. The increase in selectivity
is presumed to result from the elimination of deleterious silicon
co-catalysis.
Key words
homoenolates - homoaldol additions - asymmetric
catalysis - titanium(IV) fluorides
References
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6 A survey of other ligands, including
3,3′-disubstituted binaphthols, F8 -Binol and
TADDOL did not afford any increase in enantioselectivity.
7
Sample Experimental
Procedure . A solution of titanium(IV) fluoride (12 mg, 0.095
mmol, 0.1 equiv) in acetonitrile (1.5 mL) was added to a solution
of (R )-2,2′-binaphthol (56 mg,
0.195 mmol, 0.2 equiv) in acetonitrile (1.5 mL) in a flame dried
Schlenk flask. The resulting red mixture was stirred at 21 °C
for 1 h and then the solvent was removed in vacuo. The resulting
oil was redissolved in acetonitrile (1.5 mL), allyltrimethylsilane
(62 µL, 0.392 mmol, 0.4 equiv) was added and the resulting
solution was allowed to stir for 3 h during which time a precipitate
was observed to form. To this mixture was added 1-ethoxy-1-(trimethylsilyloxy)cyclopropane
(300 µL, 1.50 mmol, 1.5 equiv), and after 10 min, benzaldehyde
(100 µL, 0.99 mmol, 1 equiv) was added. This final solution
was continuously stirred over 4 days. The reaction was quenched
by addition of 1 M HCl (30 mL) and the products were extracted into ethyl
acetate (2 × 30 mL). The organic layer was washed once
with brine (30 mL), dried over Na2 SO4 , filtered
and concentrated. The crude reaction mixture was dissolved in benzene
(6 mL) and p -TsOH(cat) was added. The
reaction mixture was stirred overnight. The reaction was quenched
by addition of saturated NaHCO3 (30 mL) and the product
was extracted into ethyl acetate (2 × 30 mL). The organic
layer was washed once with brine (30 mL), dried over Na2 SO4 , filtered
and concentrated. Purification of the residue by column chromatography
on silica gel using 30 % hexanes in methylene chloride
as eluent afforded 128 mg of the lactone (66% yield, 72% ee). 1 H
NMR (CDCl3 ) δ 7.24-7.39 (m, 5 H), 5.46
(dd, 1 H, J = 7.9 Hz, 6.2 Hz),
2.54-2.67 (m, 3 H), 2.04-2.22 (m, 1 H); 13 C
NMR (CDCl3 ) δ 176.8, 139.2, 128.5, 125.1, 81.0,
30.7, 28.7. Anal. Calcd for C10 H10 O2 :
C, 74.06; H, 6.21. Found: C, 73.73; H, 6.02.