Phosphine effects in the copper(I) hydride-catalyzed hydrogenation of ketones and regioselective 1,2-reduction of α,β-unsaturated ketones and aldehydes. Hydrogenation of decalin and steroidal ketones and enones

Article abstract of DOI:10.1016/S0040-4020(00)00133-2

The stereoselectivity and regioselectivity of the catalytic hydrogenation of ketones and α,β-unsaturated ketones and aldehydes using soluble copper(I) hydride catalysts have been investigated as a function of the ancillary phosphine ligand. While a relatively narrow range of aryldialkylphosphine ligands produce active hydrogenation catalysts, some ligands provide higher selectivity for 1,2-reduction of acyclic unsaturated carbonyl substrates than observed using the previously reported dimethylphenylphosphine-stabilized catalyst. The synthetic utility of this class of hydridic hydrogenation catalysts is illustrated by the hydrogenation of decalin and steroidal ketones and enones, the latter giving allylic alcohols with high selectivity. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00133-2

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 2789±2798
Phosphine Effects in the Copper(I) Hydride-Catalyzed
Hydrogenation of Ketones and Regioselective 1,2-Reduction of
a,b-Unsaturated Ketones and Aldehydes. Hydrogenation of
Decalin and Steroidal Ketones and Enones
*
Jian-Xin Chen, John F. Daeuble and Jeffrey M. Stryker
Department of Chemistry, University of Alberta, Edmonton, Alberta T6G 2G2, Canada
Received 6 January 2000; revised 19 January 2000; accepted 20 January 2000
AbstractÐThe stereoselectivity and regioselectivity of the catalytic hydrogenation of ketones and a,b-unsaturated ketones and aldehydes
using soluble copper(I) hydride catalysts have been investigated as a function of the ancillary phosphine ligand. While a relatively narrow
range of aryldialkylphosphine ligands produce active hydrogenation catalysts, some ligands provide higher selectivity for 1,2-reduction of
acyclic unsaturated carbonyl substrates than observed using the previously reported dimethylphenylphosphine-stabilized catalyst. The
synthetic utility of this class of hydridic hydrogenation catalysts is illustrated by the hydrogenation of decalin and steroidal ketones and
enones, the latter giving allylic alcohols with high selectivity. q 2000 Elsevier Science Ltd. All rights reserved.
Introduction
The structure, reactivity and selectivity of copper(I) hydride
catalysts are a complex and subtle function of the ancillary
ligand.1,4 For the hydrogenation of isolated ketones, ef®cient
catalysts appear to be limited to complexes stabilized by
monodentate phosphine ligands, despite considerable effort
to identify alternative ligand systems.8 The dimethylphenyl-
phosphine-stabilized copper(I) hydride catalyst alone leads
to useful selectivity for 1,2-reduction of a,b-unsaturated
aldehydes and ketones to allylic alcohols. The complex
derived from the sterically and electronically similar
diethylphenylphosphine ligand, for example, is a very
poor catalyst for ketone hydrogenation, illustrating the
exceptional sensitivity of the catalyst to structural variation
in the ancillary ligand.
We recently reported that the dimethylphenylphosphine-
stabilized copper(I) hydride catalyst mediates the highly
chemoselective carbonyl hydrogenation of unsaturated
ketone and aldehydes, including the selective 1,2-reduction
of conjugated substrates (Eq. (1)).1±3 The catalyst is remark-
ably chemoselective, reducing ketones and aldehydes with-
out competitive hydrogenation or hydrogenolysis of
alkenes, alkynes, dienes, or benzyl ethers, all preferentially
reduced by standard hydrogenation catalysts. The regio-
selectivity for 1,2-reduction of a,b-unsaturated substrates
is complementary to that obtained from copper(I) hydride
catalysts derived from triarylphosphine ligands, which
mediate highly selective conjugate reduction4 and conjugate
hydrosilylation reactions.5 The latter have been recently
extended to include ef®cient catalytic asymmetric conjugate
reductions of a,b-unsaturated esters6 and tandem catalytic
conjugate reduction/alkylation and crossed aldol reactions.7
Despite the generally high regioselectivity observed in the
hydrogenation of acyclic substrates, the dimethylphenyl-
phosphine-derived catalyst delivers only modest selectivity
for 1,2-reduction of simple cyclohexenone derivatives.1b In
addition, dimethylphenylphosphine is achiral, providing
no basis for the development of an asymmetric hydro-
genation catalyst. In this report, the reactivity of
copper(I) catalysts derived from an expanded range of
monodentate dialkylarylphosphine ligands is described
for the reduction of isolated and conjugated ketones.
In addition, the selectivity of the dimethylphenyl-
phosphine-derived catalyst toward cyclohexanone and
cyclohexenone hydrogenation is further investigated for
the reduction of synthetically relevant bicyclic and steroidal
substrates.
ꢀ1†
Keywords: copper and compounds; hydrogenation; catalysis; carbonyl
compounds.
* Corresponding author. Tel.: 1780-492-3891; fax: 1780-492-8231;
e-mail: jeff.stryker@ualberta.ca
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00133-2

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J.-X. Chen et al. / Tetrahedron 56 (2000) 2789±2798
Table 1. Hydrogenation of 4-tert-butylcyclohexanone using dialkylarylphosphine-stabilized copper(I) hydride catalysts and hydrogen (conditions: 0.83 mol%
[(Ph3P)CuH]6, 6 equiv. R2PAr/Cu, 20±40 equiv. tBuOH/Cu, C6H6, 1 atm H2, RT. Details in the Experimental section)
Entry
Phosphine
Reaction time
Stereoselectivity (trans/cis)
Yield (%)a
11b
2
3
4
PhPMe2
PhP(Me)Et
PhP(CH2)4
PhP(Me)Cy
18
20
24
24
3:1
1:1
2.5:1
1:2
97
94
92
71c
b
a Yields refer to isolated puri®ed products, stereochemical assignments by comparison to authentic materials.
b Phenylphospholane.
c Conversion; remaining material is unconverted substrate (29%).
Results and Discussion
several observations are noteworthy. The catalyst derived
from ethylmethylphenylphosphine, sterically `halfway'
between the dimethylphenylphosphine and diethylphenyl-
phosphine ligands, is surprisingly effective, although
unselective stereochemically (entry 2). Constraining the
ethyl groups of diethylphenylphosphine into cyclic form is
also effective: the phenylphospholane [1-(phenyl)phos-
phacyclopentane] ligand also provides a functional catalyst,
although the rate of the reduction is signi®cantly attenuated
(entry 3). While no catalyst gave higher stereoselectivity
for axial hydride addition than that obtained from
dimethylphenylphosphine (entry 1),10 the catalyst
derived from the sterically larger cyclohexylmethyl-
phenylphosphine ligand provides inverted stereoselec-
tivity, leading to preferential equatorial addition of the
hydride (entry 3).
Catalytic ketone hydrogenation mediated by dialkyl-
arylphosphine copper(I) hydride derivatives
To assess the dramatic differences in the reactivity of the
dimethylphenylphosphine and diethylphenylphosphine
catalysts, the reactivity of three analogous dialkylphenyl-
phosphine ligands was investigated for the reduction of
the conformationally unambiguous and sterically unbiased
substrate 4-tert-butylcyclohexanone (Table 1). The catalysts
were prepared in situ by phosphine exchange starting with
the commercially available triphenylphosphine complex,
[(Ph3P)CuH]6,9 and the hydrogenation reactions were
conducted at atmospheric pressure. While none of the phos-
phine ligands provided signi®cantly enhanced performance,
Table 2. Hydrogenation of a,b-unsaturated ketones using phosphine-stabilized copper(I) hydride catalysts and hydrogen (conditions: 0.83 mol%
[(Ph3P)CuH]6, 6 equiv. R2PAr/Cu, 40 equiv. tBuOH/Cu, C6H6, 500 psi H2, RT. Details in the Experimental section)
Entry
Phosphine
Reaction time
Regioselectivitya
Yield (%)b
c
1
nBu3P
PhPMe2
PhP(Me)Et
PhP(CH2)4
PhP(Me)Cy
18
26
21
21
24
4:1
49:1
.50:1
19:1
20:1
21b
3
97
95
84
87
d
4
5
6
nBu3P
PhPMe2
PhPMe2
PhP(Me)Et
PhP(CH2)4
PhP(Me)Cy
18
30
25
20
20
24
1 (3:1)e:5 (1:1)
2.7 (12:1):1f
4.4 (12:1):1f
3 (7.3:1):1f
1f:2f
85
90
92
71b
81b
9
g
89
d
c
10
11
3 (4.9:1):1f
88
a Products identi®ed by comparison to authentic materials prepared by unambiguous synthesis. See Experimental section.
b Isolated yield after puri®cation by chromatography.
c Complete conversion; isolated yield not determined.
d Phenylphospholane.
e Major allylic alcohol stereoisomer as indicated; minor isomer epimeric at hydroxyl center.
f Stereochemical ratio not determined.
g Catalyst derived from CuCl (5 mol%) and NaOtBu (5 mol%) in the presence of Me2PPh (6 equiv./Cu).

J.-X. Chen et al. / Tetrahedron 56 (2000) 2789±2798
2791
Catalytic hydrogenation of a,b-unsaturated ketones and
aldehydes using dialkylarylphosphine copper(I) hydride
derivatives
phosphine catalyst, a result not easily reconciled with the
low selectivity obtained in the reduction of a,b-unsaturated
ketones using this catalyst.
Two further dialkylarylphosphine ligands were evaluated,
both previously unreported monodentate axially chiral
binaphthyl derivatives analogous to Hayashi's `MOP'
ligands.12 The compounds were prepared by palladium-
catalyzed monophosphinylation of the (racemic) 2,20-
bis(tri¯uoromethanesulfonyloxy)-1,10-binaphthyl (1) under
modi®ed conditions, which gives a mixture of the 20-hydrox-
ylated dimethylphosphinyl derivative 2 and the deoxy-
genated dimethylphosphinyl compound 3 after basic
hydrolysis. After separation by chromatography, deoxy-
genation under standard conditions gave the air-sensitive
2-(dimethylphosphino)-1,10-binaphthyl ligands 4 and 5 in
good yields. Inexplicably, however, copper(I) hydride
complexes of neither ligand function as hydrogenation
catalysts for ketone reduction (Scheme 1).
To compare the regioselectivity of dialkylphenylphosphine
catalysts for the reduction of a,b-unsaturated ketones, the
hydrogenation of one acyclic and one cyclic substrate was
evaluated under standard conditions1b (ambient tempera-
ture, 500 psi H2). The reduction of b-ionone proceeds
with high regioselectivity for all three phosphines (Table
2, entries 3±5), although only the ethylmethylphenyl-
phosphine-derived catalyst (entry 3) provides improved
selectivity over the dimethylphenylphosphine catalyst
(entry 2). For comparison, the catalyst derived from tri-n-
butylphosphine (entry 1) provides only a 4:1 ratio favoring
the 1,2-reduction product and the use of stoichiometric
[(Ph3P)CuH]6 leads, as expected, to exclusive conjugate
reduction.11
As anticipated, the regioselectivity obtained in the hydro-
genation of 3,5-dimethylcyclohexenone was notably
attenuated. While both ethylmethylphenylphosphine (entry
9) and cyclohexylmethylphenylphosphine (entry 11)
provide regioselectivity equivalent to that obtained from
dimethylphenylphosphine (entry 7), the phenylphospholane
ligand surprisingly favors conjugate reduction (entry 10),
although not to the same extent as the tri-n-butylphosphine
catalyst (entry 6) or [(Ph3P)CuH]6 itself, which provides
complete selectivity.4 As observed for the hydrogenation
of tert-butylcyclohexanone, the dimethylphenylphosphine-
derived catalyst is the most stereoselective, again favoring
pseudo-axial delivery of the hydride. In contrast to the
dimethylphenylphosphine catalyst (cf. entry 8), no further
improvement in regioselectivity is obtained using catalyst
formulations free of residual triphenylphosphine.1b For the
reduction of unsaturated aldehydes (Table 3), the selectivity
of the phenylphospholane-derived catalyst exceeds the
already high selectivity obtained from the dimethylphenyl-
Catalytic reduction of cyclohexanone and cyclohexenone
substrates. Hydrogenation of decalin and steroidal
derivatives
The relatively modest stereoselectivity and regioselectivity
obtained in the reduction of sterically unbiased cyclo-
hexanone and cyclohexenone substrates prompted further
investigation. Using the catalyst derived from dimethyl-
phenylphosphine, the hydrogenation of a series of trans-
and cis-fused decalin and steroidal ketones was evaluated
(Table 4). Greater stereoselectivity is observed in the hydro-
genation of trans-fused substrates (entries 1±3), with the
major products resulting from preferential axial hydride
addition to the conformationally de®ned ring systems.13 In
the cis-fused series, reduction of the decalone system (entry
4) proceeds with poor selectivity and unexpectedly returns
the b-hydroxydecalin as the major product, in contrast to the
preferential formation of the a-hydroxy epimer from both
Table 3. Hydrogenation of a,b-unsaturated aldehydes using phosphine-stabilized copper(I) hydride catalysts and hydrogen (conditions: 0.83 mol%
[(Ph3P)CuH]6, 6 equiv. R2PAr/Cu, 40 equiv. tBuOH/Cu, C6H6, 500 psi H2, RT. Details in the Experimental section)
Entry
Phosphine
Reaction time
Regioselectivitya
Yield (%)b
11b
2
PhPMe2
PhP(CH2)4
18
18
32:1c
38:1c
95
83
d
31b
4
PhPMe2
PhP(CH2)4
4
18
32:1
80:1
94
89
d,e
a Products identi®ed by comparison to authentic materials prepared by unambiguous synthesis. See Experimental section.
b Isolated yield after puri®cation by chromatography.
c Stereochemical ratio not determined.
d Phenylphospholane.
e 70 psi H2.

2792
J.-X. Chen et al. / Tetrahedron 56 (2000) 2789±2798
Scheme 1.
Table 4. Catalytic reduction of decalin and steroidal ketones using Me2PPh-stabilized copper(I) hydride and hydrogen
aReaction conditions. A: 0.83 mol% [(Ph3P)CuH]6 (5 mol% Cu), PhPMe2 (8 equiv./Cu), 1 atm H2, C6H6 (0.4±0.8 M in substrate), tert-butanol (10±20 equiv./
Cu), RT. B: as A, except PhPMe2 (6 equiv./Cu). C: as A, except PhPMe2 (10 equiv./Cu).
bMajor product indicated; minor product is epimeric alcohol. Product ratio is given in parentheses.
cIsolated yields after puri®cation by chromatography. Products identi®ed by comparison with authentic materials prepared by unambiguous synthesis (see the
Experimental section).
d6% diols also isolate as a mixture of stereoisomers.

J.-X. Chen et al. / Tetrahedron 56 (2000) 2789±2798
2793
Scheme 2.
steroid substrates (entries 5, 6). Although this stereo-
chemical reversal is dif®cult to rationalize, we note that
the conformationally mobile decalone substrate preferen-
tially adopts the non-steroid conformation,14 based on the
equatorial disposition of the acetate methine hydrogen.15 In
this conformation, axial addition of the hydride leads to the
observed major product. A consistent preference for axial
hydride delivery also accounts for the major product
obtained from the cis-fused steroid substrates.16
hydrometallation of the B-ring ketone, followed by retro-
aldol fragmentation of the intermediate copper(I) alkoxide
complex. Subsequent aldol condensation and base-
catalyzed elimination provides the rearranged a,b-unsatu-
rated ketone, which then undergoes highly selective 1,2-
reduction to give the observed product (Scheme 3). This
mechanistic rationale is supported by the isolation of the
known hydroxy enone 1317 from reductions run to partial
conversion.
Catalytic hydrogenation of the cis-fused diketone 6
(Scheme 2) leads to the isolation of the stereoisomeric
diols 7 and 8 in high yield, the product of highly stereo-
selective reduction of the B-ring ketone, but nonselective
reduction in the A-ring. To determine the relative rates of
hydrogenation of the two carbonyl groups, partial reduction
was obtained by using a lower catalyst loading and shorter
reaction time, providing a high yield of the isomeric
ketoalcohols 9 and 10 in a 3:1 ratio favoring reduction of
the A-ring ketone.
The catalytic hydrogenation of 4-cholesten-3-one 14, in
contrast, proceeds as anticipated to give a mixture of four
products, two allylic alcohol stereoisomers 15 and two
stereoisomeric saturated alcohols 16 (Eq. (2)). The reaction
is substantially more regioselective than corresponding
reductions of simple cyclohexenone substrates, promoting
1,2-reduction over conjugate reduction by a factor of 10:1.
Finally, the regioselectivity of the hydrogenation of poly-
cyclic a,b-unsaturated ketones was evaluated. The reduc-
tion of the Wieland±Miescher ketone 11, however, was
accompanied by molecular rearrangement, providing the
unexpected alcohol 12 exclusively in high yield (Scheme
3). The structure of the product was unambiguously
determined by one- and two-dimensional NMR spectro-
scopic analysis (Experimental section). The rearrange-
ment is readily rationalized by proposing kinetic
ꢀ2†
Scheme 3.

2794
J.-X. Chen et al. / Tetrahedron 56 (2000) 2789±2798
Conclusions
NaBH4/CeCl3 in methanol.26 Fully reduced alcohols were
prepared by catalytic hydrogenation of the allylic alcohols
using Pd/C and H2 (1 atm)27 or, in the case of a,b-unsatu-
rated aldehydes, by reduction using stoichiometric
[(Ph3P)CuH]6 (0.4±0.5 equiv.).28
An expanded range of copper(I) catalysts has been devel-
oped for the chemoselective hydrogenation of isolated
ketones and for the dif®cult problem of regioselective
catalytic 1,2-reduction of a,b-unsaturated aldehydes and
ketones. While a number of structurally similar dialkyl-
arylphosphine ligands can be used, the catalyst derived
from dimethylphenylphosphine combines useful levels of
selectivity with the convenience of using a commercially
available phosphine ligand. The catalyst can be generated
in situ either by phosphine exchange from the thermally
stable [(Ph3P)CuH]6 or, less expensively, by direct synthesis
from copper(I) chloride, sodium tert-butoxide, and the
phosphine under hydrogen.1b
General procedure for reduction of saturated ketones
using [(Ph3P)CuH]6 and tertiary phosphine
In the glove box, [(Ph3P)CuH]6 (5 mol% Cu), the phosphine
(6 equiv./Cu) and tert-butanol (10±40 equiv./Cu) were
combined in a Schlenk ¯ask and dissolved in benzene. To
this solution was added a solution of the substrate
(20 equiv./Cu) in benzene (0.4±0.8 M in substrate). The
¯ask was sealed and placed under a slight positive pressure
of hydrogen after one freeze±pump±thaw degassing cycle.
The resulting yellow-orange homogeneous solution was
allowed to stir until complete by TLC analysis. The reaction
mixture was exposed to air, diluted with ether, and treated
with a small amount of silica gel. This mixture was stirred in
the air for $0.5 h prior to ®ltration, concentration in vacuo,
and puri®cation by ¯ash chromatography. When the polarity
of the product was similar to that of the residual phosphine,
the crude mixture was treated with sodium hypochlorite (5%
aqueous solution) and ®ltered through silica gel/MgSO4
prior to chromatography.
Experimental
General experimental
Unless otherwise noted, all manipulations were performed
under an inert atmosphere using standard Schlenk line or
glove box techniques (#5 ppm O2). Reactions run under
hydrogen pressure were performed in a magnetically stirred,
glass-lined, Parr stainless steel autoclave (75±1500 psi)
equipped with Swagelok Quick-connects and pressure
gauges. All solvents, reagents and commercial substrates
were puri®ed by standard methods. Toluene, benzene,
diethyl ether, hexanes, pentane and tetrahydrofuran were
dried and deoxygenated by distillation from sodium or
potassium benzophenone ketyl. Product puri®cations were
performed by ¯ash chromatography18 using E. Merck
Kieselgel 60, 230±400 mesh.
Reduction of 4-tert-butylcyclohexanone; ethylmethyl-
phenylphosphine (Table 1, entry 2). Using the general
procedure, 4-tert-butylcyclohexanone (49 mg, 0.32 mmol),
[(Ph3P)CuH]6 (5.2 mg, 0.0027 mmol), tert-butanol
(0.048 g, 0.65 mmol), and ethylmethylphenylphosphine
(15 mg, 0.098 mmol) were combined and hydrogenated
(1 atm) for 20 h, giving 4-tert-butylcyclohexanol
(47 mg, 94%, 1:1 trans:cis) after ¯ash chromatography.
The products were identi®ed by comparison to commer-
cial samples.
Materials
tert-Butanol was distilled from sodium, deaerated and
stored under N2. [(Ph3P)CuH]6,9c 1-Phenylphospholane,19
ethylmethylphenylphosphine,20 cyclohexylmethylphenyl-
Reduction of 4-tert-butylcyclohexanone; 1-phenylphos-
pholane (Table 1, entry 3). Using the general procedure,
4-tert-butylcyclohexanone (49 mg, 0.32 mmol), [(Ph3P)CuH]6
(5.2 mg, 0.0027 mmol), tert-butanol (48 mg, 0.65 mmol), and
1-phenylphospholane (16 mg, 0.097 mmol) were combined
and hydrogenated (1 atm) for 24 h, giving 4-tert-butylcyclo-
hexanol (46 mg, 92%, 2.5:1 trans:cis).
phosphine,20
2,20-bis(tri¯uoromethanesulfonyloxy)-1,10-
binaphthyl,12 5a-androstane-3,17-dione (Table 4, entry 2),21
5a-cholestane-3-one (Table 4, entry 3),22 1b-acetoxy-8ab-
methyl-1,2,3,4,4ab,5,8,8a-octahydronaphthalene-6(7H)-one
(Table 4, entry 4),23 5b-androstane-3,17-dione (Table 4,
entry 5),24 5b-cholestane-3-one (Table 4, entry 6),22 and
8ab-methyl-3,4,4ab,5,8,8a-hexahydronaphthalene-1,6(2H,
7H)-dione (6)25 were prepared according to previously
published procedures. Cinnamaldehyde, perillaldehyde,
b-ionone, 4-tert-butylcyclohexanone, 3,5-dimethyl-2-
cyclohexenone, 3,4,8,8a-tetrahydro-8a-methyl-1,6(2H,7H)-
naphthalenedione (Wieland±Miescher ketone, 11), 4-
androstene-3,17-dione, and (1)-4-cholesten-3-one (14)
were purchased from commercial suppliers.
Reduction of 4-tert-butylcyclohexanone; cyclohexyl-
methylphenylphosphine (Table 1, entry 4). Using the
general procedure, 4-tert-butylcyclohexanone (49 mg,
0.32 mmol), [(Ph3P)CuH]6 (5.2 mg, 0.0027 mmol), tert-
butanol (48 mg, 0.65 mmol), and cyclohexylmethylphenyl-
phosphine (20 mg, 0.097 mmol) were combined and
hydrogenated (1 atm) for 24 h, giving starting material
(29%) and 4-tert-butylcyclohexanol (34 mg, 70%, 1:2
trans:cis).
Product identi®cation
Reduction of 5a-androstane-3,17-dione (Table 4, entry
2). Using the general procedure, 5a-androstane-3,17-
dione (75 mg, 0.26 mmol), [(Ph3P)CuH]6 (4.2 mg,
0.0021 mmol), tert-butanol (9.6 mg, 0.13 mmol), and
dimethylphenylphosphine (13 mg, 0.078 mmol) were
combined and hydrogenated (1 atm) for 24 h, giving an
inseparable mixture of 3b-hydroxy-5a-androstan-17-one21
Reaction products were identi®ed spectroscopically and
compared to authentic materials prepared by unambiguous
synthesis. Isolated alcohols were prepared by standard
ketone reduction using NaBH4 in methanol or LiAlH4 in
diethyl ether. Allylic alcohols were prepared from a,b-
unsaturated aldehydes and ketones by treatment with

J.-X. Chen et al. / Tetrahedron 56 (2000) 2789±2798
2795
1
hexanes/EtOAc); Partial H NMR (500 MHz, CDCl3) d
3.63 (overlapping multiplets), 0.93 (s), 0.72 (s).
and 3a-hydroxy-5a-androstan-17-one21 (70 mg, 93%, 3b/
3aˆ6:1) after ¯ash chromatography (2:1 hexanes/EtOAc).
Reduction of 5a-cholestane-3-one (Table 4, entry 3).
Using the general procedure, 5a-cholestane-3-one (75 mg,
0.19 mmol), [(Ph3P)CuH]6 (3.2 mg, 0.0016 mmol), tert-
butanol (7.2 mg, 0.097 mmol), and dimethylphenyl-
phosphine (8.0 mg, 0.058 mmol) were combined and hydro-
genated (1 atm) for 28 h, giving a mixture of 3b-hydroxy-
5a-cholestanol22 and 3a-hydroxy-5a-cholestanol22 (75 mg,
100%, 3b/3aˆ5:1) after ¯ash chromatography (5:1
hexanes/EtOAc).
Reduction of 5b-cholestane-3-one (Table 4, entry 6).
Using the general procedure, 5b-cholestane-3-one (75 mg,
0.19 mmol), [(Ph3P)CuH]6 (3.2 mg, 0.0016 mmol), tert-
butanol (7.2 mg, 0.097 mmol), and dimethylphenyl-
phosphine (8.0 mg, 0.058 mmol) were combined and hydro-
genated (1 atm) for 24 h, giving an inseparable mixture of
3a-hydroxy-5b-cholestanol22 and 3b-hydroxy-5b-cholesta-
nol22 (75 mg, 100%, 3a/3bˆ3.5:1) after ¯ash chromato-
1
graphy (10:1 hexanes/EtOAc). Major 3a-isomer: H NMR
(500 MHz, CDCl3, partial data only) d 3.62 (1H, tt, Jˆ4.7,
1
11.0 Hz). Minor 3b-isomer: H NMR (500 MHz, CDCl3,
partial data only) d 4.10 (1H, bm).
Reduction of 1b-acetoxy-8ab-methyl-1,2,3,4,4ab,5,8,8a-
octahydronaphthalene-6(7H)-one (Table 4, entry 4).
Using the general procedure, 1b-acetoxy-8ab-methyl-
1,2,3,4,4ab,5,8,8a-octahydronaphthalene-6(7H)-one (38 mg,
0.17 mmol), [(Ph3P)CuH]6 (2.8 mg, 0.0014 mmol), tert-buta-
nol (13 mg, 0.17 mmol), and dimethylphenylphosphine
(14 mg, 0.102 mmol) were combined and hydrogenated
(1 atm) for 48 h, giving 1b-acetoxy-6b-hydroxy-8ab-
methyl-1,2,3,4,4ab,5,6,7,8,8a-decahydronaphthalene (20 mg,
53%) and 1b-acetoxy-6a-hydroxy-8ab-methyl-1,2,3,4,
4ab,5,6,7,8,8a-decahydronaphthalene (11 mg, 29%) after
separation by ¯ash chromatography (5:1 hexanes/EtOAc).
Major 6b-isomer: TLC Rfˆ0.33 (1:1 hexanes/EtOAc); IR
(CHCl3, cm21) 3620, 3450, 2940, 2870, 1725, 1470, 1445,
1375, 1260, 1175, 1130; 1H NMR (500 MHz, CDCl3) d 5.00
(1H, bs), 4.04 (1H, bs), 2.04 (3H, s), 1.89 (1H, m), 1.84±
1.64 (4H, m), 1.63±1.20 (9H, m), 1.01 (3H, s); 13C{1H}
NMR (125 MHz, CDCl3) d 170.8, 66.7, 36.6, 36.3, 34.5,
29.7, 28.5, 26.9, 26.6, 21.9, 21.2, 20.2. HRMS (CI) calcd
for C13H23O3ˆ227.1648 (M111), foundˆ227.1664; Minor
6a-isomer: TLC Rfˆ0.29, (1:1 hexanes/EtOAc); mpˆ105±
1078C; IR (CHCl3, cm21) 3610, 3450, 2940, 2870, 1725,
Reduction of 8ab-methyl-3,4,4ab,5,8,8a-hexahydro-
naphthalene-1,6 (2H,7H)-dione (6). Using the general
procedure, 8ab-methyl-3,4,4ab,5,8,8a-hexahydronaphtha-
lene-1,6 (2H,7H)-dione (50 mg, 0.27 mmol), [(Ph3P)CuH]6
(9.1 mg, 0.0046 mmol), tert-butanol (4.1 mg, 0.56 mmol),
and dimethylphenylphosphine (46 mg, 0.33 mmol) were
combined and hydrogenated (1 atm) for 48 h, giving 1a,
6a-dihydroxy-8ab-methyl-1,2,3,4,4ab,5,6,7,8a-decahydro-
naphthalene30 7 (28.5 mg, 57%) and 1a,6b-dihydroxy-8ab-
methyl-1,2,3,4,4ab,5,6,7,8a-decahydronaphthalene30 8 (17.5
mg, 35%) after separation by ¯ash chromatography (2:1
hexanes/EtOAc). Major 6a-isomer 7: TLC Rfˆ0.18 (1:1
hexanes/EtOAc); mpˆ108±1108C; IR (CDCl3, cm21
)
3610, 2980, 2930, 2860, 1465, 1380, 1090, 1030, 1010;
1H NMR (500 MHz, CDCl3) d 4.00 (1H, bs), 3.34 (1H,
dd, Jˆ2.9, 10.0 Hz), 1.97±1.67 (7H, m), 1.63±1.42 (3H,
m), 1.37±1.27 (3H, m), 1.26±1.17 (2H, m), 1.05 (3H, s);
Difference NOE spectrum (400 MHz, CDCl3): Irr. at d 3.34
(C1-methine) $ d 1.05 (1.8%, 8a-methyl), Irr. at 1.05 $ d
3.34 (7.8%); 13C{1H} NMR (125 MHz, CDCl3) d 79.1,
67.8, 39.9, 37.7, 34.7, 30.7, 29.8, 29.7, 23.9, 22.9, 22.8;
HRMS (CI) calcd for C11H21O2ˆ185.1542 (M111),
foundˆ185.1523. Minor 6b-isomer 8: TLC Rfˆ0.12 (1:1
1
1470, 1445, 1375, 1260, 1070, 1050, 1030, 970; H NMR
(500 MHz, CDCl3) d 5.21 (1H, dd, Jˆ5.0, 10.7 Hz), 3.61
(1H, tt, Jˆ4.4, 10.8 Hz), 2.03 (3H, s), 1.85±1.45 (10H, m),
1.43 (1H, bs), 1.25 (2H, m), 1.04 (1H, dt, Jˆ3.8, 14.0 Hz),
0.99 (3H, s); 13C{1H} NMR (125 MHz, CDCl3) d 170.8,
71.3, 70.9, 41.9, 36.6, 36.0, 31.0, 29.7, 27.4, 26.6, 21.6,
21.2, 20.3; HRMS (CI) calcd for C13H23O3ˆ227.1648
(M111), foundˆ227.1636.
hexanes/EtOAc); mpˆ158±1608C; IR (CDCl3, cm21
)
3620, 2990, 2930, 2860, 1470, 1380, 1250, 1100, 1050;
1H NMR (500 MHz, CDCl3) d 3.86 (1H, apparent septet
(tt), Jobservedˆ5.0 Hz), 3.36 (1H, dd, Jˆ4.3, 11.6 Hz), 1.89
(1H, m), 1.75±1.23 (14H, m), 1.16 (3H, s); 13C{1H}
NMR (100 MHz, CDCl3) d 79.9, 67.3, 41.9, 37.7, 36.5,
31.2, 30.2, 28.1, 24.3, 23.5, 22.6; HRMS (CI) calcd for
C11H21O2ˆ185.1542 (M111), foundˆ 185.1556.
Reduction of 5b-androstane-3,17-dione (Table 4, entry
5). Using the general procedure, 5a-androstane-3,17-dione
(0.065 g, 0.23 mmol), [(Ph3P)CuH]6 (0.0037 g, 0.0019
mmol), tert-butanol (0.010 g, 0.14 mmol), and dimethyl-
phenylphosphine (0.016 g, 0.11 mmol) were combined
and hydrogenated (1 atm) for 30 h, giving 3a-hydroxy-5b-
androstane-17-one29 (0.040 g, 61%), 3b-hydroxy-5b-andro-
stan-17-one29 (0.016 g, 24%), and 5b-androstane-3,17b-
diol (3a/3b mixture, 0.004 g, 6%) after chromatography
(5:1 hexanes/EtOAc). Major 3a-isomer: TLC Rfˆ0.23, (1:1
hexanes/EtOAc); mpˆ148.0±150.08C, lit. mpˆ150.0±
151.08C; IR (CDCl3, cm21) 3600, 2930, 2880, 2860, 1730,
Partial reduction of 8ab-methyl-3,4,4ab,5,8,8a-hexa-
hydronaphthalene-1,6 (2H,7H)-dione (6). Using the
general procedure, 8ab-methyl-3,4,4ab,5,8,8a-hexahydro-
naphthalene-1,6 (2H,7H)-dione (50 mg, 0.27 mmol),
[(Ph3P)CuH]6 (4.5 mg, 0.0023 mmol), tert-butanol (21 mg,
0.28 mmol), and dimethylphenylphosphine (23 mg, 0.17
mmol) were combined and hydrogenated (1 atm) for 15 h,
giving a mixture containing 6-hydroxy-8ab-methyl-3,4,
4ab,5,6,7,8,8a-octahydronaphthalene-1(2H)-one30 9 (6a/
6bˆ1:1), 1a-hydroxy-8ab-methyl-1,2,3,4,4ab,5,8,8a-octa-
hydronaphthalene-6(7H)-one 10, and diols 7 and 8 (as a
mixture) in quantitative yield (51 mg, 100%, 9/10/
1
1445, 1045, 1025; Partial H NMR (500 MHz, CDCl3) d
3.64 (1H, tt, Jˆ4.7, 11.0 Hz), 0.95 (3H, s), 0.85 (3H, s).
Minor 3b-isomer: TLC Rfˆ0.33, (1:1 hexanes/EtOAc);
mpˆ150.5±152.08C, lit. mpˆ 151.0±152.08C; IR (CDCl3,
cm21) 3610, 2930, 2880, 2855, 1730,1445, 1045, 1025;
1
718ˆ69:23:8). Partial H NMR data (500 MHz, CDCl3) 9
1
Partial H NMR (500 MHz, CDCl3) d 4.11 (1H, bm), 0.98
(3H, s), 0.85 (3H, s). Trace diols: TLC Rfˆ0.16, (1:1
(6a): d 4.06 (quintet, Jˆ4.6 Hz); 9 (6b): d 3.60 (tt, Jˆ4.0,
11.2 Hz).

2796
J.-X. Chen et al. / Tetrahedron 56 (2000) 2789±2798
General procedure for reduction of a,b-unsaturated
ketones and aldehydes using [(Ph3P)CuH]6 and tertiary
phosphine
were combined and hydrogenated (500 psi) for 18 h, giving
an inseparable 1:5 mixture of the allylic alcohol (cis/
transˆ3:1) and saturated alcohol. The products were puri-
®ed by ¯ash chromatography and identi®ed by spectro-
scopic comparison to authentic samples; details have been
previously discussed.1b
In the glove box, [(Ph3P)CuH]6 (5 mol% Cu), Me2PPh
(6 equiv./Cu) and tert-butanol (40 equiv./Cu) were
dissolved in benzene. The substrate (20 equiv./Cu) was
added and the resulting solution was rapidly transferred to
a steel autoclave equipped with a stirbar (total volume: 0.4±
0.8 M in substrate). The apparatus was sealed and connected
to a tank of pre-puri®ed hydrogen. After pressurizing and
releasing several times to ¯ush the apparatus, the vessel was
charged to the desired pressure and stirred for the indicated
reaction time. After releasing the pressure, the contents were
exposed to air, stirred several minutes, and ®ltered through
celite. The solvent was removed in vacuo and the crude
Reduction of 3,5-dimethyl-2-cyclohexenone; ethylmethyl-
phenylphosphine (Table 2, entry 9). Using the general
procedure, 3,5-dimethyl-2-cyclohexenone (40 mg, 0.32
mmol), [(Ph3P)CuH]6 (5.3 mg, 0.0027 mmol), tert-butanol
(48 mg, 0.65 mmol), and ethylmethylphenylphosphine
(15 mg, 0.097 mmol) were combined and hydrogenated
(500 psi) for 20 h, giving a 3:1 mixture of the allylic alcohol
(cis/transˆ7.3:1) and saturated alcohol (36 mg, 90%) after
¯ash chromatography.
1
mixture analyzed by H NMR spectroscopy (integration at
Reduction of 3,5-dimethyl-2-cyclohexenone; 1-phenyl-
phospholane (Table 2, entry 10). Using the general proce-
dure, 3,5-dimethyl-2-cyclohexenone (40 mg, 0.32 mmol),
[(Ph3P)CuH]6 (5.3 mg, 0.0027 mmol), tert-butanol (48 mg,
0.65 mmol), and 1-phenylphospholane (16 mg, 0.097
mmol) were combined and hydrogenated (500 psi) for
20 h, giving complete conversion to a 1:2 ratio of the allylic
alcohol and saturated alcohol products.
long pulse delay) to determine product ratios. Puri®cation
and isolation of the product(s) was accomplished by ¯ash
chromatography on silica gel.
Reduction of b-ionone; tri-n-butylphosphine (Table 2,
entry 1). Using the general procedure, b-ionone (62 mg,
0.32 mmol), [(Ph3P)CuH]6 (5.3 mg, 0.0027 mmol), tert-
butanol (48 mg, 0.65 mmol), and tri-n-butylphosphine
(19 mg, 0.097 mmol) were combined and hydrogenated
(500 psi) for 18 h, giving complete conversion to a 3.9:1
mixture of the inseparable allylic alcohol and saturated
alcohol. The products were identi®ed by comparison to
authentic samples.1b
Reduction of 3,5-dimethyl-2-cyclohexenone; cyclohexyl-
methylphenylphosphine (Table 2, entry 11). Using the
general procedure, 3,5-dimethyl-2-cyclohexenone (40 mg,
0.32 mmol), [(Ph3P)CuH]6 (5.3 mg, 0.0027 mmol), tert-
butanol (48 mg, 0.65 mmol), and cyclohexylmethylphenyl-
phosphine (20 mg, 0.097 mmol) were combined and hydro-
genated (500 psi) for 21 h, giving a 3:1 mixture of the allylic
alcohol (cis/transˆ4.9:1) and saturated alcohols (35 mg,
88%) after ¯ash chromatography.
Reduction of b-ionone; ethylmethylphenylphosphine
(Table 2, entry 3). Using the general procedure, b-ionone
(62 mg, 0.32 mmol), [(Ph3P)CuH]6 (5.3 mg, 0.0027 mmol),
tert-butanol (48 mg, 0.65 mmol), and ethylmethylphenyl-
phosphine (15 mg, 0.097 mmol) were combined and hydro-
genated (500 psi) for 21 h, giving a .50:1 mixture of the
allylic alcohol and saturated alcohol (60 mg, 95%) after
¯ash chromatography.
Reduction of perillaldehyde; 1-phenylphospholane (Table
3, entry 2). Using the general procedure, (S)-(2)-perillalde-
hyde (49 mg, 0.32 mmol), [(Ph3P)CuH]6 (5.3 mg, 0.0027
mmol), tert-butanol (48 mg, 0.65 mmol) and 1-phenylphos-
pholane (16 mg, 0.097 mmol) were combined and hydro-
genated (500 psi) for 18 h, giving (S)-(2)-perillyl alcohol
and 1-hydroxymethyl-4-isopropenyl-1-cyclohexane31 in a
ratio of 38:1 (41 mg, 83%) after ¯ash chromatography.
Reduction of b-ionone; 1-phenylphospholane (Table 2,
entry 4). Using the general procedure, b-ionone (62 mg,
0.32 mmol), [(Ph3P)CuH]6 (5.3 mg, 0.0027 mmol), tert-
butanol (48 mg, 0.65 mmol), and 1-phenylphospholane
(16 mg, 0.097 mmol) were combined and hydrogenated
(500 psi) for 21 h, giving a 19:1 ratio of the allylic alcohol
and saturated alcohol products (53 mg, 84%) after ¯ash
chromatography.
Reduction of cinnamaldehyde; 1-phenylphospholane
(Table 3, entry 4). Using the general procedure, trans-cinnam-
aldehyde (43 mg, 0.32 mmol), [(Ph3P)CuH]6 (5.3 mg,
0.0027 mmol), tert-butanol (48 mg, 0.65 mmol) and
1-phenylphospholane (16 mg, 0.097 mmol) were combined
and hydrogenated (500 psi) for 18 h, giving cinnamyl
alcohol and 3-phenyl-1-propanol in a ratio of 80:1 (38 mg,
89%) after chromatography.
Reduction of b-ionone; cyclohexylmethylphenylphos-
phine (Table 2, entry 5). Using the general procedure,
b-ionone (62 mg, 0.32 mmol), [(Ph3P)CuH]6 (5.3 mg,
0.0027 mmol), tert-butanol (48 mg, 0.65 mmol), and cyclo-
hexylmethylphenylphosphine (20 mg, 0.097 mmol) were
combined and hydrogenated (500 psi) for 24 h, giving a
20:1 mixture of the allylic and saturated alcohols (55 mg,
87%) after puri®cation.
Reduction of Wieland±Miescher ketone (11). Using the
general procedure, Wieland±Miescher ketone (58 mg,
0.32 mmol), [(Ph3P)CuH]6 (5.3 mg, 0.0027 mmol), tert-
butanol (48 mg, 0.65 mmol) and dimethylphenylphosphine
(13 mg, 0.097 mmol) were combined and hydrogenated
(800 psi) for 18 h, giving 4-methyl-1,2,3,5,6,7-hexahydro-
naphthalen-1-ol 12 (44 mg, 82%) after ¯ash chromato-
graphy (4:1 hexanes/EtOAc). FTIR (KCl) 3100±3600 (br s),
2924 (s), 1644 (m), 1372 (m), 1357 (w), 1340 (w), 1163 (w),
Reduction of 3,5-dimethyl-2-cyclohexenone; tri-n-butyl-
phosphine (Table 2, entry 6). Using the general procedure,
3,5-dimethyl-2-cyclohexenone
(40 mg,
0.32 mmol),
[(Ph3P)CuH]6 (5.3 mg, 0.0027 mmol), tert-butanol (48 mg,
0.65 mmol), and tri-n-butylphosphine (19 mg, 0.097 mmol)

J.-X. Chen et al. / Tetrahedron 56 (2000) 2789±2798
2797
1093 (s), 1020 (w), 925 (w), 878 (w), 865 (w), 801 (w)
CDCl3) d 8.05 (m, 2H), 7.95 (m, 2H), 7.85 (m, 1H), 7.57
(m, 2H), 7.30 (m, obscured by solvent), 7.15 (m, 2H), 6.67
(m, 1H), 1.40 (m, 3H), 1.20 (m, 3H); 31P NMR (81 MHz,
CDCl3) d 47.2; HRMS calcd for C22H19O2P 346.11227,
found 346.11208. Data for 3: Rf 0.35 (CHCl3/MeOH
20:1); FTIR (KBr) 3439 (br w), 3053 (w), 1504 (w), 1383
(w), 1298 (w), 1176 (s), 1027 (w), 950 (s), 903 (m), 862 (m),
1
cm21; H NMR (300 MHz, CDCl3) d 5.71 (t, Jˆ4.0 Hz,
1H), 4.19 (t, Jˆ3.6 Hz, 1H), 2.30 (m, 3H), 2.15 (m, 3H),
1.80 (m, 2H), 1.70 (m, 6H); 13C{1H} NMR (75 MHz,
CDCl3, APT) d 137.5, 128.2, 125.4, 122.8, 70.2, 30.5,
28.6, 26.1, 25.5, 22.8, 19.0; INAPT (75 MHz, C6D6) irradi-
ate dˆ5.71$d 125.4, 70.1, 25.5, 22.8; irradiate dˆ4.19$d
137.4, 125.4, 122.8, 30.4, 28.6; HMQC (300 MHz, CDCl3,
selected data only) d 122.8$d 5.71; d 70.2$d 4.19;
HMBC (300 MHz, CDCl3, selected data only) d 4.19$d
137.4, 125.4, 122.8, 28.6; d 5.71$d 125.4, 70.1, 25.5, 22.8;
HRMS calcd m/z for C11H16O 164.12012, found 164.12120.
820 (m), 774 (m), 748 (m), 708 (m) cm21 1H NMR
;
(300 MHz, CDCl3) d 8.15 (m, 1H), 8.05 (m, 1H), 7.95 (m,
2H), 7.40±7.65 (m, 6H), 7.31 (m, 1H), 7.15 (m, 1H), 7.05
(m, 1H), 1.51 (d, Jˆ11.6 Hz, 3H), 1.00 (d, Jˆ11.6 Hz, 3H);
31P NMR (81 MHz, CDCl3) d 43.7; HRMS calcd for
C22H19OP 330.11734, found 330.11661.
Reduction of 4-cholesten-3-one (14). Using the general
procedure, 4-cholesten-3-one (62 mg, 0.16 mmol),
[(Ph3P)CuH]6 (2.7 mg, 0.0014 mmol), tert-butanol
(0.5 mL, excess used to solubilize the cholestenone) and
dimethylphenylphosphine (7.0 mg, 0.048 mmol) were
combined and hydrogenated (200 psi) for 22 h, giving an
inseparable 10:1 mixture of stereoisomeric 4-cholesten-3-
ols (3b/3aˆ6:1) and stereoisomeric cholestan-3-ols (3b/
3aˆ5:1) after ¯ash chromatography (59 mg, 95%). The
products were identi®ed spectroscopically by comparison
to authentic samples prepared by unambiguous synthe-
sis.22,32
2-Dimethylphosphino-20-methoxy-1,10-binaphthyl (4). To
a
solution of 2-dimethylphosphinyl-20-hydroxy-1,10-
binaphthyl 2 (0.346 g, 1.0 mmol) in acetone (15 mL) were
added potassium carbonate (0.552 g, 4.0 mmol) and methyl
iodide (0.568 g, 4 mmol). The resulting solution was heated
to re¯ux for 16 h, after which additional methyl iodide
(0.568 g, 4 mmol) was added to the reaction mixture.
After heating to re¯ux for an additional 8 h, the solution
was cooled to room temperature, ®ltered, and the residue
washed with diethyl ether (5 mL). The ether washes were
combined with the ®ltrate and concentrated in vacuo. The
residue was puri®ed by ¯ash chromatography (chloroform/
methanol 10:1) to afford 2-dimethylphosphinyl-20-
methoxy-1,10-binaphthyl (0.340 g, 94%) as a pale yellow
solid. Rf 0.6 (10:1 CHCl3/MeOH). To a cold (08C) solution
of this material (0.210 g, 0.58 mmol) and triethylamine
(1.172 g, 11.6 mmol) in xylenes (10 mL) was added
trichlorosilane (0.405 g, 3 mmol, 08C) dropwise. The result-
ing solution was warmed to room temperature, followed by
heating to 1208C for 2 h. After cooling, the reaction mixture
was diluted with diethyl ether (10 mL) and quenched with
5 mL saturated sodium bicarbonate. The resulting mixture
was ®ltered through celite and the organic layer was dried
over sodium sulfate. The solvent was evaporated in vacuo
and the residue puri®ed by ¯ash chromatography under a
nitrogen atmosphere (10:1 hexanes/ethyl acetate), giving
2-dimethylphosphino-20-methoxy-1,10-binaphthyl 4 (150 mg,
78%) as a white solid. Rf 0.4 (10:1 hexanes/ EtOAc); FTIR
(KBr) 3052 (w), 3004 (w), 2954 (w), 2932 (w), 2835 (w), 1620
(w), 1508 (s), 1414 (w), 1331 (s), 1215 (w), 1118 (s), 907 (m),
784 (s), 703 (s), 674 (w) cm21; 1H NMR (300 MHz, C6D6) d
7.70±7.85 (m, 5H), 7.45 (m, 1H), 7.18 (m, obscured by
solvent), 6.90±7.11 (m, 4H), 3.25 (s, 3H), 1.12 (d,
Jˆ3.7 Hz, 3H), 0.92 (d, Jˆ3.7 Hz, 3H); 31P NMR
(162 MHz, C6D6) d 255.3; HRMS calcd for C23H21OP
3344.13300, found 344.13277.
2-Dimethylphosphinyl-20-hydroxy-1,10-binaphthyl (2)
and 2-dimethylphosphinyl-1,10-binaphthyl (3). Into a
50 mL Schlenk ¯ask containing a stirbar were added 2,20-
bis-(tri¯uoromethanesulfonyloxy)-1,10-binaphthyl 1 (1.25 g,
2.26 mmol), DMSO (5 mL), dimethylphosphine oxide
(0.35 g, 4.52 mmol, prepared according to the literature33),
diisopropylethylamine (1.16 g, 9.04 mmol), and sodium
formate (31 mg, 0.46 mmol). Pd(OAc)2 (52 mg,
0.23 mmol), 1,3-bis(diphenylphosphino)propane (95 mg,
0.23 mmol), and DMSO (3 mL) were combined and trans-
ferred to the Schlenk ¯ask, rinsing with an additional
0.5 mL of DMSO. The reaction mixture was placed under
nitrogen, stirred, and heated to 90±1008C for 3 h. After
cooling, the solution was concentrated in vacuo and the
residue diluted with ethyl acetate (30 mL), washed with
water (3£40 mL) and brine, and dried over sodium sulfate.
The solvent was evaporated in vacuo and the residue puri-
®ed by ¯ash chromatography, giving a light yellow solid
(0.95 g), which consisted of two compounds by 31P NMR
spectroscopy (d 43.8 and 37.5). To this mixture (0.800 g),
dissolved in dioxane (10 mL) and methanol (5 mL), was
added an aqueous solution of NaOH (3N, 22.5 mL). The
resulting solution was stirred at room temperature for 8 h,
followed by heating to 808C for 2 h until complete by TLC
analysis. The solution was cooled to room temperature,
acidi®ed with concentrated HCl (to pH 1), and extracted
with several portions of ethyl acetate. The combined
extracts were dried over sodium sulfate and concentrated
in vacuo. The residue was puri®ed by ¯ash chromatography
(20:1 chloroform/methanol), to afford a mixture of 2-
dimethylphosphinyl-20-hydroxy-1,10-binaphthyl 2 (0.36 g)
as a white solid, along with 2-dimethylphosphinyl-1,10-
binaphthyl 3 (0.18 g) as a yellow solid (81% combined
yield). Data for 2: Rf 0.2 (CHCl3/MeOH 20:1); FTIR
(KBr) 2400±3400 (br s), 1622 (m), 1584 (w), 1502 (m),
1434 (m), 1365 (s), 1299 (m), 1275 (w), 1166 (s), 1066
2-Dimethylphosphino-20-methoxy-1,10-binaphthyl (5).
Using the procedure described above, 2-dimethylphos-
phinyl-1,10-binaphthyl 3 (0.150 g, 0.46 mmol), triethyl-
amine (0.919 g, 9 mmol), xylenes (10 mL), and
trichlorosilane (0.310 g, 2.3 mmol) were combined and the
resulting solution warmed to room temperature and then
heated at 1208C for 2 h. After work-up, 2-dimethyl-
phosphino-1,10-binaphthyl 5 was obtained as a pale yellow
solid (0.126 g, 88%). Rf 0.7 (10:1 hexanes/ethyl acetate);
FTIR (KBr) 3053 (m), 3006 (w), 2955 (m), 2925 (m),
2898 (m), 1591 (w), 1554 (w), 1414 (m), 1316 (m), 1232
(m), 1137 (m), 1042 (m), 962 (s), 703 (s), 673 (s) cm21; 1H
1
(w), 976 (s), 908 (s), 865 (s) cm21; H NMR (300 MHz,

2798
J.-X. Chen et al. / Tetrahedron 56 (2000) 2789±2798
(b) Original report: Bezman, S. A.; Churchill, M. R.; Osborn, J.
A.; Wormald, J. J. Am. Chem. Soc. 1971, 93, 2063. (c) To avoid the
variable quality of material provided by some commercial produ-
cers, the complex is best prepared rather than purchased. Benchtop,
One-Pot Preparation: Brestensky, D. M.; Huseland, D. E.;
McGettigan, C.; Stryker, J. M. Tetrahedron Lett. 1988, 29, 3749.
10. The catalyst derived from the marginally smaller trimethyl-
phosphine ligand was also effective, but gave an identical 3:1
selectivity for axial hydrogenation. The triethylphosphine-derived
catalyst provided poor turnover and was stereochemically
unselective.1a
NMR (360 MHz, C6D6) d 7.82 (m, 1H), 7.61±7.75 (m, 4H),
7.35 (m, 4H), 7.19 (m, 2H, obscured by solvent), 6.98 (m,
2H), 1.04 (d, Jˆ4.8 Hz, 3H), 0.83 (d, Jˆ4.8 Hz, 3H); 31P
NMR (162 MHz, C6D6) d 257.6; HRMS calcd for C22H19P
314.12244, found 314.12108.
Acknowledgements
Financial support from NSERC of Canada and the
University of Alberta is gratefully acknowledged, as is the
generous assistance of Prof. Bruce Lipshutz (University of
California, Santa Barbara).
11. Daeuble, J. F. Ph.D. dissertation, Indiana University, 1993.
12. Uozumi, Y.; Tanahashi, A.; Lee, S.-Y.; Hayashi, T. J. Org.
Chem. 1993, 58, 1945.
13. (a) The stereoselectivity in the trans-fused series is roughly
comparable to that obtained from reductions using NaBH4; see, for
example: (b) Lin, Y. Y.; Jones, J. B. J. Org. Chem. 1973, 38, 3575.
14. Browne, L. M.; Klinck, R. E.; Stothers, J. B. Org. Magn.
Reson. 1979, 12, 561. Kesselmans, R. P.; Wijnberg, J. B. P. A.;
de Groot, A.; de Vries, N. K. J. Org. Chem. 1991, 56, 7232.
15. The equatorial orientation is supported by the small vicinal
References
1. (a) Daeuble, J. F., Stryker, J. M. Catalysis of Organic
Reactions; Scaros, M. G., Prunier, M. L., Eds.; Marcel Dekker:
New York, 1995; pp 235±247 (Chem. Ind. 1995, 62). (b) Chen,
J.-X.; Daeuble, J. F.; Brestensky, D. M.; Stryker, J. M. Tetrahedron
(Symposium-in-Print, `Transition Metal Organometallics in
Organic Synthesis') 2000, 56, 2153±2166.
1
coupling constants observed in the 500 MHz H NMR spectrum
of this methine resonance (d 5.05, br s).
2. The ruthenium hydrogenation catalyst reported by Noyori et al.,
is also selective for the 1,2-reduction of unsaturated carbonyl
compounds, including asymmetric hydrogenation: Ohkuma, T.;
Ooka, H.; Ikariya, T.; Noyori, R. J. Am. Chem. Soc. 1995, 117,
10417.
16. The possibility that the stereoselectivity is affected by
reversible hydride insertion cannot be conclusively discounted;
however, no stereomutation of copper(I) cyclohexoxide inter-
mediates is observed in control experiments conducted with
other phosphine-stabilized catalysts.1b
3. For references to other catalysts for the chemoselective hydro-
genation and hydrosilylation of unsaturated carbonyl compounds,
see the citations provided in Ref. 1b.
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