New chiral phosphorus catalysts derived from (S)-binaphthol for highly enantioselective reduction of acetophenone by borane

Article abstract of DOI:10.1016/S0957-4166(99)00323-7

New chiral (+)-2,2'-O,O-(1,1'-binaphthyl)-dioxo-N,N-diethylphospholidine 1 and its borane complex 3 were prepared from (S)-binaphthol and their use as catalysts in enantioselective borane reductions of prochiral acetophenone were investigated. Enantiomeri

Full text of DOI:10.1016/S0957-4166(99)00323-7

Pergamon
Tetrahedron: Asymmetry 10 (1999) 3259–3261
New chiral phosphorus catalysts derived from (S)-binaphthol for
highly enantioselective reduction of acetophenone by borane
Margaret F. P. Ma,a Kangying Li,a Zhenghong Zhou,a Chuchi Tang a,∗ and Albert S. C. Chan b
aInstitute of Elemento-Organic Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Nankai University,
Tianjin 300071, PR China
bDepartment of Applied Biology and Chemical Technology, the Hong Kong Polytechnic University, Hong Kong
Received 9 June 1999; accepted 29 July 1999
Abstract
New chiral (+)-2,20-O,O-(1,10-binaphthyl)-dioxo-N,N-diethylphospholidine 1 and its borane complex 3 were
prepared from (S)-binaphthol and their use as catalysts in enantioselective borane reductions of prochiral aceto-
phenone were investigated. Enantiomeric excesses of up to 98.5% have been obtained using 6 mol% of 1 at room
temperature and using 6 mol% of 3 at 100°C. © 1999 Elsevier Science Ltd. All rights reserved.
The asymmetric borane reduction of prochiral ketones to enantiomerically enriched alcohols is a
pivotal transformation in synthetic organic chemistry.1 Many asymmetric catalysts have been developed
for this asymmetric reaction. Oxazaborolidines strongly catalyze the reduction reaction and provide
alcohols with excellent enantioselectivity.2 Phosphinamide containing a N–P_O unit, which has been
reported by Wills,3 and tricoordinated phosphorus borane complexes, reported by Buono,4 are efficient
catalysts for the asymmetric reduction of ketones by borane. In addition, other researchers have reported
related catalysts that also give modest or excellent results.5 In this paper, we describe an optimized
catalyst 1 and a procedure for its use in asymmetric carbonyl reduction by borane. To the best of our
knowledge, these kinds of trivalent phosphorus compounds have rarely been utilized as chiral catalysts
in the asymmetric reduction of ketones. Chiral nonracemic tricoordinated phosphorus borane complex 3
was also investigated.
Chiral (+)-2,20-O,O-(1,10-binaphthyl)-dioxo-N,N-diethylphospholidine 1 (Scheme 1) was derived
from (S)-binaphthol and triethylaminophosphorus [triethylaminophosphorus was heated under reflux
with (S)-binaphthol until no further diethylamine could be detected in the nitrogen stream from the
reaction (1: [α]D +473.8 (c=0.34, chloroform); m.p. 205–220°C; prepared in 90% yield)]. Compound
1 contains a stereogenic trivalent phosphorus atom which can donate a lone pair of electrons and the C2
symmetry for the whole molecule, so it can efficiently catalyze the borane reduction and get the higher
enantiomeric excesses of up to 98.5%.
∗
Corresponding author. E-mail: yungming@public1.tpt.tj.cn
0957-4166/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(99)00323-7

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M. F. P. Ma et al. / Tetrahedron: Asymmetry 10 (1999) 3259–3261
Scheme 1.
Table 1
Enantioselective synthesis of 2 using chiral catalyst 16 (Scheme 2)
The use of a catalytic amount (6 mol%) of 1 in the enantioselective borane reduction of acetophenone
led to phenethyl alcohol with 98.5% enantiomeric excess (Table 1, entry 1). As the catalytic amount
increases (from 2 mol% to 6 mol%), the e.e. increases (from 79.5% to 98.5%). Table 1 shows that
compound 1 dramatically increases the reaction rate and asymmetric induction is very high.
We also prepared the tricoordinated phosphorus complex 3 from 1 (Scheme 1) [compound 1 and
1 equiv. of borane, reflux, 3 h, under nitrogen (3: [α]D +470 (c=0.40, chloroform); m.p. 144–146°C;
prepared in 98% yield)], as the chiral catalyst for the borane reduction of acetophenone (Scheme 2).
Scheme 2.
Table 2 shows that compound 3 dramatically increases the reaction rate and the asymmetric induction
is very high. Furthermore, it shows the effect of temperature. The enantiomeric excess of 2 was higher
(98.4%) at elevated temperatures (Table 2, entry 3) than that (81.1%) at room temperature (Table 2, entry
1).
With the same catalytic amount (6 mol%) and the same reaction temperature (25°C), the enantiomeric
Table 2
Enantioselective synthesis of 2 using chiral catalyst 36 (Scheme 2)

M. F. P. Ma et al. / Tetrahedron: Asymmetry 10 (1999) 3259–3261
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excess of 2 using catalyst 1 (Table 1, entry 1, 98.5%) was higher than that using catalyst 3 (Table 2, entry
1, 81.1%).
We suggested that the efficient catalytic activity and asymmetric induction of 1 and 3 could result from
the rigid C2 symmetry of the binaphthol unit and its ability to donate a lone pair of electrons.
As described, new chiral nonracemic compounds 1 and 38 derived from (S)-binaphthol are highly
enantioselective catalysts for the asymmetric reduction of acetophenone by borane. Further investigation
of the catalytic ability and the asymmetric induction in the enantioselective reductions of prochiral
ketones are still in progress and our findings will be reported in due course.
Acknowledgements
We are grateful to the National Natural Science Foundation (no. 29872016) for generous financial
support.
References
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6. Typical reduction experiment (Table 1, entry 1): 1 M BH3·THF (3 ml) was added to a toluene solution (5 ml) of
acetophenone (0.3 g, 2.5 mmol) and catalyst 1 (0.06 g, 0.15 mmol) under nitrogen steam at room temperature. The mixture
was then stirred for 1 h and 5 ml 2N hydrochloric acid was then added to the solution. The oil extract was dried (Na2SO4),
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(R)-(+)-2 with e.e. 98.5% was obtained in 95% yield.
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8. All new compounds were characterized by NMR (1H, 31P), IR and elemental analysis.