Desymmetrizing hydroformylation of diallylcarbinols with the aid of a planar-chiral, catalyst-directing group

Article abstract of DOI:10.1002/ejoc.200500294

The desymmetrizing hydroformylation of diallylcarbinols has been achieved by employing a planar-chiral, substrate-bound catalyst-directing group - the ortho-(diphenylphosphanyl)ferrocenylcarbonyl group (o-DPPF). The method allows the simultaneous construction of two stereogenic centers in a 1,3-relative position with high levels of stereocontrol. The diastereoselectivity was investigated as a function of substrate structure. Determination of the relative and absolute configuration of the product aldehydes (chemical derivatization and X-ray crystallographic studies), as well as the conditions for removal and recovery of the catalyst-directing o-DPPF group, are described. Furthermore, a model is suggested that rationalizes the experimentally observed stereochemical result based on the minimization of syn-pentane interactions. Wiley-VCH Verlag GmbH & Co. KGaA, 2005.

Full text of DOI:10.1002/ejoc.200500294

FULL PAPER
Desymmetrizing Hydroformylation of Diallylcarbinols with the Aid of a
Planar-Chiral, Catalyst-Directing Group[‡]
Bernhard Breit*[a] and Daniel Breuninger[a]
Keywords: Asymmetric synthesis / Catalysis / C–C coupling / Desymmetrization / Hydroformylation
The desymmetrizing hydroformylation of diallylcarbinols has
been achieved by employing a planar-chiral, substrate-
bound catalyst-directing group − the ortho-(diphenylphos-
phanyl)ferrocenylcarbonyl group (o-DPPF). The method al-
lows the simultaneous construction of two stereogenic cen-
ters in a 1,3-relative position with high levels of stereocontrol.
The diastereoselectivity was investigated as a function of
substrate structure. Determination of the relative and abso-
lute configuration of the product aldehydes (chemical
derivatization and X-ray crystallographic studies), as well as
the conditions for removal and recovery of the catalyst-di-
recting o-DPPF group, are described. Furthermore, a model
is suggested that rationalizes the experimentally observed
stereochemical result based on the minimization of syn-pen-
tane interactions.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2005)
nols 3.[9] This allows for the preparation of enantiomerically
and diastereomerically pure acyclic aldehyde building
blocks 4 with two new stereogenic centers − a secondary
alcohol and a tertiary carbon center − in a 1,3-position, a
structural motif which is found in a number of biologically
important natural products (Scheme 1).
Introduction
The hydroformylation of alkenes is a synthetically at-
tractive catalytic carbon–carbon bond-forming reaction
which is in agreement with the criteria of atom economy.[1]
The control of stereochemistry can be achieved either by
employing catalysts modified with chiral phosphorus-based
ligands[2] or, alternatively, by relying on substrate-bound
catalyst-directing groups (CDG).[3,4] In the latter case, ef-
ficient 1,2- and 1,3-asymmetric induction employing chiral
allylic or homoallylic alcohol derivatives has been achieved
using the ortho-(diphenylphosphanyl)benzoate function (o-
DPPB) as the catalyst-directing group.[4] For instance, hy-
droformylation of homomethallylic o-DPPB esters 1 fur-
nishes the anti-aldehydes 2 with good levels of acyclic ste-
reocontrol.[5] However, if prochiral substrates are to be em-
ployed, the chirality information has to reside in the cata-
lyst-directing group. As a first example of this approach, we
recently introduced the planar-chiral ortho-(diphenylphos-
phanyl)ferrocenylcarbonyl function (o-DPPF),[6–8] which
was used successfully as a chiral catalyst-directing group to
achieve desymmetrizing hydroformylation of dialkenylcar-
binols (see preceding paper in this journal).[7] Furthermore,
the same group has been successfully applied as a reagent-
directing leaving group for enantioselective allylic substitu-
tion with organocopper reagents.[8]
Scheme 1. Concept of desymmetrizing hydroformylation of dial-
lylcarbinols with the aid of o-DPPF as a planar-chiral, substrate-
bound catalyst-directing group (CDG*).
We report herein, in full detail, the extension of this con-
cept to a desymmetrizing hydroformylation of diallylcarbi-
Results
[‡] Substrate-Directed Diastereoselective Hydroformylations, 6.
Part 5: Ref.[7]
Diallylcarbinols of structure 6 are rare in the literature.
A general procedure for their preparation involves addition
of allylmetal reagents derived from bromides 5a–e to ethyl
formate (Table 1). Notably, reactions involving allylzinc rea-
[a] Albert-Ludwigs-Universität Freiburg, Institut für Organische
Chemie und Biochemie
Albertstr 21, 79104 Freiburg, Germany
Fax: +49-761-203-8715
E-mail: bernhard.breit@organik.chemie.uni-freiburg.de
3930
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejoc.200500294
Eur. J. Org. Chem. 2005, 3930–3941

Desymmetrizing Hydroformylation of Diallylcarbinols
FULL PAPER
gents proceeded with best chemoselectivity due to the sig- Table 2. Prepartion of diallylcarbinol o-DPPF esters 7.
nificantly reduced amount of homocoupling products.[10]
Table 1. Preparation of diallylcarbinols 6a–e.
Entry
R
Product
ee [%][a]
Yield [%][b]
1
2
3
4
5
6
7
8
9
Me
Me
Et
Et
iPr
iPr
Ph
Ph
rac-7a
(Rp)-7a
rac-7b
(Rp)-7b
rac-7c
–
Ͼ99
–
Ͼ99
–
64
61
69
85
67
93
67
69
64
83
(Rp)-7c
rac-7d
(Rp)-7d
rac-7e
Ͼ99
–
Ͼ99[c]
–
CH2OTBS
CH2OTBS
10
(Rp)-7e
Ͼ99
Entry
R
Product
Method
Yield [%]
[a] Determined by HPLC. [b] Isolated yield after chromatographic
separation. [c] Determined at the stage of diol anti-11d by HPLC
(OD-H).
1
2
3
4
5
Me
Et
iPr
6a
6b
6c
6d
6e
1A
1B
1B
1B
1B
52
96
98
93
39
Ph
CH2OTBS
Hydroformylation of Diallylcarbinol o-DPPF Esters
Stereoselective mono(hydroformylation) of diallylcarbi-
Since traditional esterification protocols failed to form nol o-DPPF esters requires a simultaneous differentiation
reasonable amounts of the desired diallylcarbinol o-DPPF of diastereotopic alkene faces and diastereotopic alkene
esters 7, we employed our recently developed dual acti- groups. Hence, four different diastereomeric monoal-
vation strategy.[7] In situ activation of the carboxylic acid dehydes may be formed. Additionally, the situation may be
with BOP as the hydroxybenzotriazol ester, followed by ad- complicated by dialdehyde formation.
dition of the alcohol 6 activated as the corresponding so-
With these difficulties in mind it is remarkable to note
dium alkoxide, led to the formation of the desired bis(ho- that hydroformylation of o-DPPF ester 7 proceeded
moallylic) o-DPPF esters 7 in satisfactory to good yields smoothly at temperatures between 40 and 60 °C and 40 bar
(Table 2). These compounds were obtained as orange solids of syngas at catalyst loadings of 1.8 mol-% to give essen-
or oils, which needed to be stored under argon to avoid tially a single monoaldehyde diastereomer anti-9 in good
phosphane oxidation. HPLC analysis on chiral columns yield (Table 3). The reactions were complete in most cases
(see Exp. Sect.) established enantiomeric purities of Ͼ99%. after approximately 24 h. However, since at conversions
Table 3. Desymmetrizing hydroformylation of diallylcarbinol o-DPPF esters 7.
Entry
Substrate
R
T [°C]
t [h]
Conv.[a] [%]
dr[a] anti-9/syn-9
Yield[b] [%]
1
2
3
4
5
6
7
8
9
rac-7a
rac-7a
(Rp)-7a
rac-7b
(Rp)-7b
rac-7c
Me
Me
Me
Et
Et
iPr
iPr
iPr
Ph
50
40
50
50
50
60
50
60
70
70
50
50
21.5
48
21.5
21
21
24
48
24
24
24
88
80
91
84
83
87
72
81
81
96:4
97:3
96:4
95:5
95:5
87:13
87:13
86:14
94:6
94:6
95:5
96:4
89[c]
79[c]
83[c]
88[c]
85[c]
91[c]
91[c]
84[c]
84[c]
90[c]
85
rac-7c
(Rp)-7c
rac-7d
(Rp)-7d
rac-7e
10
11
12
Ph
CH2OTBS
CH2OTBS
82
quant.
quant.
16
16
(Rp)-7e
80
[a] Determined from the 1H NMR spectrum of the crude product. [b] Isolated yield after chromatographic purification. [c] Based on
recovered starting material.
Eur. J. Org. Chem. 2005, 3930–3941
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© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3931

B. Breit, D. Breuninger
FULL PAPER
greater than 90% unselective dialdehyde formation could hydroxide solution gave the alcohols 13 as well as o-DPPFA
be detected, the reactions were usually stopped at conver- (8) [Equation (2)] in good yields.
sions of less than 90%. The diastereoselectivity was found
to be almost independent of the nature of the substituent
R. Thus, 7 with methyl, ethyl, phenyl, and (silyloxy)methyl
substituents yielded diastereoselectivities in the order of
Ͼ94:6. An exception is the isopropyl substituent (Table 3,
Entries 6–8), which gave a slightly reduced diastereoselectiv-
ity of 87:13.
(2)
In order to check that hydroformylation with enantio-
merically pure derivatives 7 proceeded without racemiza-
tion, the enantiomeric purity of the aldehyde products 9
had to be determined. Unfortunately, these aldehydes were
not stable enough under the conditions of HPLC analysis,
which required subsequent transformation to a derivative
more suitable to chromatographic analysis. In the case of
anti-9e the aldehyde was reduced to the corresponding pri-
mary alcohol, and HPLC analysis showed anti-10e to be an
essentially enantiomerically pure compound [Equation (1)].
Determination of the Relative and Absolute Configuration
of Product Aldehydes 9
In order to determine the relative and absolute configu-
ration of aldehydes 9, the aldehyde function from rac-anti-
13 was liberated and the resulting lactol was oxidized to
give the δ-lactone 14. NOESY experiments established the
diequatorial arrangement of the substituents at C-4 and C-
6, which is equivalent to the anti relation for the acyclic
structure (Scheme 2).
(1)
In all other cases (9a–d) the o-DPPF group was removed
reductively with DIBAL prior to analysis of the enantio-
meric purity of the resulting diols 11a–d (Table 4).
Table 4. Reductive removal of o-DPPF and determination of ee.
Scheme 2. Determination of the relative configuration.
In order to determine the absolute configuration of the
hydroformylation products 9, alcohol (–)-13c [dr 95:5, ob-
tained from the hydroformylation of (Rp)-7c] was subjected
to a Mosher ester analysis. Comparison of the chemical-
shift differences in both diastereomeric Mosher esters al-
lowed us to assign the (S)-configuration for the stereogenic
center at C1 (Scheme 3).[11] Hence, the major dia-
stereomeric aldehyde anti-9c obtained by hydroformylation
of the dipropenylcarbinol o-DPPF ester (Rp)-7c has the
configuration (Rp,3S,5S)-9c. The absolute and relative con-
figuration of aldehydes 9a,b,d,e was assigned by analogy.
Final unequivocal proof for the relative configuration of
stereogenic centers at C-1 and C-3 came from an X-ray
crystal structure analysis of rac-anti-9a (Figure 1). The ab-
solute configuration of the minor diastereomer syn-9 has
not been determined explicitly. However, it is likely that the
minor diastereomer will have the same absolute configura-
Entry Substrate
Yield [%]
o-DPPFCH2OH (12)
Yield [%]
ee [%]
11
1
2
3
4
5
6
7
8
rac-9a
(Rp)-9a
rac-9b
(Rp)-9b
rac-9c
(Rp)-9c
rac-9d
(Rp)-9d
78
79
54
74
89
91
75
78
90
91
86
78
63
82
96
86
–
Ͼ99[a]
–
Ͼ99[a]
–
Ͼ99[a]
–
Ͼ99[b]
[a] Determined by GC (Supelco BetaDex110). [b] Determined by
HPLC (OD-H).
Removal and Recovery of the Catalyst-Directing o-DPPF
Group
The o-DPPF group could be removed and recovered af- tion at C-1 (Scheme 3) as determined for the major dia-
ter protection of the aldehyde as the dimethyl acetal. Sa- stereomer anti-9c. This assumption is reasonable since pre-
ponification of the ester function with ethanolic potassium vious investigations on hydroformylation of the closely re-
3932
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2005, 3930–3941

Desymmetrizing Hydroformylation of Diallylcarbinols
FULL PAPER
Discussion and Model for 1,3-Asymmetric
Induction
From the absolute and relative configuration of monoal-
dehydes 9a it follows that the hydroformylation of dial-
lylcarbinol o-DPPF esters 7 occurs with excellent dia-
stereotopic face discrimination and presumably perfect dia-
stereotopic group discrimination. Diastereotopic face dis-
crimination is almost independent of the nature of the R
substituent: only in the case of the isopropyl substituent,
which has an increased steric demand (Table 3, Entries 6–
8), was a diminished diastereoselection noted. Hence, dis-
crimination of the diastereomeric alkene faces seems to be
inherent to the 2-substituted homoallylic system. A similar
observation has been made previously when studying the o-
DPPB-directed hydroformylation of chiral homomethallylic
alcohol o-DPPB esters (Scheme 1, 1 Ǟ 2).[5] In this case a
stereochemical model based on force-field conformational
studies as well as NMR studies in solution could be de-
vised. Thus, a chelating binding mode of the substrate
through coordination of the alkene and the catalyst-direct-
ing o-DPPB group, which provides the most stable hydro-
metalation transition state, controls the stereochemical out-
come of the o-DPPB-directed hydroformylation reac-
tion.[4,5,12] In the course of this model minimization of the
syn-pentane interaction in the substrate skeleton between
the 2-substituent at the alkene and the C–O bond attached
to the catalyst-directing group proved decisive.
Scheme 3. Determination of the absolute configuration of (–)-13
[obtained from (Rp)-7c] by Mosher ester analysis [δS and δR refer to
the absolute configuration of the Mosher acid (MTBA) employed].
lated chiral homomethallylic o-DPPB esters 1 (Scheme 1)
have shown that a minor syn diastereomer of aldehyde 2 is
expected from imperfect diastereofacial discrimination.
A similar model, modified by exchanging o-DPPB with
the planar-chiral o-DPPF group, allows us to rationalize
the stereochemical outcome of the directed desymmetrizing
hydroformylation of diallylcarbinol o-DPPF esters
7
(Scheme 4).
Comparison of the relative stabilities of the chelating (al-
kene)rhodium complexes A–D, which serve as models for
the competing rate- and selectivity-determining hydrometal-
ation transition states, should allow us to predict the stereo-
chemistry of the directed hydroformylation. Thus, for (Rp)-
o-DPPF esters 7 the relative stabilities of the two dia-
stereomeric complexes A and B, and the corresponding
transition states for hydrometalation, decide the alkene face
Figure 1. X-ray crystal structure analysis of rac-anti-9a.
Scheme 4. Model for desymmetrizing hydroformylation of dialkenylcarbinol o-DPPF esters 7.
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B. Breit, D. Breuninger
FULL PAPER
momethyl)-1-butene (5b),[13] 2-(bromomethyl)-3-methyl-1-butene
(5c),[14] 1-bromo-2-phenyl-2-propene (5d),[15] 2-[(tert-butylsilyloxy)-
methyl]-2-propen-1-ol,[16] and o-DPPFA (8).[17] PE = petroleum
ether; MTBE = tert-butyl methyl ether; Cy = cyclohexane; EE =
ethyl acetate; BOP = (benzotriazol-1-yloxy)tris(dimethylamino)-
phosphonium hexafluorophosphate; PCC = pyridinium chloro-
chromate.
diastereoselectivity of the reaction. Minimization of the
syn-pentane interaction should lead, via A, to the major
diastereomer anti-9. The reaction via chelation mode B pre-
sumably furnishes the minor diastereomer syn-9. In fact,
NOESY experiments indicate a preferred ground-state con-
formation similar to the one depicted for A. Interestingly,
inspection of the X-ray plot of anti-9a depicted in Figure 1
shows the same conformation for the alkene moiety of anti-
9a in the solid state.
Group diastereoselectivity is determined by the relative
stabilities of the hydrometalation transition states resulting
from chelate complexes C and D vs. A and B. Thus, coordi-
nation of the opposite diastereotopic alkene group requires
a bond-rotation process (i in Scheme 4). However, such a
chelating binding mode is prohibited because of severe ste-
ric hindrance between the ferrocene nucleus and the rho-
dium center.[7] Hence, alkene group diastereoselectivity is
perfect and neither the diastereomer syn-9aЈ nor anti-9aЈ is
observed.
Synthesis of Diallylcarbinols 6
2,6-Dimethylhepta-1,6-dien-4-ol (6a): Freshly distilled 3-bromo-2-
methylprop-1-ene (5a; 6.70 g, 0.05 mol) in Et2O (40 mL) was
added, over 2 h, to magnesium turnings (3.61 g, 0.149 mol,
3.0 equiv.) in Et2O (20 mL) while the temperature was kept at
25 °C. After stirring for an additional 10 min, the supernatant solu-
tion was transferred into a separate flask, cooled to 0 °C, and a
solution of ethyl formate (1.83 g, 0.025 mol, 0.5 equiv.) in Et2O
(4 mL) was added slowly. The solution was allowed to warm to
room temperature and was stirred for 1 h. The reaction mixture
was quenched by addition of satd. aqueous NH4Cl solution
(100 mL), the organic phase was separated, and the aqueous phase
was extracted with Et2O (3×30 mL). The combined organic phases
were dried (Na2SO4), concentrated, and purified by flash
chromatography (PE/MTBE, 50:1) to furnish 6a (1.81 g, 0.013 mol,
1
52%) as a colorless liquid. Rf (PE/MTBE, 50:1) = 0.05. H NMR
(400 MHz, CDCl3): δ = 1.77 (s, 6 H), 1.83 (br. s, 1 H), 2.15 (dd, J
= 14.0, 8.2 Hz, 2 H), 2.20 (dd, J = 14.0, 5.2 Hz, 2 H), 3.89 (tt, J =
8.2, 5.2 Hz, 1 H), 4.80 (s, 2 H), 4.87 (quint, 2 H, J = 1.7 Hz) ppm.
13C NMR (100.6 MHz, CDCl3): δ = 22.6 (2 C), 45.8 (2 C), 66.6,
113.3 (2 C), 142.8 (2 C) ppm.
Conclusions
Use of the chiral, substrate-bound, catalyst-directing o-
DPPF group allows a desymmetrizing hydroformylation of
diallylcarbinols to be achieved with excellent levels of ste-
reocontrol. Thus, two new stereogenic centers in a 1,3-rela-
tion, namely a tertiary carbon center and a secondary O-
substituted stereocenter, are formed simultaneously. The
catalyst-directing o-DPPF group can be removed and reco-
vered easily, thus furnishing interesting chiral building
blocks in enantiomerically pure form.
General Procedure 1 (GP1). Reaction of Allylzinc Reagents with
Ethyl Formate: In a three-necked flask equipped with a reflux con-
denser and argon inlet, zinc dust (Ͻ45 µm, 2.0 equiv.) was flame-
dried under vacuum until sublimation occurred. After cooling to
25 °C, the thermally activated zinc was suspended in THF (2 mL/
mmol allyl bromide) and subsequently treated with 1,2-dibromo-
ethane (3 cycles, total 0.2 equiv.) followed by refluxing. Then,
TMSCl was added (3 cycles, total 0.08 equiv.) without external
heating and, after cooling to 25 °C, allyl bromide (5) was added
(1 equiv.) dropwise from a syringe and the mixture was stirred for
the indicated period of time. Then, ethyl formate (0.3 equiv.) was
added in one portion and the mixture was again stirred at 25 °C for
6–8 h until complete consumption of the starting material. After
quenching of the reaction mixture with satd. aqueous NH4Cl
(2 mL/mmol allyl bromide) and addition of MTBE (2 mL/mmol
allyl bromide), the phases were separated. The aqueous phase was
extracted with MTBE (4 times) and the combined organic phases
were dried (Na2SO4), concentrated, and the residue was purified
by flash chromatography to furnish the diallylcarbinols 6 in analyti-
cally pure form.
Experimental Section
General: Reactions were performed in flame-dried glassware under
argon. The solvents were dried by standard procedures, distilled,
and stored under argon. All temperatures quoted are not corrected.
NMR spectra were obtained with a Varian Mercury spectrometer
(300 MHz, 121.5 MHz, and 75.5 MHz for H, 31P, and 13C respec-
1
1
tively), a Bruker AMX 400 (400 MHz and 100.6 MHz for H and
13C, respectively), or a Bruker DRX 500 (500 MHz and 125 MHz
1
for H and 13C, respectively) and are referenced internally accord-
ing to residual protonated solvent signals (31P NMR: 85% H3PO4
as external standard). Melting points: Melting point apparatus by
Dr. Tottoli (Büchi). Elemental analyses: Elementar Vario EL (Ele- 3,7-Dimethylenenonan-5-ol (6b): Zinc dust (990 mg, 15.1 mmol,
mentar-Analysensysteme GmbH). Flash chromatography: Silica
gel Si 60, E. Merck AG, Darmstadt, 40–63 µm. High-resolution
mass spectra were obtained with a Finnigan MAT 8200 instrument.
Enantiomeric excesses (ee) were determined by HPLC using Daicel
Chiralpak AD, AD-H, and Chiralcel OD-H columns (wavelengths
245 nm) with 2-propanol/heptane as the eluent or by GC using a
Supelco Betadex 110 (30 m×0.25 mm, 0.25 µm film thickness) with
helium 4.6 (Messer-Griesheim). Optical rotations were measured
with a Perkin–Elmer 241 polarimeter. Hydroformylation reactions
were performed in 50- and 100-mL stainless-steel autoclaves
equipped with magnetic stirrers. Gases: carbon monoxide 3.7, hy-
drogen 4.3 (1:1, Messer-Griesheim). The following compounds
2.0 equiv.) in THF (15 mL) was activated with dibromoethane
(129 µL, 1.5 mmol, 0.20 equiv.) and TMSCl (75 µL, 0.6 mmol,
0.08 equiv.) according to GP1. After addition of 2-(bromomethyl)-
1-butene (5b; 1.112 g, 7.5 mmol) and stirring for 16 h, ethyl formate
(166 mg, 2.2 mmol, 0.30 equiv.) was added to the mixture by sy-
ringe. After workup and flash chromatography (PE/MTBE, 25:1),
the title compound 6b (361 mg, 2.1 mmol, 95%) was isolated as a
colorless liquid. Rf (Cy/EE, 10:1) = 0.14. 1H NMR (300 MHz,
CDCl3): δ = 1.05 (t, J = 7.5 Hz, 6 H), 1.86 (d, J = 2.1 Hz, 1 H),
2.00–2.30 (m, 8 H), 3.87 (mc, 1 H), 4.83 (s, 2 H), 4.88 (q, J =
1.6 Hz, 2 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 12.4 (2 C),
28.9 (2 C), 44.4 (2 C), 67.0, 111.0 (2 C), 148.4 (2 C) ppm. C11H20O
were prepared according to literature procedures: 2-(bro- (168.3): calcd. C 78.51, H 11.98; found C 78.25, H 11.68.
3934 © 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim www.eurjoc.org
Eur. J. Org. Chem. 2005, 3930–3941

Desymmetrizing Hydroformylation of Diallylcarbinols
FULL PAPER
2,8-Dimethyl-3,7-dimethylenenonan-5-ol (6c): Zinc dust (6.664 g,
101.9 mmol, 2.0 equiv.) in THF (100 mL) was activated with dibro-
moethane (0.87 mL, 10.1 mmol, 0.20 equiv.) and TMSCl (0.53 mL,
4.1 mmol, 0.08 equiv.) according to GP1. After addition of 2-(bro-
momethyl)-3-methyl-1-butene (5c; 8.281 g, 50.8 mmol) and stirring
for 12.5 h, ethyl formate (1.19 g, 16.1 mmol, 0.30 equiv.) was added
to the mixture by syringe. After workup and flash chromatography
(PE/MTBE, 25:1), the title compound 6c (3.089 g, 15.7 mmol,
98%) was isolated as a colorless liquid. Rf (Cy/EE, 10:1) = 0.26.
1H NMR (400 MHz, CDCl3): δ = 1.04 (d, J = 6.9 Hz, 6 H), 1.06
(d, J = 6.9 Hz, 6 H), 1.92 (d, J = 1.7 Hz, 1 H), 2.16 (dd, J = 14.2,
8.2 Hz, 2 H), 2.26 (sept, J = 6.9 Hz, 2 H), 2.28 (dd, J = 14.2,
0.9 Hz, 2 H), 3.88 (mc, 1 H), 4.82 (d, J = 1.3 Hz, 2 H), 4.91 (s, 2
H) ppm. 13C NMR (100.6 MHz, CDCl3): δ = 21.8 (2 C), 22.0 (2
C), 33.7 (2 C), 42.9 (2 C), 67.6, 109.5 (2 C), 153.0 (2 C) ppm.
C13H24O (196.3): calcd. C 79.53, H 12.32; found C 79.33, H 12.46.
0.92 (s, 18 H), 2.16 (dd, J = 14.1, 8.2 Hz, 2 H), 2.30 (dd, J = 14.1,
4.3 Hz, 2 H), 3.01 (d, J = 2.8 Hz, 1 H), 3.87 (mc, 1 H), 4.11 (s, 4
H), 4.93 (s, 2 H), 5.14 (d, J = 1.6 Hz, 2 H) ppm. 13C NMR
(75.5 MHz, CDCl3): δ = –5.3 (4 C), 18.5 (2 C), 26.0 (6 C), 41.6 (2
C), 66.6 (2 C), 69.0, 112.8 (2 C), 145.8 (2 C) ppm. C21H44O3Si2
(400.8): calcd. C 62.94, H 11.07; found C 63.12, H 11.20.
General Procedure 2 (GP2). Esterification Protocol: Under light
protection, o-DPPFA (8) and the alcohol 6 were dissolved in THF
(10 mL/mmol o-DPPFA) and BOP (1.0–1.1 equiv.) was added.
NaH (2.5–3.0 equiv.) was added to this mixture and the reaction
mixture was stirred at 25 °C for the indicated period of time. The
reaction mixture was quenched with water (2 equiv.), silica gel was
added, and all volatile components were removed in vacuo. Flash
chromatography [the product fraction (orange) was collected in a
flask under argon and the solvents were removed in an argon-
purged rotary evaporator due to the air sensitivity of the o-DPPF
esters] furnished the corresponding ester 7, which was dried at
60 °C/0.1 mbar overnight.
2,6-Diphenyl-1,6-heptadien-4-ol (6d): Zinc dust (3.52 g, 53.8 mmol,
2.0 equiv.) in THF (54 mL) was activated with dibromoethane
(465 µL, 5.4 mmol, 0.20 equiv.) and TMSCl (270 µL, 2.1 mmol,
0.08 equiv.) according to GP1. After addition of 1-bromo-2-phenyl-
2-propene (5d; 5.31 g, 26.9 mmol) and stirring for 14 h, ethyl for-
mate (0.66 mL, 8.2 mmol, 0.30 equiv.) was added to the mixture by
syringe. After workup and flash chromatography (PE/MTBE,
10:1), the title compound 6d (2.01 g, 7.6 mmol, 93%) was isolated
as a white solid. Rf (Cy/EE, 10:1) = 0.10; m.p. 55 °C. 1H NMR
(400 MHz, CDCl3): δ = 1.84 (br. s, 1 H), 2.69 (dd, J = 14.2, 7.3 Hz,
2 H), 2.80 (ddd, J = 14.2, 5.2, 0.9 Hz, 2 H), 3.79 (mc, 1 H), 5.18
(d, J = 0.9 Hz, 2 H), 5.43 (d, J = 1.3 Hz, 2 H), 7.25–7.36 (m, 10
H) ppm. 13C NMR (100.6 MHz, CDCl3): δ = 43.1 (2 C), 67.8,
115.2 (2 C), 126.2 (4 C), 127.7 (2 C), 128.4 (4 C), 140.3 (2 C), 145.3
(2 C) ppm. C19H20O (264.4): calcd. C 86.32, H 7.63; found C 85.93,
H 7.83.
[3-Methyl-1-(2-methylallyl)but-3-enyl] (Rp)-2-(Diphenylphosphanyl)-
ferrocenecarboxylate (7a). rac-7a: As described in GP2, rac-o-
DPPFA (8; 563 mg, 1.36 mmol), alcohol 6a (212 mg, 1.51 mmol,
1.1 equiv.), BOP (644 mg, 1.46 mmol, 1.1 equiv.), and NaH
(135 mg, 60% in mineral oil, 3.41 mmol, 2.5 equiv.) in THF
(14 mL) gave, after 19.5 h and flash chromatography (PE/EE, 25:1),
the title compound rac-7a (470 mg, 0.88 mmol, 64%) as an orange
solid. (Rp)-7a: (Rp)-o-DPPFA (8; 532 mg, 1.28 mmol, ee Ͼ 99%) in
THF (13 mL) was deprotonated with tBuLi (0.78 mL, 1.65  in
pentane, 1.29 mmol, 1.01 equiv.) at –78 °C and was then added to
a solution of BOP (612 mg, 1.38 mmol, 1.08 equiv.) in THF
(13 mL) at 25 °C over 30 min. After stirring for 1 h, the alcohol 6a
(213 mg, 1.52 mmol, 1.19 equiv.) in THF (6 mL) was deprotonated
with tBuLi (0.92 mL, 1.65  in pentane, 1.52 mmol, 1.19 equiv.) in
a separate flask at –78 °C and the alkoxide solution was then added
[2-(Bromomethyl)allyloxy](tert-butyl)dimethylsilane (5e): PPh3
(6.460 g, 24.6 mmol, 1.3 equiv.) in CH2Cl2 (80 mL) was cooled to to the reaction mixture. After stirring for 2 h, workup as described
–78 °C and NBS (4.399 g, 24.7 mmol, 1.3 equiv.) was added in one
portion. After stirring for 15 min, 2-[(tert-butylsilyloxy)methyl]-2-
propen-1-ol (3.910 g, 19.3 mmol) was added and the solution was
allowed to warm to –60 °C and was stirred for 1 h. Then, the mix-
ture was allowed to warm to –20 °C during 1 h, stirred at this tem-
perature for another 30 min, and was then quenched with satd.
aqueous NaHCO3 solution (80 mL). The aqueous phase was ex-
tracted with CH2Cl2 (50 mL) and the combined organic phases
were dried (MgSO4) and concentrated. Flash chromatography
(neutral Al2O3, deactivated with 10% water, PE/MTBE, 25:1) af-
forded the title compound 5e (3.814 g, 14.4 mmol, 75%) as a color-
in GP2, and flash chromatography (PE/EE, 25:1), the title com-
pound (Rp)-7a (420 mg, 0.78 mmol, 61%, ee Ͼ 99%) was obtained
as an orange solid. Data for 7a: Rf (Cy/EE, 10:1) = 0.38; m.p. 98 °C.
1H NMR (400 MHz, CDCl3): δ = 1.68 (s, 3 H), 1.71 (s, 3 H), 1.88
(dd, J = 14.2, 5.6 Hz, 1 H), 2.04 (dd, J = 14.2, 7.3 Hz, 1 H), 2.18
(dd, J = 14.2, 4.2 Hz, 1 H), 2.31 (dd, J = 14.2, 8.6 Hz, 1 H), 3.64
(br. s, 1 H), 4.17 (s, 5 H), 4.38 (pseudo t, J = 2.5 Hz, 1 H), 4.53 (s,
1 H), 4.69 (s, 1 H), 4.76 (s, 1 H), 4.84 (s, 1 H), 5.01 (br. s, 1 H),
5.29 (mc, 1 H), 7.15–7.20 (m, 2 H), 7.21–7.25 (m, 3 H), 7.32–7.36
(m, 3 H), 7.41–7.47 (m, 2 H) ppm. 13C NMR (100.6 MHz, CDCl3):
δ = 22.46, 22.53, 42.6, 42.8, 70.2, 71.1 (5 C), 71.5, 74.0, 75.2 (d,
JC,P = 4.4 Hz), 76.1 (d, JC,P = 14.5 Hz), 79.4 (d, JC,P = 17.4 Hz),
1
less liquid. Rf (Cy/EE, 5:1) = 0.61. H NMR (300 MHz, CDCl3):
δ = 0.10 (s, 6 H), 0.92 (s, 9 H), 4.01 (s, 2 H), 4.27 (s, 2 H), 5.22–
113.1, 113.5, 127.9, 128.1 (d, JC,P = 5.8 Hz, 2 C), 128.2 (d, JC,P =
5.26 (m, 2 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ = –5.3 (2 C), 7.3 Hz, 2 C), 129.0, 132.5 (d, JC,P = 18.9 Hz, 2 C), 135.1 (d, JC,P
18.4, 26.0 (3 C), 32.9, 63.6, 114.9, 145.0 ppm. C10H21BrOSi (265.3):
calcd. C 45.28, H 7.98; found C 45.34, H 7.94.
= 21.8 Hz, 2 C), 138.6 (d, JC,P = 14.6 Hz), 139.9 (d, JC,P = 14.6 Hz),
141.8, 141.9, 170.7 (d, JC,P = 2.9 Hz) ppm. 31P NMR (121.5 MHz,
CDCl3): δ = –15.8 ppm. C32H33FeO2P (536.4): calcd. C 71.65, H
6.20; found C 71.30, H 6.30. HPLC [AD, heptane/2-propanol
(99:1), 15 °C, 0.8 mLmin–1]: tR[(Sp)-7a] = 10.25 min; tR[(Rp)-7a] =
13.05 min. [α]2D0 = +153 (c = 0.875, CHCl3).
2,6-Bis[(tert-butyldimethylsilyloxy)methyl]hepta-1,6-dien-4-ol (6e):
Zinc dust (1.875 g, 28.7 mmol, 2.0 equiv.) in THF (29 mL) was acti-
vated with dibromoethane (0.25 mL, 2.9 mmol, 0.20 equiv.) and
TMSCl (0.15 mL, 1.2 mmol, 0.08 equiv.) according to GP1. After
addition of [2-(bromomethyl)allyloxy](tert-butyl)dimethylsilane
(5e; 3.81 g, 14.4 mmol) and stirring for 14 h, ethyl formate (0.36 g,
4.8 mmol, 0.30 equiv.) was added to the mixture by syringe. After
workup, the crude product was stirred with K2CO3 (0.50 g) in
methanol (5 mL) for 90 min. Filtration, removal of the solvent, and
flash chromatography (PE/TBME, 50:1) afforded the title com-
pound 6e (0.752 g, 1.9 mmol, 39%) as a colorless liquid. Rf (Cy/
3-Methylene-1-(2-methylenebutyl)pentyl
(Rp)-2-(Diphenylphos-
phanyl)ferrocenecarboxylate (7b). rac-7b: As described in GP2, rac-
o-DPPFA (8; 565 mg, 1.36 mmol), alcohol 6b (248 mg, 1.47 mmol,
1.1 equiv.), BOP (627 mg, 1.42 mmol, 1.0 equiv.), and NaH
(131 mg, 60% in mineral oil, 3.30 mmol, 2.4 equiv.) in THF
(11 mL) gave, after 16 h and flash chromatography (PE/EE, 50:1),
the title compound rac-7b (529 mg, 0.94 mmol, 69%) as an orange
solid. (Rp)-7b: As described in GP2, (Rp)-o-DPPFA (460 mg,
1
EE, 10:1) = 0.12. H NMR (300 MHz, CDCl3): δ = 0.08 (s, 12 H),
Eur. J. Org. Chem. 2005, 3930–3941
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3935

B. Breit, D. Breuninger
FULL PAPER
1.11 mmol, ee
Ͼ
99%), alcohol 6b (201 mg, 1.19 mmol,
DPPFA (8; 425 mg, 1.02 mmol), alcohol 6d (297 mg, 1.12 mmol,
1.1 equiv.), BOP (518 mg, 1.17 mmol, 1.2 equiv.), and NaH
(107 mg, 60% in mineral oil, 2.69 mmol, 2.6 equiv.) in THF
(20 mL) gave, after 18 h, workup, and flash chromatography (PE/
EE, 25:1), the title compound rac-7d (453 mg, 0.69 mmol, 67%) as
an orange solid. (Rp)-7d: As described in GP2, (Rp)-o-DPPFA (8;
1.07 equiv.), BOP (527 mg, 1.19 mmol, 1.1 equiv.), and NaH
(113 mg, 60% in mineral oil, 2.85 mmol, 2.57 equiv.) in THF
(11 mL) gave, after 19.5 h and flash chromatography (PE/EE, 50:1),
the title compound (Rp)-7b (535 mg, 0.95 mmol, 85%, ee Ͼ 99%)
as an orange solid. Data for 7b: Rf (Cy/EE, 10:1) = 0.45; m.p. 91–
1
94 °C. H NMR (500 MHz, CDCl3): δ = 0.96 (t, J = 7.4 Hz, 3 H), 569 mg, 1.37 mmol, ee Ͼ 99%), alcohol 6d (403 mg, 1.52 mmol,
0.99 (t, J = 7.4 Hz, 3 H), 1.88 (dd, J = 14.2, 5.8 Hz, 1 H), 1.94–
2.13 (m, 5 H), 2.23 (dd, J = 14.3, 4.5 Hz, 1 H), 2.29 (dd, J = 14.3,
1.11 equiv.), BOP (628 mg, 1.42 mmol, 1.04 equiv.), and NaH
(140 mg, 60% in mineral oil, 3.52 mmol, 2.57 equiv.) in THF
8.5 Hz, 1 H), 3.64 (ddd, J = 2.5, 1.4, 0.9 Hz, 1 H), 4.19 (s, 5 H), (14 mL) gave, after 19 h, workup, and flash chromatography (PE/
4.40 (pseudo t, J = 2.5 Hz, 1 H), 4.60 (s, 1 H), 4.72 (d, J = 1.5 Hz, EE, 25:1) the title compound (Rp)-7d (620 mg, 0.94 mmol, 69%, ee
1 H), 4.77 (d, J = 1.5 Hz, 1 H), 4.89 (s, 1 H), 5.02 (pseudo quint, Ͼ 99%) as an orange solid. Data for 7d: Rf (Cy/EE, 10:1) = 0.35;
1
J = 1.2 Hz, 1 H), 5.27 (mc, 1 H), 7.17–7.21 (m, 2 H), 7.22–7.26 m.p. 119 °C. H NMR (400 MHz, CDCl3): δ = 2.13 (dd, J = 14.2,
(m, 3 H), 7.34–7.38 (m, 3 H), 7.44–7.49 (m, 2 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 12.23, 12.26, 28.67, 28.70, 41.1, 41.4, 70.7,
7.1 Hz, 1 H), 2.65 (dd, J = 14.2, 6.9 Hz, 1 H), 2.76 (d, J = 6.5 Hz,
2 H), 3.65 (br. s, 1 H), 4.16 (s, 5 H), 4.39 (pseudo t, J = 2.5 Hz, 1
H), 4.93 (m, 2 H), 5.12 (quint, J = 6.9 Hz, 1 H), 5.32 (d, J = 0.9 Hz,
1 H), 5.34 (s, 1 H), 5.40 (d, J = 1.3 Hz, 1 H), 7.17–7.51 (m, 20 H)
ppm. 13C NMR (100.6 MHz, CDCl3): δ = 39.2, 39.4, 71.2 (5 C),
71.5, 71.6, 74.0, 75.4 (d, JC,P = 4.4 Hz), 75.7 (d, JC,P = 13.1 Hz),
79.5 (d, JC,P = 16.0 Hz), 115.0, 115.6, 126.18 (2 C), 126.21 (2 C),
127.5, 127.7, 128.2, 128.26 (d, JC,P = 6.7 Hz, 2 C), 128.28 (d, JC,P
71.1 (5 C), 71.6, 74.0, 75.3 (d, JC,P = 4.8 Hz), 76.1 (d, JC,P
=
14.5 Hz), 79.4 (d, JC,P = 16.7 Hz), 110.7, 111.0 (d, JC,P = 1.8 Hz),
128.0, 128.1 (d, JC,P = 6.7 Hz, 2 C), 128.2 (d, JC,P = 7.3 Hz, 2 C),
129.0, 132.5 (d, JC,P = 19.7 Hz, 2 C), 135.1 (d, JC,P = 21.8 Hz, 2
C), 138.6 (d, JC,P = 14.5 Hz), 139.9 (d, JC,P = 13.9 Hz), 147.3,
147.4, 170.8 (d, JC,P = 3.3 Hz) ppm. 31P NMR (121.5 MHz,
CDCl3): δ = –16.8 ppm. C34H37FeO2P (564.5): calcd. C 72.34, H
6.61; found C 72.18, H 6.71. HPLC [AD, heptane/2-propanol
(200:1), 15 °C, 0.5 mLmin–1]: tR[(Rp)-7b] = 9.71 min; tR[(Sp)-7b] =
15.31. [α]2D0 = +140 (c = 0.735, CHCl3).
= 7.0 Hz, 2 C), 128.4 (2 C), 128.5 (2 C), 129.0, 132.6 (d, JC,P
18.9 Hz, 2 C), 135.0 (d, JC,P = 20.4 Hz, 2 C), 138.5 (d, JC,P
=
=
13.1 Hz), 139.9, 140.1 (d, JC,P = 13.1 Hz), 140.2, 144.32, 144.36,
170.8 (d, JC,P = 2.9 Hz) ppm. 31P NMR (121.5 MHz, CDCl3): δ
= –16.5 ppm. C42H37FeO2P (660.6): calcd. C 76.37, H 5.65; found
C 76.13, H 5.80. HPLC: baseline separation of the enantiomers
could not be achieved. [α]2D0 = +107 (c = 0.62, CHCl3).
4-Methyl-3-methylene-1-(3-methyl-2-methylenebutyl)pentyl (Rp)-2-
(Diphenylphosphanyl)ferrocenecarboxylate (7c). rac-7c: As de-
scribed in GP2, rac-o-DPPFA (8; 1.61 g, 3.89 mmol), alcohol 6c
(0.84 g, 4.27 mmol, 1.1 equiv.), BOP (1.90 g, 4.30 mmol, 1.1 equiv.),
and NaH (0.41 g, 60% in mineral oil, 10.3 mmol, 2.6 equiv.) in
THF (40 mL) gave, after 15 h, workup, flash chromatography (PE/
3-[(tert-Butyldimethylsilyloxy)methyl]-1-{2-[(tert-butyldimethylsil-
yloxy)methyl]allyl}but-3-enyl (Rp)-2-(Diphenylphosphanyl)ferrocene-
carboxylate (7e). rac-7e: As described in GP2, rac-o-DPPFA (8;
EE, 50:1), and drying of the product at 80 °C/0.1 mbar, the title 622 mg, 1.50 mmol), alcohol 6e (605 mg, 1.51 mmol, 1.0 equiv.),
compound rac-7c (1.55 g, 2.62 mmol, 67%) as an orange oil, which
crystallized slowly on standing at 4 °C. (Rp)-7c: As described in
GP2, (Rp)-o-DPPFA (8; 424 mg, 1.02 mmol, ee Ͼ 99%), alcohol 6c
BOP (698 mg, 1.58 mmol, 1 equiv.), and NaH (150 mg, 60% in
mineral oil, 3.79 mmol, 2.5 equiv.) in THF (15 mL) gave, after 21 h,
workup, and flash chromatography (PE/EE, 50:1), the title com-
(213 mg, 1.08 mmol, 1.06 equiv.), BOP (482 mg, 1.09 mmol, pound rac-7e (766 mg, 0.96 mmol, 64%) as an orange oil. (Rp)-7e:
1.07 equiv.), and NaH (119 mg, 60% in mineral oil, 2.99 mmol,
2.94 equiv.) in THF (10 mL) gave, after 16.5 h, workup, flash
chromatography (PE/EE, 50:1), and drying of the product at 80 °C/
As described in GP2, (Rp)-o-DPPFA (8; 424 mg, 1.02 mmol, ee Ͼ
99%), alcohol 6e (410 mg, 1.02 mmol, 1.00 equiv.), BOP (476 mg,
1.08 mmol, 1.06 equiv.), and NaH (116 mg, 60% in mineral oil,
0.1 mbar, the title compound (Rp)-7c (563 mg, 0.95 mmol, 93%, ee 2.92 mmol, 2.87 equiv.) in THF (10 mL) gave, after 18 h, workup,
Ͼ 99%) as an orange oil, which crystallized slowly on standing at and flash chromatography (PE/EE, 50:1), the title compound (Rp)-
4 °C. Data for 7c: Rf (Cy/EE, 10:1): 0.59; m.p. 70–71 °C. 1H NMR 7e (678 mg, 0.85 mmol, 83%, ee Ͼ 99%) as an orange oil. Data for
(400 MHz, CDCl3): δ = 0.97 (d, J = 6.9 Hz, 3 H), 0.98 (d, J =
7e: Rf (Cy/EE, 10:1) = 0.55. 1H NMR (400 MHz, CDCl3): δ = 0.06
7.3 Hz, 3 H), 1.00 (d, J = 7.3 Hz, 3 H), 1.01 (d, J = 6.9 Hz, 3 H), (s, 6 H), 0.07 (s, 6 H), 0.90 (s, 9 H), 0.91 (s, 9 H), 1.98 (d, J =
1.84 (dd, J = 14.6, 6.4 Hz, 1 H), 2.07 (dd, J = 14.6, 6.9 Hz, 1 H),
2.20 (sept, J = 6.9 Hz, 1 H), 2.28 (d, J = 6.5 Hz, 2 H), 2.30 (m, 1
H), 3.65 (br. s, 1 H), 4.20 (s, 5 H), 4.40 (pseudo t, J = 2.6 Hz, 1
H), 4.63 (s, 1 H), 4.78 (s, 1 H), 4.80 (s, 1 H), 4.91 (s, 1 H), 5.03
(pseudo quint, J = 1.3 Hz, 1 H), 5.29 (pseudo quint, J = 6.6 Hz, 1
6.4 Hz, 2 H), 2.26 (dd, J = 14.6, 8.2 Hz, 1 H), 2.34 (dd, J = 14.6,
4.3 Hz, 1 H), 3.66 (br. s, 1 H), 3.97 (d, J = 14.0 Hz, 1 H), 4.04 (d,
J = 10.3 Hz, 2 H), 4.12 (d, J = 14.0 Hz, 1 H), 4.18 (s, 5 H), 4.40
(pseudo t, J = 2.6 Hz, 1 H), 4.67 (s, 1 H), 5.00–5.04 (m, 3 H), 5.10
(d, J = 1.7 Hz, 1 H), 5.25 (mc, 1 H), 7.16–7.26 (m, 5 H), 7.34–7.37
H), 7.18–7.26 (m, 5 H), 7.34–7.38 (m, 3 H), 7.44–7.49 (m, 2 H) (m, 3 H), 7.44–7.50 (m, 2 H) ppm. 13C NMR (100.6 MHz, CDCl3):
ppm. 13C NMR (100.6 MHz, CDCl3): δ = 21.7, 21.8 (2 C), 22.0,
δ = –5.26 (2 C), –5.23 (2 C), 18.4 (2 C), 26.03 (3 C), 26.06 (3 C),
33.3, 33.5, 39.4, 39.7, 71.1 (5 C), 71.3, 71.5, 74.0, 75.2 (d, JC,P 37.8, 37.9, 65.7, 65.9, 70.6, 71.2 (5 C), 71.6, 74.1, 75.3 (d, JC,P
4.4 Hz), 76.0 (d, JC,P = 14.5 Hz), 79.3 (d, JC,P = 17.4 Hz), 111.6,
112.1, 128.0, 128.17 (d, JC,P = 5.8 Hz, 2 C), 128.23 (d, JC,P
=
=
4.4 Hz), 76.1 (d, JC,P = 14.5 Hz), 79.5 (d, JC,P = 17.4 Hz), 109.4,
109.6, 128.0, 128.1 (d, JC,P = 7.3 Hz, 2 C), 128.2 (d, JC,P = 7.3 Hz,
2 C), 129.0, 132.5 (d, JC,P = 20.3 Hz, 2 C), 135.1 (d, JC,P = 10.4 Hz,
2 C), 138.7 (d, JC,P = 14.5 Hz), 139.9 (d, JC,P = 14.5 Hz), 151.7,
151.9, 170.8 (d, JC,P = 2.9 Hz) ppm. 31P NMR (121.5 MHz,
CDCl3): δ = –16.8 ppm. C36H41FeO2P (592.5): calcd. C 72.97, H
6.97; found C 72.82, H 6.99. HPLC [AD-H, heptane/2-propanol
(400:1), 20 °C, 0.5 mLmin–1]: tR[(Rp)-7c] = 9.25 min; tR[(Sp)-7c] =
12.84 min. [α]2D0 = +129 (c = 1.435, CHCl3, ee Ͼ 99%).
=
7.3 Hz, 2 C), 129.0, 132.5 (d, JC,P = 20.3 Hz, 2 C), 135.1 (d, JC,P
= 21.8 Hz, 2 C), 138.6 (d, JC,P = 14.5 Hz), 140.0 (d, JC,P = 13.1 Hz),
144.5, 144.6, 170.7 ppm. 31P NMR (121 MHz, CDCl3): δ =
–17.01 ppm. C44H61FeO4PSi2 (797.0): calcd. C 66.31, H 7.71; found
C 66.53, H 7.70. HPLC [AD-H, heptane/2-propanol (400:1), 20 °C,
0.5 mLmin–1]: tR[(Sp)-7e] = 9.36 min; tR[(Rp)-7e] = 11.51 min.
[α]2D0 = +110 (c = 0.73, CHCl3).
3-Phenyl-1-(2-phenylallyl)but-3-enyl (Rp)-2-(Diphenylphosphanyl)- Rhodium-Catalyzed Desymmetrizing Hydroformylation of Dial-
ferrocenecarboxylate (7d). rac-7d: As described in GP2, rac-o-
lylcarbinol o-DPPF Esters 7
3936
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 3930–3941

Desymmetrizing Hydroformylation of Diallylcarbinols
FULL PAPER
General Procedure 3 (GP3). Hydroformylation Protocol: The ester
7 was dissolved in THF and [Rh(CO)2acac] was added (a small gas
evolution of CO was visible). After addition of P(OPh)3, the orange
solution was transferred with a syringe into an oven-dried (70 °C)
stainless-steel tube autoclave; the flask and syringe were rinsed
twice with THF (final ester concentration: 0.1 ). The argon in the
autoclave was removed by a pressurizing/depressurizing cycle (three
times 20 bar H2/CO), and finally the autoclave was pressurized with
40 bar H2/CO and heated in an oil bath to the reaction temperature
for the indicated period of time. Subsequently, the autoclave was
cooled to 25 °C, depressurized, and the solution was filtered
through a plug of Celite, washed with MTBE, and the solvents
were removed in vacuo. Conversion and diastereoselectivity were
determined by NMR analysis of the crude mixture (in CDCl3, con-
version was determined by integration of the aldehyde signals rela-
tive to the NMR signals of the olefinic protons of the starting ma-
terial; diastereoselecitivity was determined by integration of the al-
dehyde signals). Purification of the products was achieved by flash
chromatography (the orange fraction was collected in a flask under
argon and the solvents were removed in an argon-purged rotary
evaporator) followed by drying of the product aldehyde 9 at 60 °C/
0.1 mbar for several hours.
7.38 (m, 3 H), 7.43–7.48 (m, 2 H), 9.86 (pseudo t, J = 2.0 Hz, 1 H)
ppm. 13C NMR (125 MHz, CDCl3): δ = 19.3, 22.4, 24.9 (d, JC,P
=
3.3 Hz), 41.3, 43.4, 51.7, 69.7, 71.1 (5 C), 71.7, 74.2, 75.4 (d, JC,P
= 4.2 Hz), 75.9 (d, JC,P = 14.8 Hz), 79.4 (d, JC,P = 15.4 Hz), 113.4,
128.1, 128.2 (d, JC,P = 7.0 Hz, 2 C), 128.3 (d, JC,P = 7.3 Hz, 2 C),
129.1, 132.5 (d, JC,P = 19.7 Hz, 2 C), 135.0 (d, JC,P = 21.5 Hz, 2
C), 138.2 (d, JC,P = 13.6 Hz), 139.8 (d, JC,P = 13.2 Hz), 141.5, 171.0
(d, JC,P = 3.0 Hz), 202.7 ppm. 31P NMR (121.5 MHz, CDCl3): δ
= –16.3 ppm. C33H35FeO3P (566.5): calcd. C 69.97, H 6.23; found
C 69.81, H 6.19. [α]2D0 = +121 (c = 0.79, CHCl3, dr 96:4).
(1S,3S)-3-Ethyl-1-(2-methylenebutyl)-5-oxopentyl (Rp)-2-(Diphenyl-
phosphanyl)ferrocenecarboxylate (9b). rac-9b: According to GP3,
hydroformylation of rac-7b (290.3 mg, 0.51 mmol) was carried out
with [Rh(CO)2acac] (2.4 mg, 9.3 µmol, 0.018 equiv.) and P(OPh)3
(9.6 µL, 0.037 mmol, 0.072 equiv.) in THF (5.1 mL) at 50 °C for
21 h. The NMR spectrum of the crude product showed a conver-
sion of 84% and the resulting aldehydes were obtained in a dia-
stereomeric ratio of 95:5. Flash chromatography (PE/EE, 50:1) fur-
nished starting material (35.1 mg, 0.06 mmol, 12%) and, after in-
creasing the polarity of the eluent (PE/EE, 10:1), the aldehyde rac-
9b (235.2 mg, 0.40 mmol, 88% based on recovered starting mate-
rial, dr 96:4) as an orange solid. (Rp)-9b: According to GP3, hydro-
formylation of (Rp)-7b (482.8 mg, 0.86 mmol) was carried out with
[Rh(CO)2acac] (4.0 mg, 15.5 µmol, 0.018 equiv.) and P(OPh)3
(16.1 µL, 0.061 mmol, 0.072 equiv.) in THF (8.6 mL) at 50 °C for
21 h. The NMR spectrum of the crude product showed a conver-
sion of 83% and the resulting aldehydes were obtained in a dia-
stereomeric ratio of 96:4. Flash chromatography (PE/EE, 50:1) fur-
nished starting material (59.5 mg, 0.11 mmol, 12%) and, after in-
creasing the polarity of the eluent (PE/EE, 10:1), the aldehyde (Rp)-
9b (380.1 mg, 0.64 mmol, 85% based on recovered starting mate-
rial, dr 96:4) as an orange solid. Data for 9b: Rf (Cy/EE, 10:1) =
(1S,3S)-3-Methyl-1-(2-methylallyl)-5-oxopentyl (Rp)-2-(Diphenyl-
phosphanyl)ferrocenecarboxylate (9a)
rac-9a. Variation 1: According to GP3, hydroformylation of rac-7a
(261.3 mg, 0.49 mmol) was carried out with [Rh(CO)2acac]
(2.3 mg, 8.9 µmol, 0.018 equiv.) and P(OPh)3 (9.2 µL, 0.035 mmol,
0.072 equiv.) in THF (4.9 mL) at 50 °C for 21.5 h. The NMR spec-
trum of the crude product showed a conversion of 88% and the
resulting aldehydes were obtained in a diastereomeric ratio of 96:4.
Flash chromatography (PE/EE, 20:1), furnished starting material
(25.5 mg, 0.05 mmol, 10%) and after increasing the polarity of the
eluent (PE/EE, 10:1) the aldehyde rac-9a (222.2 mg, 0.39 mmol,
89% based on recovered starting material, dr 97:3) as an orange
solid. Variation 2: According to GP3, hydroformylation of rac-7a
(209.7 mg, 0.39 mmol) was carried out with [Rh(CO)2acac]
(1.8 mg, 7.0 µmol, 0.018 equiv.) and P(OPh)3 (7.4 µL, 0.028 mmol,
0.072 equiv.) in THF (3.9 mL) at 40 °C for 48 h. The NMR spec-
trum of the crude product showed a conversion of 80% and the
resulting aldehydes were obtained in a diastereomeric ratio of 97:3.
Flash chromatography (PE/EE, 20:1) furnished the starting mate-
rial (40.3 mg, 0.08 mmol, 19%) and, after increasing the polarity
of the eluent (PE/EE, 10:1), the aldehyde rac-9a (140.6 mg,
0.25 mmol, 79% based on recovered starting material, dr 97:3) as
an orange solid.
1
0.20; m.p. 96–97 °C. H NMR (500 MHz, CDCl3): δ = 0.80 (t, J =
7.4 Hz, 3 H), 0.99 (t, J = 7.4 Hz, 3 H), 1.29 (dq, J = 21.1, 7.4 Hz,
1 H), 1.46–1.56 (m, 3 H), 1.69 (dd, J = 14.1, 6.9 Hz, 1 H), 1.99
(mc, 2 H), 2.08 (dd, J = 14.1, 6.7 Hz, 1 H), 2.15–2.23 (mc, 1 H),
2.30 (ddd, J = 16.0, 7.4, 2.8 Hz, 1 H), 2.46 (ddd, J = 16.0, 6.2,
2.2 Hz, 1 H), 3.66 (ddd, J = 2.5, 1.5, 0.9 Hz, 1 H), 4.21 (s, 5 H),
4.43 (d pseudo t, J = 2.5, 0.5 Hz, 1 H), 4.57 (s, 1 H), 4.72 (d, J =
1.7 Hz, 1 H), 5.06 (ddd, J = 2.5, 1.4, 1.1 Hz, 1 H), 5.16 (mc, 1 H),
7.17–7.22 (m, 2 H), 7.23–7.26 (m, 3 H), 7.34–7.38 (m, 3 H), 7.43–
7.48 (m, 2 H), 9.86 (dd, J = 2.8, 2.2 Hz, 1 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 10.4, 12.3, 25.6, 28.7, 30.8 (d, JC,P
=
2.4 Hz), 38.4, 41.8, 48.3, 70.2, 71.1 (5 C), 71.7, 74.1, 75.4 (d, JC,P
= 4.5 Hz), 75.8 (d, JC,P = 14.8 Hz), 79.4 (d, JC,P = 15.7 Hz), 111.1,
128.1, 128.2 (d, JC,P = 7.0 Hz, 2 C), 128.3 (d, JC,P = 7.3 Hz, 2 C),
129.1, 132.5 (d, JC,P = 19.4 Hz, 2 C), 135.0 (d, JC,P = 21.5 Hz, 2
C), 138.2 (d, JC,P = 13.6 Hz), 139.8 (d, JC,P = 13.4 Hz), 147.0, 171.1
(d, JC,P = 3.0 Hz), 203.3 (d, JC,P = 1.8 Hz) ppm. 31P NMR
(121.5 MHz, CDCl3): δ = –16.5 ppm. C35H39FeO3P (594.5): calcd.
C 70.71, H 6.61; found C 70.48, H 6.63. [α]2D0 = +111 (c = 0.61,
CHCl3, dr 96:4).
(Rp)-9a: According to GP3, hydroformylation of (Rp)-7a (262.4 mg,
0.49 mmol) was carried out with [Rh(CO)2acac] (2.3 mg, 8.9 µmol,
0.018 equiv.) and P(OPh)3 (9.3 µL, 0.036 mmol, 0.072 equiv.) in
THF (4.9 mL) at 50 °C for 21.5 h. The NMR spectrum of the crude
product showed a conversion of 91% and the resulting aldehydes
were obtained in a diastereomeric ratio of 96:4. Flash chromatog-
raphy (PE/EE, 20:1) furnished starting material (16.3 mg,
0.03 mmol, 6%) and, after increasing the polarity of the eluent (PE/
EE, 10:1), the aldehyde (Rp)-9a (217.3 mg, 0.38 mmol, 83% based
on recovered starting material, dr 96:4) as an orange solid.
(1S,3S)-4-Methyl-1-(3-methyl-2-methylenebutyl)-3-(2-oxoethyl)pen-
tyl (Rp)-2-(Diphenylphosphanyl)ferrocenecarboxylate (9c)
rac-9c. Variation 1: According to GP3, hydroformylation of rac-7c
(337.2 mg, 0.57 mmol) was carried out with [Rh(CO)2acac]
(2.6 mg, 10.1 µmol, 0.018 equiv.) and P(OPh)3 (10.7 µL,
0.041 mmol, 0.072 equiv.) in THF (5.7 mL) at 60 °C for 24 h. The
NMR spectrum of the crude product showed a conversion of 87%
and the resulting aldehydes were obtained in a diastereomeric ratio
of 87:13. Flash chromatography (PE/EE, 50:1, stationary phase
neutral Al2O3 deactivated with 10% water) furnished starting mate-
Data for 9a: Rf (Cy/EE, 5:1) = 0.26; m.p. 117 °C. 1H NMR
(500 MHz, CDCl3): δ = 0.97 (d, J = 6.3 Hz, 3 H), 1.32 (ddd, J =
13.9, 9.7, 2.6 Hz, 1 H), 1.60 (ddd, J = 13.9, 10.6, 3.1 Hz, 1 H), 1.68
(s, 3 H), 1.71 (dd, J = 13.7, 7.4 Hz, 1 H), 2.02 (dd, J = 13.7, 6.9 Hz,
1 H), 2.30–2.45 (m, 3 H), 3.67 (br. s, 1 H), 4.22 (s, 5 H), 4.43
(pseudo t, J = 2.5 Hz, 1 H), 4.48 (s, 1 H), 4.69 (s, 1 H), 5.06 (br. s,
1 H), 5.21 (mc, 1 H), 7.18–7.22 (m, 2 H), 7.23–7.26 (m, 3 H), 7.34–
Eur. J. Org. Chem. 2005, 3930–3941
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3937

B. Breit, D. Breuninger
FULL PAPER
rial (29.7 mg, 0.05 mmol, 9%) and, after increasing the polarity of
the eluent (PE/EE, 25:1), the aldehyde rac-9c (294.0 mg, 0.47 mmol,
91% based on recovered starting material, dr 87:13) as an orange
oil which crystallized slowly on standing at 4 °C. Variation 2: Ac-
cording to GP3, hydroformylation of rac-7c (297.1 mg, 0.50 mmol)
was carried out with [Rh(CO)2acac] (2.3 mg, 8.9 µmol,
0.018 equiv.) and P(OPh)3 (9.5 µL, 0.036 mmol, 0.072 equiv.) in
THF (5.0 mL) at 50 °C for 48 h. The NMR spectrum of the crude
product showed a conversion of 72% and the resulting aldehydes
were obtained in a diastereomeric ratio of 87:13. Flash chromatog-
raphy (PE/EE, 50:1, stationary phase neutral Al2O3 deactivated
with 10% water) furnished starting material (75.4 mg, 0.13 mmol,
25%) and, after increasing the polarity of the eluent (PE/EE, 25:1),
the aldehyde rac-9c (211.0 mg, 0.34 mmol, 91% based on recovered
starting material, dr 87:13) as an orange oil which crystallized
slowly on standing at 4 °C.
sion of 82% and the resulting aldehydes were obtained in a dia-
stereomeric ratio of 94:6. Flash chromatography (PE/EE, 10:1) fur-
nished starting material (59.5 mg, 0.09 mmol, 14%) and, after in-
creasing the polarity of the eluent (PE/EE, 5:1), the aldehyde (Rp)-
9d (352.2 mg, 0.51 mmol, 90% based on recovered starting mate-
rial, dr 94:6) as an orange solid. Data for 9d: Rf (Cy/EE, 10:1) =
1
0.16; m.p. 158–162 °C (decomp.). H NMR (400 MHz, CDCl3): δ
= 1.67 (ddd, J = 14.2, 9.9, 3.9 Hz, 1 H), 1.80 (m, 2 H), 2.59 (ddd,
J = 16.1, 6.9, 2.6 Hz, 1 H), 2.67 (ddd, J = 16.1, 8.2, 2.2 Hz, 1 H),
2.78 (dd, J = 14.2, 6.6 Hz, 1 H), 3.55 (mc, 1 H), 3.68 (br. s, 1 H),
4.25 (s, 5 H), 4.45 (pseudo t, J = 2.6 Hz, 1 H), 4.68 (mc, 1 H), 4.81
(s, 1 H), 5.05 (br. s, 1 H), 5.23 (s, 1 H), 6.86–7.53 (m, 20 H), 9.73
(t, J = 2.2 Hz, 1 H) ppm. 13C NMR (100.6 MHz, CDCl3): δ = 36.7
(d, JC,P = 2.9 Hz), 39.2, 39.7, 51.3, 71.06, 71.13 (5 C), 71.8, 74.4,
75.6 (d, JC,P = 4.4 Hz), 75.9 (d, JC,P = 14.5 Hz), 79.2 (d, JC,P
=
16.0 Hz), 115.0, 126.2 (2 C), 126.7, 127.4 (2 C), 127.7, 128.2, 128.3
(d, JC,P = 7.3 Hz, 2 C), 128.37 (d, JC,P = 8.7 Hz, 2 C), 128.42 (2
C), 128.7 (2 C), 129.2, 132.5 (d, JC,P = 18.9 Hz, 2 C), 135.1 (d, JC,P
(Rp)-9c: According to GP3, hydroformylation of (Rp)-7c (301.1 mg,
0.51 mmol) was carried out with [Rh(CO)2acac] (2.4 mg, 9.3 µmol,
0.018 equiv.) and P(OPh)3 (9.6 µL, 0.037 mmol, 0.072 equiv.) in
THF (5.1 mL) at 60 °C for 24 h. The NMR spectrum of the crude
product showed a conversion of 81% and the resulting aldehydes
were obtained in a diastereomeric ratio of 86:14. Flash chromatog-
raphy (PE/EE, 50:1, stationary phase neutral Al2O3 deactivated
with 10% water) furnished starting material (45.1 mg, 0.08 mmol,
15%) and, after increasing the polarity of the eluent (PE/EE, 25:1),
the aldehyde (Rp)-9c (227.5 mg, 0.37 mmol, 84% based on reco-
vered starting material, dr 86:14) as an orange oil.
= 20.3 Hz, 2 C), 138.2 (d, JC,P = 13.1 Hz), 139.9, 140.0 (d, JC,P
=
13.1 Hz), 142.2, 144.3, 170.9 (d, JC,P = 2.9 Hz), 201.9 ppm. 31P
NMR (121.5 MHz, CDCl3): δ = –15.8 ppm. C43H39FeO3P (690.6):
calcd. C 74.79, H 5.69; found C 74.56, H 5.74. [α]2D0 = +48 (c =
0.67, CHCl3, dr 94:6).
(1S,3S)-3-[(tert-Butyldimethylsilyloxy)methyl]-1-{2-[(tert-butyldime-
thylsilyloxy)methyl]allyl}-5-oxopentyl (Rp)-2-(Diphenylphosphanyl)-
ferrocenecarboxylate (9e). rac-9e: According to GP3, hydrofor-
mylation of rac-7e (327.4 mg, 0.41 mmol) was carried out with
[Rh(CO)2acac] (1.9 mg, 7.4 µmol, 0.018 equiv.) and P(OPh)3
(7.8 µL, 0.030 mmol, 0.072 equiv.) in THF (4.1 mL) at 50 °C for
16 h. The NMR spectrum of the crude product showed a quantita-
tive conversion and the resulting aldehydes were obtained in a dia-
stereomeric ratio of 95:5. Flash chromatography (PE/EE, 10:1) fur-
nished the aldehyde rac-9e (287.8 mg, 0.35 mmol, 85%, dr 95:5) as
an orange oil which crystallized slowly upon standing at 4 °C. (Rp)-
9e: According to GP3, hydroformylation of (Rp)-7e (592.5 mg,
0.74 mmol) was carried out with [Rh(CO)2acac] (3.5 mg,
13.6 µmol, 0.018 equiv.) and P(OPh)3 (14.0 µL, 0.053 mmol,
0.072 equiv.) in THF (7.4 mL) at 50 °C for 16 h. The NMR spec-
trum of the crude product showed a quantitative conversion and
the resulting aldehydes were obtained in a diastereomeric ratio of
96:4. Flash chromatography (PE/EE, 10:1) furnished the aldehyde
(Rp)-9e (492.5 mg, 0.60 mmol, 80%, dr 96:4) as an orange oil which
crystallized slowly upon standing at 4 °C. Data for 9e: Rf (Cy/EE,
Data for 9c: Rf (Cy/EE, 5:1) = 0.44; m.p. 70–71 °C. 1H NMR
(400 MHz, CDCl3): δ = 0.75 (d, J = 6.4 Hz, 3 H), 0.84 (d, J =
6.9 Hz, 3 H), 0.97 (d, J = 7.3 Hz, 3 H), 0.99 (d, J = 7.3 Hz, 3 H,
3 H), 1.36 (ddd, J = 14.2, 9.9, 4.3 Hz, 1 H), 1.53–1.67 (m, 2 H),
1.88 (mc, 1 H), 2.09–2.33 (m, 4 H), 2.43 (dd, J = 10.8, 1.7 Hz, 1
H), 3.67 (br. s, 1 H), 4.22 (s, 5 H), 4.43 (pseudo t, J = 2.6 Hz, 1
H), 4.61 (s, 1 H), 4.78 (s, 1 H), 5.06 (pseudo quint, J = 1.3 Hz, 1
H), 5.14 (mc, 1 H), 7.17–7.26 (m, 5 H), 7.34–7.38 (m, 3 H), 7.43–
7.48 (m, 2 H), 9.87 (pseudo t, J = 2.4 Hz, 1 H) ppm. 13C NMR
(100.6 MHz, CDCl3): δ = 16.9, 20.5, 21.7, 21.8, 28.6, 33.6, 34.9,
36.3, 40.0, 44.9, 70.5, 71.1 (5 C), 71.7, 74.1, 75.4 (d, JC,P = 4.4 Hz),
75.9 (d, JC,P = 14.5 Hz), 79.5 (d, JC,P = 16.0 Hz), 109.7, 128.1,
128.2 (d, JC,P = 7.3 Hz, 2 C), 128.3 (d, JC,P = 7.3 Hz, 2 C), 129.1,
132.5 (d, JC,P = 18.9 Hz, 2 C), 135.0 (d, JC,P = 21.8 Hz, 2 C), 138.3
(d, JC,P = 14.5 Hz), 139.8 (d, JC,P = 14.5 Hz), 151.5, 171.1 (d,
JC,P
=
2.9 Hz), 203.6 (CHO) ppm. 31P NMR (121.5 MHz,
1
10:1) = 0.35; m.p. 93 °C. H NMR (500 MHz, CDCl3): δ = 0.007
CDCl3): δ = –16.6 ppm. C37H43FeO3P (622.6): calcd. C 71.38, H
6.96; found C 71.11, H 6.99. [α]2D0 = +106 (c = 0.39, CHCl3, dr
86:14).
(s, 3 H), 0.014 (s, 3 H), 0.046 (s, 3 H), 0.050 (s, 3 H), 0.86 (s, 9 H),
0.89 (s, 9 H), 1.47 (ddd, J = 14.3, 10.4, 3.8 Hz, 1 H), 1.67 (ddd, J
= 14.3, 9.5, 2.9 Hz, 1 H), 1.82 (dd, J = 14.3, 6.1 Hz, 1 H), 1.94 (dd,
J = 14.3, 7.2 Hz, 1 H), 2.36–2.44 (m, 2 H), 2.56 (ddd, J = 17.7, 9.1,
2.5 Hz, 1 H), 3.48 (dd, J = 10.0, 5.8 Hz, 1 H), 3.58 (dd, J = 10.0,
3.5 Hz, 1 H), 3.67 (ddd, J = 2.5, 1.5, 0.9 Hz, 1 H), 3.95 (d, J =
14.1 Hz, 1 H), 4.01 (d, J = 14.1 Hz, 1 H), 4.21 (s, 5 H), 4.43 (pseudo
t, J = 2.5 Hz, 1 H), 4.62 (d, J = 0.8 Hz, 1 H), 5.00 (q, J = 1.7 Hz,
1 H), 5.05 (pseudo quint, J = 1.4 Hz, 1 H), 5.13 (mc, 1 H), 7.17–
7.26 (m, 5 H), 7.34–7.38 (m, 3 H), 7.43–7.48 (m, 2 H), 9.87 (pseudo
t, J = 2.3 Hz, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = –5.47,
–5.45, –5.28, –5.25, 18.3, 18.4, 25.97 (3 C), 26.00 (3 C), 32.9 (d,
JC,P = 2.7 Hz), 35.9, 38.4, 47.3, 64.2, 65.6, 70.1, 71.1 (5 C), 71.7,
[(1S,3S)-5-Oxo-3-phenyl-1-(2-phenylallyl)pentyl] (Rp)-2-(Diphenyl-
phosphanyl)ferrocenecarboxylate (9d). rac-9d: According to GP3,
hydroformylation of rac-9d (431.0 mg, 0.65 mmol) was carried out
with [Rh(CO)2acac] (3.0 mg, 11.6 µmol, 0.018 equiv.) and P(OPh)3
(12.3 µL, 0.047 mmol, 0.072 equiv.) in THF (6.5 mL) at 70 °C for
24 h. The NMR spectrum of the crude product showed a conver-
sion of 81% and the resulting aldehydes were obtained in a dia-
stereomeric ratio of 94:6. Flash chromatography (PE/EE, 10:1) fur-
nished starting material (63.5 mg, 0.10 mmol, 15%) and, after in-
creasing the polarity of the eluent (PE/EE, 5:1), the aldehyde rac-
9d (321.0 mg, 0.47 mmol, 84% based on recovered starting mate-
rial, dr 94:6) as an orange solid. (Rp)-9d: According to GP3, hydro-
formylation of (Rp)-9d (433.2 mg, 0.66 mmol) was carried out with
[Rh(CO)2acac] (3.0 mg, 11.6 µmol, 0.018 equiv.) and P(OPh)3
(12.4 µL, 0.047 mmol, 0.072 equiv.) in THF (6.6 mL) at 70 °C for
24 h. The NMR spectrum of the crude product showed a conver-
74.3 (d, JC,P = 4.2 Hz), 75.9 (d, JC,P = 14.8 Hz), 79.2 (d, JC,P
=
15.7 Hz), 111.9, 128.1, 128.2 (d, JC,P = 7.0 Hz, 2 C), 128.3 (d, JC,P
= 7.0 Hz, 2 C), 129.1, 132.5 (d, JC,P = 19.7 Hz, 2 C), 135.0 (d, JC,P
= 21.5 Hz, 2 C), 138.1 (d, JC,P = 13.3 Hz), 139.9 (d, JC,P = 13.0 Hz),
144.1, 171.0 (d, JC,P = 2.7 Hz), 202.7 ppm. 31P NMR (121.5 MHz,
CDCl3): δ = –16.6 ppm. C45H63FeO5PSi2 (827.0): calcd. C 65.36,
3938
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 3930–3941

Desymmetrizing Hydroformylation of Diallylcarbinols
FULL PAPER
H 7.68; found C 65.34, H 7.65. [α]2D0 = +86 (c = 0.92, CHCl3, dr
97:3).
Ͼ 99%) as a colorless liquid. Data for 11a: Rf (Cy/EE, 5:1) = 0.08.
1H NMR (500 MHz, CDCl3): δ = 0.95 (d, J = 6.6 Hz, 3 H), 1.18
(ddd, J = 12.2, 6.5, 2.8 Hz, 1 H), 1.48–1.54 (m, 3 H), 1.75 (s, 3 H),
1.87 (mc, 1 H), 2.11–2.14 (m, 2 H), 2.1–2.4 (br. s, 1 H), 3.66 (dt, J
= 10.9, 3.7 Hz, 1 H), 3.71 (dt, J = 10.9, 6.7 Hz, 1 H), 3.82 (mc, 1
H), 4.77 (s, 1 H), 4.86 (s, 1 H) ppm. 13C NMR (125 MHz, CDCl3):
δ = 20.0, 22.5, 26.2, 40.5, 44.0, 47.1, 60.5, 66.8, 113.5, 142.8 ppm.
HRMS (EI; C10H20O2 [M – C4H7], 172.3): calcd. 117.0913; found
117.0916. GC (Betadex 110, 105 °C, 18 psi): tR[(4R,6S)-11a] =
99.4 min; tR[(4S,6R)-11a] = 104.0 min. [α]2D0 = –32 (c = 0.895,
CHCl3, dr Ͼ 99:1). Data for 12: Rf (Cy/EE, 1:1) = 0.38; m.p.
Determination of the Enantiomeric Purity of the Hydroformylation
Products. NaBH4 Reduction of 9e
(1S,3R)-3-[(tert-Butyldimethylsilyloxy)methyl]-1-{2-[(tert-butyldi-
methylsilyloxy)methyl]allyl}-5-hydroxypentyl (Rp)-2-(Diphenylphos-
phanyl)ferrocenecarboxylate (10e). rac-10e: rac-9e (73.0 mg,
0.088 mmol, dr 96:4) in methanol (2.0 mL) was treated with NaBH4
(3.5 mg, 0.100 mmol, 1.1 equiv.) at room temperature for 120 min.
Quenching with water (4 equiv.), removal of all volatile components
in vacuo, and subsequent flash chromatography (PE/EE, 25:1) fur-
nished the title compound rac-10e (52.8 mg, 0.064 mmol, 72%, dr
1
146 °C. H NMR (400 MHz, CDCl3): δ = 1.47 (br. t, J = 6.0 Hz,
1 H), 3.76 (br. s, 1 H), 4.10 (s, 5 H), 4.30 (pseudo t, J = 2.6 Hz, 1
H), 4.42 (dd, J = 12.5, 6.0 Hz, 1 H), 4.52 (br. s, 1 H), 4.54 (ddd, J
= 12.5, 6.0, 1.7 Hz, 1 H), 7.19–7.24 (m, 2 H), 7.25–7.29 (m, 3 H),
Ͼ
99:1) as an orange solid. (Rp)-10e: (Rp)-9e (109.3 mg,
0.132 mmol, dr 97:3) in methanol (2.5 mL) was treated with NaBH4
(5.8 mg, 0.153 mmol, 1.2 equiv.) at room temperature for 80 min.
Quenching with water (4 equiv.), removal of all volatile material,
and subsequent flash chromatography (PE/EE, 25:1) furnished the
title compound (Rp)-10e (91.9 mg, 0.111 mmol, 84%, dr Ͼ 99:1, ee
Ͼ 99%) as an orange solid. Data for 10e: Rf (Cy/EE, 10:1) = 0.23;
m.p. 87–89 °C. 1H NMR (500 MHz, CDCl3): δ = 0.03 (s, 3 H), 0.04
(s, 3 H), 0.05 (s, 3 H), 0.06 (s, 3 H), 0.88 (s, 9 H), 0.89 (s, 9 H),
1.51–1.58 (m, 3 H), 1.63 (dd, J = 14.2, 7.2 Hz, 1 H), 1.74 (dd, J =
14.2, 7.2 Hz, 1 H), 1.84 (mc, 1 H), 2.06 (br. s, 1 H), 3.48 (dd, J =
13.2, 7.2 Hz, 1 H), 3.60–3.65 (m, 3 H), 3.73–3.88 (m, 2 H), 3.91 (d,
J = 14.1 Hz, 1 H), 3.97 (d, J = 14.1 Hz, 1 H), 4.23 (s, 5 H), 4.44
(pseudo t, J = 2.5 Hz, 1 H), 4.48 (s, 1 H), 4.93 (s, 1 H), 5.09 (s, 1
H), 5.19 (pseudo quint, J = 6.6 Hz, 1 H), 7.21–7.30 (m, 5 H), 7.34–
7.38 (m, 3 H), 7.43–7.48 (m, 2 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = –5.40, –5.37, –5.30, –5.27, 18.3, 18.4, 26.0 (6 C), 33.4
(d, JC,P = 2.7 Hz), 34.7, 36.2, 38.6, 59.9, 65.1, 65.5, 70.2, 71.2 (5
C), 71.7, 74.8, 75.6 (d, JC,P = 3.9 Hz), 76.0 (d, JC,P = 15.2 Hz), 79.9
(d, JC,P = 15.4 Hz), 111.7, 128.3, 128.4 [d, JC,P = 6.7 Hz, 4 C],
129.3, 132.5 (d, JC,P = 19.4 Hz, 2 C), 135.0 (d, JC,P = 20.9 Hz, 2
C), 138.2 (d, JC,P = 9.1 Hz), 139.1 (d, JC,P = 8.8 Hz), 144.2, 170.9
(d, JC,P = 2.7 Hz) ppm. 31P NMR (121.5 MHz, CDCl3): δ =
–16.6 ppm. C45H65FeO5PSi2 (829.0): calcd. C 65.20, H 7.90; found
C 65.26, H 7.84. HPLC [AD-H, heptane/2-propanol (98:2), 20 °C,
0.8 mLmin–1]: tR[(Rp,1S,3R)-10e] = 8.56 min; tR[(Sp,1R,3S)-10e] =
12.21 min. [α]2D0 = +89 (c = 0.515, CHCl3, dr Ͼ 99:1).
7.37–7.41 (m,
(100.6 MHz, CDCl3): δ = 60.0 (d, JC,P = 10.2 Hz), 69.5 (5 C), 69.7,
71.6 (d, JC,P = 4.4 Hz), 71.7 (d, JC,P = 2.9 Hz), 76.2 (d, JC,P
7.3 Hz), 92.8 (d, JC,P = 23.3 Hz), 128.31 (d, JC,P = 7.3 Hz, 2 C),
3 H), 7.50–7.56 (m, 2
H) ppm. 13C NMR
=
128.32, 128.5 (d, JC,P = 5.8 Hz, 2 C), 129.3, 132.5 (d, JC,P
17.4 Hz, 2 C), 134.9 (d, JC,P = 20.3 Hz, 2 C), 137.0 (d, JC,P
=
=
8.7 Hz), 139.7 (d, JC,P = 10.2 Hz) ppm. 31P NMR (121 MHz,
CDCl3): δ = –22.4 ppm. C23H21FeOP (400.2): calcd. C 69.02, H
5.29; found C 68.81, H 5.49. [α]2D0 = +273 (c = 0.78, CHCl3).
(3R,5S)-3-Ethyl-7-methylenenonane-1,5-diol (11b). rac-11b: rac-9b
(117.2 mg, 0.20 mmol, dr 96:4) in CH2Cl2 (4 mL) was treated with
DIBALH (0.70 mL, 0.70 mmol, 3.5 equiv.) for 2.5 h as described
in GP4. Flash chromatography (PE/TBME, 1:1) furnished rac-12
(68.2 mg, 0.17 mmol, 86%) and, after increasing the polarity of the
eluent (PE/TBME, 1:2), rac-11b (21.2 mg, 0.11 mmol, 54%, dr
96:4) as a colorless liquid. (–)-11b: (Rp)-9b (187.4 mg, 0.32 mmol,
dr 95:5) in CH2Cl2 (6 mL) was treated with DIBALH (1.10 mL,
1.10 mmol, 3.5 equiv.) for 2 h as described in GP4. Flash
chromatography (PE/TBME, 1:1) furnished (Rp)-12 (93.4 mg,
0.23 mmol, 74%) and, after increasing the polarity of the eluent
(PE/TBME, 1:2), (–)-11b (49.0 mg, 0.25 mmol, 78%, dr 98:2, ee Ͼ
99%) as a colorless liquid. Data for 11b: Rf (Cy/EE, 1:1) = 0.16.
1H NMR (500 MHz, CDCl3): δ = 0.88 (t, J = 7.5 Hz, 3 H), 1.04
(t, J = 7.4 Hz, 3 H), 1.29–1.48 (m, 5 H), 1.63–1.72 (m, 2 H), 1.97–
2.12 (m, 4 H), 2.21 (dd, J = 13.7, 3.5 Hz, 1 H), 2.37 (br. s, 1 H),
3.63–3.80 (m, 3 H), 4.82 (s, 1 H), 4.88 (d, J = 1.5 Hz, 1 H) ppm.
13C NMR (125 MHz, CDCl3): δ = 10.8, 12.3, 27.4, 28.7, 32.8, 36.9,
40.8, 45.7, 60.6, 67.9, 111.3, 148.3 ppm. HRMS (EI; C12H24O2
[M – C5H9], 200.3): calcd. 131.1066; found 131.1072. GC (Betadex
110, 140 °C, 10 psi): tR[(3S,5R)-11b] = 58.8 min; tR[(3R,5S)-11b] =
60.3 min. [α]2D0 = –40 (c = 1.395, CHCl3, dr 98:2).
General Procedure 4 (GP4). DIBALH Reduction of 9a–d: The corre-
sponding aldehyde 9 was dissolved in CH2Cl2 and the solution was
cooled to –78 °C. DIBALH (1  solution in cyclohexane) was
added dropwise with a syringe and the reaction mixture was stirred
at –78 °C. The reaction mixture was allowed to warm to 0 °C and
was subsequently quenched with satd. aqueous NH4Cl solution
(6 mL/mmol) and 1  HCl (12 mL/mmol). The aqueous phase was
extracted four times with CH2Cl2, dried (Na2SO4), and all volatile
components removed in vacuo. Purification of the residue by flash
chromatography furnished o-DPPF-CH2OH (12) as well as the cor-
responding diol 11.
(3R,5S)-3-Isopropyl-8-methyl-7-methylenenonane-1,5-diol
(11c).
rac-11c: rac-9c (171.3 mg, 0.28 mmol, dr 87:13) in CH2Cl2 (6 mL)
was treated with DIBALH (1.10 mL, 1.10 mmol, 4.0 equiv.) for 4 h
as described in GP4. Flash chromatography (PE/TBME, 1:1) fur-
nished rac-12 (69.0 mg, 0.17 mmol, 63%) and rac-11c (69.0 mg,
0.25 mmol, 89%, dr = 95:5) as a colorless liquid. Separation of the
(4S,6R)-2,6-Dimethyloct-1-ene-4,8-diol (11a). rac-11a: rac-9a
(85.4 mg, 0.15 mmol, dr 96:4) in CH2Cl2 (2 mL) was treated with diastereomers by a second flash chromatography step (PE/TBME,
DIBALH (0.53 mL, 0.53 mmol, 3.5 equiv.) for 2 h as described in
GP4. Flash chromatography (PE/TBME, 1:1) furnished rac-12
(54.2 mg, 0.14 mmol, 90%) and, after increasing the polarity of the
eluent (PE/TBME, 1:2), rac-11a (20.3 mg, 0.12 mmol, 78%, dr Ͼ
99:1) as a colorless liquid. (–)-11a: (Rp)-9a (85.7 mg, 0.15 mmol,
dr 96:4) in CH2Cl2 (2 mL) was treated with DIBALH (0.57 mL,
0.57 mmol, 3.8 equiv.) for 2 h as described in GP4. Flash
chromatography (PE/TBME, 1:1) furnished (Rp)-12 (55.2 mg,
0.14 mmol, 91%) and, after increasing the polarity of the eluent
(PE/TBME, 1:2), (–)-11a (20.6 mg, 0.12 mmol, 79%, dr Ͼ 99:1, ee
2:1) delivered a diastereomeric mixture of rac-anti/syn-11c (9.5 mg,
0.04 mmol, 15%, dr 85:15) and then pure rac-11c (44.0 mg,
0.19 mmol, 70%, dr Ͼ 99:1) as colorless liquids. (–)-11c: (Rp)-9c
(80.3 mg, 0.13 mmol, dr 87:13) in CH2Cl2 (3 mL) was treated with
DIBALH (0.52 mL, 0.52 mmol, 4.0 equiv.) for 4 h as described in
GP4. Flash chromatography (PE/TBME, 2:1) furnished (Rp)-12
(42.2 mg, 0.11 mmol, 82%), a diastereomeric mixture of anti-/syn-
11c (5.7 mg, 0.03 mmol, 19%, dr 81:19), and (–)-11c (21.3 mg,
0.09 mmol, 72%, dr Ͼ 99:1, ee Ͼ 99%) as a colorless liquid. Data
1
for 11c: Rf (Cy/EE, 1:1) = 0.15. H NMR (500 MHz, CDCl3): δ =
Eur. J. Org. Chem. 2005, 3930–3941
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© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3939

B. Breit, D. Breuninger
0.82 (d, J = 6.8 Hz, 3 H), 0.86 (d, J = 6.9 Hz, 3 H), 1.01 (d, J = toluenesulfonic acid monohydrate (3.3 mg, 0.02 mmol, 0.05 equiv.)
FULL PAPER
6.8 Hz, 3 H), 1.03 (d, J = 6.9 Hz, 3 H), 1.25–1.35 (m, 2 H), 1.42
(ddd, J = 14.5, 6.2, 3.2 Hz, 1 H), 1.57–1.65 (m, 2 H), 1.70 (mc, 1
H), 2.07 (dd, J = 14.2, 9.1 Hz, 1 H), 2.21 (sept, J = 6.8 Hz, 1 H),
2.24 (ddd, J = 14.2, 4.0, 0.8 Hz, 1 H), 2.4–2.9 (br. s, 2 H), 3.60–
3.75 (m, 3 H), 4.78 (s, 1 H), 4.90 (pseudo t, J = 1.2 Hz, 1 H) ppm.
13C NMR (125 MHz, CDCl3): δ = 18.6, 19.4, 21.7, 22.0, 31.2, 33.6,
34.1, 37.1, 37.9, 44.0, 60.9, 69.4, 109.8, 152.9 ppm. HRMS (EI;
in methanol (5 mL) and then with satd. ethanolic KOH (5 mL) for
14 h as described in GP5. Workup and flash chromatography (PE/
MTBE, 5:1) furnished rac-13 (83 mg, 0.30 mmol, 84%, dr 87:13) as
a colorless liquid. o-DPPFA was not isolated in this case. (–)-13:
The aldehyde (Rp)-9c (159 mg, 0.26 mmol, dr 86:14) was treated
with HC(OMe)3 (0.14 mL, 1.28 mmol, 5 equiv.) and para-tolu-
enesulfonic acid monohydrate (2.5 mg, 0.01 mmol, 0.05 equiv.) in
C14H28O2 [M – C6H11], 228.4): calcd. 145.1229; found 145.1229. methanol (4 mL) and then with satd. ethanolic KOH (4 mL) for
GC (Betadex 110, 130 °C, 20 psi): tR[(3S,5R)-11c] = 85.7 min;
tR[(3R,5S)-11c] = 90.4 min. [α]2D0 = –27 (c = 0.80, CHCl3, dr Ͼ
99:1).
13 h as described in GP5. Workup gave (Rp)-o-DPPFA (8; 98 mg,
0.24 mmol, 92%) and flash chromatography (PE/MTBE, 5:1) fur-
nished a diastereomeric mixture of anti/syn-13 (15 mg, 0.05 mmol,
21%, dr 51:49) and (–)-13 (47 mg, 0.17 mmol, 67%, dr 96:4) as a
colorless liquid. Data for 13: Rf (Cy/EE) = 0.09. 1H NMR
(500 MHz, CDCl3): δ = 0.81 (d, J = 6.9 Hz, 3 H), 0.86 (d, J =
6.9 Hz, 3 H), 1.02 (d, J = 6.9 Hz, 3 H), 1.04 (d, J = 6.8 Hz, 3 H),
1.33 (ddd, J = 14.2, 8.3, 5.8 Hz, 1 H), 1.42–1.49 (m, 2 H), 1.50–
1.56 (m, 1 H), 1.64 (ddd, J = 13.8, 6.3, 4.6 Hz, 1 H), 1.75 (dsept,
J = 6.9, 3.4 Hz, 1 H), 2.07 (ddd, J = 14.2, 8.8, 0.6 Hz, 1 H), 2.19–
2.27 (m, 3 H), 3.28 (s, 3 H), 3.32 (s, 3 H), 3.73 (mc, 1 H), 4.46
(pseudo t, J = 6.2 Hz, 1 H), 4.78 (s, 1 H), 4.88 (t, J = 1.3 Hz, 1 H)
ppm. 13C NMR (125 MHz, CDCl3): δ = 18.3, 19.2, 21.7, 22.0, 30.4,
33.5, 34.0, 36.6, 39.0, 43.7, 51.8, 53.4, 68.5, 103.8, 109.5,
153.1 ppm. HRMS (EI; C16H32O3 [M – MeOH], 272.4): calcd.
241.2170; found. 241.2168. [α]2D0 = –11.6 (c = 0.86, CH2Cl2, dr
96:4).
(4S,6R)-2,6-Diphenyloct-1-ene-4,8-diol (11d). rac-11d: rac-9d
(168.1 mg, 0.24 mmol, dr 94:6) in CH2Cl2 (4 mL) was treated with
DIBALH (0.84 mL, 0.84 mmol, 3.5 equiv.) for 2.5 h as described
in GP4. Flash chromatography (PE/EE, 1:2) furnished rac-12
(93.3 mg, 0.23 mmol, 96%) and, after increasing the polarity of the
eluent (PE/EE, 1:4), rac-11d (53.2 mg, 0.18 mmol, 75%, dr 94:6) as
a white solid. (–)-11d: (Rp)-9d (199.3 mg, 0.29 mmol, dr 94:6) in
CH2Cl2 (5 mL) was treated with DIBALH (1.01 mL, 1.01 mmol,
3.5 equiv.) for 2.5 h as described in GP4. Flash chromatography
(PE/EE, 1:2) furnished (Rp)-12 (99.7 mg, 0.25 mmol, 86%) and, af-
ter increasing the polarity of the eluent (PE/EE, 1:4), (–)-11d
(67.1 mg, 0.23 mmol, 78%, dr 98:2, ee Ͼ 99%) as a white solid.
Data for 11d: Rf (Cy/EE, 1:1) = 0.12; m.p. 83 °C. 1H NMR
(500 MHz, CDCl3): δ = 1.38 (br. s, 1 H), 1.64 (br. s, 1 H), 1.77–
1.86 (m, 4 H), 2.54 (ddd, J = 14.2, 8.2, 0.8 Hz, 1 H), 2.61 (ddd, J
= 14.2, 4.9, 1.1 Hz, 1 H), 3.01 (mc, 1 H), 3.40–3.57 (m, 3 H), 5.06
(d, J = 1.3 Hz, 1 H), 5.35 (d, J = 1.6 Hz, 1 H), 7.09–7.18 (m, 3 H),
7.20–7.35 (m, 7 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 39.1,
40.3, 43.6, 44.4, 61.1, 67.8, 115.2, 126.2 (2 C), 126.4, 127.71 (2 C),
127.72, 128.4 (2 C), 128.6 (2 C), 140.5, 144.5, 145.3 ppm. HRMS
(EI; C20H24O2 [M – C9H9], 296.4): calcd. 179.1068; found 179.1073.
HPLC [OD-H, heptane/2-propanol (95:5), 20 °C, 0.8 mLmin–1,
242 nm]: tR[(4R,6S)-11d] = 30.24 min; tR[(4S,6R)-11d] = 35.39.
[α]2D0 = –21 (c = 0.835, CHCl3, dr 98:2).
Determination of the Relative and Absolute Configuration of Product
Aldehydes 9
(4S*,6S*)-4-Isopropyl-6-(3-methyl-2-methylenebutyl)tetrahydropy-
ran-2-one (14): The dimethyl acetal rac-13 (71.4 mg, 0.26 mmol, dr
87:13) in THF (3 mL) was treated with aqueous HCl (3 mL, 3 )
at 25 °C for 16 h. The reaction mixture was then poured into satd.
aqueous NaHCO3 solution (20 mL) and the aqueous phase was
extracted with Et2O (3×15 mL). The combined organic phases
were dried (Na2SO4) and concentrated. The crude product was dis-
solved in CH2Cl2 (4 mL), NaOAc (15.0 mg, 0.18 mmol) and PCC/
Al2O3 (532.7 mg, 1 mmol PCC/g, 0.53 mmol) were added, and the
mixture was stirred for 24.5 h. The solids were removed by fil-
tration, washed with Et2O, and the filtrate was concentrated. Flash
chromatography of the residue (PE/MTBE, 5:1) furnished rac-14
(30.1 mg, 0.134 mmol, 50%, dr 94:6) as a colorless liquid. Data for
Cleavage and Recovery of the Catalyst-Directing Group
General Procedure 5 (GP5). Aldehyde Protection and Alkaline Ester
Hydrolysis: The aldehyde 9 was suspended in methanol (10 mL/
mmol), trimethyl orthoformate (5 equiv.) and para-toluenesulfonic
acid monohydrate (0.05 equiv.) were added, and the mixture was
heated to reflux for 2 h. After cooling to 25 °C, all volatile material
was evaporated at 0.1 mbar and satd. KOH/EtOH (10 mL/mmol,
degassed) was added to the red-brown solid residue. After heating
again to reflux for several hours, satd. aqueous NaHCO3 solution
(30 mL/mmol) and Et2O (30 mL/mmol) were added to the brown
reaction mixture and the mixture was stirred until a brown solid
precipitated. The solid material was collected by filtration and
washed several times with water and Et2O. The solid was then sus-
pended in 1  HCl (20 mL/mmol) and CH2Cl2 (20 mL/mmol) and
the mixture was stirred until the solid had completely dissolved in
the organic phase. The aqueous phase was extracted with CH2Cl2
(10 mL/mmol), the combined organic phases were dried (Na2SO4),
and the solvent was removed in vacuo (employing an argon-purged
rotary evaporator) to give o-DPPFA (8) as an orange-brown solid
(partially oxidized). The aqueous phase of the filtrate was extracted
three times with Et2O (10 mL/mmol), the combined organic phases
were dried (Na2SO4), and the solvent was removed in vacuo. Flash
chromatography of the residue gave the pure dimethyl acetal 13.
1
14: Rf (Cy/EE, 5:1) = 0.19. H NMR (500 MHz, CDCl3): δ = 0.89
(d, J = 6.8 Hz, 3 H), 0.90 (d, J = 6.8 Hz, 3 H), 1.03 (d, J = 6.9 Hz,
6 H), 1.16 (dt, J = 13.8, 11.7 Hz, 1 H), 1.50 (oct, J = 6.8 Hz, 1 H),
1.72 (m, 1 H), 1.97 (dquint, J = 13.8, 2.0 Hz, 1 H), 2.14 (dd, J =
17.8, 10.4 Hz, 1 H), 2.23 (sept, J = 6.9 Hz, 1 H), 2.27 (dd, J = 14.8,
7.1 Hz, 1 H), 2.53 (ddd, J = 14.8, 6.2, 0.6 Hz, 1 H), 2.64 (ddd, J =
17.8, 6.5, 1.8 Hz, 1 H), 4.37 (mc, 1 H), 4.79 (q, J = 0.8 Hz, 1 H),
4.89 (s, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 19.1, 19.3,
21.7, 21.8, 32.3, 32.4, 33.83, 33.84, 37.9, 41.3, 79.4, 110.2, 150.7,
172.1 ppm. HRMS (EI; C14H24O2, 224.3): calcd. 224.1780; found
224.1776. 2D NMR experiments and coupling constants estab-
lished the syn relationship of the two substituents in the lactone
14.
(3S,5S)-3-Isopropyl-1,1-dimethoxy-8-methyl-7-methylenenonan-5-ol
(13). rac-13: The aldehyde rac-9c (224 mg, 0.36 mmol, dr 87:13) was
treated with HC(OMe)3 (0.20 mL, 1.83 mmol, 5 equiv.) and para-
3940
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2005, 3930–3941

Desymmetrizing Hydroformylation of Diallylcarbinols
FULL PAPER
Determination of the Absolute Configuration of (–)-13. Preparation
of (R) Mosher Ester: The alcohol (–)-13 (5.6 mg, 21 µmol) in
CH2Cl2 (1 mL) was treated with pyridine (0.50 mL), DMAP
(4.7 mg, 39 µmol, 1.9 equiv.), and (+)-(S)-α-methoxy-α-(trifluoro-
methyl)phenylacetyl chloride (19.2 µL, 103 µmol, 5 equiv.) at 25 °C
for 3 h. The reaction was quenched with satd. aqueous NaHCO3
(2 mL), stirred for 30 min, and the aqueous phase was extracted
with Et2O (3×5 mL). The combined organic phases were dried
(Na2SO4), concentrated, and the residue was dissolved in benzene
(10 mL) and again concentrated in vacuo (two times) to remove
excess pyridine. Flash chromatography of the residue (PE/MTBE,
10:1) furnished the (R) Mosher ester (8.7 mg, 18 µmol, 86%) as a
colorless liquid. Rf (Cy/EE, 10:1) = 0.18. 1H NMR (300 MHz,
CDCl3): δ = 0.78 (d, J = 6.9 Hz, 3 H), 0.87 (d, J = 6.9 Hz, 3 H),
0.98 (d, J = 6.9 Hz, 3 H), 1.01 (d, J = 6.9 Hz, 3 H), 1.30–1.40 (m,
1 H), 1.44–1.53 (m, 1 H), 1.57–1.71 (m, 3 H), 1.84 (dsept, 1 H, J
= 6.9, 2.9 Hz), 2.22 (sept, J = 6.9 Hz, 1 H), 2.26 (dd, J = 14.2,
6.3 Hz, 1 H), 2.39 (dd, J = 14.2, 7.0 Hz, 1 H), 3.26 (s, 3 H), 3.30
(s, 3 H), 3.54 (q, J = 1.0 Hz, 1 H), 4.39 (pseudo t, J = 6.2 Hz, 1
H), 4.70 (s, 1 H), 4.78 (s, 1 H), 5.31 (quint, J = 6.7 Hz, 1 H), 7.35–
7.43 (m, 3 H), 7.50–7.57 (m, 2 H) ppm. Preparation of (S) Mosher
Ester: As described above, the alcohol (–)-13 (6.0 mg, 22 µmol) in
CH2Cl2 (1 mL) and pyridine (0.5 mL) was converted with DMAP
(5.4 mg, 44 µmol, 2 equiv.) and (–)-(R)-α-methoxy-α-(trifluorome-
thyl)phenylacetyl chloride (20.7 µL, 111 µmol, 5 equiv.) into the
corresponding (S) Mosher ester (9.7 mg, 20 µmol, 89%, colorless
Acknowldegements
This work was supported by the Fonds der Chemischen Industrie
and the Alfried-Krupp Award for young university teachers. We
thank M. Lutterbeck and S. Preuss for technical assistance, Dr. R.
Krieger and G. Fehrenbach for analytical assistance, and Dr. M.
Keller, Universität Freiburg, for the X-ray crystal structure analysis
of compounds 7a and 8a.
[1]
[2]
B. Breit, W. Seiche, Synthesis 2001, 1–36.
a) K. Nozaki, I. Ojima, in Catalytic Asymmetric Synthesis, 2nd
ed. (Ed.: I. Ojima) Wiley-VCH, New York, 2000, pp. 429–463;
b) M. Diéguez, O. Pàmies, C. Claver, Tetrahedron: Asymmetry
2004, 15, 2113–2122; c) F. Agbossou, J. F. Carpentier, A. Mor-
treux, Chem. Rev. 1995, 95, 2485–2506.
[3]
S. D. Burke, J. E. Cobb, Tetrahedron Lett. 1986, 27, 4237–4240;
R. W. Jackson, P. Perlmutter, E. E. Tasdelen, J. Chem. Soc.,
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J. L. Leighton, J. Am. Chem. Soc. 2001, 123, 11514–11515.
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[5]
[6]
B. Breit, Acc. Chem. Res. 2003, 36, 264–275, and references
cited therein.
B. Breit, Chem. Commun. 1997, 591–592; B. Breit, Eur. J. Org.
Chem. 1998, 1123–1134.
B. Breit, D. Breuninger, J. Am. Chem. Soc. 2004, 126, 10244–
10245.
1
liquid). Rf (Cy/EE, 10:1) = 0.13. H NMR (300 MHz, CDCl3): δ =
0.75 (d, J = 6.9 Hz, 3 H), 0.83 (d, J = 6.9 Hz, 3 H), 1.03 (d, J = [7]
6.8 Hz, 3 H), 1.05 (d, J = 6.8 Hz, 3 H), 1.25–1.37 (m, 2 H), 1.51–
B. Breit, D. Breuninger, Eur. J. Org. Chem. 2005, 3916–3929,
preceding paper.
[8]
[9]
[10]
1.65 (m, 3 H), 1.78 (dsept, 1 H, J = 6.9, 2.3 Hz), 2.29 (sept, J =
6.8 Hz, 1 H), 2.33 (dd, J = 14.4, 6.0 Hz, 1 H), 2.46 (dd, J = 14.4,
7.2 Hz, 1 H), 3.21 (s, 3 H), 3.28 (s, 3 H), 3.54 (q, J = 1.0 Hz, 3 H),
4.31 (t, J = 5.5 Hz, 1 H), 4.80 (s, 1 H), 4.88 (s, 1 H), 5.34 (quint, J
= 7.2 Hz, 1 H), 7.36–7.41 (m, 3 H), 7.51–7.57 (m, 2 H) ppm.
B. Breit, D. Breuninger, Synthesis 2005, 147–157.
M. C. Willis, J. Chem. Soc., Faraday Trans. 1 1999, 1765–1784.
M. Oestreich, F. Sempere-Culler, Chem. Commun. 2004, 692–
693.
[11] I. Ohtani, T. Kusumi, Y. Kashman, H. Kakisawa, J. Am. Chem.
Soc. 1991, 113, 4092–4096.
[12] B. Breit, G. Heckmann, S. K. Zahn, Chem. Eur. J. 2003, 9, 425–
434.
Crystal Structure Analysis of rac-9a: C33H35FeO3P, Mr = 566.43,
monoclinic, space group: P21/a, a = 8.6402(2), b = 33.3015(8), c =
10.0997(3) Å, β = 96.4913(14)°, V = 2887.97(13) Å3, ρcalcd.
=
[13] M. E. Kuehne, T. Wang, P. J. Seaton, J. Org. Chem. 1996, 61,
1.303 gcm–3,
Z = 4, F(000) = 1192; crystal dimensions:
6001–6008.
0.30×0.15×0.10 mm. A total of 21143 reflections were collected at
293 K with a Nonius Kappa CCD area detector diffractometer
using ω-scans in the θ range 2.12–27.45°, 6532 reflections were
unique (Rint = 0.0513). The structure was solved by direct meth-
ods.[18] Full-matrix least-squares refinement[19] was based on F2,
with all non-hydrogen atoms anisotropic and hydrogen atoms iso-
tropic. The refinement converged at R1 = 0.0683, wR2 = 0.1209 for
all data; final GOF: 1.052; largest peak/hole in the final difference
Fourier map: 0.988/–0.547 eÅ–3. CCDC-270161 contains the sup-
plementary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
[14] D. H. R. Barton, T. Shioiri, D. A. Widdowson, J. Chem. Soc.
C 1971, 1968–1974.
[15] E. M. Driggers, H. S. Cho, C. W. Liu, C. P. Katzka, A. C. Bra-
isted, J. Am. Chem. Soc. 1998, 120, 1945–1958.
[16] S. J. Danishefsky, N. Mantlo, J. Am. Chem. Soc. 1988, 110,
8129–8133.
[17] D. Breuninger, B. Breit, Synthesis, submitted.
[18] G. M. Sheldrick, SHELXS-97, Program for Solving Crystal
Structures, University of Göttingen, 1997.
[19] G. M. Sheldrick, SHELXL-97, Program for Refining Crystal
Structures, University of Göttingen, 1997.
Received: April 26, 2005
Published Online: August 1, 2005
Eur. J. Org. Chem. 2005, 3930–3941
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3941