Catalytic enantioselective hydrosilylation of ketones with rhodium- phosphite complexes containing a TADDOLate and a dihydrooxazole unit

Article abstract of DOI:10.1002/(SICI)1522-2675(19990707)82:7<1096::AID-HLCA1096>3.0.CO;2-I

New types of chiral phosphorus/nitrogen ligands, capable of forming six- membered-ring metal chelates have been prepared from α,α,α',α'-tetraaryl- 1,2-dioxolane-4,5-dimethanols (TADDOLs), PCl₃, and dihydrooxazole alcohols (from amino acids) (7 in Scheme 1). The X-ray crystal structure of a Rh complex of one of these ligands, 8b, has been determined (Scheme 2 and Fig.). Enantioselective hydrosilylations of dialkyl and aryl alkyl ketones with Ph₂SiH₂/0.01 equiv. Rh¹·7 have been studied and found to provide secondary alcohols in enantiomer ratios of up to 97:3 (Scheme 3 and Table). The ligand prepared from (R,R)-TADDOL and the (R)-valine-derived (R)-α,α- dimethyl-4-isopropyl-4,5-dihydrooxazole-2-methanol gives better results than the (R,R,S)-isomer (7d vs. 7c in Scheme 3), and an i-Pr group on the 4,5- dihydrooxazole ring gives rise to a slightly better selectivity than a Ph group. With the (R,R,R)-ligands the hydrogen transfer occurs from the Re face of the oxo groups (Scheme 4).

Full text of DOI:10.1002/(SICI)1522-2675(19990707)82:7<1096::AID-HLCA1096>3.0.CO;2-I

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Helvetica Chimica Acta ± Vol. 82 (1999)
Catalytic Enantioselective Hydrosilylation of Ketones with Rhodium-
Phosphite Complexes Containing a TADDOLate and a Dihydrooxazole Unit
1
by Dieter K. Heldmann ) and Dieter Seebach*
Laboratorium für Organische Chemie der Eidgenössischen Technischen Hochschule, ETH-Zentrum,
Universitätstrasse 16, CH-8092 Zürich
New types of chiral phosphorus/nitrogen ligands, capable of forming six-membered-ring metal chelates
have been prepared from a,a,a',a'-tetraaryl-1,2-dioxolane-4,5-dimethanols (TADDOLs), PCl3, and dihy-
drooxazole alcohols (from amino acids) (7 in Scheme 1). The X-ray crystal structure of a Rh complex of one of
these ligands, 8b, has been determined (Scheme 2 and Fig.). Enantioselective hydrosilylations of dialkyl and aryl
alkyl ketones with Ph2SiH2/0.01 equiv. RhI ´ 7 have been studied and found to provide secondary alcohols in
enantiomer ratios of up to 97: 3 (Scheme 3 and Table). The ligand prepared from (R,R)-TADDOL and the (R)-
valine-derived (R)-a,a-dimethyl-4-isopropyl-4,5-dihydrooxazole-2-methanol gives better results than the
(R,R,S)-isomer (7d vs. 7c in Scheme 3), and an i-Pr group on the 4,5-dihydrooxazole ring gives rise to a
slightly better selectivity than a Ph group. With the (R,R,R)-ligands the hydrogen transfer occurs from the Re
face of the oxo groups (Scheme 4).
1. Introduction. ± Since we first described the use [1] and preparation [2] of a
a,a,a',a'-tetraaryl-1,2-dioxolane-4,5-dimethanol (TADDOL) 1, there have been nu-
merous applications of such ligands in stoichiometric, catalytic, and Lewis-acid-
mediated enantioselective reactions [3]. In the beginning, we focused mainly on the use
of the alkoxide oxygens for complexing polar metals such as alkali, alkaline-earth, and
early-transition metals, especially titanium. More recently, a considerable effort has
been undertaken to replace the OH groups of TADDOLs with other heteroatoms, such
as nitrogen and sulfur [4] [5], in order to effect coordination to late-transition metals
like copper. Thus, nitrogen- and sulfur-containing ligands have been successfully
applied in the copper-catalyzed addition of Grignard reagents to cyclic enones [6].
The preparation of cyclic monodentate phosphonites and phosphites, derived from
TADDOL, appeared to be a promising approach for creating chiral coordination
spheres for late-transition metals such as Rh or Pd. The preparation of the first
examples of this class of compounds 2 (R' ˆ aryl, aryloxy) and their application to RhI-
catalyzed enantioselective reactions have been described previously [7]. Also, the
combination with chiral alcohols and amines (R' in 2) led to ligands which were used in
conjugate additions of Et2Zn to a,b-unsaturated carbonyl compounds [8]. However, it
is well-known that enantioselective catalysis is generally more efficient with bidentate
than with monodentate ligands (for reviews, see [9]). Unfortunately, the C2-symmetric
bis(diphenylphosphinite) 3 of TADDOL was found to be unstable and could only be
characterized as the borane adduct or the PdCl2 complex [10]. The latter, on the other
1
)
Postdoctoral Fellowship, ETH Zürich, 1998/99, partially financed by Deutsche Forschungsgemeinschaft.

Helvetica Chimica Acta ± Vol. 82 (1999)
1097
hand, gave quite good enantioselectivities in 1,3-diphenylallylations of nucleophiles
[10]. Replacement of one or both of the TADDOL OH groups by PR2, to give a
TADDOL-based analog of 2,2'-bis(diphenylphosphanyl)-1,1'-binaphthalene (BINAP)
has so far not been achieved [11]2).
Following an approach chosen by Pfaltz and co-workers, who have developed a new
class of bidentate ligands 4 derived from 1,1'-binaphthalene-2,2'-diol (BINOL) and
chiral dihydrooxazole alcohols for Pd-catalyzed allylic substitutions and for conjugate
additions [13], we have now prepared analogous chelating P,N ligands from the much
cheaper TADDOL. In this paper, we describe, in full detail, the preparation and the
first successful application of this new type of ligands.
2. Synthesis of the Ligands derived from TADDOL and Chiral Dihydrooxazoles. ±
By the strategy described for the BINOL-derived ligands 4 [13], a number of
enantiomerically pure dihydrooxazole alcohols 6 were easily obtained via thermally
induced condensation of a chiral amino alcohol with 2-hydroxy-2-methylpropanoic
acid, followed by azeotropic removal of H2O formed [14]. The ligands 7 were then
prepared in a one-pot procedure, in which the first step involved addition of TADDOL
1 to a solution of PCl3 ( 308, 2 equiv. Et3N, CH2Cl2) to form the chloro phosphonite 5
(31P-NMR shift d 148 ppm), which, in turn, was combined in situ with the correspond-
ing dihydrooxazole alcohol 6 (in the presence of a fivefold excess of Et3N). The
phosphites 7 were obtained as colorless powders after aqueous workup and purification
by chromatography on silica gel. The pure samples are stable towards air and moisture
and can be stored in an O2-containing atmosphere. The preparation of 7 with Ph- and i-
Pr-substituted dihydrooxazoles is summarized in Scheme 1.
2
)
Attempts included: 1) tosylation of 1 with or without added AgNO3, followed by treatment with HPEt2 or
LiPR2; 2) replacement of the OH group in 1 with halogens (F, Cl, Br), followed by treatment with LiPR2
(R ˆ H, Et); 3) reaction of the dichloro compound with PH3 in an autoclave at various temperatures and
pressures (up to 200 bar), and in the presence of tertiary amines or Lewis acids; 4) reaction of dihalo
derivatives with Rieke magnesium and XPR2; and 5) treatment of the sulfite derivative of TADDOL with
an oxidizing agent (RuCl3/NaIO4, or m-chloroperbenzoic acid (mCPBA)) did not afford the expected
sulfate, which would have been expected to react with phosphines and BuLi to give the target structure (cf.
the preparation of the DUPHOS ligands [12]).

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Helvetica Chimica Acta ± Vol. 82 (1999)
Scheme 1
Entry
Product
Arl
R1
R2
Yield [%]
1
2
3
4
5
7a
7b
7c
7d
7e
Ph
Ph
Ph
H
Ph
H
i-Pr
i-Pr
Ph
H
i-Pr
H
29a)
66
63
68
48
Ph
b-Npb)
H
a) Reaction carried out with only 1 equiv. of NEt3 in the second step. b) b-Np ˆ Naphthalen-2-yl.
3. Structural Investigations. ± The knowledge of the exact structure of a
coordinating ligand, particularly when bound to the metal, is a valuable hint for its
further structural evolution. As none of the phosphites 7 showed any tendency to
crystallize from any of the solvents tested, we prepared two representative cationic RhI
complexes by adding a solution of [Rh(cod)Cl]2 (cod ˆ cycloocta-1,5-diene) in CH2Cl2
to the corresponding ligand. Exchange of Cl for PF6 gave the yellow complexes 8 in
ca. 90% yield (Scheme 2). The complexation was evident from the 31P-NMR spectra of
8: the P-atom of the ligand couples with 103Rh, giving rise to a doublet (1J(P,Rh) ˆ 255
and 265 Hz, resp.) at a lower chemical shift (d ˆ 103 and 108 vs. ca. 135 ppm).
Scheme 2
Slow evaporation of a CHCl3 solution of 8b yielded yellow needles suitable for X-
ray crystal-structure determination. The crystals contained 8b and CHCl3 (not included
in the Fig.) in a 1 :1 ratio.

Helvetica Chimica Acta ± Vol. 82 (1999)
1099
Figure. X-Ray structure of the RhI complex 8b ´ CHCl3. H-Atoms, the hexafluorophospate counterion, and
CHCl3 have been omitted for clarity; C-atoms in grey, N-atoms in blue, O-atoms in red, P-atoms in yellow, and
Rh-atoms in pink. The structure was determined by PD Dr. V. Gramlich. The presentations were generated with
the MolMol program [15] and ray-traced by POV-Ray. The adjacent quasi-equatorial Ph substituent forces the
i-Pr group to present itself towards the Rh-center like a t-Bu group. a) Stereo representation of 8b. b) The
chelating part of the ligand and the Rh-center form a six-membered ring, in which the atoms Rh, P, O, C, C, N
adopt a boat conformation. c) This view reveals the envelope conformation (O-atom out of plane) of the
dioxolane ring and a chair-type conformation of the seven-membered ring formed by four C- and two O-atoms
of the tetraphenylerythritol moiety and the P-atom; the quasi-equatorial and quasi-axial disposition of the Ph
groups on this seven-membered ring is prototypal for TADDOLs and their metal complexes [16].
The TADDOL part adopts the typical conformation with the dioxolane ring as an
envelope (the O-atom out of plane) and the Ph substituents in quasi-equatorial and
quasi-axial positions on the seven-membered ring formed by the C C bonds of the
acetal ring and the two diphenylmethylene groups connected via the O
P O bridge.
Interestingly, the two Me groups of the i-Pr moiety on the dihydrooxazole ring point in
the same direction as one of the Ph rings of the adjacent diphenylmethylene group, thus
shielding the Rh-atom in this half-space; the metal center is more readily accessible from
the other half-space. This might be the reason for the better performance of the ligand 7d
with (R)-configuration on the dihydrooxazole ring, as compared to its ꢀmismatchedꢁ
diastereoisomer, in the enantioselective hydrosilylations described in Chapt. 4. Unfortu-
nately, we did not succeed in obtaining crystals of complex 8a suitable for X-ray analysis,
thus a direct comparison of the two diastereoisomeric structures is not possible.

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Helvetica Chimica Acta ± Vol. 82 (1999)
4. Catalytic Enantioselective Hydrosilylation of Ketones. ± We first turned our
attention to the enantioselectively catalyzed reductions of ketones by hydrosilylations.
This is a typical reaction for the exploration of the potential of a chiral ligand in late-
transition-metal-catalyzed reactions, and it has been studied previously by several
groups3). The asymmetric reduction of simple ketones can also be achieved with
impressive levels of enantioselectivity via other catalytic4) or stoichiometric5)
transformations. Thus, only highly effective catalytic processes can possibly compete
with known techniques.
With our test substrate for RhI-catalyzed hydrosilylations, acetophenone (9), and
0.1 mol-% of the complex prepared in situ from [Rh(cod)Cl]2 and the ligand 7d, the
product of reduction, 1-phenylethanol (10), was obtained in an enantiomer ratio of
94 :6.
Our optimization experiments with the acetophenone (9) reduction revealed the
following. i) A Rh/ligand ratio of 1:1.2 is sufficient for obtaining the highest
enantioselectivity6). ii) At 08, a reaction time of ca. 24 h is sufficient for complete
1
conversion with 1 mol-% catalyst (sampling and H-NMR analysis). iii) The stereo-
genic centers of (R,R)-TADDOL, and (R)- or (S)-dihydrooxazole give rise to two
diastereoisomeric ligands 7, the configuration of the product 10, however, is mainly
determined by the configuration of the dihydrooxazole moiety (cf. Entries 1 with 2, and
3 with 4 in Scheme 3). Still, the TADDOL part exhibits a significant effect (83 vs. 93%
enantioselectivity; see Entries 3 and 4). Thus, the (R,R)-TADDOL/(R)-dihydrooxazo-
le combination represents what is often dubbed the ꢀmatched caseꢁ. The ligand 7d with
an i-Pr substituent on the dihydrooxazole ring (Entry 4) gave a slightly better
enantioselectivity of 93% than did 7b, which bears a Ph substituent (91%, Entry 2). iv)
In contrast to the results obtained with monodentate phosphites derived from
TADDOL [7], replacement of the Ph by naphthalen-2-yl groups in the diarylmethoxy
positions (ligand 7e) led to a decrease of selectivity (Entry 5)7). v) The temperature-
dependence is rather small: at lower temperature a slightly better enantioselectivity
was observed8), while, at ambient temperature, the enantioselectivity was poorest, and,
furthermore, 5% of silylenol ether was formed as a by-product (detected by 1H-NMR
spectroscopy)9). vi) Using toluene as solvent gave slightly higher enantiomer ratios, as
3
)
)
For reviews, see [17].
4
Cf. the borane reduction catalyzed by chiral oxaborolidines (Corey-Itsuno method [18a]; for reviews, see
[18b]), which usually requires 10 mol-% of an amino-acid-derived amino alcohol.
Stoichiometric chiral reducing reagents have also been used successfully, in particular BINAL-H by
Noyori et al. [19] and LiAlH(OEt)-TADDOLate by our group [20a] (for a comparison of TADDOLates
and BINOLates, see [20b]). However, these methods require at least a two-fold excess of the chiral
reducing agent.
Using a five-fold amount of ligand, as it is common with nitrogen-only ligands [17], gave neither better
selectivities nor improved yields under the standard conditions. Obviously, the P-center improves
coordination to the metal.
5
)
)
6
7
8
9
)
)
)
A similar effect has been observed for the enantioselective LiAlH(OEt)-TADDOLate reduction of
acetophenone (9) [20].
Of course at the expense of reduced rate: (S)-1-phenylethanol was formed in ꢀ 90% yield with the
following selectivities/specified temperatures/reaction times: 86%/‡ 208/ < 1 d, 93%/08/1 d, 94%/ 208/7 d.
This competing reaction is often a serious problem with nitrogen-only ligands [21].

Helvetica Chimica Acta ± Vol. 82 (1999)
1101
compared to THF10). However, it was necessary to use THF to solubilize ketones
bearing additional polar functional groups, such as 2,3-dihydro-4,4-dimethylfuran-2,3-
dione, which was not sufficiently soluble in toluene, since chlorinated solvents such as
CH2Cl2 or especially CCl4, which is the solvent of choice for nitrogen-only ligands [21],
inhibit the catalytic activity. vii) Almost identical enantioselectivities were obtained for
catalyst amounts ranging from 2 to 0.1 mol-%11). viii) In the presence of [Ir(cod)Cl]2 as
a metal source in place of [Rh(cod)Cl]2, hydrosilylation of acetophenone (9) with
ligand 7d afforded 1-phenylethanol having the same configuration with low enantio-
selectivity12).
Scheme 3
Entry
1
2
3
4
5
Ligand 7
a
b
c
d
e
Yield of 10 [%]
(R)/(S) in 10
97
86
92
89
89
85:15
9:91
83:17
7:93
15:85
To test the scope of the new catalyst system, we examined a number of related
aromatic ketones as substrates in the enantioselective hydrosilylation (see the Table).
The enantioselectivities were determined by NMR or GC analysis, and the absolute
configurations assigned by optical comparison or by analogy (see Exper. Part). For
aromatic residues larger than Ph, such as naphthyl, the reduction provided alcohols 11
and 12 with (S)-configuration in similar selectivities. On the other hand, alkyl groups
bulkier than Me led to decreased reactivity and selectivity (products 13 ± 15).
Particularly, the hydrosilylation of isobutyrophenone and pivalophenone did not
proceed at 08 within an acceptable period of time. Thus, we reduced these ketones at
ambient temperature, with the result that the enantioselectivity decreased to nearly
zero13). On the other hand, phenacyl chloride was reduced smoothly, providing the
corresponding (R)-2-chloro-1-phenylethanol (16) with 91.5% enantioselectivity14).
10
)
)
(S)-1-Phenylethanol was formed in > 98% yield with enantioselectivities of 92% in toluene, 90% in THF,
and 88% neat (0.5 mol-% catalyst).
Of course at the expense of reduced rate: (S)-1-phenylethanol was formed in ꢀ 90% yield with the
following selectivities/amounts of catalyst/reaction times: 93%/2 mol-%/ < 1 d, 93%/1 mol-%/1 d, 92%/
0.5 mol-%/2 d, 93%/0.25 mol-%/4 d, 94%/0.1 mol-%/10 d.
(S)-1-Phenylethanol was formed in 83% yield with an enantioselectivity of only 65%.
In fact, the lowest selectivity obtained was for isobutyrophenone. The bulkier t-Bu group in pivalophenone
led to reversal of selectivity from (S)- to (R)-configuration, but with no practically useful degree of
selectivity.
The switch from (S)- to (R)-configuration with the chloro alcohol 16, as compared with the other products
of reduction, is an ꢀartefactꢁ of the priority rules of the CIP-convention.
11
12
13
)
)
14
)

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Helvetica Chimica Acta ± Vol. 82 (1999)
Reduction of fused alkyl aryl ketones such as a-tetralone and chroman-4-one gave the
corresponding alcohols 17 and 18 (both (S)-configuration) with enantioselectivities of
90 and 93%, respectively15).
Besides aromatic ketones, aliphatic ketones can also be reduced by silanes in the
presence of RhI complexes. However, the enantioselectivities reported in the literature
are significantly lower than those obtained with aromatic ketones [17]. Surprisingly,
our ligand 7d acted effectively, not only with aryl ketones, but also with alkyl methyl
ketones (see products 19 ± 23 in the Table). Thus, our catalyst system is able to
differentiate reasonably well even between the enantiotopic faces of alkyl methyl
ketones16), with selectivities increasing from Et to i-Pr to t-Bu17). To the best of our
knowledge, the value obtained for 21 is the best ever reported for an enantioselective
hydrosilylation of pinacolone18). Surprisingly, octan-2-ol (22) was obtained with lower
selectivity than was butan-2-ol (19, 78%), and, likewise, 1-cyclohexylethanol (23) was
formed less selectively than 3-methylbutan-1-ol (20). Ketones bearing additional
functional groups could also be selectively reduced: thus, (‡)-(S)-pantolactone (24),
( )-(S)-g-valerolactone (25), and ethyl (‡)-(S)-4-hydroxypentanoate (26) were
obtained from the corresponding oxo derivatives with selectivities of ca. 90%19).
5. Conclusion. ± The catalyst prepared in situ from [Rh(cod)Cl]2 and the P,N ligand
7d directs silyl hydride addition from Ph2SiH2 to the Re faces of ketones with good-to-
excellent selectivities (Scheme 4). The contribution of the TADDOL moiety to this
enantioselectivity is minor, as compared to that of the dihydrooxazole unit. Still, it is
interesting to point out that Si topicity of addition is observed in hydrosilylations with
Rh and the monodentate TADDOL phosphite 2 [7], and Re topicity with a
TADDOLate from LiAlH4 [20]. The Re topicity of ketone hydrosilylation is also
observed with the bidentate nitrogen-only (R)-dihydrooxazole ligands ꢀPymoxꢁ, while
the analogous tridentate ligands containing two (R)-dihydrooxazole and a central
pyridine moiety give rise to opposite topicity! [17]. Further work with the goal to
elaborate the potential of the new ligands 7 in other transition-metal-catalyzed
reactions is currently in progress.
We thank the Deutsche Forschungsgemeinschaft for a postdoctoral fellowship granted to D. K. H.
Continuing support by the Novartis Pharma AG, Basel, is gratefully acknowledged. Degussa AG, Hanau-
Wolfgang, donated enantiomerically pure amino acids, in particular d-valine. We thank PD Dr. V. Gramlich of
the Laboratorium für Kristallographie, ETH-Zürich, for the determination of the X-ray crystal structure of 8b,
and K. Gademann for help with the preparation of the Figure.
15
)
Hydrosilylation of 2,4-dimethoxyacetophenone did not yield the expected sec-alcohol, but the
corresponding racemic methyl ether. We assume that the silyl ether primarily formed undergoes Sn1
substitution during workup (MeOH/H ). The formation of the methyl ether has also been observed in the
‡
NaBH4 reduction of the same substrate [22].
No by-products were detected with > 99% conversion (sampling and H-NMR analysis).
An enantiomer ratio of 96.5:3.5 was observed for 21 under the standard conditions (08, 24 h), while at
208 the selectivity was 97.5 : 2.5.
1
16
17
)
)
18
19
)
)
With a chiral (dihydrooxazolyl)ferrocene-phosphine hybrid ligand (S,S,S)-DIPOF, 93.5% (R)-selectivity
was observed in the hydrosilylation of tert-butyl methyl ketone [23].
Compounds 24 and 25 can be obtained from the same starting material, ethyl laevulinate, depending on
the workup. Desilylation of silylated ethyl laevulinate with acidic MeOH provides the lactone, whereas the
hydroxy ester is obtained with pure MeOH.

Helvetica Chimica Acta ± Vol. 82 (1999)
1103
Table. Asymmetric Hydrosilylation of Various Ketones by RhI-7d Complexes. The reactions were carried out in
the presence of [Rh(cod)Cl]2 (0.5 mol-%) and 7d (1.2 mol-%) with Ph2SiH2 (2.2 mmol) and ketones (2.0 mmol)
in toluene at the temperature and with the reaction times indicated. Yields refer to purified products. The
enantiomer ratios were determined by GC (10 ± 25) or via the MTPA ester (26); for details and for
configurational assignments, see the Exper. Part.
Product
No.
Yield
[%]
Reaction
time
[h]
Temp.
Enantiomer
ratio
[%]
Abs.
configu-
ration
[8]
89
91
24
168
0
20
93 : 7
94 : 6
(S)
(S)
10
11
12
81
87
24
24
0
0
94.5 : 5.5
90 : 10
(S)
(S)
13
14
15
81
87
69
240
24
0
20
20
82 : 18
(S)
(S)
(R)
51.5 : 48.5
53 : 47
24
16
17
89
70
24
42
0
0
91.5 : 8.5
90 : 10
(R)
(S)
18
19
86
24
24
0
0
93.5 : 6.5
78 : 22
(S)
(S)
n.d.a)
20
n.d.a)
24
0
88 : 12
(S)

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Helvetica Chimica Acta ± Vol. 82 (1999)
Table. (cont.)
Product
No.
Yield
[%]
Reaction
Time
[h]
Temp.
Enantio-
selectivity
[%]
Abs.
Configu-
ration
[8]
21
22
n.d.a)
96
24
20
0
97.5 : 2.5
96.5 : 3.5
(S)
89
40
42
0
0
71 : 29
84 : 16
(S)
23
24
82
76
(S)
(S)
120b)
0
92 : 8
25
26
71
86
24b)
24
0
0
87: 13
90 : 10
(S)
(S)
a
) No by-products detectable, > 99% conversion determined by H-NMR analysis. b) THF used as solvent.
1
Scheme 4
(hydrogen transfer with ligand 7d from Re face, CIP priority O > Rl > Rs)
Experimental Part
1. General. All reactions were carried out under Ar in flame-dried glassware. Toluene, xylene (isomers
mixture), and THF were distilled from Na/K; CH2Cl2 p.A. (Baker) was stored over activated molecular sieves
(4 Š) for at least 48 h and filtered through basic Al2O3 (activity I) directly prior to use. Solvents for flash
chromatography (FC) and workup: Et2O was distilled from KOH/FeSO4, AcOEt from Sikkon (Fluka).
Pentane and hexane were used as received. TADDOLs 1a (Arl ˆ Ph), 1b (Arl ˆ naphthalen-2-yl) [2] and d-

Helvetica Chimica Acta ± Vol. 82 (1999)
1105
valinol [24] were prepared according to literature procedures. Liquid ketones were degassed by three freeze-
thaw cycles. All other reagents were used as received from Fluka or Aldrich. TLC: Macherey-Nagel Alugram
SIL G/UV254 plates; detection by UV or common detecting agents (alcaline KMnO4 soln., anisaldehyde/H2SO4
soln., Ce(SO4)2/phosphomolybdic acid soln.), followed by heating. FC: Fluka silica gel 60 (0.040 ± 0.063 mm),
pressure 0.4 bar. GC: Carlo Erba GC8000 TOP with ChromCard Software and Supelco b-Dex 120 capillary
column (30 m  0.25 mm i.d., 0.25 mm film) for enantiomer separations. M.p.: Büchi-510 apparatus, uncorrect-
ed. Optical rotations: Perkin-Elmer 241 polarimeter (10 cm, 1 ml cell) at r.t.. IR Spectra: Perkin-Elmer-1600-
FT-IR spectrometer. NMR Spectra: Varian-Gemini 200 (1H: 200 MHz, 13C: 50 MHz) or Varian-Gemini 300
(1H: 300 MHz, 13C: 75 MHz, and 31P: 122 MHz); chemical shifts (d) are reported in ppm downfield to TMS
(d ˆ 0.0 ppm) as internal standard, J values are given in Hz. MS: VG Tribrid (EI) or FG ZAB-2 SEQ (FAB; in a
3-nitrobenzyl-alcohol matrix) spectrometer; in m/z (% of basic peak). Elemental analyses were performed by
the Microanalytical Laboratory of the Laboratorium für Organische Chemie, ETH Zürich.
2. Preparation of Dihydrooxazole Alcohols
6 [14]. General Procedure 1 (GP 1). 2-Hydroxy-2-
methylpropanoic acid (1 equiv.) and the corresponding amino alcohol (1 equiv.) were dissolved in xylene
(complete dissolution occurred during heating) and heated to reflux in a Dean-Stark apparatus (oil-bath temp.
1808). After 30 h, no more H2O was formed. The mixture was allowed to cool, and the solvent was removed
under reduced pressure. Purification was carried out as described for each individual compound.
3. Preparation of the Ligands 7. General Procedure 2 (GP 2). PCl3 (1 equiv.) in CH2Cl2 (2 ml/mmol) was
cooled to 308 prior to the addition of NEt3 (2 equiv.). The soln. was stirred for 5 min. TADDOL (1 equiv.)
dissolved in CH2Cl2 (4 ml/mmol) was added dropwise over 15 min. The mixture (which contained a colorless
precipitate) was slowly warmed to 108 (ca. 1 h). Then the bath was removed and the reaction mixture allowed
to reach r.t. NEt3 (2 ± 5 equiv.) was then added, and the mixture was stirred at ambient temp. for further 5 min,
before the corresponding dihydrooxazole alcohol 6 (1 equiv., dissolved in CH2Cl2 (2 ml/mmol)) was added
dropwise. The mixture was stirred at r.t., until no further product formation was detectable by sampling and
1H-NMR and 31P-NMR-analysis (3 ± 5 days). The mixture was extracted with H2O (Ar-saturated, 10 ml/mmol),
and the aq. phase was then extracted with CH2Cl2 (2 Â 10 ml/mmol). The combined org. extracts were washed
with brine (10 ml/mmol) and dried (Na2SO4). Most of the solvent was removed in a rotary evaporator to afford
a pale-yellow oil, which was loaded directly on a silica gel column (12 g/mmol, pentane/Et2O 85 : 15). FC
provided the ligands 7 as colorless solid foams after complete removal of the solvent.
4. Preparation of the RhI Complexes 8. General Procedure 3 (GP 3). To a stirred soln. of the ligand 7 (1 equiv.)
in CH2Cl2 (5 ml/mmol) was added [Rh(cod)Cl]2 (1 equiv. with respect to Rh) in CH2Cl2 (2.5 ml/mmol). The
yellow soln. was stirred for 2 h, then excess NH4PF6 (1.4 equiv.) was added. After stirring overnight at ambient
temp., the inorg. salts were filtered by suction (G4) and rinsed with CH2Cl2 (10 ml/mmol). Pentane (25 ml/
mmol) was added to the filtrate to precipitate the complexes 8 as yellow powders.
5. Hydrosilylation of Ketones. General Procedure 4 (GP 4). [Rh(cod)Cl]2 (0.005 equiv.) and the ligand 7
(0.01 equiv.) were dissolved in toluene or THF (0.5 ml/mmol substrate). The resulting yellow soln. was stirred at
r.t. for 60 min. Then, the ketone (1.0 equiv.) was added. After 3 min, the mixture was cooled to the specified
reaction temp. (08 for most cases). Precooled diphenylsilane (1.1 equiv.) was added dropwise over 2 min. The
1
progress of the reaction was monitored by sampling and H-NMR. To determine the end of the reaction, the
characteristic resonances of the residual ketone were compared with those of the silylated alcohol formed. In the
cases where substrates did not exhibit characteristic resonances, the disappearance of the Si H resonance of the
silane at 4.9 ppm was used. The silyl ether was cleaved by addition of MeOH (0.7 ml, containing 1% of 4-
toluenesulfonic acid, except 26: pure MeOH). Stirring was continued until gas evolution ceased (3 ± 12 h). The
mixture was loaded directly on a silica gel column (8 g/mmol) and chromatographed (pentane/Et2O ratios
between 80 :20 and 90 :10, depending on the relative polarity of the compounds). Yields refer to isolated pure
compounds (> 95% by 1H-NMR and GC). The spectra of the products of reduction are as expected. The
1
conversion for low-boiling and volatile compounds (19 ± 21) was calculated from the H-NMR spectra of the
silylated products.
(S)-4,5-Dihydro-a,a-dimethyl-4-phenyloxazole-2-ethanol (6a): (‡)-(S)-2-Amino-2-phenylethanol (2.65 g,
19.3 mmol) was treated with 2-hydroxy-2-methylpropanoic acid (1.99 g, 19.1 mmol) in xylene (50 ml) according
to GP 1. The resulting yellow oil was purified by FC (60 g; CH2Cl2/EtOAc 70 :30) to afford 5a (784 mg, 20%).
Colorless crystals. Rf (hexane/AcOEt 50 :50) 0.30. M.p. 73 ± 748. [a]Dr:t:
ˆ
76.4 (c ˆ 1.00, CHCl3). IR (neat):
3500w, 3066w, 2984s, 2903w, 1662s, 1494w, 1454w, 1338w, 1177s, 1134s, 960s, 922w. 1H-NMR (300 MHz, CDCl3):
1.52 (d, J ˆ 5.8, Me2C); 3.22 (br. s, OH); 4.20 ± 4.26 (m, 1 H); 4.71 ± 4.78 (m, 1 H); 5.19 ± 5.25 (m, 1 H); 7.21 ±
7.39 (m, arom. H). 13C-NMR (75 MHz, CDCl3): 27.7; 28.1; 68.9; 69.0; 76.3; 126.4; 127.7; 128.8; 141.9; 173.7.
Anal. calc. for C12H15NO2 (205.3): C 70.22, H 7.37, N 6.82; found: C 70.13, H 7.36, N 6.75.

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Helvetica Chimica Acta ± Vol. 82 (1999)
(R)-4,5-Dihydro-a,a-dimethyl-4-phenyloxazole-2-ethanol (6b): ( )-(R)-2-Amino-2-phenylethanol (2.06 g,
15.0 mmol) was treated with 2-hydroxy-2-methylpropanoic acid (1.56 g, 15.0 mmol) in xylene (45 ml) according
to GP 1. The resulting yellow oil was purified by FC (60 g; CH2Cl2/AcOEt 65 :35) to afford 5b (837 mg, 27%).
Colorless crystals. An anal. pure sample was prepared by recrystallization from hexane. M.p. 738. [a]rD:t: ˆ‡ 75.8
(c ˆ 1.00, CHCl3). Spectroscopic and chromatographic data match those of the enantiomer 6a. EI-MS: 205(24,
‡
M ), 117(100), 90(17), 59(16). Anal. calc. for C12H15NO2 (205.3): C 70.22, H 7.37, N 6.82; found: C 70.17,
H 7.25, N 6.70.
(S)-4,5-Dihydro-a,a-dimethyl-4-isopropyloxazole-2-ethanol (6c). (S)-(‡)-2-Amino-3-methylbutan-1-ol
(2.15 g, 20.8 mmol) was treated with 2-hydroxy-2-methylpropanoic acid (2.13 g, 20.5 mmol) in xylene (60 ml)
according to GP 1. The resulting pale-yellow oil was distilled (b.p. 66 ± 708/0.3 Torr). The colorless liquid (1.62 g)
thus obtained was subjected to FC (50 g; hexane/AcOEt 85 :15 ! 65 : 35). The product 5c solidified upon
cooling in an ice bath (1.30 g, 31%). Rf (hexane/AcOEt 50 : 50) 0.32. M.p. 33 ± 348. [a]Dr:t:
ˆ
78.5 (c ˆ 1.07,
CHCl3). IR (neat): 3284s, 2959s, 1665s, 1466m, 1358m, 1250m, 1181s, 1127s, 1042w, 964m, 935w, 850w. 1H-NMR
(300 MHz, CDCl3): 0.88 (d, J ˆ 6.9, MeCH); 0.95 (d, J ˆ 6.9, MeCH); 1.44 (s, Me2COH); 1.73 ± 1.80 (m,
Me2CH); 3.27 (br. s, OH); 3.90 ± 3.98 (m, 1 H); 4.07 ± 4.12 (m, 1 H); 4.32 ± 4.38 (m, 1 H). 13C-NMR (75 MHz,
‡
CDCl3): 17.8; 18.5; 27.7; 27.9; 32.4; 68.8; 71.4; 71.7; 172.3. EI-MS: 171(1, M ), 156(12), 128(47), 112(14),
98(100), 59(24). Anal. calc. for C9H17NO2 (171.2): C 63.13, H 10.01, N 8.18; found: C 62.97, H 10.29, N 8.13.
(R)-a,a-4,5-Dihydro-dimethyl-4-isopropyloxazole-2-ethanol (6d):
( )-(R)-2-Amino-2-phenylethanol
(5.15 g, 50.0 mmol) was treated with 2-hydroxy-2-methyl-propanoic acid (5.20 g, 50.0 mmol) in xylene
(80 ml) according to GP 1. The resulting pale-yellow oil was distilled (b.p. 66 ± 708/0.3 Torr). The colorless
liquid obtained (3.08 g) was subjected to FC (50 g; CH2Cl2/AcOEt 65 :35). The product solidified upon cooling
in an ice bath (2.66 g, 31%). M.p. 348. [a]rD:t: ˆ‡ 78.1 (c ˆ 0.85, CHCl3). Spectroscopic and chromatographic data
match those of the enantiomer 6c. Anal. calc. for C9H17NO2 (171.2): C 63.13, H 10.01, N 8.18; found: C 63.27,
H 10.02, N 7.98.
(3aR,8aR)-6-{1-[(4S)-4,5-Dihydro-4-phenyloxazol-2-yl]-1-methylethoxy}-3a,4,8,8a-tetrahydro-4,4,8,8-tetra-
phenyl-1,3,5,7-tetraoxa-6-phosphazulene (7a): According to GP 2, PCl3 (0.22 ml, 2.51 mmol) was treated with
NEt3 (1) 0.73 ml, 5.22 mmol; 2) 0.36 ml, 2.60 mmol), (R,R)-TADDOL 1a (1.17 g, 2.50 mmol), and 6a (515 mg,
2.51 mmol) to yield 7a (515 mg, 29%). Rf (hexane/AcOEt 80 :20) 0.29. M.p. 86 ± 888. [a]Dr:t:
ˆ
240.5 (c ˆ 0.84,
CHCl3). IR (CHCl3): 3062w, 3007m, 2937w, 1656m, 1600w, 1494m, 1447m, 1383m, 1164m, 976s, 887s. 1H-NMR
(300 MHz, CDCl3): 0.70 (s, 2 Me); 1.26 (s, Me); 1.37 (s, Me); 3.98 ± 4.03 (m, 1 H); 4.53 ± 4.59 (m, 1 H); 5.05 ± 5.13
(m, 2 H); 5.51 (d, J ˆ 8.0, 1 H); 7.12 ± 7.33 and 7.45 ± 7.58 (m, 25 arom. H). 13C-NMR (75 MHz, CDCl3): 26.4;
26.5; 27.4; 27.5; 69.6; 74.7; 74.8; 75.2; 80.1; 82.1; 84.1; 85.5; 112.9; 126.8; 127.0; 127.1; 127.2; 127.3; 127.3; 127.5;
127.6; 127.6; 127.7; 128.0; 128.7; 129.2; 129.2; 141.8; 142.1; 142.1; 146.4; 146.6; 170.3. 31P-NMR (122 MHz,
‡
CDCl3): 134.8. FAB-MS: 700(43, [M ‡ H] ), 431(100), 345(34), 268(95), 237(37), 207(23), 195(30),
188(70), 179(91), 167(55), 105(25). Anal. calc. for C43H42NO6P (699.79): C 73.80, H 6.05, N 2.00; found:
C 73.84, H 6.25, N 2.12.
(3aR,8aR)-6-{1-[(4R)-4,5-Dihydro-4-phenyloxazol-2-yl]-1-methylethoxy}-3a,4,8,8a-tetrahydro-4,4,8,8-tetra-
phenyl-1,3,5,7-tetraoxa-6-phosphazulene (7b). According to GP 2, PCl3 (0.22 ml, 2.51 mmol) was treated with
NEt3 (1) 0.73 ml, 5.22 mmol; 2) 0.73 ml, 5.22 mmol), (R,R)-TADDOL 1a (1.17 g, 2.50 mmol) and 6b (515 mg,
2.51 mmol) to yield 7a (1.15 g, 66%). Rf (hexane/AcOEt 80 :20) 0.31. M.p. 84 ± 858. [a]Dr:t:
ˆ
123.9 (c ˆ 0.82,
CHCl3). IR (CHCl3): 3060w, 2992m, 2936w, 1659m, 1601w, 1494m, 1448m, 1383m, 1164m, 1088w, 1052w, 978s,
1
887s. H-NMR (300 MHz, CDCl3): 0.69 (s, Me); 0.70 (s, Me); 1.31 (s, Me); 1.34 (s, Me); 4.00 ± 4.06 (m, 1 H);
4.49 ± 4.58 (m, 1 H); 5.04 ± 5.10 (m, 2 H); 5.52 (d, J ˆ 8.4, 1 H); 7.11 ± 7.35 and 7.45 ± 7.58 (m, 25 arom. H).
13C-NMR (75 MHz, CDCl3): 26.5; 26.6; 27.4; 27.8; 69.6; 74.7; 74.9; 75.2; 80.2; 82.2; 83.8; 85.4; 112.8; 126.7;
126.9; 127.0; 127.1; 127.1; 127.2; 127.4; 127.4; 127.5; 127.6; 127.9; 128.1; 128.6; 129.0; 129.1; 141.8; 142.1; 146.2;
‡
146.4; 146.4; 170.1. 31P-NMR (122 MHz, CDCl3): 135.0. FAB-MS: 716(16), 699(51, M ), 431(77), 345(26),
268(42), 237(16), 178(100), 167(40), 165(45), 152(20). Anal. calc. for C43H42NO6P (699.79): C 73.80, H 6.05,
N 2.00; found: C 73.75, H 6.23, N 2.00.
(3aR,8aR)-6-{1-[(4S)-4,5-Dihydro-4-isopropyloxazol-2-yl]-1-methylethoxy}-3a,4,8,8a-tetrahydro-4,4,8,8-
tetraphenyl-1,3,5,7-tetraoxa-6-phosphazulene (7c). According to GP 2, PCl3 (0.27 ml, 3.09 mmol) was treated
with NEt3 (1) 0.87 ml, 6.24 mmol; 2) 1.75 ml, 12.5 mmol), (R,R)-TADDOL 1a (1.40 g, 3.00 mmol), and 6c
(513 mg, 3.00 mmol) to yield 7c (1.25 g, 63%). Rf (hexane/AcOEt 75 :25) 0.42. M.p. 75 ± 778. [a]Dr:t:
ˆ
210.8
(c ˆ 0.74, CHCl3). IR (CHCl3): 3063w, 3007m, 2964m, 1660m, 1600w, 1494m, 1447m, 1383m, 1164m, 1088w,
1052w, 957s, 887s. 1H-NMR (300 MHz, CDCl3): 0.71 (s, Me); 0.72 (s, Me); 0.79 (d, J ˆ 6.9, 3 H, Me2CH); 0.89 (d,
J ˆ 6.9, 3 H, Me2CH); 1.20 (s, Me); 1.30 (s, Me); 3.84 ± 3.95 (m, 2 H); 4.13 ± 4.20 (m, 1 H); 5.05 (d, J ˆ 7.5, 1 H);
5.49 (d, J ˆ 7.5, 1 H); 7.18 ± 7.38 and 7.45 ± 7.61 (m, 20, arom. H). 13C-NMR (75 MHz, CDCl3): 17.7; 18.8; 26.6;

Helvetica Chimica Acta ± Vol. 82 (1999)
1107
27.5; 27.6; 32.3; 70.1; 71.9; 74.8; 80.1; 82.1; 84.0; 85.3; 112.8; 126.9; 127.0; 127.1; 127.3; 127.4; 127.6; 127.6; 127.9;
129.1; 129.2; 141.8; 142.1; 146.4; 146.6; 168.6. 31P-NMR (122 MHz, CDCl3): 134.4. FAB-MS: 682(7), 665(24,
‡
M ), 431(83), 345(30), 234(100), 179(75), 167(38), 154(30). Anal. calc. for C40H44NO6P (665.77): C 72.16,
H 6.66, N 2.10; found: C 72.16, H 6.63, N 2.14.
(3aR,8aR)-6-{1-[(4R)-4,5-Dihydro-4-isopropyloxazol-2-yl]-1-methylethoxy}-3a,4,8,8a-tetrahydro-4,4,8,8-
tetraphenyl-1,3,5,7-tetraoxa-6-phosphazulene (7d). According to GP 2, PCl3 (0.44 ml, 5.00 mmol) was treated
with NEt3 (1) 1.40 ml, 10.0 mmol; 2) 3.50 ml, 25.0 mmol), (R,R)-TADDOL 1a (2.33 g, 5.00 mmol), and 6d
(856 mg, 5.00 mmol) to yield 7d (2.26 g, 68%). Rf (pentane/Et2O 80 :20) 0.31. M.p. 73 ± 758. [a]Dr:t:
ˆ
155.2 (c ˆ
0.52, CHCl3). IR (CHCl3): 3059w, 3008m, 2964w, 1659m, 1599w, 1494w, 1447m, 1383m, 1164m, 1088w, 1052w,
957s, 886s, 835w. 1H-NMR (300 MHz, CDCl3): 0.69 (s, Me); 0.70 (s, Me); 0.77 (d, J ˆ 6.7, 3 H, Me2CH); 0.88 (d,
J ˆ 6.7, 3 H, Me2CH); 1.22 (s, Me); 1.26 (s, Me); 1.66 ± 1.72 (m, Me2CH); 3.79 ± 3.87 (m, 1 H); 3.90 ± 3.95 (m, 1
H); 4.09 ± 4.15 (m, 1 H); 5.03 (d, J ˆ 8.4, 1 H); 5.47 (d, J ˆ 8.4, 1 H); 7.16 ± 7.35 and 7.45 ± 7.58 (m, 20 arom. H).
13C-NMR (75 MHz, CDCl3): 17.7; 18.7; 26.5; 27.4; 27.7; 32.3; 70.1; 71.9; 74.9; 80.2; 82.1; 83.7; 85.2; 112.7; 126.9;
126.9; 127.0; 127.1; 127.2; 127.4; 127.5; 127.6; 127.9; 129.1; 129.1; 141.8; 142.1; 146.2; 146.5; 168.5. 31P-NMR
‡
(122 MHz, CDCl3): 134.9. FAB-MS: 665(8, M ), 431(23), 345(9), 234(100), 179(100), 167(58), 154(67).
Anal. calc. for C40H44NO6P (665.77): C 72.16, H 6.66, N 2.10; found: C 72.30, H 6.81, N 2.11.
(3aR,8aR)-6-{1-[(4R)-4,5-Dihydro-4-isopropylaoxazol-2-yl]-1-methylethoxy}-3a,4,8,8a-tetrahydro-4,4,8,8-
tetra(naphthalen-2-yl)-1,3,5,7-tetraoxa-6-phosphazulene (7e). According to GP 2, PCl3 (0.26 ml, 3.00 mmol) was
treated with NEt3 (1) 0.84 ml, 6.00 mmol; 2) 2.10 ml, 15.0 mmol), (R,R)-TADDOL 1b (2.00 g, 3.00 mmol), and
6e (514 mg, 3.00 mmol) to yield 7e (1.61 mg, 48%). Rf (pentane/Et2O 50 :50) 0.26. M.p. > 1308 (slow continuous
shrinking, no sharp m.p.). [a]Dr:t:
ˆ
176.4 (c ˆ 1.25, CHCl3). IR (CHCl3): 3060m, 2981m, 2961m, 1660m, 1600w,
1
1505m, 1464w, 1382m, 1161s, 1126w, 981s, 900s, 863s, 824w. H-NMR (300 MHz, CDCl3): 0.67 (d, J ˆ 6.9, 3 H,
Me2CH); 0.75 (s, 2 Me); 0.78 (d, J ˆ 6.7, 3 H, Me2CH); 1.14 (s, Me); 1.28 (s, Me); 1.52 ± 1.59 (m, Me2CH); 3.63 ±
3.68 (m, 1 H); 3.77 ± 3.82 (m, 1 H); 3.92 ± 3.98 (m, 1 H); 5.41 (d, J ˆ 8.4, 1 H); 5.85 (d, J ˆ 8.4, 1 H); 7.42 ± 7.91
and 7.45 ± 7.58 (m, 24 arom. H); 8.17 (s, 2 H); 8.31 (s, 1 H); 8.44 (s, 1 H). 13C-NMR (75 MHz, CDCl3): 17.7; 18.6;
26.8; 27.4; 27.7; 32.2; 70.2; 71.7; 75.1; 80.5; 82.4; 84.3; 85.5; 113.0; 125.3; 125.4; 125.6; 125.7; 125.8; 125.9; 126.0;
126.1; 126.2; 126.3; 126.8; 127.2; 127.3; 127.5; 127.8; 128.3; 128.4; 128.6; 128.7; 132.5; 132.6; 132.6; 132.8; 132.8;
139.1; 139.4; 143.2; 143.6; 168.3. 31P-NMR (122 MHz, CDCl3): 135.1. FAB-MS: M not detectable, 631(61),
‡
337(31), 307(19), 295(32), 279(100), 267(59), 234(46), 155(45), 127(15). Compound 7e was much less stable
than the phenyl analogue 7d during workup and purification, thus we were unable to obtain a correct elemental
analysis. Anal. calc. for C58H52NO6P (890.03): C 78.27, H 5.89, N 1.57; found: C 77.74, H 6.42, N 1.49.
(
)-(h4-Cycloocta-1,5-diene)((3aR,8aR)-6-{1-[(4S)-4,5-dihydro-4-isopropyloxazol-2-yl]-1-methylethoxy}-
3a,4,8,8a-tetrahydro-4,4,8,8-tetraphenyl-1,3,5,7-tetraoxa-6-phosphazulene-P,N)rhodium(I) (8a). Compound 7c
(68.0 mg, 0.10 mmol) was treated with [Rh(cod)Cl]2 (25.0 mg, 0.05 mmol) and NH4PF6 (22.1 mg, 0.13 mmol)
according to GP 3 to yield 8a (95.5 mg, 91%). M.p. > 2008 (dec.). [a]Dr:t:
ˆ
88.8 (c ˆ 0.74, CHCl3). IR (CHCl3):
3039w, 2962w, 2887w, 1626m, 1494w, 1448m, 1374m, 1053w, 975s, 909s, 852s. 1H-NMR (300 MHz, CDCl3): 0.41
(s, Me); 0.76 (s, Me); 0.81 (d, J ˆ 6.5, 3 H, Me2CH); 0.94 (s, Me); 1.04 (d, J ˆ 6.5, 3 H, Me2CH); 1.23 ± 1.32 (m, 1
H); 1.55 (s, Me); 1.89 ± 2.15 (m, 5 H); 2.20 ± 2.42 (m, 3 H); 2.50 ± 2.65 (m, 1 H); 3.82 ± 3.90 (m, 1 H); 3.95 ± 4.02
(m, 1 H); 4.35 ± 4.45 (m, 2 H); 4.77 (m, 1 H); 5.03 (d, J ˆ 7.8, 1 H); 5.20 ± 5.31 (m, 1 H); 5.64 (d, J ˆ 7.8, 1 H);
5.78 ± 5.90 (m, 1 H); 6.97 ± 7.05 (m, 2 H); 7.26 ± 7.32 (m, 8 arom. H); 7.40 ± 7.61 (m, 10 arom. H). 31P-NMR
‡
(122 MHz, CDCl3): 107.6 (d, J(P, Rh) ˆ 254.9); 143.5 (sept., J(P,F) ˆ 712, PF6 ). FAB-MS: 876.2(100, M ).
Anal. calc. for C48H56NF6O6P2Rh (1021.82): C 56.42, H 5.52, N 1.37; found: C 56.46, H 5.63, N 1.41.
(
)-(h4-Cycloocta-1,5-diene)((3aR,8aR)-6-{1-[(4R)-4,5-dihydro-4-isopropyloxazol-2-yl]-1-methylethoxy}-
3a,4,8,8a-tetrahydro-4,4,8,8-tetraphenyl-1,3,5,7-tetraoxa-6-phosphazulene-P,N)rhodium(I) (8b). Compound 7d
(133 mg, 0.20 mmol) was treated with [Rh(cod)Cl]2 (49.3 mg, 0.10 mmol) and NH4PF6 (44.8 mg, 0.27 mmol)
according to GP 3 to yield 8a (158 mg, 90%). M.p. 214-2158 (dec.). [a]Dr:t:
ˆ
85.8 (c ˆ 0.62, CHCl3). IR
(CHCl3): 3039w, 2950w, 1624m, 1495w, 1448m, 1374w, 1010m, 968s, 850s. 1H-NMR (300 MHz, CDCl3): 0.32 (s,
Me); 0.64 (s, Me); 0.87 (d, J ˆ 6.5, 3 H, Me2CH); 1.07 (s, Me); 1.39 (d, J ˆ 6.5, 3 H, Me2CH); 1.50 ± 1.65 (m, 1 H);
1.97 (s, Me); 1.80 ± 2.22 (m, 4 H); 2.45 ± 2.78 (m, 4 H); 3.55 ± 3.65 (m, 1 H); 3.82 ± 3.92 (m, 1 H); 4.21 ± 4.28 (m, 2
H); 4.70 ± 4.80 (m, 1 H); 4.93 (d, J ˆ 7.9, 1 H); 5.19 ± 5.31 (m, 1 H); 5.66 (d, J ˆ 7.9, 1 H); 5.80 ± 5.92 (m, 1 H);
7.20 ± 7.49 (m, 20 arom. H). 31P-NMR (122 MHz, CDCl3): 103.4 (d, J(P, Rh) ˆ 264.9); 143.86 (sept, J(P, F) ˆ
‡
713, PF6 ). FAB-MS: 876.3(100, M ). Inclusion of varying amounts of solvent precluded correct elemental
analysis. See also the stoichiometric inclusion of CHCl3 in the crystal used for the X-ray structure determination.
X-Ray Crystal-Structure Analysis of 8b: C48H56NF6O6P2Rh ´ CHCl3. Suitable crystals were obtained by slow
evaporation of a CHCl3 soln. A Picker-Stoe 4-circle diffractometer equipped with a graphite monochromator
(CuKa, l ˆ 1.5418 Š) was used. Crystal temp. 293 K, crystal size 0.2  0.1  0.1 mm, orthorhombic crystal

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Helvetica Chimica Acta ± Vol. 82 (1999)
system, space group P212121, cell: a ˆ 10.334(10), b ˆ 13.861(14), c ˆ 36.46(5) Š, a ˆ b ˆ g ˆ 908, Vˆ
5222(10) Š3, Z ˆ 4, 1calc. ˆ 1.435 g cm 3, m ˆ 5.217 mm 1, F(000) ˆ 2316. Number of reflections measured 3073
(w scan 2.42 < 2q < 50.098); 3073 independent reflections, of which 2369 with I > 2s(I) were used for the
determination. The structure was solved by direct methods with SHELXS-86 and refined by full-matrix least-
squares analysis on F2 with SHELXL-93. Goodness of fit on F2 ˆ 1.024; Final agreement factors (observed
refl.): R ˆ 0.0685 (wR2 ˆ 0.1620); D1 (max, min) ˆ 1.527,
1.140 e Š 3. Crystallographic data (excluding
structure factors) for the structure reported in this paper have been deposited with the Cambridge
Crystallographic Data Centre as deposition No. CCDC-118729. Copies of the data can be obtained, free of
charge, on application to the CCDC, 12 Union Road, Cambridge CB21EZ UK (fax: ‡ 44 (1223) 336033; e-
mail: deposit@ccdc.cam.ac.uk).
(S)-1-Phenylethanol (10). Acetophenone (234 m l, 2.00 mmol) was treated with Ph2SiH2 (406 ml, 2.20 mmol)
according to GP 4 at 08 to yield 10 (218 mg, 89%). [a]Dr:t:
1.0, MeOH)). E.r. (S)/(R) 93 : 7. tR (R) 6.85, tR (S) 7.10 min. T 110 ! 1228 with 1.58/min, 130 kPa.
ˆ
39.8 (c ˆ 0.93, MeOH), ([25]: [a]Dr:t:
ˆ
45.5 (c ˆ
(S)-1-(Naphthalen-1-yl)ethanol (11): 1-(Naphthalen-1-yl)ethanone (305 ml, 2.00 mmol) was treated with
Ph2SiH2 (406 ml, 2.20 mmol) according to GP 4 at 08 to yield 11 (280 mg, 81%). [a]Dr:t:
68.5 (c ˆ 1.07, MeOH)
([26]: [a]rD:t:
77 (c ˆ 2.8, MeOH)). E.r. (S)/(R) 94.5 : 5.5, tR (R) ˆ 19.77, tR (S) ˆ 19.20 min. Tˆ 150 ! 1728
with 18/min, 130 kPa.
(S)-1-(Naphthalen-2-yl)ethanol (12): 1-(Naphthalen-2-yl)ethanone (340 mg, 2.00 mmol) was treated with
Ph2SiH2 (406 ml, 2.20 mmol) according to GP 4 at 08 to yield 12 (301 mg, 87%). [a]Dr:t:
30.5 (c ˆ 1.00,
MeOH) ([27]: [a]Dr:t:
41.1 (c ˆ 6.01, EtOH)). E.r. (S)/(R) 90 : 10. tR (R) ˆ 18.60, tR (S) 18.92 min. T 150 !
1708 with 18/min, 130 kPa.
ˆ
ˆ
ˆ
ˆ
(S)-1-Phenylpropan-1-ol (13). Propiophenone (266 ml, 2.00 mmol) was treated with Ph2SiH2 (406 ml,
2.20 mmol) according to GP 4 at 08 to yield 13 (221 mg, 81%). [a]Dr:t:
ˆ
27.3 (c ˆ 1.21, CHCl3) ([28]: [a]Dr:t:
ˆ
46.3 (c ˆ 1.12, CHCl3)). E.r. (S)/(R) 82 : 18. tR (R) 9.95, tR (S) ˆ 10.20 min. T 110 ! 1288 with 1.58/min, 130 kPa.
(S)-1-Phenyl-2-methylpropan-1-ol (14). Isobutyrophenone (305 ml, 2.00 mmol) was treated with Ph2SiH2
(406 ml, 2.20 mmol) according to GP 4 at r.t. to yield 14 (258 mg, 87%). [a]Dr:t:
ˆ
1.1 (c ˆ 3.40, Et2O) ([29]:
35 (c ˆ 1.0, MeCN)). E.r. (S)/(R) 51.5 : 48.5. tR (R) 19.49, tR (S) 20.00 min. Tˆ 100 ! 1228 with 18/
min, 130 kPa.
[a]rD:t:
ˆ
(R)-1-Phenyl-2,2-dimethylpropan-1-ol (15). Pivalophenone (336 ml, 2.00 mmol) was treated with Ph2SiH2
(406 ml, 2.20 mmol) according to GP 4 at r.t. to yield 15 (224 mg, 69%). [a]rD:t: ˆ ‡ 2.2 (c ˆ 2.00, Et2O) ([30]:
[a]Dr:t: ˆ ‡ 39.2 (c ˆ 0.12, Et2O, (R)-isomer)). E.r. (R)/(S) 53 : 47. tR (S) 32.53, tR (R) 32.97 min. T 90 ! 1258
with 18/min, 130 kPa.
(R)-2-Chloro-1-phenylethanol (16): Phenacyl chloride (309 mg, 2.00 mmol) was treated with Ph2SiH2
(406 ml, 2.20 mmol) according to GP 4 at 08 to yield 16 (279 mg, 89%). [a]Dr:t:
ˆ
38.4 (c ˆ 2.15, C6H12) ([31]:
49.9 (c ˆ 2.00, C6H12, (R)-isomer)). E.r. (R)/(S) 91.5 : 8.5. tR (R) 29.17, tR (S) 29.95 min. Tˆ 100 !
1328 with 18/min, 130 kPa.
[a]rD:t:
ˆ
(‡)-(S)-1,2,3,4-Tetrahydronaphthalen-1-ol (17). 1,2,3,4-Tetrahydronaphthalen-1-one (267 ml, 2.00 mmol)
was treated with Ph2SiH2 (406 ml, 2.20 mmol) according to GP 4 at 08 to yield 17 (206 mg, 70%). [a]rD:t: ˆ ‡ 28.5
(c ˆ 0.70, CHCl3) ([32]: [a]rD:t: ˆ ‡ 34.4 (c ˆ 1.01, CHCl3)). E.r. (S)/(R) 90 : 10. tR (R) 33.13 min, tR (S)
32.53 min. Tˆ 100 ! 1358 with 18/min, 130 kPa.
(
)-(S)-3,4-Dihydro-2H-1-benzopyran-4-ol (18). 3,4-Dihydro-2H-1-benzopyran-4-one (296 mg, 2.00 mmol)
was treated with Ph2SiH2 (406 ml, 2.20 mmol) according to GP 4 at 08 to yield 18 (258 mg, 86%). [a]Dr:t:
ˆ
59.7
(c ˆ 1.48, CHCl3) ([33]: [a]Dr:t:
ˆ
69.1 (c ˆ 1.1, CHCl3)). E.r. (S)/(R) 93.5 : 6.5. tR (R) 44.12, tR (S) 44.46 min.
Tˆ 90 ! 1408 with 18/min, 130 kPa.
(S)-Butan-2-ol (19). Butan-2-one (180 ml, 2.00 mmol) was treated with Ph2SiH2 (406 ml, 2.20 mmol)
according to GP 4 at 08 to yield 19 (> 99% conversion by 1H-NMR). The (S)-configuration was determined by
comparison of the tR values with an enantiomerically pure sample of the commercially available (S)-isomer. E.r.
(S)/(R) 78 : 22. tR (R) 12.06, tR (S) ˆ 12.40 min. Tˆ 35 ! 458 with 0.58/min, 40 kPa.
(S)-3-Methylbutan-2-ol (20): 3-Methylbutan-2-one (214 ml, 2.00 mmol) was treated with Ph2SiH2 (406 ml,
1
2.20 mmol) according to GP 4 at 08 to yield 20 (> 99% conversion by H-NMR). The (S)-configuration was
assigned by analogy to 19, 22, and 23. E.r. (S)/(R) 88 : 12. tR 12.73, 13.08 min. Tˆ 40 ! 558 with 18/min, 60 kPa.
(S)-3,3-Dimethylbutan-2-ol (21). 3,3-Dimethylbutan-2-one (247 ml, 2.00 mmol) was treated with Ph2SiH2
(406 ml, 2.20 mmol) according to GP 4 at 08 to yield 21 (> 99% conversion by 1H-NMR). The (S)-configuration
was assigned by analogy to 19, 22, and 23. E.r. (S)/(R) 96.5 : 3.5. tR 15.74, 16.57 min. Tˆ 508, 80 kPa.
(‡)-(S)-Octan-2-ol (22). Octan-2-one (315 ml, 2.00 mmol) was treated with Ph2SiH2 (406 ml, 2.20 mmol)
according to GP 4 at 08 to yield 22 (238 mg, 91%). [a]rD:t: ˆ ‡ 4.0 (c ˆ 1.00, EtOH) ([34]: [a]rD:t: ˆ ‡ 10.5 (c ˆ 0.2,

Helvetica Chimica Acta ± Vol. 82 (1999)
1109
EtOH)). E.r. (S)/(R) 71 : 29. tR (R) 36.83, tR (S) 35.99 min (trifluoroacetyl (TFA) derivative). Tˆ 50 ! 608
with 0.258/min, 40 kPa.
(S)-1-Cyclohexylethanol (23). 1-Cyclohexylethanone (275 ml, 2.00 mmol) was treated with Ph2SiH2 (406 ml,
2.20 mmol) according to GP 4 at 08 to yield 23 (216 mg, 84%). [a]rD:t: ˆ ‡ 5.0 (c ˆ 2.00, Et2O) ([35]: [a]rD:t:
ˆ
8.1 (c ˆ 0.48, Et2O, (R)-isomer)). E.r. (S)/(R) 84 : 16. tR (R) 24.84, tR (S) 24.23 min (TFA derivative).
T 60 ! 758, 60 kPa.
(
)-(S)-2,3,4,5-Tetrahydro-3-hydroxy-4,4-dimethylfuran-2-one (( )-d-Pantolactone) (24). 2,3,4,5-Tetrahy-
dro-4,4-dimethylfuran-2,3-dione (256 mg, 2.00 mmol) was treated with Ph2SiH2 (406 ml, 2.20 mmol) according to
GP 4 (THF was used as solvent) at 08 to yield 24 (198 mg, 76%). [a]rD:t: ˆ ‡ 40.0 (c ˆ 1.20, CHCl3) ([36]: [a]rD:t:
‡ 49.9 (c ˆ 1.00, CHCl3)). E.r. (S)/(R) 92 : 8. tR (S) 10.64, tR (R) 11.82 min. Tˆ 1108, 130 kPa.
ˆ
(
)-(S)-2,3,4,5-Tetrahydro-5-methylfuran-2-one (25). Ethyl 4-oxopentanoate (285 ml, 2.00 mmol) was
treated with Ph2SiH2 (406 ml, 2.20 mmol) according to GP 4 (THF was used as solvent) at 08 to yield 25 (142 mg,
71%) after desilylation with acidic MeOH. [a]Dr:t:
ˆ
22.0 (c ˆ 0.98, CHCl3). ([37]: [a]Dr:t:
ˆ
29 (c ˆ 2.25,
CHCl3)). E.r. (S)/(R) 87 : 13. tR (R) 18.40, tR (S) 18.71 min. Tˆ 60 ! 808 with 18/min, 130 kPa.
Ethyl (‡)-(S)-3-Hydroxypentanoate (26): Ethyl 4-oxopentanonate (285 ml, 2.00 mmol) was treated with
Ph2SiH2 (406 ml, 2.20 mmol) according to GP 4 at 08 to yield 26 (142 mg, 71%) after desilylation with pure
MeOH. [a]rD:t: ˆ ‡ 10.7 (c ˆ 1.45, CHCl3) ([38]: [a]Dr:t: ˆ ‡ 12.8 (c ˆ 2.37, CHCl3)). E.r. (S)/(R) 90 : 10.
1
Determination of e.r. by H- and 19F-NMR of the 3,3,3-trifluoro-2-methoxy-2-phenylpropanoic acid (MTPA)
ester, d(MeO) 3.56 for (R)- and 3.54 for (S)-enantiomer; d(CF3)
71.43 for (R)- and
71.47 for (S)-
enantiomer.
Derivatization with Trifluoroacetic Anhydride. The alcohol (0.05 mmol) was dissolved in CH2Cl2 (0.3 ml).
Trifluoroacetic anhydride (0.5 mmol) was added and the mixture kept at ambient temp. for 5 h, concentrated in
a stream of Ar and dissolved in Et2O (1 ml). The soln. was used directly for the GC determination of the e.r.
Preparation of the Mosher Ester. The alcohol (0.03 mmol), 4-(dimethylamino)pyridine (DMAP)
(0.3 mmol) and (R)-MTPA-Cl (0.04 mmol) were added to CDCl3 (0.5 ml). The mixture was shaken and kept
for 10 min. Et2O (10 ml) was added and the mixture extracted with 1m HCl, H2O and sat. NaHCO3 soln. (10 ml
each). The org. phase was concentrated, the residue of which was dissolved in CDCl3 and filtered to be analyzed.
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Received April 19, 1999