Nucleophilic addition of α-metallated carbamates to planar chiral cationic η3-allylmolybdenum complexes: A stereochemical study

Article abstract of DOI:10.1055/s-2004-834917

Chiral α-(O-carbamoyl)alkyl- and α-(N-carbamoyl)alkylcopper(I) reagents derived from (-)-sparteine-mediated asymmetric lithiation of hindered carbamates react with cationic η³-allylmolybdenum complexes with retention of configuration.

Full text of DOI:10.1055/s-2004-834917

PAPER
75
Nucleophilic Addition of a-Metallated Carbamates to Planar Chiral Cationic
h3-Allylmolybdenum Complexes: A Stereochemical Study
N
a
ucleophilic
A
h
ddition Rea
i
ctions
o
l
f
a
-M
i
etallate
p
dCarbamates J. Kocienski,*a John A. Christopher,b,c Richard Bell,c Bernhard Ottoa
Department of Chemistry, Leeds University, Leeds LS2 9JT, UK
Fax +44(113)3436401; E-mail: p.kocienski@chemistry.leeds.ac.uk
b
c
Department of Chemistry, Glasgow University, Glasgow G12 8QQ, UK
GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, UK
Received 9 September 2004
OTBDPS
O
LDBB, THF
–78 °C
OTBDPS
O
Abstract: Chiral a-(O-carbamoyl)alkyl- and a-(N-carbamoyl)al-
kylcopper(I) reagents derived from (–)-sparteine-mediated asym-
metric lithiation of hindered carbamates react with cationic h3-
allylmolybdenum complexes with retention of configuration.
–PhSLi
SPh
M
Key words: (–)-sparteine, nucleophilic addition, h3-allylmolybde-
num complexes, asymmetric deprotonation, carbamates, a-(O-car-
bamoyl)alkylcopper(I), a-(N-carbamoyl)alkylcopper(I)
1
2 M = Li
3 M = Cu
CuBr
+
OTBDPS
O
–
BF4
O2
44% from 1
2
4
A powerful method for the stereoselective appendage of a
carbon chain to an oxacyclic ring with simultaneous cre-
ation of two stereogenic centres is exemplified by the ad-
dition of tetrahydropyran-2-ylcopper(I) reagent 3 to the
cationic planar chiral h3-allylmolybdenum complex 4 to
–78 °C
Mo
Cp
OC
NO
(2R,4S)-4
5
give adduct
5
after oxidative decomplexation
(Scheme 1).1 The reaction occurs with clean retention in
the organocopper(I) nucleophile which adds regioselec-
tively to the allyl ligand anti to the molybdenum. The re-
quisite a-alkoxyalkylcopper(I) reagent 3 was generated
stereoselectively by a 2-step sequence involving first re-
ductive lithiation of the O,S-acetal 12 using lithium di-
tert-butylbiphenylide (LDBB)3 to give the axial organo-
lithium 2 owing to the radical anomeric effect.4,5 The sec-
ond step, transmetallation with CuBr, occurred with
retention of configuration.6,7 However, the reductive lithi-
ation is only stereoselective when the oxygen atom is con-
tained in a six-membered ring and many functional groups
are incompatible with the powerful reductive conditions.8
A milder alternative is illustrated by the generation of or-
ganocopper(I) reagent 9 from the enantiomerically pure
stannane 7 by two sequential transmetallation reactions,
both of which occurred with retention of configuration.9
In order to extend the scope of the chemistry depicted in
Scheme 1, especially to acyclic systems, we required ac-
cess to a readily available configurationally stable carbon
nucleophile whose addition to cationic h3-allylmolybde-
num complexes occurs with high and predictable stereo-
selectivity. We now report that chiral a-(O-
carbamoyl)alkyl- and a-(N-carbamoyl)alkylcopper(I) re-
agents derived from hindered carbamates react with cat-
ionic h3-allylmolybdenum complexes with retention of
OBn
O
OBn
Bu3SnLi, THF
BnO
BnO
O
BnO
BnO
–78 °C, 1 h
70%
M
Cl
7
M = SnBu3
M = Li
6
BuLi
8
9
CuBr
M = Cu
OBn
O
4
CAN
BnO
BnO
49% from 7
–78 °C
10
Scheme 1
configuration to provide an acyclic variant of the chemis-
try described above.
At the heart of our work is the convenient and general syn-
thesis of enantioenriched a-(O-carbamoyl)alkyllithiums
invented by Hoppe and co-workers.10,11 The procedure is
illustrated by the synthesis of the a-(O-carbamoyl)alkyl-
stannane 11:12 ligand-directed deprotonation of the pro-S
proton of the racemic carbamate 11 with s-butyllithium
and (–)-sparteine followed by addition of chlorotributyl-
stannane gave the (1S,2S)-stannane 12 in 23% yield (er =
>97:3), the (1S,2R)-stannane (46%, er = 88:12) and re-
covered starting material 11 (14%) after column chroma-
tography. The minor (1S,2S)-isomer was used in the next
step owing to its higher enantiopurity. Thus treatment of
stannane 12 with BuLi in Et2O–THF (1:1) at –78 °C fol-
SYNTHESIS 2005, No. 1, pp 0075–0084
x
x
.
x
x
.2
0
0
4
Advanced online publication: 17.11.2004
DOI: 10.1055/s-2004-834917; Art ID: Z17304SS
© Georg Thieme Verlag Stuttgart · New York

76
P. J. Kocienski et al.
PAPER
lowed by addition of CuBr·SMe2 generated the organo-
copper(I) reagent 14 to which was added a freshly
prepared solution of the cationic complex (2S,4R)-4 in
acetonitrile. After aqueous workup, the crude h2-adduct
was treated with oxygen in chloroform to give the crystal-
line adduct 15 in 35% overall yield from stannane 12
(Scheme 2). An X-ray crystal structure of adduct 15
(Figure 1) revealed the relative stereochemistry to be 1,2-
syn-2,3-anti indicating that the transmetallation of lithium
to copper(I) occurred with retention13 and the a-(O-car-
bamoyl)alkylcopper(I) reagent 14 added to the cationic
h3-allylmolybdenum complex (2S,4R)-4 with retention of
configuration.
HS
HR
SnBu3
Ph
Ph
(a) s-BuLi, (–)-sparteine
(b) Bu3SnCl
O
O
O
O
N
N
Figure 1 X-ray crystal structure of adduct 15
O
O
11
12
(79% yield) followed by ozonolysis of the alkene 17 re-
turned (2R,3R,4S)-diol 18 after reductive workup
(Scheme 2). The H NMR spectrum of (2R,3R,4S)-18
BuLi
1
M
N
compared favourably with data reported by Matsumoto
Ph
Ph
and co-workers for the racemic modification.14
O
O
O
O
(a) (2R,4S)-4, –78 °C
The second a-(O-carbamoyl)alkylcopper(I) nucleophile
in this study was selected to determine the consequence,
if any, of a chelating heteroatom substitutent b to the car-
banionic centre. The requisite stannane 19, easily pre-
pared by the procedure of Hoppe and co-workers,15 was
converted to the organocopper(I) reagent as before. Addi-
tion of the h3-allylmolybdenum complex (2R,4S)-4 in
MeCN gave olefin 20 in 57% overall yield from stannane
(b) O2, CHCl3, r.t.
N
35% from 12
O
O
15 (mp 79–81 °C)
13
14
M = Li
CuBr
X-ray
M = Cu
(a) (2S,4R)-4, –78 °C
(b) O2, CHCl3, r.t.
1
+
BF4
19 after oxidative decomplexation (Scheme 3). H NMR
–
spectroscopy and GC/MS of the crude reaction mixture
revealed a mixture of 4 isomers in the approximate ratio
95:2:2:1. The 1,2-anti stereochemistry of the major ad-
duct 20 was assigned on the assumption that the nucleo-
phile added with retention of configuration anti to the
molybdenum.
Ph
O
O
Mo
OC
NO
N
Cp
(2S,4R)-4
O
16
(a) MeSO3H, MeOH
(b) K2CO3, MeOH
79%
Proof that the alkylation reaction proceeds with retention
of configuration in the nucleophile was obtained once
again by correlation with a known compound. The a-(O-
carbamoyl)alkylcopper(I) intermediate derived from stan-
nane 19 was treated with the simple h3-allylmolybdenum
complex 21. The resultant adduct 22 (dr = 50:1) was ob-
tained in 61% overall yield from 19. Reductive cleavage
of the carbamate group gave the (S)-alcohol 23 (49%)
whose optical rotation and 1H and 13C NMR spectroscopic
data correlated with literature values.16,17
(a) O3, –78 °C
Ph
Ph
(b) NaBH4
43% from 16
OH
17
OH OH
18
Scheme 2
The organocopper(I) reagent 14 was also added to the
enantiomeric h3-allylmolybdenum complex (2R,4S)-4 in
order to establish that the stereoselectivity of the addition
was not a consequence of matched-pair effects. The dia-
stereoisomeric 1,2-syn-2,3-syn adduct 16 was isolated in
52% overall yield from stannane 12 along with 15% of
(S)-11. Adduct 16 was not crystalline and hence its rela-
tive configuration was established by correlation with a
known compound. Methanolysis of the carbamate 16
The regiochemistry of ligand-directed carbamate metalla-
tion is structure dependent. Beak and co-workers showed
that carbamates devoid of a proton adjacent to oxygen
metallate adjacent to nitrogen instead to give a-(N-car-
bamoyl)alkyllithiums.18 Thus asymmetric metallation of
N-Boc-indoline 24 with s-BuLi and (–)-sparteine fol-
lowed by alkylation with allyl chloride and DMPU gave
Synthesis 2005, No. 1, 75–84 © Thieme Stuttgart · New York

PAPER
Nucleophilic Addition Reactions of a-Metallated Carbamates
77
(a) s-BuLi / (–)-sparteine
cumene, –78 °C, 6 h
O
O
(b) allyl chloride / DMPU
(a)
(b)
O
n-BuLi, –78 °C
CuBr•SMe2, –78 °C
N
N
–78 °C → r.t.; 15%
Boc
Boc
(S)-25
er = 7 : 3
O
N
24
(c)
(d)
Complex (2R,4S)-4,
O2, CHCl3, r.t.
O
(a) s-BuLi, (–)-sparteine, t-BuOMe, –78 °C
(b) CuBr•SMe2, (i-Pr)2S-THF
(c) Complex 21
57% overall
55%
20
(d) CAN, NaOAc
O
O
O
O
(a) n-BuLi, –78 °C
(b) CuBr•SMe2, –78 °C
O
O
+
1:1
1
N
R
N
O
N
O
N
(c) Complex 21
(d) O2, CHCl3, r.t.
R
Bu3Sn
O
O
2
61% overall
(S)-25
(S)-27
R = Boc
R = Boc
R = H
26
28
(a) TFA (73%)
19
22
(b) separate
R = H
LiAlH4 49%
(R)-O-acetylmandelic acid
DCC, DMAP, CH2Cl2, 0 °C
87%
O
O
+
BF4
–
+
BF4
–
OC Mo NO
Cp
OH
N
Mo
OAc
Ph
21
OC
NO
Cp
O
29
23
21
Scheme 4
Scheme 3
lute stereochemistry depicted in 32 based on the precedent
provided in the three preceding examples (Scheme 5).
2-allylindoline (S)-25 in 15% yield (S:R = 99:1) as shown
in Scheme 4.19 By using allyl bromide as the alkylating
agent, the yield improved to 28% but the er of the reaction
plummeted (S:R = 7:3). The low yield and variable enan-
tioselectivity in this reaction prompted us to examine the
alkylation of N-Boc-indoline 24 with the simple cationic
h3-allylmolybdenum complex 21.20 Asymmetric lithiation
of N-Boc-indoline 24 with s-BuLi/(–)-sparteine, trans-
metallation to the organocopper(I) reagent, and reaction
with 21 gave an inseparable equimolar mixture of 2- and
7-substituted indolines 25 and 26 (55%) together with 9%
of recovered indoline 24. Comparison of the sign of opti-
cal rotation of the mixture 25 and 26 [+44.2, (c = 0.55,
CHCl3)] with that reported by Beak19 [+29 (c = 0.01,
CHCl3), 36% ee] indicated that the lithiation–transmetal-
lation–allylation sequence returned 25 with the (S)-con-
figuration. Protonolysis of the N-Boc group gave the
separable amines (S)-27 and 28. The 2-allyl derivative
(S)-27 gave (R)-O-acetylmandelamide 29 as a single dia-
stereoisomer according to 1H and 13C NMR spectroscopy
and GC/MS. Hence, the transmetallation (Li to Cu) and
nucleophilic addition reactions occurred with clean reten-
tion of stereochemistry.
(a)
s-BuLi, (–)-Sparteine
t-BuOMe, –78 °C, 3.5 h
Cu
(b)
CuBr•SMe2, (i-Pr)2S-THF
–78 °C, 30 min
N
Boc
N
Boc
Cl
Cl
30
31
(a)
(b)
(2R,4S)-4,
–78 °C → r.t.
2
N
Boc
O
2, CHCl3
r.t., 3.5 h
Cl
46% from 30
32
Scheme 5
Synthesis of the Cationic h3-Allylmolybdenum Com-
plexes (2R,4S)-4 and (2S,4R)-4
We previously prepared the cationic complex (2R,4S)-4
by a 4-step sequence first described by Faller and
Linebarrier21 (Scheme 6). The principal detraction to this
route was the Sharpless kinetic resolution22 used to pre-
pare the allylic alcohol 33. Although the enantiomeric pu-
rity of 33 was excellent (er = 97:3), the yield was low
(26%) and the reaction was awkward to conduct on a large
scale. Moreover, two separate kinetic resolutions were re-
quired to prepare both enantiomers of 33.
In order to avoid the complications of arene metallation
observed with N-Boc indoline, we performed an asym-
metric lithiation of N-Boc-7-chloroindoline 30 and its
transmetallation with CuBr·SMe2, to give the organocop-
per(I) reagent 31. Addition of 31 to cationic h3-allylmo-
lybdenum complex (2R,4S)-4 gave an inseparable mixture
of 4 isomeric adducts (57%) in the ratio 4:9:81:6 accord-
ing to GC/MS. The major product was assigned the abso-
Synthesis 2005, No. 1, 75–84 © Thieme Stuttgart · New York

78
P. J. Kocienski et al.
PAPER
(a)
(b)
Mo(CO)3(MeCN)3
MeCN, reflux, 40 h
NaBH4, CeCl3•7H2O
MeOH, 0 °C to r.t., 18 h
62%
LiCp, THF, r.t.
66%
OR
Mo
Cp
O
OH
( )-37
OC
CO
36
33 R = H
Ac2O
DMAP
86%
Novozyme 435
vinyl acetate, pentane, r.t., 2 h
then column chromatograhy
34 R = Ac
(–)-(2R,4S)-35
+
BF4
NOBF4
MeCN–Et2O
–
2
4
+
0 °C, 5 min
91%
Mo
OAc
OH
OC
NO
Cp
(R)-38 (49%)
(S)-37 (44%)
(2R,4S)-4
(a) K2CO3, MeOH
(b) BzCl, DMAP
55%
BzCl, DMAP 86%
Scheme 6
A more efficient and scalable route to (2R,4S)-4 and its
enantiomer has been achieved (Scheme 7) featuring two
significant improvements. Firstly, the Sharpless kinetic
resolution has been replaced by a much faster, easier and
more convenient enzymatic resolution of the racemic al-
cohol ( )-37 using Novozyme 435 and vinyl acetate.23
The easily separable allylic alcohol (S)-37 and the allylic
acetate (R)-38 were obtained in 44% yield (er = 99:1) and
49% yield (er = 96:4) respectively. Note that both prod-
ucts of the single kinetic resolution were transformed to
the desired enantiomeric complexes.24 Secondly, the yield
and quality of the neutral complexes (–)-(2R,4S)-35 and
(+)-(2S,4R)-35 were enhanced by the use of allylic ben-
zoates (R)-39 and (S)-39 as precursors instead of the cor-
responding allylic acetates and Mo(CO)4(THF)2 instead
of Mo(CO)3(MeCN)3 as the Mo(0) source.25
OBz
OBz
(R)-39
(S)-39
(a)Mo(CO)4(THF)2, THF, reflux, 36 h
(b) LiCp, THF, r.t., 1 h
88%
90%
2
2
4
4
Mo
Mo
OC
CO
OC
CO
Cp
(–)-(2R,4S)-35
Cp
(+)-(2S,4R)-35
+
BF4
+
BF4
–
–
2
2
4
4
Mo
Cp
Mo
Cp
OC
NO
OC
NO
In summary, we have established that a-(O-carbam-
oyl)alkyl- and a-(N-carbamoyl)alkylcopper(I) reagents
derived from the asymmetric metallation of hindered car-
bamates add to planar chiral cationic h3-allylmolybdenum
complexes with clean retention of configuration.26 In the
case of complexes (2R,4S)-4 and (2S,4R)-4, the addition
occurred regioselectively at the less hindered terminus
anti to the molybdenum in accord with previous observa-
tions.1,9 The method provides a potentially useful chain
extension in which two adjacent stereogenic centres are
created in a single step and it represents a relatively rare
procedure in asymmetric synthesis, the direct and ste-
reospecific connection of a carbocation equivalent and a
carbanion equivalent27 (Figure 2). Compared with the re-
ductive cleavage and transmetallation procedures used
(2S,4R)-4
(2R,4S)-4
Scheme 7
stirred and were monitored by TLC using silica gel pre-coated alu-
minum foil sheets, layer thickness 0.25 mm. Compounds were visu-
alised by UV (254 nm), 20 wt% phosphomolybdic acid in EtOH,
anisaldehyde, vanillin followed by H2SO4, KMnO4 or cerium(IV)
sulfate solutions.
Specific optical rotations ([a]D) were measured on an Optical Activ-
ity polAAr 2000 polarimeter using a 5 mL cell with a 1 dm path
length or a 0.5 mL cell with a 0.05 dm path length. IR spectra were
recorded on a Nicolet Impact 410 FT-IR spectrometer using a thin
film supported between NaCl plates or a KBr disk, unless otherwise
specified. 1H and 13C NMR spectra were recorded in Fourier Trans-
form mode at the field strength specified. All spectra were obtained
previously to generate the a-alkoxyalkyllithiums, in CDCl3 or CD3CN solution in 5 mm diameter tubes, and the chem-
ical shift in ppm is quoted relative to the residual signals of CHCl3
Hoppe’s asymmetric metallation protocol provides a
(dH 7.27, dC 77.2) or MeCN (dH 2.00, dC 117.7) unless specified oth-
more general and versatile route to enantioenriched car-
bon nucleophiles. Although the stereoselectivity of the ad-
dition is excellent, the yield is modest at best and needs
improvement.
erwise. Coupling constants (J) are reported in Hz. The number of
protons attached to the carbon in the 13C spectra was ascertained by
the Distortionless Enhancement by Phase Transfer (DEPT) tech-
nique with secondary pulses at 90° and 135°. Signal assignments
are based on COSY and HMQC correlations. Low- and high-reso-
lution mass spectra were run on a JEOL MStation JMS-700 spec-
trometer. Ion mass/charge (m/z) ratios are reported as values in
atomic mass units followed, in parenthesis, by the peak intensity
relative to the base peak (100%). GC/MS was performed on the
above spectrometer, using a Chrompack WCOT Fused Silica col-
umn (25 m × 0.25mm, CP-SIL 8CB-MS stationary phase), initial
temperature and heating rates are specified for individual cases.
(–)-Sparteine was purified by Kugelrohr distillation immediately
prior to use. CuBr·SMe2 was prepared by the procedure of Theis and
Townsend28 and purified by recrystallisation before use. Commer-
cial n-BuLi and s-BuLi solutions were titrated against 1,3-diphenyl-
acetone-p-tosylhydrazone.29 Organic extracts were dried over
MgSO4 and concentrated using a rotary evaporator at diaphragm
pump pressure (5–20 mmHg). All reactions were magnetically
Synthesis 2005, No. 1, 75–84 © Thieme Stuttgart · New York

PAPER
Nucleophilic Addition Reactions of a-Metallated Carbamates
79
5
5
7
7
2
6
2
6
3
1
3
1
Ph
5
Ph
7
4
4
3
1
2
2
6
4
3
Ph
1
O
O
O
O
Ph
4
OH OH
OH
N
N
8
9
8
9
10
10
O
O
18
17
15
16
O
5
O
4
O
10
8
11
9
3
2
6
O
5
10
8
4
7
3
1
O
N
8
O
9
4
5
O
3
6
2
4
7
3
O
6
2
1
O
N
8
9
5
6
N
10
7
2
7
13
OAc
11
O
N
O
9
11
10
12
Boc
Ph
Cl
11
20
22
29
32
O
5
Cp
Mo
δ
H 3.95
δH 3.45
CO
OC
Cp
O
4
O
O
5
3
2
6
H
H
O
(a) s-BuLi, (–)-sparteine
(b) Bu3SnCl
OC
Mo
7
4
O
1
O
N
8
3
6
2
2
OC
7
2
1
O
N
8
4
4
Bu2Sn
O
9
O
10
Exo-(+)-(2S,4R)-35
Endo-(+)-(2S,4R)-35
11
12
40
19
Figure 2 Atom numbering scheme used in assigning the 1H and 13C NMR data in the experimental section
2,2,4,4-Tetramethyloxazolidine-3-carboxylic Acid (1S,2S)-1-
Tributylstannyl-2-phenylpropyl Ester (12)
crystals; mp 79–81 °C (CH2Cl2) and (S)-15 (15.1 mg, 26%) as a co-
lourless oil; [a]D22 +38.6 (c = 0.80, CHCl3).
The title compound was prepared in 22% yield from racemic
2,2,4,4-tetramethyloxazolidine-3-carboxylic acid 2-phenylpropyl
ester (11) according to the procedure of Hoppe and co-workers;12
[a]D18 –22.4 (c = 1.2, acetone) {Lit.12 [a]D20 –20.3 (c = 1.2, ace-
tone)}.
IR (film): 1690 (s) cm–1.
1H NMR (500 MHz, CDCl3): d (mixture of rotamers) = 7.32–7.27
(2 H, m, Ar), 7.24–7.18 (3 H, m, Ar), 5.41–5.29 (1 H, m, C4H), 5.22
(1 H, dd, J = 6.4 15.4 Hz, C5H), 5.16 (1 H, dd, J = 2.3 10.1 Hz,
C2H), 3.76 (2 H, s, C10H2), 3.01–2.91 (1 H, m, C1H), 2.26 (1 H,
apparent octet, J = 6.6 Hz, C6H), 2.14–2.05 (1 H, m, C3H), 1.63/
1.61, 1.60/1.56, 1.47/1.46 and 1.45/1.42 (3 H each, s, 4 CH3), 1.25–
1.20 (3 H, m, C1CH3), 1.01 (3 H, d, J = 6.7 Hz, C7H3), 0.98 (3 H,
d, J = 6.7 Hz, C6CH3), 0.95–0.90 (3 H, m, C3CH3).
13C NMR (75 MHz, CDCl3,): d (mixture of rotamers) = 153.3/152.5
(C=O), 144.2 (C, Ar), 139.6/139.5 (C5H), 128.7 (2 CH, Ar), 128.1
(2 CH, Ar), 127.3/127.1 (C4H), 126.6 (CH, Ar), 96.2/94.9 (C8),
81.3 (C2H), 76.6/76.3 (C10H2), 60.9/59.9 (C9), 43.0 (C1H), 38.6/
38.5 (C3H), 31.3 (C6H), 27.3/26.9, 25.8, 25.7/25.8 and 24.5/24.4 (4
CH3), 22.8 (C6CH3), 22.7 (C7H3), 19.4 (C1CH3), 18.8 (C3CH3).
2,2,4,4-Tetramethyloxazolidine-3-carboxylic Acid (1S,2S,3E)-
2,5-Dimethyl-1-[(1S)-1-phenylethyl]hex-3-enyl Ester (15)
Stannane 12 (116 mg, 0.200 mmol) was dissolved in THF (2 mL)
and Et2O (2 mL) and the solution was stirred at –78 °C for 10 min.
n-BuLi (0.15 mL, 0.22 mmol, 1.51 M in hexane) was added drop-
wise and the resulting colourless solution was stirred for 40 min at
–78 °C. A solution of CuBr·SMe2 (49 mg, 0.240 mmol) in Et2O
(0.3 mL) and diisopropyl sulfide (0.25 mL) was then added drop-
wise. The resulting brown solution was stirred for 4 h at –78 °C. In
another flask neutral molybdenum complex (+)-(2S,4R)-35 (94 mg,
0.30 mmol) was dissolved in MeCN (1 mL) and cooled to 0 °C. Ni-
trosonium tetrafluoroborate (43 mg, 0.36 mmol) was added in one
portion and the mixture was stirred for 10 min at 0 °C before adding
to the organocopper(I) reagent via syringe. The resulting brown so-
lution was stirred for 1 h at –78 °C and then warmed to r.t. where-
upon aq NH4Cl (5 mL), Et2O (10 mL) and ammonia (5 mL) were
added sequentially. The blue aqueous layer was extracted with Et2O
(2 × 10 mL) and the combined organic layers were washed with
brine (10 mL), dried and concentrated. The crude product was dis-
solved in CHCl3 (30 mL) and oxygen was bubbled through the so-
lution. After 15 h, the mixture was concentrated and the residue
purified by column chromatography (SiO2, hexanes–Et2O, 20:1 to
8:1) to give the title compound 15 (27.1 mg, 35%) as colourless
For the atom numbering scheme see Figure 2.
HRMS (ES); m/z calcd for C24H37NO3Na: 410.2671; found:
410.2675.
Anal. Calcd for C24H37NO3: C, 74.38; H, 9.62; N, 3.61. Found: C,
74.3; H, 9.3; N, 3.55.
X-ray structure of 1530
C24H37NO3, monoclinic, space group P21, a = 7.3615(4) Å,
b = 20.3854(8) Å, c = 7.9378(4) Å, b = 103.1410(19)°,
V = 1160.01(10) Å3, Z = 2, rcalc = 1.11 Mg/m3, m = 0.072 mm–1,
crystal size: 0.13 × 0.12 × 0.02 mm, data collection range: 2.82 £ q
£ 26°, 6320 measured reflections, final R(wR) values: 0.1155,
(0.3059) for 3503 independent data and 279 parameters [I >2s(I)],
Synthesis 2005, No. 1, 75–84 © Thieme Stuttgart · New York

80
P. J. Kocienski et al.
PAPER
largest residual peak and hole: 0.432, –0.473 e Å–3. Reflections
were weak possibly because of the poor crystal quality. This factor,
together with the disorder of the CH=CHCHMe2 group, which was
modelled over two equally occupied positions, led to a structure of
only moderate precision. All hydrogen atoms were placed in idea-
lised positions with the following C–H distances: aromatic, 0.95 Å;
olefinic, 0.95 Å; methyl, 0.98 Å; methylene, 0.99 Å; methine, 1.00
Å. In the absence of significant anomalous scattering effects, only
the relative stereochemistry was determined and Friedel pairs
merged.
(C2H), 42.7 (C1H), 39.3 (C3H), 31.2 (C6H), 22.8 (C7H3 and
C6CH3), 15.8 (C1CH3), 14.6 (C3CH3).
For the atom numbering scheme see Figure 2.
HRMS (ES): m/z calcd for (M – OH)+: 215.1800; found: 215.1799.
Anal. Calcd for C16H24O: C, 82.70; H, 10.41. Found: C, 82.5; H,
10.24.
(2R,3R,4S)-2-Methyl-4-phenylpentane-1,3-diol (18)
Ozone was bubbled through a solution of alcohol 17 (18 mg,
0.077 mmol) in CH2Cl2 (5 mL) at –78 °C. After 5 min, the solution
turned blue and oxygen was bubbled through the solution for 20
min. NaBH4 (31 mg, 0.82 mmol) in MeOH (1 mL) was added at
–78 °C and the resulting mixture was stirred for 2 h at 0 °C. Aq
NH4Cl (5 mL) and CH2Cl2 (5 mL) were added and the aqueous layer
was extracted with CH2Cl2 (2 × 5 mL). The combined organic layers
were dried and evaporated. The residue was purified by column
chromatography (SiO2, hexanes–Et2O, 4:1 then 1:1, followed by
1:2) to give the title compound 18 (9.3 mg, 62%) as a colourless sol-
id: mp 61–63 °C (hexane) (Lit.14 mp 98.0–98.5 °C); [a]D24 –6.7 (c =
0.67, CHCl3). The 1H NMR spectroscopic data were in accordance
with the literature data.14
2,2,4,4-Tetramethyloxazolidine-3-carboxylic Acid (3E,1S,2R)-
2,5-Dimethyl-1-[(1S)-1-phenylethyl)hex-3-enyl Ester (16)
The title compound was prepared reaction of stannane 12 with cat-
ionic complex 4 was performed on a 0.20 mmol scale according to
the procedure described above. Compound 16 (40 mg, 52%) was
obtained as a colourless oil together with (S)-11 (8.5 mg, 15%);
[a]D22 +34.3 (c = 0.97, CHCl3).
IR (film): 1695 (s) cm–1.
1H NMR (500 MHz, CDCl3): d (mixture of rotamers) = 7.32–7.17
(5 H, m, Ar), 5.37–5.26 (2 H, m, C4H and C5H), 5.24–5.18 (1 H, m,
C2H), 3.73 (2 H, s, C10H2), 3.08–2.98 (1 H, m, C1H), 2.26–2.13 (2
H, m, C3H and C6H), 1.62/1.57, 1.55/1.50, 1.47/1.42 and 1.40/1.37
(3 H each, s, 4 CH3), 1.29–1.24 (3 H, m, C1CH3), 1.02–0.95 (3 H,
m, C3CH3), 0.92 (6 H, d, J = 6.8 Hz, C6CH3 and C7H3).
13C NMR (75 MHz, CDCl3): d = 144.8 (C, Ar), 128.8 (2 CH, Ar),
127.6 (2 CH, Ar), 126.6 (CH, Ar), 79.2 (C3H), 68.4 (C1H2), 44.0
(C4H), 36.1 (C2H), 19.3 (C4CH3), 9.1 (C2CH3).
13C NMR (75 MHz, CDCl3): d (mixture of rotamers) = 152.9/152.1
(C=O), 144.3 (C, Ar), 137.4 (C5H), 129.6 (C4H), 128.7 (2 CH, Ar),
127.8 (2 CH, Ar), 126.6 (CH, Ar), 96.1/94.8 (C8), 80.6/80.5 (C2H),
76.6/76.2 (C10H2), 60.8/59.8 (C9), 42.2 (C1H), 37.8/37.8 (C3H),
31.2 (C6H), 27.6/27.0, 25.9/25.8, 25.6/25.3 and 24.4/24.3 (4 CH3),
22.7/22.7 (C7H3 and C6CH3), 18.4/18.3 (C1CH3), 14.3/14.1
(C3CH3).
For the atom numbering scheme see Figure 2.
2,2,4,4-Tetramethyloxazolidine-3-carboxylic Acid (1S)-2-[(4S)-
2,2-Dimethyl-[1,3]dioxolan-4-yl]-1-(tributylstannyl)ethyl Ester
(19)
Carbamate 40 was prepared in 91% yield on a 32 mmol scale by the
method of Hoppe.31 1H NMR spectroscopic data were in accordance
with literature data;15 [a]D –9.47 (c = 5.08, MeOH) {Lit.15 [a]D
20
For the atom numbering scheme see Figure 2.
–11.4 (c = 5.3, MeOH)}.
HRMS (ES): m/z calcd for C24H37NO3Na: 410.2671; found:
410.2677.
Carbamate 40
13C NMR (100 MHz, CDCl3): d (mixture of rotamers) = 153.4 (0.55
C, C=O), 152.8 (0.45 C, C=O), 109.1 (C5), 96.0 (0.55 C, C6), 94.9
(0.45 C, C6), 76.5 (0.55 C, C7H2), 76.2 (0.45 C, C7H2), 73.4 (C3H),
69.5 (C4H2), 61.6 (C1H2), 60.7 (0.45 C, C8), 59.8 (0.55 C, C8), 33.3
(C2H2), 27.1 (2 CH3), 26.7 (CH3), 25.8 (CH3), 25.4 (CH3), 24.3
(CH3).
Anal. Calcd for C24H37NO3: C, 74.38; H, 9.62; N, 3.61. Found: C,
74.1; H, 9.35; N, 3.65.
(2S,3S,4R,5E)-4,7-Dimethyl-2-phenyloct-5-en-3-ol (17)
Carbamate 16 (38 mg, 0.098 mmol) in MeOH (2 mL) containing
MeSO3H (10.4 mg, 0.108 mmol) was refluxed for 3 h and the sol-
vent was evaporated. The residue was dissolved in Et2O (12 mL)
and extracted with aq NH4Cl (2 × 5 mL). The aqueous layer was ex-
tracted with Et2O (3 × 5 mL). The combined organic layers were
dried and evaporated. The crude product (31.3 mg, 0.90 mmol) was
dissolved in MeOH (3 mL) and K2CO3 (20 mg, 0.144 mmol) was
added. The reaction mixture was refluxed for 2 h. The solvent was
evaporated and the residue was dissolved in CH2Cl2 (10 mL) and
extracted with aq 2 M HCl (2 × 10 mL). The aqueous layer was ex-
tracted with CH2Cl2 (3 × 10 mL). The combined organic layers were
dried and evaporated and the residue purified by column chroma-
tography (SiO2, hexanes–Et2O, 20:1) to give the title compound 17
(18.0 mg, 79%) as a colourless oil; [a]D22 +5.3 (c = 0.72, CHCl3).
13C NMR (100 MHz, CDCl3, 52 °C): d = 138.4, 109.2, 76.6, 73.6,
69.6, 61.7, 33.5, 27.2, 26.8, 25.8, 25.6, 24.4.
Three quaternary signals were not observed. For the atom number-
ing scheme see Figure 2.
s-BuLi [22.9 mL of a 1.28 M solution in cyclohexane–hexane
(92:8), 29.4 mmol] was added dropwise to a solution of carbamate
40 (8.04 g, 26.7 mmol) and (–)-sparteine (6.88 g, 29.4 mmol) in
Et2O (140 mL) at –78 °C under N2. The clear yellow solution was
stirred at –78 °C for 3 h before the dropwise addition of Bu3SnCl
(10.9 mL, 40.0 mmol) and the solution was allowed to warm grad-
ually to r.t. over 12 h. Aq 1 M HCl (100 mL) and Et2O (50 mL) were
added and after stirring for 10 min, the phases were separated. The
aqueous phase was extracted with Et2O (2 × 50 mL), and the com-
bined organic phases were washed with brine (50 mL), dried, fil-
tered and concentrated in vacuo. The residue was purified by
column chromatography (SiO2, Et2O–hexanes, 1:4) to give the title
compound 19 (10.8 g, 69%) as a colourless oil; [a]D +15.3 (c = 0.85,
CHCl3).
IR (film): 3456 (br m) cm–1.
1H NMR (500 MHz, CDCl3): d = 7.33–7.28 (2 H, m, Ar), 7.24–7.18
(3 H, m, Ar), 5.45 (1 H, dd, J = 6.6 15.8 Hz, C5H), 5.33 (1 H, dd,
J = 7.2 15.4 Hz, C4H), 3.56–3.51 (1 H, m, C2H), 2.90 (1 H, appar-
ent quintet, J = 6.7 Hz, C1H), 2.27 (1 H, apparent octet, J = 6.7 Hz,
C6H), 2.12 (1 H, apparent octet, J = 6.6 Hz, C3H), 1.47 (1 H, br s,
OH), 1.30 (3 H, d, J = 6.8 Hz, C1CH3), 1.01–0.95 (9 H, m, C7H3,
C3H3, C6CH3).
IR (film): 1680 (s) cm–1.
1H NMR (400 MHz, CDCl3): d = 4.76 (1 H, dt, J = 9.6, 4.1 Hz,
C1H), 4.17 (1 H, apparent septet, J = 6.2 Hz, C3H), 4.10 (1 H, dd,
J = 6.0, 6.0 Hz, C4HAHB), 3.72 (2 H, s, C7H2), 3.55 (1 H, dt,
13C NMR (75 MHz, CDCl3): d = 145.4 (C, Ar), 138.4 (C5H), 130.1
(C4H), 128.7 (2 CH, Ar), 127.8 (2 CH, Ar), 126.5 (CH, Ar), 79.5
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Nucleophilic Addition Reactions of a-Metallated Carbamates
81
J = 3.1, 7.4 Hz, C4HAHB), 2.31–2.20 (1 H, m, C2HAHB), 1.95 (1 H,
ddd, J = 14.4, 6.8, 4.1 Hz, C2HAHB), 1.55–1.26 (30 H, m), 0.92–
0.85 (15 H, m).
73.7 (C1H or C3H), 69.7 (C4H2), 60.8 (0.4 C, C8), 59.9 (0.6 C, C8),
41.0 (C9H), 36.3 (C2H2), 31.2 (C12H), 27.1 (CH3), 26.8 (CH3),
25.8 (CH3), 25.7 (0.5 C, CH3), 25.6 (0.5 C, CH3), 25.4 (CH3), 24.4
(CH3), 22.7 (C13H3), 22.6 (C12CH3), 17.0 (C9CH3).
13C NMR (100 MHz, CDCl3): d (mixture of rotamers) = 153.3 (0.6
C, C=O), 152.6 (0.4 C, C=O), 109.1 (C5), 96.1 (0.6 C, C6), 94.8
(0.4 C, C6), 76.5 (0.6 C, C7), 76.2 (0.4 C, C7), 74.7 (C3H), 69.6
(C4H2), 67.7 (C1H), 60.8 (0.4 C, NCMe2CH2), 59.6 (0.6 C,
For the atom numbering scheme see Figure 2.
LRMS (CI mode, isobutane): m/z = 398.2 [(M + H)+, 95%], 340.2
(100), 225.2 (62), 167.2 (59).
3
NCMe2CH2), 38.5 (C2H2), 29.3 (3 × C11H2, JC,Sn 9.8), 27.7 (3 ×
2
Anal Calcd for C22H39NO5: C, 66.47; H, 9.89; N, 3.52. Found: C,
66.56; H, 9.83; N, 3.47.
C10H2, JC,Sn 28.8), 27.2 (CH3), 26.9 (0.5 C, CH3), 26.7 (0.5 C,
CH3), 25.8 (CH3), 25.5 (2 CH3), 24.4 (0.5 C, CH3), 24.3 (0.5 C,
CH3), 13.9 (3 × C12H3), 10.1 (3 × C9H2, 1JC,Sn 162.9, 155.9).
2,2,4,4-Tetramethyloxazolidine-3-carboxylic Acid (1S)-1-[(4S)-
2,2-Dimethyl-1,3-dioxolan-4-ylmethyl]but-3-enyl Ester (22)
To a solution of stannane 19 (4.09 g, 6.93 mmol) in THF (100 mL)
at –78 °C under N2 was added n-BuLi (5.4 mL of a 1.42 M solution
in hexanes, 7.6 mmol) dropwise and the resulting light-yellow solu-
tion was stirred at –78 °C for 20 min. The mixture was cooled to ap-
proximately –90 °C and a solution of CuBr·SMe2 (1.71 g, 8.32
mmol) in diisopropyl sulfide (3 mL) and THF (10 mL) was added
dropwise. After stirring at –78 °C for 30 min, the orange-brown so-
lution was re-cooled to –90 °C and a solution of cationic complex
21 [which had been freshly prepared from (h5-cyclopentadie-
nyl)(h3-propenyl)(dicarbonyl)molybdenum (1.12 g, 4.34 mmol)
and NOBF4 (558 mg, 4.77 mmol) in MeCN (12 mL) at 0 °C for 10
min] was added via cannula keeping the internal temperature below
–75 °C. The brown solution was stirred at –78 °C for 1 h before
aqueous workup and decomplexation (O2, light, r.t., 19 h) as de-
scribed above for olefin 20. Concentration in vacuo and purification
of the residue by column chromatography (SiO2, Et2O–
hexanes, 1:4) yielded the title compound 22 (1.45 g, 61%) as a pale
yellow oil; [a]D +22.1 (c = 1.02, CHCl3).
For the atom numbering scheme see Figure 2.
LRMS (CI mode, isobutane): m/z = 592.0 [(M + H)+, 11%], 590.1
(10), 534.0 (100), 532.0 (75), 476.0 (8), 474.0 (6), 291.0 (6), 289.0
(5).
Anal. Calcd for C27H53NO5Sn: C, 54.92; H, 9.05; N, 2.37. Found:
C, 54.99; H, 9.04; N, 2.28.
2,2,4,4-Tetramethyloxazolidine-3-carboxylic Acid (1R,2S,3E)-
1-[(4S)-2,2-Dimethyl-1,3-dioxolan-4-ylmethyl)-2,5-dimethyl-
hex-3-enyl Ester (20)
n-BuLi (4.6 mL of a 1.42 M solution in hexanes, 6.5 mmol) was
added dropwise to a solution of stannane 19 (3.49 g, 5.92 mmol) in
THF (100 mL) at –78 °C under N2. The light yellow solution was
stirred at –78 °C for 30 min. The mixture was cooled to approxi-
mately –90 °C whereupon a solution of CuBr·SMe2 (1.46 g, 7.10
mmol) in diisopropyl sulfide (2.5 mL) and THF (10 mL) was added
dropwise. The brown-orange solution was allowed to warm to
–78 °C over 45 min before re-cooling to approximately –90 °C. A
solution of cationic complex (2R,4S)-4 [which had been freshly pre-
pared from neutral complex (–)-(2R,4S)-35 (1.55 g, 4.93 mmol)
and NOBF4 (633 mg, 5.42 mmol) in MeCN (10 mL) at 0 °C for 10
min] was added dropwise. After warming to –78 °C and stirring for
1.5 h, aq NH4Cl (40 mL), Et2O (30 mL) and aq NH3 (5 mL) were
added and the mixture warmed to r.t. After filtration of the mixture
through Celite, and thorough washing of the Celite with Et2O (2 ×
30 mL), the phases were separated and the aqueous phase was ex-
tracted with Et2O (3 × 30 mL). The combined organic phases were
washed with brine (50 mL), dried, filtered and concentrated in vac-
uo. The resulting yellow-brown oil was dissolved in CHCl3 (250
mL) and stirred at r.t. while bubbling oxygen through the solution
for 44 h with irradiation from a standard household light-bulb (150
W) for the last 26 h. The dark-brown mixture was concentrated in
vacuo, dissolved in CH2Cl2 (5 mL) and flushed through a plug of
SiO2 (4 cm depth, Et2O) before purification by column chromatog-
raphy (SiO2, Et2O–hexanes, 0:1 to 1:1) to yield the title olefin 20
(1.12 g, 57%) as a pale yellow oil. GC/MS (160 °C, 1 min, 3 °C
min–1 to 200 °C, 5 °C to 250 °C) showed 4 isomers in the ratio
1:95:2:2 with retention times of 9.32, 10.03, 10.19, 10.36 min re-
spectively; [a]D +10.3 (c = 1.3, CHCl3). Stannane 19 (93 mg, 4%)
was also recovered.
IR (film): 1696 (s) cm–1.
1H NMR (400 MHz, CDCl3): d = 5.84–5.72 (1 H, m, C10H), 5.10
(1 H, d, J = 17.9 Hz, C11HAHB), 5.09 (1 H, d, J = 9.5 Hz,
C11HAHB), 4.99–4.93 (1 H, m, C1H), 4.15 (1 H, br quintet, J = 6.4
Hz, C3H), 4.09 (1 H, dd, J = 7.6, 5.8 Hz, C4HAHB), 3.72 (2 H, s,
C7H2), 3.56 (1 H, t, J = 7.6 Hz, C4HAHB), 4.47–4.37 (2 H, m,
C9H2), 2.03–1.93 (1 H, m, C2HAHB), 1.81–1.71 (1 H, m, C2HAHB),
1.55 (3 H, s, CH3), 1.53 (3 H, s, CH3), 1.51 (3 H, s, CH3), 1.41–1.33
(9 H, 3 CH3).
13C NMR (100 MHz, CDCl3): d (mixture of rotamers) = 152.4 (0.6
C, C = O), 151.6 (0.4 C C=O), 133.8 (C10H), 118.3 (C11H2), 109.1
(C6), 96.1 (0.6 C, C5), 95.0 (0.4 C, C5), 76.5 (0.6 C, C7H2), 76.2
(0.4 C, C7H2), 73.3 (C3H), 71.1 (C1H), 69.6 (C4H2), 60.8 (0.4C,
C8), 59.9 (0.6 C, C8), 39.5 (0.6 C, C9H2), 39.4 (0.4 C, C9H2), 38.0
(0.6 C, C2H2), 37.9 (0.4 C, C2H2), 27.2 (CH3), 26.9 (CH3), 25.8
(CH3), 25.7 (0.5 C, CH3), 25.6 (0.5 C, CH3), 25.5 (0.5 C, CH3), 25.4
(0.5 C, CH3), 24.4 (CH3).
For the atom numbering scheme see Figure 2.
LRMS (EI mode GC/MS, 150 °C, 2 min, 5 °C/min to 200 °C,
10 °C/min to 250 °C, retention time = 6.31 min): m/z = 341 [(M+·),
2%], 326 (100), 158 (85), 156 (35), 101 (87). A minor diastereoiso-
mer (2%) was observed, with a retention time of 6.47 min.
HRMS (CI mode, isobutane): m/z calcd for C18H32O5N [MH]+:
342.2280; found: 342.2283.
IR (film): 1694 (s) cm–1.
1H NMR (400 MHz, CDCl3): d = 5.45 (1 H, dd, J = 15.6, 6.3 Hz,
C11H), 5.31 (1 H, dd, J = 15.6, 7.9 Hz, C10H), 4.83 (1 H, dt,
J = 9.9, 3.9 Hz, C1H), 4.15–4.07 (2 H, m, C3H, C4HAHB), 3.75 (2
H, s, C7H2), 3.58–3.52 (1 H, m, C4HAHB), 2.44–2.34 (1 H, m,
C9H), 2.25 (1 H, apparent octet, J = 6.8 Hz, C12H), 1.98 (1 H, dt,
J = 9.9, 4.7 Hz, C2HAHB), 1.70–1.63 (1 H, m, C2HAHB), 1.55 (6 H,
br s, CH3), 1.41 (3 H, s, CH3), 1.40 (3 H, s, CH3), 1.38 (3 H, s, CH3),
1.32 (3 H, s, CH3), 1.03 (1.5 H, d, J = 6.8 Hz, C9CH3), 1.02 (1.5 H,
d, J = 6.8 Hz, C9CH3), 0.96 (6 H, d, J = 6.8 Hz, C13H3, C12CH3).
13C NMR (100 MHz, CDCl3): d = 152.7 (0.6 C, C=O), 152.6 (0.4 C,
C=O), 139.4 (C10H or C11H), 127.9 (0.6 C, C10H or C11H), 127.8
(0.4 C, C10H or C11H), 108.9 (C5), 96.1 (0.6 C, C6), 95.0 (0.4 C,
C6), 76.6 (0.6 C, C7H2), 76.2 (0.4 C, C7H2), 74.9 (C1H or C3H),
(2S)-1-[(4S)-2,2-Dimethyl[1,3]dioxolan-4-yl]pent-4-en-2-ol (23)
A solution of olefin 22 (1.08 g, 3.16 mmol) in THF (25 mL) was
added dropwise over 5 min to a suspension of LiAlH4 (480 mg, 12.7
mmol) in THF (35 mL) at 0 °C under N2. The mixture was then re-
fluxed for 4 d (with the addition of a further 480 mg of LiAlH4 after
44 h) and cooled to 0 °C. H2O (0.9 mL) was then added, followed
by 15% aq NaOH (0.9 mL) and H2O (2.7 mL). The mixture was
brought back to reflux for 30 min. After cooling to r.t., the mixture
was filtered through Celite and the Celite was washed thoroughly
Synthesis 2005, No. 1, 75–84 © Thieme Stuttgart · New York

82
P. J. Kocienski et al.
PAPER
with THF (3 × 15 mL). The filtrate was concentrated in vacuo and
the residue was purified by column chromatography (Et2O–
hexanes, 3:7 to 1:1) to give the title compound 23 (475 mg, 81%) as
a colourless oil. Spectroscopic data were in accordance with litera-
ture data;16,17 [a]D +11.9 (c = 3.20) {Lit.17 [a]D +14.6 (c = 3.33,
CHCl3)}.
(2S)-[N-(R)-a-Acetoxyphenylacetyl]-2-allyl-2,3-dihydroindole
(29)
A solution of DCC (87 mg, 0.42 mmol) and (R)-O-acetylmandelic
acid (82 mg, 0.42 mmol) in CH2Cl2 (5 mL) was cooled to 0 °C under
N2 and stirred for 15 min before the addition via cannula of a solu-
tion of indoline 27 (56 mg, 0.35 mmol) in CH2Cl2 (10 mL). The
cloudy mixture was stirred at 0 °C under N2 for 1 h and concentrated
in vacuo. EtOAc (25 mL) was added to the residue and the mixture
was filtered before the addition of 0.5 M HCl (15 mL). The phases
were separated and the organic phase was washed with 0.5 M HCl
(15 mL) and aqueous NaHCO3 (2 × 15 mL). The two aqueous phas-
es were extracted separately with EtOAc (2 × 15 mL) and the com-
bined organic phases dried, filtered and concentrated in vacuo. The
residue was purified by column chromatography (SiO2, Et2O–
hexanes, 4:6) to give the title amide 29 (102 mg, 87%) as a colour-
less oil. 1H and 13C NMR spectroscopic analysis indicated the pres-
ence of a single diastereoisomer within the limits of detection;
[a]D –121.9 (c = 2.04, CHCl3).
N-tert-Butoxycarbonyl-2,3-dihydroindole (24)
The title compound was prepared on a 75 mmol scale according to
the procedure of Iwao and co-workers,32 mp 43–45 °C (hexanes)
(Lit.32 mp 42–45 °C).
13C NMR (100 MHz, CDCl3, 52 °C): d = 152.8 (C), 142.9 (C),
131.4 (C), 127.5 (CH), 124.8 (CH), 122.3 (CH), 115.0 (CH), 80.9
(CMe3), 47.8 (C2H2), 28.7 [C(CH3)3], 27.5 (C3H2).
(2S)-2-Allyl-N-tert-butoxycarbonyl-2,3-dihydroindole (25) and
7-Allyl-N-tert-butoxycarbonyl-2,3-dihydroindole (26)
s-BuLi [6.4 mL of a 1.30 M solution in cyclohexane–hexane (92: 8),
8.25 mmol] was added dropwise to a solution of indoline 24 (1.39
g, 6.4 mmol) and (–)-sparteine (1.93 g, 8.25 mmol) in tert-butyl
methyl ether (65 mL) at –78 °C under N2. The light yellow solution
was stirred at –78 °C for 3.25 h before cooling to approximately
–90 °C. A solution of CuBr·SMe2 (1.83 g, 8.89 mmol) in diisopro-
pyl sulfide (5 mL) and THF (7 mL) was added dropwise, ensuring
that the internal solution temperature did not rise above –75 °C. Af-
ter stirring for 40 min at –78 °C, the solution was cooled to approx-
imately –85 °C and a solution of cationic complex 21 [which had
been freshly prepared from (h5-cyclopentadienyl)(h3-propenyl)(di-
carbonyl)molybdenum (2.69 g, 10.4 mmol) and NOBF4 (1.34 g,
11.4 mmol) in MeCN (20 mL) at 0 °C for 10 min] was added drop-
wise over 10 min. The dark-brown solution was allowed to warm
slowly to r.t. under N2 overnight, before aqueous workup in an iden-
tical fashion to that described above for olefin 20. Decomplexation
was performed using the CAN-mediated procedure described above
for olefin 20. Purification by column chromatography (SiO2, tolu-
ene–hexanes, 1:1 to 100:0 followed by Et2O–hexanes, 1:9) yielded
a mixture of 25 and 26 as a pale yellow oil (901 mg, 55%; Rf 0.39
in toluene) and recovered indoline 24 (130 mg, 9%; Rf 0.24 in tolu-
ene). 1H NMR spectroscopy revealed an approximately equimolar
ratio of 25 and 26. 1H and 13C NMR spectroscopic data for 25 and
1H NMR data for 26 were in accordance with literature data;19
[a]D +44.2 (c = 0.55, CHCl3).
IR (film): 1739 (s), 1670 (s) cm–1.
1H NMR (400 MHz, CDCl3): d = 8.24 (1 H, d, J = 8.1 Hz), 7.52 (2
H, t, J = 2.9 Hz), 7.46–7.38 (3 H, m), 7.23 (1 H, t, J = 7.7 Hz), 7.15
(1 H, d, J = 7.2 Hz), 7.05 (1 H, t, J = 7.4 Hz), 6.18 (1 H, s, C11H),
5.79 (1 H, ddt, J = 17.0, 10.0, 7.0 Hz, C9H), 5.19 (1 H, d, J = 17.0
Hz, C10HAHB), 5.16 (1 H, d, J = 10.0 Hz, C10HAHB), 4.32 (1 H, br
t, J = 8.5 Hz, C2H), 3.02 (1 H, dd, J = 15.8, 8.5 Hz, C3HAHB),
2.86–2.72 (2 H, m, C8HAHB, C3HAHB), 2.49 (1 H, dt, J = 14.4, 7.9
Hz, C8HAHB), 2.24 (3 H, s, OCOCH3).
13C NMR (100 MHz, CDCl3): d = 171.0 (C=O), 165.8 (C=O), 142.1
(C), 133.9 (C), 133.0 (C9H), 130.3 (C), 129.9 (CH), 129.4 (2 CH),
128.9 (2 CH), 127.8 (CH), 125.0 (CH), 124.7 (CH), 119.0 (C10H2),
118.2 (CH), 75.0 (C11H), 58.3 (C2H), 39.1 (C8H2), 33.7 (C3H2),
21.0 (OCOCH3).
For the atom numbering scheme see Figure 2.
HRMS (EI+ mode): m/z calcd for C21H21NO3 [M+·]: 335.1521;
found: 335.1521.
GC/MS (150 °C, 1 min/5 °C to 250 °C, Rt 14.73 min) indicated the
presence of a single amide diastereomer, within the limits of detec-
tion.
N-tert-Butoxycarbonyl-7-chloro-2,3-dihydroindole (30)
The title compound was prepared in 72% yield on a 15 mmol scale
according to the method of Iwao and Kuraishi,35 mp 84.5–85.5 °C
(pentane) [Lit.35 mp 84.5–85.0 °C (pentane)].
3C NMR (100 MHz, CDCl3): d = 153.4 (C=O), 140.7 (C, Ar), 137.2
(C, Ar), 129.1 (CH, Ar), 125.3 (CH, Ar), 124.2 (C, Ar), 122.9 (CH,
Ar), 81.6 (CMe3), 51.5 (C2H2), 30.1 (C3H2), 28.3 [C(CH3)3].
IR (film, 1:1 mixture of 25 and 26): 1703 (s) cm–1.
26
13C NMR (100 MHz, CDCl3): d = 154.0 (C=O), 142.3 (C, C6H5),
138.3 (C, C6H5), 137.1 (CH=CH2), 134.8 (C, C6H5), 128.8 (CH,
C6H5), 124.7 (CH, C6H5), 116.0 (CH=CH2), 115.4 (CH, C6H5), 80.8
(CMe3), 51.2 (C2H2), 37.9 (CH2CH=CH2), 29.8 (C3H2), 28.6
[C(CH3)3].
(2R)-N-tert-Butoxycarbonyl-7-chloro-2-[(1S,3E)-1,4-dimethyl-
pent-2-enyl]-2,3-dihydroindole (32)
s-BuLi (4.3 mL of a 1.28 M solution in cyclohexane–hexane (92:8),
5.54 mmol) was added dropwise to a solution of (–)-sparteine (1.30
g, 5.54 mmol) in tert-butyl methyl ether (70 mL) at –78 °C under
N2. The solution was stirred for 10 min before the slow addition of
a precooled (–78 °C) solution of indoline 30 (1.17 g, 4.62 mmol) in
tert-butyl methyl ether (50 mL) via cannula, ensuring the internal
solution temperature did not rise above –75 °C. The solution was
stirred at –78 °C for 3.5 h before cooling to approximately –85 °C.
A solution of CuBr·SMe2 (1.23 g, 6.01 mmol) in diisopropyl sulfide
(4 mL) and THF (6 mL) was then added ensuring that the internal
solution temperature did not rise above –75 °C. The orange solution
was stirred at –78 °C for 30 min and cooled to approximately
–85 °C. A solution of complex (2R,4S)-4 [which had been freshly
prepared from neutral complex (–)-35 (1.21 g, 3.85 mmol) and
NOBF4 (495 mg, 4.24 mmol) in MeCN (10 mL) at 0 °C for 10 min]
was then added via cannula. The brown solution was allowed to
(2S)-2-Allyl-2,3-dihydro-1H-indole (27) and 7-Allyl-2,3-dihy-
dro-1H-indole (28)
Trifluoroacetic acid (2 mL) was added to a solution of indolines 25
and 26 (ca. 1:1, 742 mg, 2.86 mmol) in CH2Cl2 (8 mL) at 0 °C under
N2. The orange-brown solution was stirred at 0 °C for 30 min and
then at r.t. for 1.5 h. The mixture was concentrated in vacuo to give
a purple oil, which was dissolved in Et2O (25 mL) and washed with
NaOH (0.5 M, 2 × 25 mL). The combined aqueous phases were ex-
tracted with Et2O (2 × 25 mL) and CH2Cl2 (3 × 25 mL) and the com-
bined organic phases washed with brine (25 mL), dried, filtered and
concentrated in vacuo. The residue was purified by column chroma-
tography (SiO2, Et2O–toluene, 2:98 to 5:95) to give indoline 27 (233
mg, 51%; Rf 0.51 in Et2O–toluene, 5:95) and indoline 28 (100 mg,
22%; Rf 0.34 in Et2O–toluene, 5: 95) as clear oils. Spectroscopic
data for 2733 {[a]D –54.3 (c = 1.18, CHCl3)) and for 2834 were in ac-
cordance with literature data.
Synthesis 2005, No. 1, 75–84 © Thieme Stuttgart · New York

PAPER
Nucleophilic Addition Reactions of a-Metallated Carbamates
83
warm gradually to r.t. over 14 h before aqueous workup in an iden-
tical fashion to that described above for olefin 20. To the crude ma-
terial following aqueous workup dissolved in acetone (250 mL) was
added NaOAc·3H2O (7.5 g) added, followed by CAN (2.5 g). The
orange-brown mixture was stirred at r.t. for 3 h before concentration
in vacuo and addition of Et2O (100 mL) and H2O (100 mL). After
stirring for 10 min, the mixture was filtered through Celite, the
phases were separated and the aqueous phase was extracted with
Et2O (2 × 50 mL). The combined organic phases were washed with
brine (50 mL), dried, filtered and concentrated in vacuo to yield a
brown oil. The residue was purified by column chromatography
(SiO2, Et2O–hexanes, 5: 95 to 10: 90) to give an inseparable mixture
of 4 isomeric adducts (766 mg, 57% from neutral complex 4) as a
pale yellow oil. 1H NMR spectroscopy indicated that 32 was the ma-
jor isomer of the whose ratio was established by GC/MS (150 °C, 2
min/5 °C to 200 °C, 10 °C/min to 250 °C) as 4:9:81:6 with retention
times of 8.66, 9.11, 9.50, 9.78 min respectively. NMR spectroscopic
data is quoted for the major isomer 32 recorded on the mixture;
[a]D +9.42 (c = 1.38, CHCl3).
2:1) to give ester (R)-38 (5.42 g, 49%) and (S)-37 (3.55 g, 44%)
both as colourless liquids.
(S)-37
Rf 0.15 (hexanes–Et2O, 4: 1); [a]D25 +81.6 (c = 1.14, CHCl3).
(R)-38
Rf 0.60 (hexanes–Et2O, 4:1); [a]D23 +76.9 (c = 1.35, MeOH).
The 1H and 13C NMR spectroscopic data for both (S)-37 and (R)-38
were in accordance with the literature data.36
Benzoic Acid (2E,5S)-5-Methylhex-3-en-2-yl Ester [(S)-39)]
To a solution of alcohol (S)-37 (2.50 g, 21.9 mmol) in CH2Cl2
(150 mL) were added Et3N (3.32 g, 32.8 mmol), benzoyl chloride
(4.62 g, 32.8 mmol) and DMAP (268 mg, 2.19 mmol). The reaction
mixture was stirred at r.t. for 18 h whereupon H2O (30 mL) was
added and the aqueous layer was extracted with CH2Cl2 (2 ×
20 mL). The combined organic layers were dried and concentrated
in vacuo. The residue was purified by column chromatography
(SiO2, hexanes–Et2O, 20:1) to give the title compound (S)-39
(4.13 g, 86%) as a colourless oil; Rf 0.73 (hexanes–Et2O, 4:1);
ee = 98.7% (chiral HPLC); [a]D25 +24.1 (c = 1.14, CHCl3).
IR (film): 1702 (s) cm–1.
1H NMR (400 MHz, CDCl3): d = 7.15 (1 H, d, J = 8.0 Hz, C6H),
7.01 (1 H, d, J = 7.2, 0.4 Hz, C4H), 6.93 (1 H, t, J = 7.6 Hz, C5H),
5.30 (1 H, ddd, J = 15.3, 6.4, 0.8 Hz, C9H), 5.06 (1 H, ddd,
J = 15.3, 8.2, 1.4 Hz, C8H), 4.45 (1 H, ddd, J = 8.5, 5.4, 1.2 Hz,
C2H), 3.35 (1 H, dd, J = 16.0, 8.5 Hz, C3HAHB), 2.61 (1 H, d,
J = 16.0 Hz, C3HAHB), 2.24 (1 H, ddq, J = 13.2, 1.2, 6.7 Hz, C7H),
2.08 (1 H, dseptet, J = 1.1, 6.7 Hz, C10H), 1.54 (9 H, s, t-C4H9),
0.99 (3 H, d, J = 6.8 Hz, C7CH3), 0.82 and 0.80 (3 H each, d,
J = 6.8 Hz, C10CH3 and C11H3).
13C NMR (100 MHz, CDCl3): d = 153.8 (C=O), 140.9 (C), 138.3
(C9H), 136.9 (C), 128.8 (CH), 127.7 (C8H), 125.2 (CH), 124.3 (C),
122.7 (CH), 81.4 (CMe3), 66.9 (C2H), 42.2 (C7H), 33.4 (C3H2),
31.0 (C10H), 28.4 [C(CH3)3], 22.6 and 22.3 (C10CH3 and C11H3),
16.7 (3, C7CH3).
IR (film): 1717 (s) cm–1.
1H NMR (500 MHz, CDCl3): d = 8.07 (2 H, d, J = 7.7 Hz, o-Ar),
7.55 (1 H, t, J = 7.3 Hz, p-Ar), 7.44 (2 H, t, J = 7.7 Hz, m-Ar), 5.77
(1 H, dd, J = 6.4, 15.0 Hz, C4H), 5.89 (1 H, apparent quintet,
J = 6.4 Hz, C2H), 5.54 (1 H, dd, J = 6.8, 15.4 Hz, C3H), 2.31 (1 H,
apparent octet, J = 6.8 Hz, C5H), 1.43 (3 H, d, J = 6.4 Hz, C1H3),
1.01 (6 H, d, J = 6.8 Hz, C6H3 and C5CH3).
13C NMR (75 MHz, CDCl3): d = 165.9 (C=O), 140.2 (C3H), 132.8
(CH, p-Ar), 131.0 (C, ipso-Ar), 129.7 (2CH, o-Ar), 128.4 (2CH, m-
Ar), 126.7 (C4H), 71.9 (C2H), 30.7 (C5H), 22.2 (C6H3 and
C5CH3), 20.7 (C1H3).
Anal. Calcd for C14H18O2: C, 77.03; H, 8.31. Found: C, 76.95; H,
8.15.
For the atom numbering scheme see Figure 2.
LRMS (EI mode): m/z = 349 [(M+·), 2%], 276 (3), 252 (6), 152
(100), 117 (11), 57 (97).
Benzoic Acid (3E,5R)-5-Methylhex-3-en-2-yl Ester [(R)-39]
To a solution of acetate (R)-38 (5.00 g, 32.0 mmol) in MeOH
(180 mL) was added K2CO3 (5.31 g, 38.4 mmol) in one portion.
The white suspension was stirred at r.t. for 3 h. H2O (300 mL) and
CH2Cl2 (400 mL) were added and the aqueous layer was extracted
with CH2Cl2 (3 × 100 mL). The combined organic layers were dried
and concentrated in vacuo to give alcohol (R)-37 (2.09 g, 57%) as a
colourless oil which was converted to benzoate (R)-39 (3.84 g,
96%) according to the procedure described above for benzoate (S)-
39; [a]D25 –23.3 (c = 1.18, CHCl3); ee = 93% (chiral HPLC).
Anal. Calcd for C20H28ClNO2: C, 68.65; H, 8.07; N, 4.00. Found: C,
68.50; H, 7.89; N, 3.96.
(E)-5-Methylhex-3-en-2-ol (37)
To a solution of enone 36 (14.7 g, 131 mmol) in MeOH (210 mL)
was added CeCl3·7H2O (53.7 g, 144 mmol) and the yellow solution
was stirred at r.t. for 30 min. The reaction mixture was cooled to
0 °C and NaBH4 (5.45 g, 144 mmol) was added in small portions in
order to keep the temperature below 7 °C. After 1 h, the addition
was complete and the white suspension was stirred at 0 °C for 1.5 h
and at r.t. for 16 h. The mixture was cooled to 5 °C and aq NH4Cl
(150 mL) was added slowly. Et2O (80 mL) was added and the aque-
ous layer was extracted with Et2O (3 × 40 mL). The combined or-
ganic layers were washed with brine (30 mL), dried and
concentrated in vacuo. The residue was distilled to give the title
compound 37 (9.50 g, 62%) as a colourless oil; bp 57–60 °C/15
(h5-Cyclopentadienyl)(5-methyl-(2S,3R,4R)-h3-hex-3-en-2-
yl)(dicarbonyl)molybdenum [(+)-35]
The title compound and its enantiomer were prepared by a
modification25 of a published procedure.1 A solution of Mo(CO)6
(3.15 g, 11.9 mmol) in THF (40 mL) was refluxed for 15 min
whereupon benzoate (S)-39 (2.00 g, 9.17 mmol) in THF (10 mL)
was added. The reaction mixture was refluxed for 3 d. The dark
brown solution was allowed to cool to r.t. In a separate flask, cyclo-
pentadiene (727 mg, 11.0 mmol) was dissolved in THF (30 mL)
and cooled to 0 °C. BuLi (7.75 mL, 11.0 mmol, 1.42 M in hexane)
was added dropwise and the resulting yellow solution was stirred
for 15 min at 0 °C. The ice bath was removed and the LiCp solution
was added dropwise at r.t. to the molybdenum complex. After 1 h,
the brown solution was filtered through a pad of activated alumina
and washed with THF (200 mL). The yellow filtrate was concen-
trated under reduced pressure to give a brown solid (2.86 g), which
was recrystallised from petroleum ether (60–80 °C, 4 mL) to give
the neutral complex (+)-(2S,4R)-35 as yellow needles (2.60 g,
1
mmHg. The H and 13C NMR spectroscopic data were in accor-
dance with the literature data.36
Enzymatic Resolution of ( )-37
To a solution of ( )-alcohol 37 (8.00 g, 70.1 mmol) and vinyl ace-
tate (30.2 g, 350 mmol) in pentane (60 mL) was added freshly acti-
vated 4Å molecular sieves (crushed, 4.00 g, 50 wt%) and
Novozyme 435 (0.80 g, 10 wt%). The reaction mixture was stirred
1
at r.t. and after 2 h, H NMR spectroscopic analysis of the crude
product indicated 50% conversion. After filtration through Celite,
the solution was concentrated in vacuo. The residue was purified by
column chromatography (SiO2, hexanes–Et2O, 6:1, then 4:1, then
Synthesis 2005, No. 1, 75–84 © Thieme Stuttgart · New York

84
P. J. Kocienski et al.
PAPER
90%): Rf 0.77 (hexanes–Et2O, 8:1); mp 63–65 °C (hexane) [Lit.1
Synthesis; Hodgson, D. M., Ed.; Springer: Berlin, 2003, 61–
137.
(12) Haller, J.; Hense, T.; Hoppe, D. Liebigs Ann. Chem. 1994,
489.
(13) Tomooka, K.; Shimizu, H.; Nakai, T. J. Organomet. Chem.
2001, 624, 364.
(14) Matsumoto, T.; Hosoda, Y.; Mori, K.; Fukui, K. Bull. Chem.
Soc. Jpn. 1972, 45, 3156.
(15) Helmke, H.; Hoppe, D. Synlett 1995, 978.
(16) Kocienski, P. J.; Yeates, C.; Street, S. D. A.; Campbell, S. F.
J. Chem. Soc., Perkin Trans. 1 1987, 2183.
(17) Ishikawa, T.; Ikeda, S.; Ibe, M.; Saito, S. Tetrahedron 1998,
54, 5869.
(18) Beak, P.; Johnson, T. A.; Kim, D. D.; Lim, S. H.
Enantioselective Synthesis by Lithiation Adjacent to
Nitrogen and Electrophile Incorporation, In Organolithiums
in Enantioselective Synthesis; Hodgson, D. M., Ed.;
Springer: Berlin, 2003, 140–176.
1
mp 65–67 °C (hexane)]; [a]D23 +55.9 (c = 1.09, CHCl3). H NMR
spectroscopy indicated a mixture of exo- and endo-isomers (5:1) as
judged by the integration of the C3H signals at dexo = 3.95 and
d
endo = 3.45 respectively.
95Mo NMR (13 MHz, THF): dexo = –1743, dendo = –1559.
1H and 13C NMR spectroscopic data have been recorded for the exo-
isomer.1 The signals for the endo-isomer (recorded on a 5:1 mix-
ture) are:
1H NMR (400 MHz, CDCl3): d = 5.20 (5 H, s, Cp), 3.45 (1 H, t,
J = 10.0 Hz, C3H), 2.63 (1 H, dq, J = 10.0, 6.0 Hz, C2H), 2.37 (1
H, t, J = 9.6 Hz, C4H), 2.02 (1 H, ddt, J = 13.2, 9.2, 6.6 Hz, C5H),
1.88 (3 H, d, J = 6.0 Hz, C1H3), 1.22 (3 H, d, J = 6.4 Hz, C6H3),
1.13 (3 H, d, J = 6.8 Hz, C5CH3).
13C NMR (100 MHz, CDCl3): d = 240.4 (2 C=O), 90.6 (5 CH, Cp),
90.5 (C3H), 67.6 (C4H), 51.0 (C2H), 33.7 (C5H), 28.1 (C1H3), 25.3
(C6H3), 20.5 (C5CH3).
(19) Bertini Gross, K. M.; Jun, Y. M.; Beak, P. J. Org. Chem.
1997, 62, 7679.
For the atom numbering scheme see Figure 2.
(20) Dieter and co-workers recently reported the enantioselective
alkylation of a-(N-carbamoyl)alkylcuprates with allylic
phosphates: Dieter, R. K.; Gore, V. K.; Chen, N. Org. Lett.
2004, 6, 763.
(21) Faller, J. W.; Linebarrier, D. Organometallics 1988, 7, 1670.
(22) Gao, Y.; Hanson, R. M.; Klunder, J. M.; Ko, S. Y.;
Masamune, S.; Sharpless, K. B. J. Am. Chem. Soc. 1987,
109, 5765.
Acknowledgment
We thank the Engineering and Physical Sciences Research Council
and GlaxoSmithKline for support. We also thank Dr Alexander
Kuhl and Mr James Gall (Glasgow University) for 95Mo NMR spec-
troscopy and Colin Kilner for X-ray crystallography.
(23) Anderson, E. M.; Larsson, K. M.; Kirk, O. Biocatal.
Biotransform. 1998, 16, 181.
(24) Attempts to accomplish a similar enzymatic resolution of
( )-33 failed.
(25) Cooksey, J.; Gunn, A.; Kocienski, P. J.; Kuhl, A.; Uppal, S.;
Christopher, J. A.; Bell, R. Org. Biomol. Chem. 2004, 2,
1719.
(26) Papillon and Taylor recently reported the alkylation and
conjugate addition of chiral a-(O-carbamoyl)alkylzinc
cuprates: Papillon, J. P. N.; Taylor, R. J. K. Org. Lett. 2002,
4, 119.
References
(1) Kocienski, P. J.; Brown, R. C. D.; Pommier, A.; Procter, M.;
Schmidt, B. J. Chem. Soc., Perkin Trans. 1 1998, 9.
(2) Cohen, T.; Bhupathy, M. Acc. Chem. Res. 1989, 22, 152.
(3) Freeman, P. K.; Hutchinson, L. L. J. Org. Chem. 1980, 45,
1924.
(4) Giese, B.; Dupuis, J. Tetrahedron Lett. 1984, 25, 1349.
(5) Rychnovsky, S. D.; Powers, J. P.; Lepage, T. J. J. Am. Chem.
Soc. 1992, 114, 8375.
(6) The transmetallation of chiral a-alkoxyalkyllithiums to the
corresponding cuprates and their conjugate addition to
enones occur with retention of configuration:
(a) Hutchinson, D. K.; Fuchs, P. L. J. Am. Chem. Soc. 1987,
109, 4930. (b) See also: Calter, M. A.; Bi, F. C. Org. Lett.
2000, 2, 1529.
(27) Matteson, D. S.; Tripathy, P. B.; Sarkar, A.; Sadhu, K. M. J.
Am. Chem. Soc. 1989, 111, 4399.
(28) Theis, A. B.; Townsend, C. A. Synth. Commun. 1981, 11,
157.
(29) Lipton, M. F.; Sorensen, C. M.; Sadler, A. C.; Shapiro, R. H.
J. Organomet. Chem. 1980, 186, 155.
(7) For a review see: Dieter, R. K. Heteroatom Cuprates and a-
Heteroatomalkylcuprates in Organic Synthesis, In Modern
Organocopper Chemistry; Krause, N., Ed.; Wiley: New
York, 2002, Chap. 3, 79.
(30) The supplementary crystallographic data for this structure
(CCDC 247732) can be obtained free of charge via
www.ccdc.cam.ac.uk/data_request/cif, by emailing
data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK.
(31) Hintze, F.; Hoppe, D. Synthesis 1992, 1216.
(32) Iwao, M.; Kuraishi, T.; Crowley, J.; Martin, S. F. Org. Synth.
1995, 73, 85.
(33) Meyers, A. I.; Milot, G. J. Org. Chem. 1993, 58, 6538.
(34) Anderson, W. K.; Lai, G. Synthesis 1995, 1287.
(35) Iwao, M.; Kuraishi, T. Heterocycles 1992, 34, 1031.
(36) Fleming, I.; Higgins, D.; Lawrence, N. J.; Thomas, A. P. J.
Chem. Soc., Perkin Trans. 1 1992, 3331.
(8) Sinz, C. J.; Rychnovsky, S. D. Top. Curr. Chem. 2001, 216,
51.
(9) Christopher, J. A.; Kocienski, P.; Procter, M. Synlett 1998,
425.
(10) Hoppe, D.; Hense, T. Angew. Chem., Int. Ed. Engl. 1997, 36,
2283.
(11) Hoppe, D.; Marr, F.; Brüggemann, M. Enantioselective
Synthesis by Lithiation Adjacent to Oxygen and Electrophile
Incorporation, In Organolithiums in Enantioselective
Synthesis 2005, No. 1, 75–84 © Thieme Stuttgart · New York