Copper-catalysed asymmetric conjugate addition of organometallic reagents to linear enones

Article abstract of DOI:10.1016/S0040-4020(00)00140-X

Methods for enantioselective 1,4-addition of main-group organometallics to linear enones are overviewed. Thiourethane and thioether 1,1-binaphthyl- based ligands are effective for copper-catalysed 1,4-addition of ZnEt₂ and AlR₃ (R=Me, Et) to trans-alkyl-3-en-2-ones; enantioselectivities of up to 72% e.e. are attained. In comparison 1,4-addition of ZnEt₂ to 2- cyclohexenone proceeds in up to 77% e.e. with the same ligand family. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00140-X

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 2847±2855
Copper-Catalysed Asymmetric Conjugate Addition of
Organometallic Reagents to Linear Enones
a
Simon M. W. Bennett, Stephen M. Brown, Anthony Cunningham, Michael R. Dennis,
b
c
a
b
James P. Muxworthy, Michael A. Oakley and Simon Woodward
a
c,
*
a
Department of Chemistry, University of Hull, Hull HU6 7RX, UK
Process Technology Department, Zeneca Limited, PO Box A38, Hudders®eld HD2 1FF, UK
b
c
School of Chemistry, Nottingham University, University Park, Nottingham NG7 2RD, UK
Received 1 October 1999; revised 6 January 2000; accepted 13 January 2000
AbstractÐMethods for enantioselective 1,4-addition of main-group organometallics to linear enones are overviewed. Thiourethane and
0
thioether 1,1 -binaphthyl-based ligands are effective for copper-catalysed 1,4-addition of ZnEt and AlR (RˆMe, Et) to trans-alkyl-3-en-2-
2
3
2
ones; enantioselectivities of up to 72% e.e. are attained. In comparison 1,4-addition of ZnEt to 2-cyclohexenone proceeds in up to 77% e.e.
with the same ligand family. q 2000 Elsevier Science Ltd. All rights reserved.
1
2
Introduction
trans-alkyl-3-en-2-ones (1 R ,R ˆAlkyl,Me) have served as
model enones in these copper-promoted transformations
whose recent evolution is charted in Table 1. (For develop-
ments up to 1991 Rossiter's comprehensive review should
be consulted.) Thus far, the current generation of ligands
(Table 1) have, unlike auxiliary 3, largely excluded addi-
tional alkoxide donor atoms aimed at coordinating cuprate
counter cations (Li, Mg, Zn, Al, etc.).
2
Enantioselective 1,4-addition of carbanions to linear enones
1 is an interesting challenge. Few ef®cient methods exist for
these transformations (Scheme 1), yet the products 2 are
versatile synthons for asymmetric synthesis. It is the
presence of s-trans and s-cis conformers in 1 that compli-
cates the enantiofacial selectivity issues in this chemistry.
2
1
,2
The binding of LiCuMe by the BINOL-bound a,b-unsatu-
2
Aside from the transformations of Table 1 Sewald's addi-
tions of ZnEt to nitroalkenes (also using BINOL-phosphor-
2
rated acid 3 (giving up to 87% e.e.) is a typical auxiliary
approach to the preparation of 2. However, the limitations
3
10
amidites and giving up to 86% e.e.) should be mentioned.
Since 1991, additional asymmetric catalytic 1,4-additions
using other metals have been reported. Nickel-catalysed
of auxiliary-based syntheses (the necessity for extra steps)
have lead to development of catalytic reagents for the trans-
formation 1!2 over the last decade and a half. Chalcone (1
2
1
2
addition of organozinc reagents to 1 (R ,R ˆAr,Ar)
1
2
1
2
R ,R ˆPh,Ph), benzylideneacetone (1 R ,R ˆPh,Me), and
proceeds with good levels of stereoinduction (702801% e.e.).
Scheme 1.
Keywords: asymmetric synthesis; enones; thiocarbonyl compounds; thioethers.
*
Corresponding author. Tel.: 144-115-951-3541; fax: 144-115-951-3564; e-mail: simon.woodward@nottingham.ac.uk
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00140-X

2
848
S. M. W. Bennett et al. / Tetrahedron 56 (2000) 2847±2855
Table 1. Recent copper-promoted asymmetric conjugate addition reactions to enones 1
1
2
3
a
Year [Ref.]
R
R
R
Ligand
Loading (mol%)
e.e. (c.y) (%)
84 (79)
4
1
992
Ph
Ph
Me
Me
148
5
1
994
Ph
Me
9
4
76 (97)
90 (84)
6
1
996
4-ClPh
Ph
Et
7
8
9
1997
1999
1999
Ph
Ph
Ph
Me
Ph
Ph
Et
Et
Et
12
160
2
81 (61)
90 (99)
71 (93)
9
n
11
1
999
C
5
H
Me
Et
2
67 (97)
a
Based on chiral ligand used.
1
1
Bolm's 2-pyridinyl sec-alcohols (used at 20 mol%) and
16
ArOH group, as in auxiliary 3, with a soft donor capable
1
2
Ikeda's oxazolines (used at 10 mol%) are particularly
2
of binding cuprates, [CuR ] . The compounds used in this
2
effective as the catalyst loadings are lower than those
required with older Ni(acac) -based systems. The rubidium
salt of (l)-proline (20 mol%) catalyses the Michael addition
study are available through literature procedures or by
simple procedures. The synthetic sequence, shown for
simplicity in the (R ) con®guration, is summarised in
2
2
a
t
1
2
13
of CH (CO Bu ) to 1 (R ,R ˆMe,Me) in 88% e.e. Finally,
Scheme 2.
2
2
2
Hayashi has reported an exceptional Rh/(S)-BINAP catalyst
3 mol%) for the 1,4-addition of PhB(OH) to the demand-
(
Routine screening results had revealed that ligands con-
taining the thiourethane (thiocarbamate) donors, especially
2
1
2
14
ing substrates 1 (R ,R ˆAlkyl,Me) in .92% e.e.
5
a, were effective in promoting 1,4-additions of organo-
1
5
Some time ago we set ourselves the challenge of ®nding
chiral ligands for ef®cient asymmetric 1,4-addition of
alkyl organometallics onto trans-3-alkylen-2-ones (1
metallics to linear enones. In particular, AlMe3 and
[Cu(MeCN) ]BF appeared to be the most ef®cient terminal
4
4
organometallic and catalytic copper(I) sources, respec-
tively. As initial goals the effect of changing the terminal
organometallic on the catalytic system was investigated.
The results for the 1,4-addition of various organometallics
1
2
1
2
3
R ,R ˆAlkyl,Me). The fragment 2 (R ,R ,R ˆAlkyl) is an
attractive synthon for the preparation of a number of natural
products and currently no high e.e. copper-based method-
ology is available. Full details of our initial investigations
are described here of which some elements have been
1
2
n
11
to nonenone 1 (R ,R ˆC H , Me) in the presence of
5
[Cu(MeCN) ]BF (10 mol%) and ligand 5a (20 mol%) are
4
4
1
5
communicated.
shown in Table 2.
In reactions carried out at 91 mM initial ligand concentra-
tion triorganoaluminiums were con®rmed as the optimal
reagents. The use of AlR reagents in copper-catalysed
Results and Discussion
We thought to synthesise ligands combining a directing
3
2
0
conjugate enone additions was popularised by Westermann

S. M. W. Bennett et al. / Tetrahedron 56 (2000) 2847±2855
2849
1
7
Scheme 2. Reagents: (i) R
2
NC(ˆX)Cl (RˆMe, Et; XˆO, S), NEt NC(ˆO)Cl (for 6a), or MeI (for 6b), or
2 2
N) PCl (for 6c) with appropriate bases; (iii) Lithiation of 4b followed by MeI and deprotection (for 8a), lithiation and rearrangement (for 8b), lithiation
17 n n n 17
3
, DMAP catalysis on 4a or 8a±c; (ii) Me
2
i
18
18
(
Pr
followed by Me
2
S
2
(for 8c); (iv) Monothiobinaphthol (MTB) preparation followed by Bu Li/Me
2
NC(ˆS)Cl (for 7a) or Bu Li/Bu Br (7b).
Table 2. Enantioselective 1,4-additions to trans-3-nonen-2-one (1
several repetitions of run 3 was treated with Na S O
2 2 8
1
2
n
R ,R ˆC
5 4 4 a
H11, Me) catalysed by [Cu(MeCN) ]BF (10 mol%) and (R )-5a
20 mol%) as a function of organometallic type
leading to a single new species whose formation could be
followed to completion by chiral GC. The crude H NMR
spectrum of this material was consistent with the expected
(
1
Run Organometallic Conversion (%) 1,4-Yield (%) e.e. (%) (hand)
2
2
Baeyer±Villiger product 10. Compound 10 was hydro-
lysed directly to afford (R)-(1)-11 based on polarimetric
comparison with literature values for (S)-(2)-11.
1
2
3
4
5
6
MeMgBr
ZnEt
AlMe
AlClMe
MeTi(OPr )
BEt
.99
81
95
95
22
0
81
66
80±901
,1
12
0
35 (1)
49±52 (1)
±
3 (1)
±
2
23,24
3
2
i
3
The necessity for the presence of both a hydroxy function
and an appropriate thio-donor in the ligand structure was
investigated in the reaction of AlMe with trans-3-nonen-2-
3
0
3
1
2
n
one (1 R ,R ˆC H , Me) and is summarised in Table 3.
5
11
2
1
15
and Kabara but asymmetric variants are rare. In runs 2±3
The requirement for the 2-naphtholic directing group is
con®rmed by the poor performance of ligands 6a±c (run 1
vs. runs 4±6). For effective stereoinduction the presence of a
soft ligation site is also mandatory; the carbamate 5b affords
only low yields of racemic material whereas the other hard±
soft ligands 5a, 5c, and 7a±b give a range of interesting
inductions (runs 1, 3, 7, 8).
1
2
3
n
11
(
R )-5a fashions (1)-2 (R ,R ,R ˆC H , Me, Me) as the
a
5
major enantiomer. Even at 2208C one of the catalyst
components is unstable and a black precipitate is always
formed during the course of the reaction. However, this
decomposition does not appear to affect the chemical yields
or e.e. values of the product 2 and the systems are highly
reproducible. In the case of ZnEt and AlMe the mass
2
3
balance is good and normally only small amounts of starting
enone contaminated the product. For the Grignard and
titanium reagents some 1 is consumed as non-eluting oligo-
meric material. In no case is 1,2-addition observed. The
absolute con®guration of the addition was determined by
the degradation shown in Scheme 3.
Our previous attempts to optimise the enantioselectivity
shown by the system (R )-5/Cu /AlMe by changing
I
a
3
solvents or including stoichiometic amounts of enone
activating electrophiles (TMSCl or BF ´OEt ) did not
3
2
1
5
prove effective. This lack of response left only the ligand
structure and the use of compounds expected to change the
catalyst structure as the major variables. The results of
representative modi®cations are summarised in Table 4.
1
2
3
n
11
A sample of (1)-2 (R ,R ,R ˆC H ,Me,Me) derived from
5
Scheme 3.

2
850
S. M. W. Bennett et al. / Tetrahedron 56 (2000) 2847±2855
1
2
n
Table 3. Addition of AlMe
)-7a,b (20 mol%).
3
to trans-3-nonen-2-one (1 R ,R ˆC
5 4 4
a a
H11, Me) in the presence of [Cu(MeCN) ]BF (10 mol%) and ligands (R )-5, (R )-6 and
(R
a
Run
Ligand
X
R
Conversion (%)
1,4-Yield (%)
e.e. (%) (hand)
1
2
3
4
5
6
7
8
(R
a
(R
a
(R
a
(R
a
(R
a
(R
a
(R
a
(R
a
)-5a
)-5b
)-5c
)-6a
)-6b
)-6c
)-7a
)-7b
S
O
S
±
±
±
±
±
±
±
±
95
36
93
46
69
90
95
88
801
13
75
23
31
63
70
79
50 (R)
2 (R)
40 (R)
15 (S)
12 (R)
8 (R)
C(O)NMe
Me
P(NPr
C(S)NMe
Bu
2
i
2
)
2
2
42 (R)
71 (R)
n
2
5
The results of a non-linear effect study, using ligand 5a,
are reported in Fig. 1. Together these data shed some light
on the reaction mechanism. Benchmark results under
standard conditions are given in Table 4, entries 1±3, for
comparison. As both enone and organometallic are added
during the course of the reaction the catalyst concentration
falls during the reaction. For comparison between runs it is
useful to note the initial copper(I) and ligand L concentra-
tions, normally 46 mM [Cu(MeCN) ]BF (10 mol%) and
0.2 equivalents of Me AlCl) caused a large suppression of
2
the e.e. (run 8).
Of the four ligand structures screened the sterically
buttressed dimethylbinaphthalene ligand (R )-9a was the
a
most successful (run 10) while the introduction of alterna-
tive binding sites lowered the selectivity (runs 9, 11, 12). In
0
enantioselection was reversed.
the case of the 3,3 -diamido ligand (R )-9b the sense of the
a
4
4
(
use of CuBr, Cu(OTf) , CuCN gives inferior systems
Ra)-5 91 mM (20 mol%) under standard conditions. The
Lowering the reaction concentration proved to be the
simplest way of improving the enantioselection of the
(R )-5/[Cu(MeCN) ]BF (20/10 mol%) system (Table 4,
runs 2 vs. 13±15). Thus, one explanation of the small
apparent NLE in Fig. 1 is that a mononuclear catalyst is
involved and that the slight deviation observed is due to
competing dimeric catalysts. The catalytic manifold is
2
(
runs 4±6). In general, we have noted that the presence of
halide anions can be very detrimental to the enantio-
selectivity in this reaction. Modi®cation of the Lewis acid
site in the catalyst to nominal ArO±Al(OMe) (by addition
a
4
4
2
of MeOH) did not affect the catalyst (run 7).
However, nominal ArO±AlMeCl preparation (by use of
3
1
2
n
Table 4. Optimisation of asymmetric conjugate additions of organometallics (R M) to trans-3-nonen-2-one (1 R ,R ˆC
5
H
11, Me) and comparison with
2
-cyclohexenone
3
R M
a
Con. (%)
a
1,4-Yield (%)
a
e.e. (%) (hand)
Run
Ligand (L)
Conditions/Variations
1
2
(R
(R
a
)-5a
)-5a
ZnEt
AlMe
2
Standard conditions
20 mol% L, 10 mol%, Kubas-
81
95
66
94
35 (R)
50 (R)
a
3
I b
Cu , 45 mM
3
(R
a
)-5a
AlEt
3
Initial catalyst concentration
Variations
63
40
32 (R)
c
4
5
6
7
(R
(R
(R
(R
a
a
a
a
)-5a
)-5a
)-5a
)-5a
AlMe
AlMe
AlMe
AlMe
3
3
3
3
CuBr, 10 mol%
Cu(OTf) , 10 mol%
CuCN, 10 mol%
Added MeOH, 40 mol% to
catalyst
Catalyst prepared with
95
51
92
94
83
23
71
85
0
2
7 (R)
33 (R)
52 (R)
8
9
(R
a
)-5a
AlMe
3
97
97
23 (R)
AlClMe , 20 mol%
2
0
0
(R
a
(R
a
(R
a
(R
a
(R
a
(R
a
(R
a
(R
a
-
)-8c
)-9a
)-9b
)-9c
)-5a
)-5a
)-5a
)-5a
AlMe
AlMe
AlMe
AlMe
AlMe
AlMe
AlMe
AlMe
AlMe
3
3
3
3
3
3
3
3
3
3,3 -di-SMe BINOL
3,3 -di-Me thiocarbamate
96
79
85
95
98
93
79
0
80
55
61
92
83
89
79
0
33 (R)
62 (R)
17 (S)
3 (S)
42 (R)
56 (R)
61 (R)
-
10
11
12
13
14
15
16
17
0
3,3 -di-C(O)Net thiocarbamate
3,3 -di-SMe thiocarbamate
L 145 mM, Kubas-Cu , 72 mM
2
0
I b
I b
L 46 mM, Kubas-Cu , 23 mM
I b
L 23 mM, Kubas-Cu , 11 mM
I
No Cu present, 20 mol% L
I b
No L, 10 mol% Kubas-Cu ,
4
49
33
0
6 mM
I b
1
1
8
9
(R
(R
a
)-8c
)-8c
ZnEt
ZnEt
2
L 46 mM, Kubas-Cu , 23 mM
5 mol% L/2.5 mol% Kubas-
Cu , 23 mM
100
71
.95
71
72 (R)
68 (R)
a
2
I b
I b
2
0
(R
a
)-8c
ZnEt
2
L 46 mM, Kubas-Cu , 23 mM,
cyclohex
100
78
77 (R)
d
a
b
c
d
Conversion, yield, and e.e. by GC.
I
Kubas-Cu is [Cu(MeCN)
Unless stated otherwise all other reagents and conditions are as runs 1±3.
-cyclohexenone used.
4 4
]BF at initial concentration given.
2

S. M. W. Bennett et al. / Tetrahedron 56 (2000) 2847±2855
2851
1
2
n
11, Me) catalysed by [Cu(MeCN)
Figure 1. Non-linear effect (NLE) study of the reaction of AlMe
initial conc. 46 mM) in the presence of 5a (20 mol%; initial conc. 91 mM).
3
with to trans-3-nonen-2-one (1 R ,R ˆC
5
H
4
]BF
4
(10 mol%;
1
previously. All compounds 4a, 4b, 5a,b, 6a, 7b,
9
26
18
17
17
19
complicated by the presence of achiral catalysts derived
from [Cu(MeCN) ]BF /AlMe alone that are partially active
1
8
27
i
and MeTi(OPr )3
28
8a,b,
[Cu(MeCN) ]BF4
4
were
4
4
3
(
organometallic source with ligand (R )-8c a reasonably
runs 16 and 17). Finally, we note that by changing the
prepared by literature methods. All other reagents were
commercial products.
a
selective catalyst is formed which retains its potency at
low catalyst loading and seems to recognise both acyclic
and cyclic enones (runs 18±20). Attempts to realise highly
enantioselective catalysts with related ligands are underway
in our laboratory.
0
-1,1 -binaphthalene 5c. To a stirred solution of (R )-(1)-4a
(6.6 g, 22.93 mmol) in dry dichloromethane (100 ml) under
a nitrogen atmosphere, was added 4-N,N-dimethylamino-
pyridine (700 mg, 4.73 mmol), triethylamine (2.90 g,
(R )-2-(N,N-Diethyliminothiocarbamoyloxy)-2 -hydroxy
a
0
a
4
.00 ml, 28.67 mmol) and N,N-diethylthiocarbamoyl chloride
(TOXIC! 4.00 g, 26.37 mmol). The mixture was stirred for
2 h at ambient temperature. When the reaction was
Experimental
7
General
complete (TLC) the solution was quenched with saturated
aqueous NH Cl solution, washed with water (2£10 ml),
4
N,N-Dimethylthiocarbamoyl chloride was recrystallised
dilute hydrochloric acid (2£10 ml), and saturated brine
(1£10 ml). The dichloromethane layer was collected,
dried (Na SO ) and the solvent removed to give a yellow
2 4
1
2
from pentane. trans-3-Alkylen-2-ones (1 R ,R ˆAlkyl,
Me) and 2-cyclohexenone were distilled under atmospheric
Ê
pressure and then stored over 4 A molecular sieves. THF
oil. This oil solidi®ed on treatment with petroleum spirit to
yield a pale yellow powder 5c (6.65 g, 73%), mp 142±
was distilled from Na-benzophenone under a nitrogen
atmosphere, diethyl ether and hexane were dried over
sodium wire, dichloromethane was distilled from CaH2.
Catalytic reactions were carried out under argon using
standard Schlenk techniques. Column chromatography and
TLC analyses were performed on silica gel, Rh oà ne Poulenc
Sorbsil and Merck Kieselgel 60 F2541366, respectively.
2
4
1438C; [a]
H, 5.95; N, 3.7; S, 7.5. C25
5.8; N, 3.5; S, 7.9%); nmax(KBr disc)/cm 3280br, 3060w,
2990w, 2940w, 1522s, 1215s, 819s, 753s; d NMR
(400 MHz, CDCl
) 0.47 (3H, t, Jˆ7.3 Hz, Me), 1.06 (3H,
t, Jˆ7.0 Hz, Me), 2.83±2.93 (1H, m, CH Me), 3.13±3.23
(1H, m, CH Me), 3.56±3.72 (2H, m, CH Me), 5.93 (1H, s,
OH), 7.10 (1H, d, Jˆ8.3 Hz, C8,8 ±H), 7.22 (1H, d,
Jˆ8.1 Hz, C8,8 ±H), 7.32±7.22 (3H, m, C6,6 ±H), 7.33
(1H, d, Jˆ8.8 Hz, C3,3 ±H), 7.43 (1H, d, Jˆ8.8 Hz, C3,3
H), 7.49 (1H, apparent ddd, Jˆ8.4, 1.5 Hz, C6,6
(1H, d, Jˆ7.8 Hz, C4,4 ±H), 7.86 (1H, d, Jˆ8.8 Hz, C5,5
H), 7.97 (1H, d, Jˆ8.1 Hz, C4,4
±H); d NMR (67.8 MHz, CDCl
ˆ1297 (cˆ5.0 in CHCl
); (Found: C, 74.4;
D
3
H23NO
S requires C, 74.8; H,
2
2
1
H
3
2
1
3
31
Proton, C and P NMR spectra were recorded on either
a JEOL JNMGX270 or JNMLA400. IR spectra were
recorded on either a Perkin±Elmer 983G or a Perkin±
Elmer 882 spectrometer. Mass Spectra were recorded on a
Finnigan-MAT 1020 (electron impact ionisation, EI)
machine (Hull) and a VG-ZAB (fast atom bombardment
ionisation, FAB) machine (EPSRC Service, Swansea).
Elemental analyses were performed using a Fisons Instru-
ments EA 1108 CHN elemental analyser. Optical rotations
were measured on an Optical Activity AA-10 instrument in
2
2
0
0
0 0 0
,7 7
0
0
±
±
0
0
±H), 7.82
,7,7
0
0
0
±H), 8.06 (1H, d, Jˆ8.8 Hz,
C
0
) 11.6, 12.1, 43.7,
5,5
C
3
48.1, 115.0, 119.4, 123.1, 124.1, 124.7, 125.8, 126.2,
126.5, 127.3, 127.9, 129.1, 130.0, 132.1, 133.6, 133.9,
151.2, 152.5, 186.3; m/z (EI) 401 (M , 26%).
2
1
22 21
1
units of 10 8 cm
(
g
c.y.) and enantiomeric excess (e.e.) analysis of the catalysis
(c in g/100 ml). Chemical yield
0
oxy-1,1 -binaphthalene, 6b. Sodium hydride (80 mg,
was carried out on a Varian 3380 gas chromatograph using
either LIPODEX A or octakis-(6-O-methyl-2,3-di-O-pen-
tyl)-g-cyclodextrin (g-CD) columns as described
(R
a
)-2-(N,N-Dimethyliminothiocarbamoyloxy)-2 -meth-
0
134 mg 60% w/w dispersion in mineral oil, 3.348 mmol)

2
852
S. M. W. Bennett et al. / Tetrahedron 56 (2000) 2847±2855
1
d NMR (162.0 MHz, CDCl ) 113.4; m/z (EI) 604 (M ,
5%).
was washed with dry petroleum (3£5 ml) and evacuated to
dryness. Dry THF (10 ml) was added under an inert atmos-
phere and the suspension cooled to 08C. A solution of 5a
P
3
(
1.00 g, 2.68 mmol) in dry THF (10 ml) was added drop-
0
R )-2-(N,N-Dimethyliminothiocarbamoylthio)-2 -hy-
a
(
wise over ca 5 min causing the mixture to turn yellow and
effervesced gently. This solution was then stirred at this
temperature for 0.5 h. Methyl iodide (TOXIC! 475 mg,
208 ml, 3.35 mmol) was added and the solution allowed to
warm to ambient temperature and stir overnight. The
0
droxy-1,1 -binaphthalene 7a. A standard solution of
Bu Li (0.53 ml of 1.08 M hexane solution was added to a
n
cold (2788C) solution of (R )-monothiobinaphthol
a
1
MTB) (160 mg, 0.53 mmol) in THF (3.0 ml) under an
7
(
argon atmosphere to give a dark solution. A sample of
mixture was quenched with dilute aqueous NH solution
3
N,N-dimethylthiocarbamoylchloride (TOXIC! 74 mg,
.60 mmol) dissolved in THF (2.0 ml) was added by syringe
and washed with dilute hydrochloric acid (2£10 ml) satu-
0
rated aqueous NaCl solution (1£10 ml), dried over MgSO
4
and the solution allowed to come to room temperature
overnight. The solvent was evaporated and the residue par-
titioned between dichloromethane and NH Cl(aq). The
and ®ltered. Evaporation of the solution in vacuo yielded a
white ¯uffy solid which was crystallised from hot ethanol to
yield long, colourless needles of 6b. (0.88 g, 85%), mp 161±
4
2
D
4
organic layer was washed with dilute HCl(aq) and brine,
dried (MgSO ), and the solvent removed. The compound
was puri®ed by chromatography (dichloromethane/hexane)
1
5
3
2
8
648C; [a] ˆ195 (cˆ5.0 in CHCl ); (Found: C, 74.05; H,
3
4
.5; N, 3.7; S, 8.0. C H NO S requires C, 74.4; H, 5.5; N,
24 21 2
2
1
.6; S, 8.3%); nmax(KBr disc)/cm 3038w, 3005w, 2978w,
856w, 2825w, 1539s, 1518s, 1290s, 1271s, 1220s, 1141s,
18m, 755m; dH NMR (400 MHz, CDCl ) 2.50 (3H, s,
23
(
CHCl ); n (KBr disc)/cm 3296br, w, 3062w, 2962w,
121 mg 59%) mp 209±2108C; [a] ˆ1724 (cˆ5.1 in
D
2
1
3
max
3
2
1
3
6
938w, 1621m, 1597m, 1512s, 1383s, 1251s, 1215s,
143s, 980s, 819s, 752s; dH NMR (270 MHz, CDCl3)
.35 (3H, s, NMe), 3.51 (3H, s, NMe), 6.41 (1H, s, OH),
NMe), 3.07 (3H, s, NMe), 3.75 (3H, s, OMe), 7.19±7.33
(
5H, m, Ar), 7.40 (1H, d, Jˆ9.0 Hz, Ar), 7.41±7.46 (1H, m,
Ar), 7.57 (1H, d, Jˆ9.0 Hz, Ar), 7.82 (1H, m, Jˆ8.0 Hz,
.87 (1H, d, Jˆ8.2 Hz, C
0
±H), 7.15 (1H, d, Jˆ8.5 Hz,
0 0
±H),
6,6 ,7,7
8
,8
Ar), 7.93±8.02 (3H, apparent dt, Jˆ9.5, 9.0 Hz, Ar); d
C
C
0
±H), 7.19 (1H, ddd, Jˆ1.3, 7.0, 8.5 Hz, C
8
,8
NMR (67.8 MHz, CDCl ) 37.6, 42.7, 56.7, 113.6, 117.8,
3
7
.26±7.33 (2H, m, C6
0
0
±H), 7.34 (1H, d, Jˆ9.0 Hz,
0 0
±H),
6,6 ,7,7
,6 ,7,7
1
1
1
23.5, 123.7, 125.5, 125.5, 126.0, 126.3, 126.3, 126.4,
27.6, 128.2, 128.3, 139.8, 129.8, 131.8, 133.6, 133.9,
49.6, 155.1, 186.6; m/z (EI) 387 (M , 91%).
C3,3
7.69 (1H, d, Jˆ8.8 Hz, C3,3
±H), 7.88 (1H, d, Jˆ8.8 Hz, C
0
±H), 7.54 (1H, ddd, Jˆ1.2, 6.9, 8.2 Hz, C
1
0
±H), 7.85 (1H, d, Jˆ8.0 Hz,
C
0
0
4,4
±H), 7.96 (1H, d,
0
±H); dC
4,4
5
,5
Jˆ8.0 Hz, C
0
±H), 8.05 (1H, d, Jˆ8.8 Hz, C
0
diisoproylamino)phosphite)]-1,1 -binaphthalene, 6c.
5,5
(
(
R )-2-(N,N-Dimethyliminothiocarbamoyloxy)-2 -[bis-
a
NMR (67.8 MHz, CDCl ) 42.5, 45.7, 118.0, 119.3, 123.3,
3
0
1
24.6, 126.6, 127.1, 127.2, 127.8, 128.0, 128.2, 128.7, 129.8
2C), 132.35, 133.7, 134.1, 134.4 (2C), 139.5, 153.1, 198.3;
Under an inert atmosphere N-methyl-2-pyrrolidinone
776 ml, 8.03 mmol), triethylamine (450 ml, 3.214 mmol),
and bis(diisopropylamino)chlorophosphine (TOXIC!
57 mg, 3.214 mmol) were added to a solution of 5a
1.00 g, 2.77 mmol) in dichloromethane (40 ml) and the
(
m/z (EI) 389 (M , 18%) [found (EI HRMS) M 389.0909.
(
1
1
C H NOS requires 389.0908].
19
2
3
2
8
(
0 0 0
(S )-2,2 -Dihydroxy-3,3 -dimethylthio-1,1 -binaphthalene
a
mixture stirred for up to 72 h. When complete [TLC (3:1
hexane/ethyl acetate)] the reaction was quenched with satu-
rated NH Cl solution, washed with saturated NH Cl
(aq)
0
0
8c. A. (S )-3,3 -Dimethylthio-2,2 -bis(N,N-diethylcarba-
a
0
s
moyloxy)-1,1 -binaphthalene. Bu Li in hexanes (1.3 M;
4
(aq)
4
solution (2£10 ml), saturated brine (1£20 ml), dried over
8.7 ml) was added dropwise over 9 min to a stirred solution
of (S )-4b (2.5 g, 5.16 mmol) and TMEDA (1.54 ml,
MgSO and ®ltered. This solution was then left to evaporate
4
a
overnight to give white crystals of 6c on washing with
10.3 mmol) in THF at 2788C. The reaction was stirred for
a further 5 min after then methyl disul®de (1.02 ml,
11.4 mmol) was added and the reaction allowed to warm
slowly to 2508C. The mixture was then brought to
ambient temperature and quenched with saturated aqueous
2
4
petroleum spirit (480 mg, 30%), [a] ˆ1126 (cˆ3.54 in
D
CHCl ); (Found: C, 69.3; H, 7.8; N, 6.9 C H N O PS
3
35 46
3
2
2
1
requires C, 69.6; H, 7.7; N, 7.0%); nmax(KBr disc)/cm
3
1
055w, 2970w, 2929w, 2865w, 1540m, 1221m, 1195m,
158m, 1148m, 954m, 809s, 751s, 749s; dH NMR
NH Cl solution, the volatiles removed by high vacuum,
4
(
400 MHz, CDCl ) 0.74 (6H, d, Jˆ6.6 Hz, CHMe ), 0.81
extracted into dichloromethane, the layers separated and
the organic layer dried (MgSO ). The solvent was removed
3
2
(
1
6H, d, Jˆ6.6 Hz, CHMe ), 0.96 (6H, d, Jˆ6.6 Hz, CHMe ),
2
2
4
.02 (6H, d, Jˆ6.6 Hz, CHMe ), 2.46 (3H, s, NMe), 3.00
and the product crystallised from EtOH to give white
0
2
(
m, C6
3H, s, NMe), 3.18±3.28 (4H, m, CHMe ), 7.14±7.27 (3H,
2
crystals of the 3,3 -di-SMe-bis-carbamate (2.01 g, 76%),
2
D
9
0
0
±H), 7.29 (1H, d, Jˆ7.8 Hz, C
0
±H), 7.32 (1H, d,
0 0
mp 164±1658C; [a] ˆ184 (cˆ5.0 in CHCl ); nmax(KBr
,6 7,7
8,8
3
2
1
Jˆ8.6 Hz, C
0
±H), 7.39 (1H, dt, Jˆ7.8, 1.2 Hz, C
±
disc)/cm 3080w, 2940w, 1730s, 1410s, 1280, 1220s,
1160s, 1060, 965, 850, 755; dH (400 MHz, CDCl3)
0.40±0.70 (6H, v br, CH Me), 1.0 (6H, v br, CH Me),
8
,8
6,6 ,7,7
H), 7.64 (1H, d, Jˆ8.8 Hz, C ±H), 7.68 (1H, dd, Jˆ8.8 Hz,
3
J ˆ3.9 Hz, C
PH
0
±H), 7.76 (1H, d, Jˆ7.8 Hz, C
0
±H), 7.83
0
3
5,5
2
2
(
1H, d, Jˆ9.0 Hz, C
0
±H), 7.87 (1H, d, Jˆ8.0 Hz, C ±
±H); d NMR (100.4 MHz,
2.58 (6H, s, SMe), 2.7±3.3 (8H, v br, CH Me), 7.2±7.3
2
4
,4
5,5
H), 7.88 (1H, d, Jˆ9.0 Hz, C
0
(4H, v br, Ar), 7.38 (2H, br t, Jˆ7.8 Hz, Ar), 7.68 (2H,
0
±H); dC
5,5
4
,4
C
CDCl ) 23.5, 23.55, 23.6, 23.65, 23.85, 23.9, 23.95, 24.0,
3
br s, C
0
±H), 7.77 (2H, br d, Jˆ7.8 Hz, C
4,4
3
1
1
1
1
7.9, 42.6, 44.6, 44.75, 44.8, 44.95, 117.5, 117.9, 118.1,
18.15, 123.3, 124.15, 125.3, 125.6, 125.9, 126.0, 126.4,
(100.4 MHz, CDCl ) 12.4, 13.7, 15.1, 41.75, 42.0,
3
124.4, 125.1, 125.4, 125.8, 126.2, 127.3, 131.1, 131.9,
132.5, 145.0, 152.2; m/z (EI) 576 (M , 41%) [found
1
26.6 (d, J ˆ12.2 Hz),127.2, 127.4, 127.8, 128.5, 128.9,
PC
1
28.9 (d, J ˆ3.1 Hz), 131.95, 133.8 (d, J ˆ4.9 Hz),
(EI HRMS)
576.2117].
M
576.2113. C H N S O requires
32 36 2 2 4
PC
PC
49.6, 151.75 (d, J ˆ7.4 Hz), 186.4, some signals overlap;
PC

S. M. W. Bennett et al. / Tetrahedron 56 (2000) 2847±2855
2853
0
diethylcarbamoyloxy)-1,1 -binaphthalene. LiAlH (0.33 g,
0
B. Deprotection of (S )-3,3 -Dimethylthio-2,2 -bis(N,N-
a
C5,5
(1H, s, C4,4 ±H); dC (67.8 MHz, CDCl ) 12.0, 13.6, 14.1
0
3
0
±H), 7.90 (1H, s, C4,4
0
±H), 7.93 (1H, d, C5,5
0
±H), 7.94
0
.65 mmol) was added to a stirred solution of bis-carbamate
4
8
(2C), 38.5, 38.9 (2C), 42.9 (2C), 43.9, 116.35, 124.2,
124.9, 125.8, 125.9, 126.1, 126.3, 126.8, 127.2, 127.4,
128.0, 128.2, 128.3, 128.4, 128.6, 130.2, 131.0, 133.4,
133.7, 148.6, 166.9, 168.4, 186.2; m/z (EI) 571 (M , 97%)
[found (HRMS) M 571.2511. C H N SO requires
571.2505].
prepared above (1.00 g, 1.73 mmol) in THF (12 ml) and the
mixture re¯uxed for 16 h. After cooling, the excess LiAlH4
was destroyed by cautious addition of ethyl acetate (12 ml)
followed by 2 M HCl(aq). The layers were separated and the
aqueous extracted twice with further ethyl acetate. The
1
1
33
37
3
4
combined organic layer was dried (MgSO ) and the solvent
4
0
removed to give a white powder which was crystallised
from EtOH to give white crystals of (S )-8c (0.51 g, 78%);
(S )-2 -Hydroxy-2-(N,N-dimethylthiocarbamoyloxy)-
a
0
0
3,3 -dimethylthio-1,1 -binaphthalene 9c. Prepared in a
similar manner to 9a. Puri®ed by crystallisation from
dichloromethane±pentane to give pale yellow crystals
(37%); mp 244±2478C (discolouration prior to melting);
a
2
9
mp 159±1608C; [a] ˆ287 (cˆ2.0 in CHCl ); nmax(KBr
D
3
2
1
disc)/cm 3415br, 3070w, 2925w, 1580, 1500, 1435s,
210, 1145s, 880, 850, 755; dH (400 MHz, CDCl ) 2.56
1
3
2
D
5
21
(
6H, s, SCH ), 6.05 (2H, s, OH), 7.10 (2H, d, Jˆ8.6 Hz,
[a] ˆ2345 (cˆ1.0 in CHCl ); nmax(KBr disc)/cm
3
3
C ±H), 7.24 (2H, ddd, Jˆ1.3, 6.8, 8.6 Hz, C ±H), 7.35
3280br, 3070w, 2920w, 1585s, 1400s, 1290, 1220s, 1135s,
850, 755; dH (400 MHz; CDCl /d -DMSO) 2.58 (3H, s,
8
7
6
(
2H, ddd, Jˆ1.2, 6.8, 8.0 Hz, C ±H), 7.82 (2H, d,
6
3
Jˆ8.0 Hz, C ±H), 7.95 (2H, s, C ±H); d (100.4 MHz,
Me), 2.65 (3H, s, Me), 2.72 (3H, s, Me), 3.20 (3H, s, Me),
0
5
4
C
CDCl ) 17.34, 112.68, 124.31, 124.54, 126.45, 126.92,
3
6.60 (1H, s, OH), 7.05 (1H, d, Jˆ8.3 Hz, C
±H),
7.14±7.20 (1H, m, Ar), 7.25 (1H, t, Jˆ7.1 Hz, Ar), 7.31
(1H, t, Jˆ7.4 Hz, Ar), 7.47 (1H, t, Jˆ7.6 Hz, Ar), 7.65
8,8
1
27.48, 129.45, 129.91, 132.53, 150.11; m/z (EI) 378
M
1
M , 100%) [found (EI HRMS)
1
(
C H S O requires 378.0748].
378.0750.
(1H, s, C
0
±H), 7.78 (1H, d, Jˆ8.6 Hz, C
0
±H), 7.79
0
2
2
18
2
2
4,4
5,5
(
1H, s, C4,4
0
±H), 7.87 (1H, d, Jˆ8.1 Hz, C
±H); dC
(400 MHz; CDCl -d DMSO) 14.6, 15.1, 37.95, 42.9,
5,5
0
,3 -dimethyl-1,1 -binaphthalene 9a. Compound 8a
6
(
3
R )-2 -Hydroxy-2-(N,N-dimethylthiocarbamoyloxy)-
a
3
0
0
115.2, 123.8, 124.1, 124.3, 125.1, 125.2, 125.3, 125.4,
126.1, 126.4, 126.5, 126.7, 129.1, 130.0, 130.6, 131.1,
132.1, 132.2, 148.2, 149.05, 1856.0; m/z (EI) 465 (M ,
(
0.50 g, 1.59 mmol), DMAP (39 mg, 0.32 mmol) and N,N-
dimethylthiocarbamoyl chloride (TOXIC!, 0.21 g,
.67 mmol) were dissolved in dichloromethane (40 ml).
1
1
1
4%) [found (HRMS) M 465.0887. C H NS O requires
2
5
23
3
2
NEt (231 ml, 1.67 mmol) was added and the solution stirred
3
465.0891].
for 15 days at ambient temperature. Some dichloromethane
was then removed, the reaction warmed to 408C and stirring
continued for a further 4 days. The reaction was quenched
with saturated NH Cl and the organic layer washed with
Representative copper-catalysed conjugate addition
method
4
(aq)
NH3(aq), 2 M HCl (£2), H O, brine and dried (MgSO ). The
2
4
solvent was removed and the crude product puri®ed by
column chromatography (diethyl ether-light petroleum) to
A solution of Me Al in hexanes (2.0 M; 0.43 ml,
3
0.85 mmol) was diluted with hexane to a volume of
0.8 ml in a syringe, rocking the syringe to affect mixing.
An aliquot of this solution (0.1 ml, 0.11 mmol) was added
to a stirred solution of ligand (5a±c, 6a±c, 7a±b, 8c, and
9a±c, 0.1 mmol) and [Cu(MeCN) ]BF4 (15.7 mg,
4
0.05 mmol) in THF (1.0 ml) at 2208C and the mixture
stirred for approximately 1 min.
2
9
give a white powder (46%); mp 86±888C; [a] ˆ1363
D
(
cˆ1.0 in CHCl ); (Found: C, 74.9; H, 6.05; N, 3.3; S,
3
7
8
1
.6. C H NSO requires C, 74.8; H, 5.8; N, 3.5; S,
25 23 2
2
1
.0%); nmax(KBr disc)/cm 3310br, 3070w, 2930, 1545s,
400s, 1290s, 1235s, 1135s, 885, 750s; dH (400 MHz,
CDCl ) 2.48 (6H, s, C
3
0
±Me), 2.50 (3H, s, NMe), 3.15
3,3
(
3H, s, NMe), 5.84 (1H, s, OH), 7.05 (1H, d, Jˆ8.6 Hz,
Ar), 7.16 (1H, t, Jˆ7.6 Hz, Ar), 7.20±7.28 (3H, m, Ar),
±H), 7.74
Using a syringe, THF (0.5 ml) was added to 3-nonen-2-one
1
2
n
11
7
.44 (1H, t, Jˆ7.4 Hz, Ar), 7.71 (1H, s, C
0
1 (R ,R ˆC H ,Me) (83 ml, 0.5 mmol) and the solution
4
,4
5
(
(
1H, d, Jˆ7.8 Hz, C
0
±H), 7.85±7.89 (2H, m, Ar); d
C
mixed. The resulting solution was drawn back up into the
syringe affording 0.7 ml of enone solution. This solution of
1 and the remaining Me Al solution (0.7 ml, generated
5
,5
100.4 MHz, CDCl ) 17.2, 17.5, 37.8, 43.0, 115.1, 123.3,
3
1
1
1
24.4, 124.55, 125.3, 125.6, 126.01, 126.35, 127.0, 127.5,
28.6, 129.0, 129.3, 130.3, 130.7, 132.2, 132.3, 132.5,
51.2, 151.5, 186.7; m/z (EI) 401 (M , 56%) [found
3
above) were added simultaneously to the stirred catalyst
solution (2208C) over 20 min using a syringe pump. After
addition was complete the mixture was stirred for a further
1
1
(
HRMS) M 401.1452. C H NSO requires 401.1450].
2
5
23
2
2
0 min at 2208C. Dilute HCl (2 M, 2.5 ml) was added
0
0
(
R )-3,3 -Bis(N,N-diethylcarbamoyl)-2 -hydroxy-2-(N, N-
a
cautiously and the mixture allowed to warm to room
temperature. Internal standard (undecane, 50 ml) and diethyl
ether were added, the layers separated and the organic frac-
0
dimethylthiocarbamoyloxy)-1,1 -binaphthalene 9b. Pre-
pared in a similar manner to 9a. Puri®ed by chromatography
EtOAc) to give a white powder (73%); mp 122±1268C;
1
9
(
[
3
1
tion ®ltered through silica. Typical GC analysis of the
liquid showed that it contained only undecane (rt
11.0 min), 4-methyl-2-nonanone (rt 21.2 and 22.8 min for
the (2) and (1) enantiomers, respectively, 0±71% e.e.) and
a trace of 3-nonen-2-one (rt 29.0 min.). Distillation was
carried out in some cases to con®rm the presence of isolable
2. Additions using other enones, organometallic sources,
and ligands were carried out in an analogous manner.
2
D
5
21
a] ˆ1266 (cˆ2.0 in CHCl ); nmax(KBr disc)/cm
3
240br, 3075w, 2985, 2950, 1640vs, 1545, 1460, 1400,
290, 1225, 1140, 755; dH (400 MHz, CDCl ) 1.16 (9H,
3
br t, J 7.0, 3£CH Me), 1.27 (3H, br t, Jˆ6.8 Hz, CH Me),
2
2
2
4
7
.79 (3H, br s, NMe), 3.12 (3H, s, NMe), 3.1±3.9 (8H, br m,
£CH Me), 6.54 (1H, br s, OH), 7.19±7.37 (5H, m, Ar),
2
.51 (1H, dt, Jˆ1.0, 6.8 Hz, Ar), 7.78 (1H, d, Jˆ8.5 Hz,

2
854
S. M. W. Bennett et al. / Tetrahedron 56 (2000) 2847±2855
Additions using manual sequential drop-wise additions of
organometallic and enone gave essentially identical results.
Acknowledgements
We are grateful to EPSRC (grant GR/K52263 and access to
the Mass Spectrometry Service at Swansea) and Zeneca
(CASE award to SWMB). We thank the COST-D12
programme for additional support and Prof. D.G.
Blackmond (University of Hull) for advice on non-linear
effect interpretation.
1
2
3
n
11
4
(
-Methyl-2-nonanone
2
(R ,R ,R ˆC H ,Me,Me). dH
5
400 MHz; CDCl ) 0.81±0.90 (6H, m, 2£Me), 1.26 (8H,
3
m, 4£CH ), 1.97 (1H, m, CH), 2.13 (3H, s, C(O)Me),
2
1
.18±2.43 (2H, m, CH C(O)Me); m/z (EI) 156 (M , 1%),
41 (3), 127 (3), 109 (18), 101 (25), 91 (12), 85 (28), 69
2
1
2
(
16), 58 (65), 43 (100).
1
2
3
n
11
4
(
-Ethyl-2-nonanone 2 (R ,R ,R ˆC H ,Me,Et). d NMR
5
H
400 MHz, CDCl ) 0.94±0.79 (6H, m, 2£Me), 1.40±1.15
References
3
(10H, m, alkyl C-H), 1.91-1.79 (1H, m, CH), 2.13 (3H, s,
C(O)Me), 2.33 (2H, m, CH C(O)Me).
2
1. Krause, N. Angew. Chem. Int. Ed. Engl. 1998, 37, 283±285;
Taylor, R. J. K., Ed. Organocopper Reagents, A Practical
Approach; Oxford University Press: Oxford, 1994; Perlmutter, P.
Conjugate Addition Reactions in Organic Synthesis; Pergamon:
Oxford, 1992.
1
2
3
i
4
-Ethyl-5-methyl hexane-2-one 2 (R ,R ,R ˆPr ,Me,Et). d
H
NMR (400 MHz, CDCl ) 0.90±0.78 (9H, m, 3£Me), 1.26±
3
1.13 (1H, m, CH), 1.42±1.28 (1H, m, CH), 1.82±1.65 (2H,
m, C ±CH Me), 2.15 (3H, s, C(O)Me), 2.26 (2H, m,
4
2
2. For coverage of reactions prior to 1992 see: Rossiter, B. E.;
Swingle, N. E. Chem. Rev. 1992, 92, 771±806 (especially Section
III). Very recently, Zhang has reported highly enantioselective
CH C(O)Me).
2
1
2
Baeyer±Villiger oxidation of conjugate addition
product, preparation of 2-methyl-1-heptanol acetate
copper-catalysed additions of ZnEt to 1 (R ,R ˆAryl; and
2
1
2
R ˆi2Pr, R ˆMe); see: Hu, X.; Chen, H; Zhang, X. Angew.
Chem. Int. Ed. Engl. 1999, 38, 3518±3521.
3. Fuji, K.; Tanaka, F.; Node, M. Tetrahedron Lett. 1991, 32,
7281±7282.
1
0. A sample of (1)-4-methyl-2-nonanone (1)-2 (R ,R ,
2
1
3 n
R ˆC H ,Me,Me) (119 ml ca. 50% e.e.) isolated from a
5
11
combination of catalytic runs (and therefore containing
some undecane) was slurried with acetic acid (1.3 ml) and
water (0.7 ml). Na S O (0.6 g) was added and the mixture
4. Kanai, M.; Koga, K.; Tomioka, K. Tetrahedron Lett. 1992, 33,
7193±7196.
2
2
8
stirred at room temperature. The reaction was followed by
GC and worked up after 10 days by extraction into dichloro-
methane, drying (MgSO ) and removing the solvent (by
5. van Klaveran, M.; Lambert, F.; Eijkelkamp, D. J. F. M.; Grove,
D. M.; van Koten, G. Tetrahedron Lett. 1994, 35, 6135±6138.
6. de Vries, A. H. M.; Meetsma, A.; Feringa, B. L. Angew. Chem.
Int. Ed. Engl. 1996, 35, 2374±2430.
4
careful rotary evaporation) to give 112 mg yellow oil
whose partial H NMR spectrum was consistent with forma-
1
7. Strangeland, E. L.; Sammakai, T. Tetrahedron 1997, 53,
16503±16510.
tion of 10. dH (400 MHz, CDCl ; signals due to starting
3
material and undecane not given) 0.88±0.93 (6H, m,
8. Kanai, M.; Nakagawa, Y.; Tomioka, K. Tetrahedron 1999, 55,
3831±3842.
2
1
£Me), 1.26 (8H, br m, 4£CH ), 2.10 (3 H, s, C(O)Me),
2
.97 (1H, m, CH), 3.83±3.97 (2H, m, diastereotopic CH ).
2
9. Alexakis, A.; Benha Èõ m, C.; Fournioux, X.; van der Heuvel, A.;
Lev eà que, J.-M.; March, S.; Rosset, S. Synlett 1999, 1811±1813.
10. Sewald, N.; Wendisch, V. Tetrahedron: Asymmetry 1998, 9,
1341±1344.
GC analysis (g-CD) of the product showed the presence of
undecane, a small amount of ketone 2 and two new partially
resolved peaks (rt 24.0 (small) and 26.1 (large) min; 1:3
ratio) assigned to 10. The presence of 3-nonen-2-one 1
could no longer be detected. The conversion was approxi-
mately 85%.
11. Bolm, C.; Ewald, M.; Felder, M. Chem. Ber. 1992, 125, 1205±
1215.
12. Ikeda, S.-I.; Cui, D.-M.; Sato, Y. J. Am. Chem. Soc. 1999, 121,
4
712±4713.
Preparation of (R)-(1)-2-methyl-1-heptanol (R)-(1)-11
via hydrolysis of 10. The sample of 10 (112 mg, containing
some undecane) isolated from the oxidation above was
added to excess potassium hydroxide (2 g) in methanol
13. Yamaguchi, M.; Shiraishi, T.; Hirama, M. J. Org. Chem. 1996,
61, 3520±3530.
14. Takaya, Y.; Ogasawara, M.; Hayashi, T.; Sakai, M.; Miyaura,
N. J. Am. Chem. Soc. 1998, 120, 5579±5580.
(
4.5 ml) and water (0.5 ml) and stirred at 508C (16 h). The
material was extracted into dichloromethane, dried
MgSO ) and the solvent removed by careful rotary
15. Bennett, S. M. W.; Brown, S. M.; Muxworthy, J. P.;
Woodward, S. Tetrahedron Lett. 1999, 40, 1767±1770.
16. Pearson, R. G. Coord. Chem. Rev. 1990, 100, 403±425.
17. Azad, S. M.; Bennett, S. M. W.; Brown, S. M.; Green, J.; Sinn,
E.; Topping, C. M.; Woodward, S. J. Chem. Soc., Perkin Trans. 1
1997, 687±694.
(
4
evaporation to give 102 mg of a yellow oil assigned struc-
ture (R)-(1)-11 by comparison with literature data; [a]
(
D
2
3,24
cˆ3.4 in CHCl , 288C) 13.2 [lit.
(S)-2-methyl-1-hepta-
3
nol 213.1 (cˆ1.15 in CHCl , 208C)]; d (270 MHz, CDCl ;
18. Dennis, M. R.; Woodward, S. J. Chem. Soc., Perkin Trans. 1
1998, 1081±1085.
3
H
3
signals due to undecane are not given) 0.86±0.93 (6H, m,
2
eotopic CH ); d (67.8 MHz, CDCl ) 16.6, 20.7, 22.7,
£Me), 1.26 (8H, br m, 4£CH ), 3.40±3.53 (2H, m, diaster-
19. Bennett, S. M. W.; Dennis, M. R.; Fraser, P. K.; Topping,
C. M.; Woodward, S.; Brown, S. M.; Radojevic, S.; Conole, G.;
McPartlin, M. J. Chem. Soc., Perkin Trans. 1 1999, 3127±3132.
20. Westermann, J.; Nickisch, K. Angew. Chem. Int. Ed. Engl.
1993, 32, 1368±1369.
2
2
C
3
26.65, 32.0, 33.1, 35.74, 68.44. GC analysis (g-CD) of the
product showed the complete disappearance of the ester
with new peaks at 26.4 (small) and 27.8 (large) min, not
totally resolved but in the same ratio as the starting
material 2.
21. Kabbara, J.; Flemming, S.; Nickisch, K.; Neh, H.;
Westermann, J. Tetrahedron 1995, 51, 743±754.

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