Synthesis of substituted phenols by directed ortho-lithiation of in situ N-silyl-protected O-aryl N-monoalkylcarbamates

Article abstract of DOI:10.1139/v01-146

A simple, high-yield procedure has been developed for the ortho-lithiation and subsequent ortho-substitution of phenols by a manifold of electrophiles. N,C-Dilithiation of O-aryl N-monoalkylcarbamates proved to be impossible due to a cleavage reaction of

Full text of DOI:10.1139/v01-146

1736
Synthesis of substituted phenols by directed
ortho-lithiation of in situ N-silyl-protected O-aryl
N-monoalkylcarbamates
Matthias Kauch and Dieter Hoppe
Abstract: A simple, high-yield procedure has been developed for the ortho-lithiation and subsequent ortho-substitution
of phenols by a manifold of electrophiles. N,C-Dilithiation of O-aryl N-monoalkylcarbamates proved to be impossible
due to a cleavage reaction of the monolithiated intermediates. However, in situ N-silylation of O-aryl N-
isopropylcarbamates proceeds smoothly with trialkylsilyl triflates – N,N,N>,N>-tetramethylethylenediamine (TMEDA).
Separation of the formed O-aryl N-isopropyl-N-trialkylsilylcarbamates from the byproduct TMEDA·HOTf, which is
insoluble in diethyl ether or toluene, is not required. ortho-Lithiation with n-butyllithium–TMEDA at –78°C leads to
the corresponding aryllithium, which does not undergo anionic ortho-Fries rearrangement under the reaction conditions,
but is efficiently substituted by electrophilic reagents. During the aqueous work-up, the N-silyl group is removed and
the corresponding ortho-substituted O-aryl N-isopropylcarbamate is isolated. Among the introduced electrophiles are:
Me3Si, Bu3Sn, PhS, I, Br, Cl, alkyl, a-hydroxyalkyl. Liberation of the free phenols is performed under mild alkaline
conditions.
Key words: directed ortho-metalation, ortho-lithiated O-aryl carbamates, ortho-substituted phenols, in situ protection of
N-monoalkylcarbamates.
Résumé : On a mis au point une méthode simple qui permet d’effectuer avec des rendements élevés l’ortho-lithiation
et l’ortho-substitution subséquente de phénols par un grand nombre d’électrophiles. Les N,C-dilithiations d’O-aryl
N-monoalkylcarbamates s’avèrent impossibles en raison de la réaction de clivage des intermédiaires monolithiés. Tou-
tefois, la N-silylation in situ des O-aryl N-isopropylcarbamates peut être réalisée facilement avec les couples
triflates de trialkylsilyle – N,N,N>,N>-tétraméthyléthylènediamine (TMEDA). Il n’est pas nécessaire de séparer les O-aryl
N-isopropyl-N-trialkylsilylcarbamates des sous-produits, TMEDA·HOTf qui sont insolubles dans l’éther éthylique ou le
toluène. L’ortho-lithiation avec du n-butyllithium–TMEDA, à –78°C, conduit à la formation de l’aryllithien correspondant,
qui ne donne pas lieu à un réarrangement d’ortho-Fries anionique dans les conditions de la réaction mais qui donne
lieu à des réactions de substitution sous l’influence de réactifs électrophiles. Lors de la procédure d’extraction, le
groupe N-silyle est éliminé et on peut isoler le O-aryl N-isopropylcarbamate ortho-substitué. Les électrophiles qui ont
été introduits sont: Me3Si, Bu3Sn, PhS, I, Br, Cl, alkyle, a-hydroxyalkyle. La libération des phénols se fait dans des
conditions alcalines douces.
Mots clés : ortho-métallation orientée, O-aryl carbamates ortho-lithiés, phénols ortho-substitués, protection in situ de
N-monoalkylcarbamates.
[Traduit par la Rédaction] 1746
Introduction
Kauch and Hoppreeference to milder reaction conditions, control of
regioselectivity, and the range of functional groups which
can be introduced. New applications of DoM chemistry also
include the substitution of aromatic ligands of metal complexes
leading to planar chiral ferrocenes (3) or arene tricarbonyl-
chromium complexes (for recent work in this field see
ref. 4) if chiral bases are employed.
The tertiary carbamoyloxy group has proven to be one of
the most powerful directed metalation groups (DMGs). The
Within the last two decades, the directed ortho-metalation
(DoM) reaction turned out as an important and powerful tool
for the construction of polysubstituted aromatics (for reviews
see ref. 1a–c; for a short summary of recent developments in
the Snieckus group see ref. 1d; for a critical view on DoM
and its mechanisms see ref. 2). This strategy supersedes the
classical aromatic electrophilic substitution reactions with
Received March 7, 2001. Published on the NRC Research Press Web site at http://canjchem.nrc.ca on November 14, 2001.
This paper is dedicated with friendship and admiration to Professor Victor Snieckus in recognition of his significant contributions
to carbanion chemistry.
M. Kauch and D. Hoppe.1 Organisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstrasse 40, D-48149
Münster, Germany.
1Corresponding author (telephone: +(251)8333211; fax: +(251)8339772; e-mail: dhoppe@uni-muenster.de).
Can. J. Chem. 79: 1736–1746 (2001)
© 2001 NRC Canada
DOI: 10.1139/cjc-79-11-1736

Kauch and Hoppe
1737
Scheme 1.
Scheme 2. SiPG = TMS, TBDMS, or TIPS. The following standard conditions and reagents are used unless otherwise specified:
(a) 1.05 to 1.10 equiv of TMSOTf (solution in pentane), TMEDA, Et2O, 0°C J rt, 0.5 h; (b) 2.0 equiv of n- or s-BuLi – TMEDA, –78°C,
1 h; (c) 2.5 to 3.5 equiv of EX, –78°C, 1 to 2 h; (d) MeOH, 2 M HCl, –78°C J rt.
N,N-diisopropylcarbamoyl and the N,N-diethylcarbamoyl
group were employed for the directed a-lithiation of allylic
and benzylic alcohols (for O-allyl carbamates see refs. 5a
and 5b; for O-benzyl carbamates see ref. 5c). The N,N-
diethylcarbamoyloxy group was extensively used by
Snieckus for DoM reactions of aromatic compounds (6). A
disadvantage of both DMGs is that for deprotection vigorous
conditions have to be used. Only reductive methods with
lithium aluminium hydride, diisobutylaluminium hydride, or
strong basic conditions lead to carbamate ester cleavage,
causing problems with sensitive groups. The strength of this
group lies in its capability of undergoing anionic ortho-Fries
rearrangements (1a, 6; for recent applications of further O J
C carbamoyl transfer reactions in natural product synthesis
see ref. 7).
found that the corresponding O-aryl carbamates 1 could not
be converted to the dianionic species 3. The intermediate
N-lithiated carbamates 2 undergo a cleavage reaction to
phenolates 4 and isocyanate, followed by an irreversible
addition of the alkyllithium base to the intermediate
isocyanate to give the N-lithiocarboxamide 5 (Scheme 1).
Herein we report on the simple solution of the problem.
O-Aryl N-monoalkylcarbamates 1 can be in situ transformed
into N-alkyl N-silyl derivatives 6 (12) which are stable substrates
for the directed ortho-lithiation reaction. The lithiated
carbamates 7 react with a broad range of electrophilic
reagents to the ortho-substituted protected phenols 8 in
which the N-silyl group is completely removed during aqueous
work-up. Subsequently, the carbamoyl residue can easily be
removed by mild basic hydrolysis to furnish the free phenols.
Very recently, the N-cumyl-N-methylcarbamoyl group,
offering hydrolytic lability for a two-step cleavage, was
established by Snieckus and co-workers (8). Decumylation
with trifluoroacetic acid and subsequent hydrolytic
deprotection with bases proceed under mild conditions.
In our group, several carbamoyl residues had been developed
for directed lithiation reactions of O-alkyl, O-allyl, and O-benzyl
carbamates and their S-analogues which are easier to remove
than the original N,N-diisopropylcarbamoyl group (9). N-
Monoalkylcarbamoyl groups were first used for the generation
of N,C-dilithiated intermediates from O-allyl (10) and
recently S-allyl compounds (11). In our attempt, employing
the N-isopropylcarbamoyl group for phenol activation, we
Results and discussion
The O-aryl N-isopropylcarbamates 10a, 10b, 10c, and 15
were easily prepared by addition of the corresponding phenols
onto isopropyl isocyanate (THF, DMAP, 60°C) and were
isolated as crystalline solids in high yields.
The following standard protocol was employed for
directed ortho-lithiation reactions (Scheme 2): The O-aryl
carbamates
1 were N-silyl protected by means of
trimethylsilyl triflate in the presence of TMEDA. The resulting
N-silyl intermediates 6 (SiPG = TMS) were lithiated with n- or
s-BuLi–TMEDA in diethyl ether at –78°C. The following
© 2001 NRC Canada

1738
Can. J. Chem. Vol. 79, 2001
Table 1. Results of ortho-trimethylsilylations of O-2-biphenylyl carbamate 10a to form 13aa.
Entry
Solvent
Protecting reagent
SiPG
Base
Yield (%)a
1
2
3
4
5
6
7
8
9
Et2O
Et2O
Et2O
Et2O
Et2O
Et2O
Toluene
THF
TMSOTf
TMSOTf
TMSOTf
TMSONf
TBDMSOTf
TIPSOTf
TMSOTf
TMSOTf
TMSOTf
TMS
TMS
TMS
TMS
TBDMS
TIPS
TMS
TMS
TMS
s-BuLi–TMEDA
n-BuLi–TMEDA
LDA
n-BuLi–TMEDA
s-BuLi–TMEDA
n-BuLi–TMEDA
n-BuLi–TMEDA
s-BuLi–TMEDA
s-BuLi–TMEDAb
94
97
0
93
93
91
94
97
96
Et2O
aNo starting material could be recovered, except for the reaction with LDA (entry 3) after which 98%
of carbamate 10a was reisolated.
bReverse addition in the lithiation step: (i) 1.5 equiv TMSCl; (ii) 1.1 equiv base.
Scheme 3. Conditions and reagents: (a) see Scheme 2, a; (b) 2.2 equiv of s-BuLi–TMEDA, –78°C, 1 h, then –78°C J rt, then 2 M
HCl; (c) 2.5 equiv of LDA, 0°C, 4 h, then 0°C J rt, then 2 M HCl.
It is noteable that lithiation and substitution of the
reaction with electrophiles and acidic work-up furnished the
N,N-diethylcarbamoyl-protected phenol require much
ortho-substituted products 9.
lower reaction temperatures to avoid the anionic ortho-Fries
Voyer and co-workers (12) recently reported on the
rearrangement (13). No carbamoyl migration product could
preparation and characterization, and, as well, deprotonation
be detected in reactions under the usual conditions applying
of O-methyl and O-tert-butyl N-silyl-N-benzylcarbamates
N-isopropyl-N-silylcarbamoyl phenols. Therefore, this DMG
adjacent to the nitrogen atom. In this two-step sequence, the
may be advantageously used when inter- or intramolecular
N-silyl protected amines were isolated before subjection to
attack of the carbonyl group must be avoided. Formation of
metalation. X-ray crystallography of one compound proved
the ortho-hydroxy carboxamide 12 was achieved with 63%
the N-silyl group (12c). Therefore, we strongly suggest that
yield besides 33% of the arylsilane 13aa, when the solution
silyl protection of secondary O-aryl carbamates occurs, as
of the lithiated carbamate 11 was allowed to warm to 0°C
well, at the carbamoyl nitrogen atom.
(Scheme 3). 12 was also obtained (79%) by stirring the
To investigate suitable conditions for the protection and
deprotonation step, several reagents were used for ortho-
trimethylsilylation of the 2-biphenylyl carbamate 10a with
TMSCl as electrophile (Table 1). Consecutive lithiation with
n- or s-BuLi in diethyl ether at –78°C, electrophilic quench,
and hydrolysis afforded the substitution product 13aa in
excellent yields (entries 1 and 2) whereas deprotonation with
LDA (entry 3) did not occur. Several silyl sources can be
employed in the N-protection step. The use of TMS
nonaflate (entry 4), TBDMS triflate, or even the bulkier
TIPS triflate (entries 5 and 6) did not affect the yields signif-
icantly. Although diethyl ether is employed as standard
solvent for the reaction sequence, toluene and THF were
used without loss in the yield (entries 7 and 8).
N-silyl-protected urethane with 2.5 equiv of lithium
diisopropylamide at 0°C to room temperature.
Carbamate 10a reacted under the above described standard
protocol with a variety of electrophilic reagents to give the
substituted products 13a in good to excellent yields (Table 2,
Scheme 4). In particular, introduction of heteroatom-based
functional groups occurred with high yields (entries 1–6).
Only ethylation, allylation (entries 8 and 9) or, in some
cases, the reaction with ketones bearing acidic a-hydrogen
atoms (entries 14 and 16) gave somewhat lower yields, but
these still remained above 60%.
Comparable high yields were achieved with the
unsubstituted O-phenyl carbamate 10b and the 2-chloro-
functionalized substrate 10c (Table 2, entries 17–21 and 22–
29). In the second case, n-BuLi–TMEDA could be
advantageously used to give a cleaner lithiation rather than
s-BuLi–TMEDA (entries 22 and 23). The O-1-naphthyl
carbamate 15 gave the same results concerning the yields of
DoM-substitution sequences (entries 30–34, Scheme 5). In
Under our reaction conditions, TMEDA·HOTf separates
from the reaction mixture and solidifies on cooling to below
–70°C. Although the salt is neutralized only slowly by
butyllithium, 2.0 equiv of the alkyllithium were applied for
achieving maximum yields.2
2 Using 1.1 equiv of s-BuLi after addition of 1.5 equiv TMSC1 (Table 1, entry 9) a yield of 96% of 13aa was isolated. This result demon-
strates that the C-deprotonation is much more rapid than deprotonation of the solid ammonium triflate.
© 2001 NRC Canada

Kauch and Hoppe
Table 2. Synthesis of ortho-substituted carbamates 13 and 16.
1739
Entry
Substrate
Conditionsa
R
EX
E
Product
Yield (%)
1
2
3
4
5
6
7
8
9
10a
10a
10a
10a
10a
10a
10a
10a
10a
10a
10a
10a
10a
10a
10a
10a
10b
10b
10b
10b
10b
10c
10c
10c
10c
10c
10c
10c
10c
15
B
A
B
B
B
B
A
A
A
A
A
B
B
B
B
B
B
A
A
A
B
A
B
B
B
B
B
B
B
A
A
A
A
B
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
H
TMSCl
Bu3SnCl
I2
BrCH2CH2Br
C2Cl6
(PhS)2
MeI
EtI
TMS
SnBu3
I
Br
Cl
SPh
Me
Et
13aa
13ab
13ac
13ad
13ae
13af
13ag
13ah
13ai
13aj
13ak
13al
13am
13an
13ao
13ap
13ba
13bb
13bc
13bd
13be
13ca
13ca
13cb
13cc
13cd
13ce
13cf
13cg
16a
97
86
88
91
93
94
83
68
63
74
87
85
85
70
81
64
82
85
83
81
84
82
91
87
86
86
90
84
82
91
85
86
83
87
CH2=CHCH2Br
BnBr
CH2CH=CH2
Bn
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
PhCHO
i-Pr-CHO
Ph2CO
PhMeCO
Me2CO
(CH2)5CO
TMSCl
Bu3SnCl
MeI
PhCHO
Ph2CO
TMSCl
TMSCl
Bu3SnCl
I2
CH(OH)Ph
CH(OH)-i-Pr
C(OH)Ph2
C(OH)PhMe
C(OH)Me2
C(OH)(CH2)5
TMS
SnBu3
Me
CH(OH)Ph
C(OH)Ph2
TMS
TMS
SnBu3
I
SPh
Me
H
H
H
H
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
—
—
—
—
—
(PhS)2
MeI
PhCHO
Ph2CO
TMSCl
Bu3SnCl
MeI
CH(OH)Ph
C(OH)Ph2
TMS
SnBu3
Me
15
15
15
15
16b
16c
16d
16e
PhCHO
Ph2CO
CH(OH)Ph
C(OH)Ph2
aMethod A: s-BuLi–TMEDA conditions. Method B: n-BuLi–TMEDA conditions.
Scheme 4. Conditions and reagents: (a) see Scheme 2, a–d; (b) 4.0 equiv of 2 M NaOH, EtOH, rt, 2 h; or (c) 10.0 equiv of K2CO3,
EtOH, rt, 12 h.
Scheme 5. Conditions and reagents: (a) see Scheme 2, a–d.
2-position (1a, 6). No product resulting from lithiation in the
peri-position could be detected.
Two procedures, using mild bases, have been established for
the deprotection of the ortho-substituted products (Scheme 4,
13 J 14). Treatment of several carbamates 13a and 13c with
2 M NaOH in ethanol at room temperature afforded phenols
14a and 14c in excellent to quantitative yields within 2 h (Ta-
ble 3). Even substrates 13aa and 13ca bearing a base-sensitive
TMS group could be deprotected without desilylation (entries
1 and 7). The o-iodoaryl carbamates 13ac and 13cc reacted
smoothly to yield iodophenols 14ab and 14cb with complete
retention of the iodine substituent as well (entries 3 and 8). The
accordance with observations of Snieckus with the N,N-diethyl-
carbamate, lithiation of 15 proceeded exclusively at the
© 2001 NRC Canada

1740
Can. J. Chem. Vol. 79, 2001
Table 3. Deblocking the carbamates 13a and 13c to form the free phenols 14a and 14c.
Entry
Substrate
Conditionsa
R
E
Product
Yield (%)
1
2
3
4
5
6
7
8
9
13aa
13aa
13ac
13ad
13af
13am
13ca
13cc
13cd
A
B
A
A
A
A
A
A
A
Ph
Ph
Ph
Ph
Ph
Ph
Cl
Cl
Cl
TMS
TMS
I
14aa
14aa
14ab
14ac
14ad
14ae
14ca
14cb
14cc
99
98
98
99
99
96
99
94
91
Br
SPh
C(OH)Ph2
TMS
I
SPh
aMethod A: 4.0 equiv of 2 M NaOH, EtOH, rt, 2 h. Method B: 10.0 equiv of K2CO3, EtOH, rt, 12 h.
O-2-Biphenylyl N-isopropylcarbamate (10a): 2-Hydroxy-
biphenyl (5.11 g, 30.0 mmol) was stirred with isopropyl
isocyanate (3.24 mL, 33.0 mmol) to afford 10a (7.60 g,
29.8 mmol, 99%) as a white solid, mp 89°C (Et2O–PE). IR
carbamoyl group of the N-monoalkylcarbamates can also be re-
moved by stirring with a slurry of potassium carbonate in etha-
nol at room temparature (entry 2).
1
(KBr) ꢀ (cm–1): 3322, 1710, 1539, 769, 742, 696. H NMR
3
(400 MHz) d: 1.06 (d, J = 6.0 Hz, 6H), 3.74 (m, 1H), 4.69
Experimental section
(s, 1H), 7.18–7.43 (m, 9H). 13C NMR (100 MHz) d: 22.7,
43.3, 123.2, 125.7, 127.2, 128.1, 128.3, 129.0, 130.7, 135.1,
137.9, 148.0, 153.6. Anal. calcd. for C16H17NO2 (255.32): C
75.27, H 6.71, N 5.49; found: C 75.25, H 6.92, N 5.47.
General information
All reactions were carried out under Ar in flame-dried
glassware. All solvents were purified and dried prior to use:
Et2O and toluene were distilled from sodium benzophenone
ketyl. THF was distilled from potassium benzophenone
ketyl. Pentane was distilled from CaH2. N,N,N>,N>-Tetra-
methylethylenediamine (TMEDA) was purchased from
Merck, refluxed and distilled from CaH2 before use. n-BuLi
(1.6 M in hexane) and s-BuLi (1.3 M in cyclohexane–hex-
ane = 92:8) were purchased from Acros. The solution of s-
BuLi was filtered using Celite® and titrated against phenyl-
acetic acid prior to use. Trimethylsilyl trifluoromethane-
sulfonate was purchased from Acros.
O-Phenyl N-isopropylcarbamate (10b) (14): Reaction of phenol
(2.82 g, 30.0 mmol) with isopropyl isocyanate (3.24 mL,
33.0 mmol) furnished 10b (5.03 g, 28.1 mmol, 94%) as a
white solid, mp 87°C (Et2O–PE) (lit. (14) mp 85°C). IR
(KBr) ꢀ (cm–1): 3389, 1703, 1545, 788, 703. 1H NMR
3
(300 MHz) d: 1.19 (d, J = 6.6 Hz, 6H), 3.87 (m, 1H), 4.98
(s, 1H), 7.10–7.18 (m, 3H), 7.30–7.35 (m, 2H). 13C NMR
(75 MHz) d: 22.7, 43.3, 121.5, 125.0, 129.1, 151.1, 153.6.
Anal. calcd. for C10H13NO2 (179.22): C 67.02, H 7.31,
N 7.82; found: C 67.21, H 7.41, N 8.00.
1H and 13C NMR spectra were recorded on Bruker ARX
300 or AMX 400 spectrometers in CDCl3 solutions using
tetramethylsilane as internal standard. IR spectra were
recorded on a Nicolet 5DXC spectrometer. Melting points
were obtained on Gallenkamp melting point apparatus MFB-595
and are uncorrected. Microanalyses were performed at the
Organisch-Chemisches Institut der WWU Münster with
Heraeus CHN-O-Rapid or Elementar Analysensysteme
VarioEL III analysers. HRMS were recorded on a Finnigan
MAT 8200 mass spectrometer (EI, 70 eV).
O-2-Chlorophenyl N-isopropylcarbamate (10c): 2-Chloro-
phenol (3.86 g, 30.0 mmol) was stirred with isopropyl
isocyanate (3.24 mL, 33.0 mmol) to give 10c (6.28 g,
29.4 mmol, 98%) as a white solid, mp 65°C (Et2O–PE). IR
1
(KBr) ꢀ (cm–1): 3309, 1716, 1539, 736. H NMR (400 MHz)
3
d: 1.22 (d, J = 6.5 Hz, 6H), 3.88 (m, 1H), 5.07 (s, 1H),
7.11–7.15 (m, 1H), 7.19–7.27 (m, 2H), 7.39–7.41 (m, 1H).
13C NMR (100 MHz) d: 22.7, 43.6, 124.1, 126.4, 127.3,
127.5, 130.1, 147.2, 152.6. Anal. calcd. for C10H12ClNO2
(213.66): C 56.21, H 5.66, N 6.56; found: C 56.09, H 5.65,
N 6.55.
Products were purified by flash column chromatography
on Merck silica gel 60 (0.040–0.063 mm); PE = light petroleum
ether, bp 36–46°C.
General procedure for the preparation of O-aryl N-
ispropylcarbamates 10 and 16
O-1-Naphthyl N-isopropylcarbamate (15) (15): Reaction of
1-naphthol (5.77 g, 40.0 mmol) with isopropyl isocyanate
(4.32 mL, 44.0 mmol) yielded 15 (7.97 g, 34.8 mmol, 87%)
as a white solid, mp 123°C (Et2O–PE) (lit. (15) mp 112°C).
To a cooled (0°C) solution of the phenol and DMAP
(0.10 equiv) in dry THF (0.5 mL:1 mmol phenol), isopropyl
isocyanate (1.10 equiv) was added. The reaction mixture was
stirred at 60°C for 24 h, cooled to rt, and treated with 2 M
HCl (1.0 mL:1 mmol phenol). After addition of Et2O, the
aqueous layer was separated, extracted with Et2O, and the
combined organic extracts were washed with saturated
NaHCO3 solution, dried over MgSO4, filtered, and concentrated
in vacuo. The crude product was purified by flash chroma-
tography on silica gel (Et2O–PE gradient).
1
IR (KBr) ꢀ (cm–1): 3423, 3368, 1716, 1525, 815, 788. H
3
NMR (300 MHz) d: 1.22 (d, J = 6.7 Hz, 6H), 3.91 (m, 1H),
5.12 (s, 1H), 7.27–7.30 (m, 1H), 7.40–7.51 (m, 3H), 7.67–7.69
(m, 1H), 7.80–7.85 (m, 1H), 7.90–7.96 (m, 1H). 13C NMR
(75 MHz) d: 22.8, 43.5, 118.1, 121.3, 125.4, 125.4, 126.1,
126.2, 127.5, 127.9, 134.6, 146.8, 153.7. Anal. calcd. for
C14H15NO2 (229.28): C 73.34, H 6.59, N 6.11; found: C
73.36, H 6.70, N 6.06.
© 2001 NRC Canada

Kauch and Hoppe
1741
General procedure for the ortho-lithiation of O-aryl N-
isopropylcarbamates 10 and 15
O-3-Bromo-2-biphenylyl N-isopropylcarbamate (13ad): 10a
(0.255 g) reacted with TMSOTf (1.05 mmol), n-BuLi, and
BrCH2CH2Br (0.30 mL, 3.5 mmol, 1 h) to give 13ad
(0.304 g, 0.910 mmol, 91%) as a white solid, mp 123°C
(Et2O–PE). IR (KBr) ꢀ (cm–1): 3362, 1729, 1539, 776, 760,
709. H NMR (300 MHz) d: 1.08 (d, J = 6.4 Hz, 6H), 3.75
(m, 1H), 4.74 (s, 1H), 7.14 (t, 1H), 7.26–7.43 (m, 6H), 7.57
(dd, 1H). 13C NMR (75 MHz) d: 22.6, 43.4, 118.4, 126.9,
127.6, 128.2, 128.9, 129.8, 132.3, 137.4, 138.0, 145.6,
152.2. Anal. calcd. for C16H16BrNO2 (334.21): C 57.50,
H 4.83, N 4.19; found: C 57.58, H 4.87, N 4.48.
A solution of the carbamate 10 or 15 (1.00 mmol) in dry
Et2O (10 mL) under Ar in a flask, sealed with a rubber septum,
was cooled to 0°C. TMEDA (0.128 g, 1.10 mmol,
1.10 equiv) was introduced, and to the solution was added
dropwise, via a syringe, TMSOTf (1.05 to 1.10 mmol, 1.05
to 1.10 equiv, 1.25 to 1.35 M solution in pentane). The
resulting mixture was stirred for 5 min, allowed to warm to
rt over a period of 30 min, and cooled to –78°C. TMEDA
(0.232 g, 2.00 mmol, 2.00 equiv) and n-BuLi or s-BuLi
(2.00 mmol, 2.00 equiv) were added consecutively. The
reaction mixture was stirred for 1 h and treated with the
electrophile (2.50 to 3.50 mmol, 2.50 to 3.50 equiv). After
an additional stirring for 1 to 2 h, 0.1 mL of MeOH and
5 mL of 2 M HCl were added and the mixture was allowed
to warm to rt. The phases were separated and the aqueous
layer was extracted with Et2O (3 × 20 mL). The combined
organic phases were washed with saturated NaHCO3 solution
(10 mL), dried over MgSO4, filtered, and concentrated in
vacuo to afford the crude product. Flash chromatography on
silica gel (Et2O–PE gradient) gave the ortho-substituted
carbamate.
1
3
O-3-Chloro-2-biphenylyl N-isopropylcarbamate (13ae):
Reaction of 10a (0.255 g) with TMSOTf (1.10 mmol), n-
BuLi, and C2Cl6 (0.592 g in 3 mL of Et2O, 2.5 mmol, 1 h)
afforded 13ae (0.270 g, 0.932 mmol, 93%) as a white solid,
mp 110°C (Et2O–PE). IR (KBr) ꢀ (cm–1): 3362, 1723, 1539,
1
3
779, 760, 706. H NMR (300 MHz) d: 1.09 (d, J = 6.4 Hz,
6H), 3.76 (m, 1H), 4.76 (s, 1H), 7.16–7.43 (m, 8H). 13C
NMR (75 MHz) d: 22.6, 43.5, 126.4, 127.6, 128.2, 128.9,
129.1, 129.1, 129.2, 137.2, 137.8, 144.5, 152.4. Anal. calcd.
for C16H16ClNO2 (289.76): C 66.32, H 5.57, N 4.83; found:
C 66.43, H 5.79, N 4.99.
O-3-Phenylsulfanyl-2-biphenylyl N-isopropylcarbamate (13af):
Reaction of 10a (0.255 g) with TMSOTf (1.05 mmol), n-
BuLi, and (PhS)2 (0.546 g in 3 mL of Et2O, 2.5 mmol, 1 h)
furnished 13af (0.341 g, 0.938 mmol, 94%) as a white solid,
mp 115°C (Et2O–PE). IR (KBr) ꢀ (cm–1): 3335, 1703, 1532,
778, 756, 703. H NMR (300 MHz) d: 1.04 (d, J = 6.4 Hz,
6H), 3.70 (m, 1H), 4.63 (s, 1H), 7.13–7.18 (m, 2H), 7.20–7.46
(m, 11H). 13C NMR (75 MHz) d: 22.7, 43.3, 125.2, 126.3,
127.4, 128.2, 129.0, 129.2, 129.6, 131.2, 131.5, 131.9,
134.6, 136.8, 137.7, 146.6, 152.7. Anal. calcd. for
C22H21NO2S (363.47): C 72.70, H 5.82, N 3.85; found:
C 72.79, H 5.98, N 4.01.
O-3-Trimethylsilyl-2-biphenylyl N-isopropylcarbamate (13aa):
Reaction of 10a (0.255 g) with TMSOTf (1.10 mmol),
n-BuLi, and TMSCl (0.32 mL, 2.5 mmol, 1 h) afforded
13aa (0.318 g, 0.971 mmol, 97%) as a white solid, mp
161°C (Et2O–PE). IR (KBr) ꢀ (cm–1): 3329, 1710, 1545,
1
3
1
834, 788, 755, 709. H NMR (300 MHz) d: 0.30 (s, 9H),
0.94 (d, 3J = 6.3 Hz, 6H), 3.55 (m, 1H), 4.50 (s, 1H), 7.26–7.47
(m, 8H). 13C NMR (75 MHz) d: –0.7, 22.6, 43.0, 125.7,
127.0, 128.0, 129.1, 132.1, 133.4, 134.2, 135.6, 138.5,
152.7, 152.9. Anal. calcd. for C19H25NO2Si (327.50): C
69.68, H 7.69, N 4.28; found: C 69.59, H 7.74, N 4.12.
O-3-Methyl-2-biphenylyl N-isopropylcarbamate (13ag): 10a
(0.255 g) reacted with TMSOTf (1.10 mmol), s-BuLi, and
MeI (0.20 mL, 2.5 mmol, 1 h) to give 13ag (0.223 g,
0.828 mmol, 83%) as a white solid, mp 109°C (Et2O–PE).
O-3-Tributylstannyl-2-biphenylyl N-isopropylcarbamate (13ab):
Reaction of 10a (0.255 g) with TMSOTf (1.10 mmol),
s-BuLi, and Bu3SnCl (0.68 mL, 2.5 mmol, 1 h) yielded
13ab (0.467g, 0.858 mmol, 86%) as a white solid, mp 70°C
(Et2O–PE). IR (KBr) ꢀ (cm–1): 3317, 1708, 1528, 782, 754,
1
IR (KBr) ꢀ (cm–1): 3326, 1710, 1529, 783, 761, 699. H
3
NMR (300 MHz) d: 1.05 (d, J = 6.4 Hz, 6H), 2.26 (s, 3H),
1
701. H NMR (300 MHz) d: 0.89 (t, 3J = 7.4 Hz, 9H), 0.95
3.73 (m, 1H), 4.60 (s, 1H), 7.14–7.22 (m, 3H), 7.27–7.43
(m, 5H). 13C NMR (75 MHz) d: 16.4, 22.7, 43.2, 125.7,
127.1, 128.1, 128.3, 129.1, 130.2, 131.9, 135.8, 138.4,
146.7, 153.3. Anal. calcd. for C17H19NO2 (269.34): C 75.81,
H 7.11, N 5.20; found: C 75.78, H 7.24, N 5.30.
(d, 3J = 6.4 Hz, 6H), 1.05–1.13 (m, 6H), 1.25–1.43 (m, 6H),
1.49–1.61 (m, 6H), 3.56 (m, 1H), 4.42 (d, 1H), 7.21–7.44
(m, 8H). 13C NMR (75 MHz) d: 10.0, 13.6, 22.7, 27.4, 29.1,
43.0, 125.8, 126.9, 128.0, 129.0, 131.1, 135.2, 136.0, 136.2,
139.0, 153.0, 153.2. Anal. calcd. for C28H43NO2Sn (544.36):
C 61.78, H 7.96, N 2.57; found: C 62.18, H 8.06, N 2.66.
O-3-Ethyl-2-biphenylyl N-isopropylcarbamate (13ah): 10a
(0.255 g) reacted with TMSOTf (1.05 mmol), s-BuLi, and
EtI (0.20 mL, 2.5 mmol, 2 h) to give 13ah (0.192 g,
0.678 mmol, 68%) as a white solid, mp 92°C (Et2O–PE). IR
O-3-Iodo-2-biphenylyl N-isopropylcarbamate (13ac): Reac-
tion of 10a (0.255 g) with TMSOTf (1.05 mmol), n-BuLi,
and I2 (0.761 g in 3 mL of Et2O, 3.0 mmol, 1 h) afforded
13ac (0.366 g, 0.881 mmol, 88%) as a white solid, mp
127°C (Et2O–PE). IR (KBr) ꢀ (cm–1): 3355, 1719, 1523,
1
(KBr) ꢀ (cm–1): 3347, 1709, 1528, 786, 759, 704. H NMR
3
3
(300 MHz) d: 1.02 (d, J = 6.5 Hz, 6H), 1.02 (t, J = 7.6,
3H), 2.64 (q, 2H), 3.69 (m, 1H), 4.60 (s, 1H), 7.14–7.44 (m,
8H). 13C NMR (100 MHz) d: 14.1, 22.7, 23.3, 43.2, 125.9,
127.0, 128.0, 128.3, 128.4, 129.1, 135.9, 137.5, 138.5,
146.2, 153.4. Anal. calcd. for C18H21NO2 (283.36): C 76.29,
H 7.47, N 4.94; found: C 76.11, H 7.17, N 4.85.
1
3
780, 759, 710. H NMR (400 MHz) d: 1.07 (d, J = 6.4 Hz,
6H), 3.72 (m, 1H), 4.71 (s, 1H), 7.00 (t, 1H), 7.28–7.42 (m,
6H), 7.79 (dd, 1H). 13C NMR (100 MHz) d: 22.7, 43.4, 92.8,
127.5, 127.6, 128.2, 128.8, 130.9, 137.3, 137.7, 138.4,
148.4, 152.1. Anal. calcd. for C16H16INO2 (381.21): C
50.41, H 4.23, N 3.67; found: C 50.77, H 4.48, N 3.40.
O-3-Allyl-2-biphenylyl N-isopropylcarbamate (13ai): Reaction
of 10a (0.255 g) with TMSOTf (1.10 mmol), s-BuLi, and
© 2001 NRC Canada

1742
Can. J. Chem. Vol. 79, 2001
CH2CHCH2Br (0.22 mL, 2.5 mmol, 2 h) furnished 13ai
(0.185g, 0.626 mmol, 63%) as a white solid, mp 112°C
(Et2O–PE). IR (KBr) ꢀ (cm–1): 3344, 1712, 1526, 783, 760,
126.8, 127.1, 127.4, 127.7, 128.0, 129.0, 129.9, 130.8,
137.6, 138.1, 140.4, 146.1, 146.2, 151.9. Anal. calcd. for
C29H27NO3 (437.54): C 79.61, H 6.22, N 3.20; found:
C 79.43, H 6.36, N 2.92.
1
3
702. H NMR (300 MHz) d: 1.02 (d, J = 6.5 Hz, 6H), 3.38
3
(d, J = 6.7 Hz, 2H), 3.68 (m, 1H), 4.59 (s, 1H), 5.04–5.16
O-3-(1-Hydroxy-1-phenylethyl)-2-biphenylyl N-isopropylcarba-
mate (13an): Reaction of 10a (0.255 g), with TMSOTf
(1.05 mmol), n-BuLi, and PhMeCO (0.41 mL, 3.5 mmol,
2 h) gave 13an (0.261 g, 0.695 mmol, 70%) as a white solid,
mp 127°C (Et2O–PE). IR (KBr) ꢀ (cm–1): 3253, 1698, 1542,
(m, 2H), 5.90–6.05 (m, 1H), 7.19–7.23 (m, 3H), 7.26–7.43
(m, 5H). 13C NMR (75 MHz) d: 22.7, 34.7, 43.2, 116.1,
125.9, 127.1, 128.0, 128.8, 129.1, 129.2, 133.8, 136.1,
136.2, 138.3, 146.3, 153.2. Anal. calcd. for C19H21NO2
(295.38): C 77.26, H 7.17, N 4.74; found: C 76.96, H 6.92,
N 4.69.
1
3
762, 700. H NMR (300 MHz) d: 0.78/0.83 (d, J = 6.4 Hz,
6H), 1.90 (s, 1H), 2.57 (s, 1H), 3.29 (m, 1H), 4.12 (d, 1H),
7.12–7.45 (m, 12H), 7.69 (t, 1H). 13C NMR (75 MHz) d:
22.3, 31.0, 43.0, 75.4, 124.8, 125.7, 126.9, 127.1, 127.8,
128.0, 128.0, 129.1, 130.6, 136.4, 137.6, 138.1, 140.2,
146.1, 152.3. Anal. calcd. for C24H25NO3 (375.47): C 76.77,
H 6.71, N 3.73; found: C 76.76, H 6.58, N 3.54.
O-3-Benzyl-2-biphenylyl N-isopropylcarbamate (13aj): Re-
action of 10a (0.255 g) with TMSOTf (1.05 mmol), s-BuLi,
and BnBr (0.30 mL, 2.5 mmol, 2 h) gave 13aj (0.254 g,
0.735 mmol, 74%) as a white solid, mp 109°C (Et2O–PE).
1
IR (KBr) ꢀ (cm–1): 3322, 1700, 1532, 786, 756, 702. H
3
NMR (300 MHz) d: 1.00 (d, J = 6.5 Hz, 6H), 3.66 (m, 1H),
O-3-(1-Hydroxy-1-methylethyl)-2-biphenylyl N-isopropylcarba-
mate (13ao): Reaction of 10a (0.255 g) with TMSOTf
(1.05 mmol), n-BuLi, and Me2CO (0.26 mL, 3.5 mmol, 1 h)
afforded 13ao (0.254 g, 0.810 mmol, 81%) as a white solid,
mp 154°C (Et2O–PE). IR (KBr) ꢀ (cm–1): 3568, 3307, 1715,
3.97 (s, 2H), 4.55 (d, 1H), 7.09 (dd, 1H), 7.13–7.45 (m,
12H). 13C NMR (100 MHz) d: 22.6, 36.3, 43.2, 125.8, 126.1,
127.1, 128.0, 128.4, 128.9, 129.1, 129.1, 129.8, 134.9,
136.1, 138.3, 140.1, 146.4, 153.1. Anal. calcd. for
C23H23NO2 (345.43): C 79.97, H 6.71, N 4.05; found:
C 79.82, H 6.93, N 3.86.
1
3
1531, 767, 703, 671. H NMR (300 MHz) d: 0.90 (d, J =
6.4 Hz, 6H), 1.64 (s, 6H), 2.60 (s, 1H), 3.52 (m, 1H), 4.07
(d, 1H), 7.21–7.42 (m, 7H), 7.49–7.57 (m, 1H). 13C NMR
(75 MHz) d: 22.5, 30.4, 43.2, 72.3, 125.7, 125.7, 127.1,
128.0, 129.3, 130.0, 137.4, 138.3, 140.9, 145.6, 152.8. Anal.
calcd. for C19H23NO3 (313.40): C 72.82, H 7.40, N 4.47;
found: C 75.52, H 7.18, N 4.16.
O-3-(Hydroxyphenylmethyl)-2-biphenylyl N-isopropylcarbamate
(13ak): Reaction of 10a (0.255 g) with TMSOTf
(1.10 mmol), s-BuLi, and PhCHO (0.26 mL, 2.5 mmol, 1 h)
afforded 13ak (0.316 g, 0.874 mmol, 87%) as a white solid,
mp 111°C (Et2O–PE). IR (KBr) ꢀ (cm–1): 3397, 3337, 1710,
1
1538, 789, 759, 703. H NMR (300 MHz) d: 0.99/1.03 (d,
O-3-(1-Hydroxycyclohexyl)-2-biphenylyl N-isopropylcarba-
mate (13ap): 10a (0.255 g) reacted with TMSOTf
(1.05 mmol), n-BuLi, and (CH2)5CO (0.37 mL, 3.5 mmol,
2 h) to yield 13ap (0.225 g, 0.637 mmol, 64%) as a white
solid, mp 159°C (Et2O–PE). HRMS calcd. for C22H27NO3
(353.45): 353.1991; found: 353.1983. IR (KBr) ꢀ (cm–1):
3444, 3308, 1722, 1534, 785, 757, 699. 1H NMR (300 MHz)
3J = 6.5 Hz, 6H), 3.12 (s, 1H), 3.66 (m, 1H), 4.65 (d, 1H),
6.04 (s, 1H), 7.18–7.47 (m, 13H). 13C NMR (75 MHz) d:
22.5, 43.4, 70.3, 126.3, 126.4, 127.1, 127.3, 128.1, 128.1,
128.3, 129.1, 130.2, 136.0, 137.9, 138.0, 142.6, 145.7,
154.1. Anal. calcd. for C23H23NO3 (361.44): C 76.43,
H 6.41, N 3.88; found: C 76.26, H 6.27, N 3.71.
3
d: 0.90 (d, J = 6.4 Hz, 6H), 1.53–2.08 (m, 10H), 2.38 (s,
O-3-(1-Hydroxy-2-methylpropyl)-2-biphenylyl N-isopropyl-
carbamate (13al): Reaction of 10a (0.255 g) with TMSOTf
(1.05 mmol), n-BuLi, and i-PrCHO (0.32 mL, 3.5 mmol,
2 h) yielded 13al (0.279 g, 0.853 mmol, 85%) as a white
solid, mp 88°C (Et2O–PE). HRMS calcd. for C20H25NO3
(327.18): 327.1834; found: 327.1831. IR (KBr) ꢀ (cm–1):
3498, 3307, 1720, 1546, 788, 772, 709. 1H NMR (300 MHz)
1H), 3.52 (m, 1H), 4.65 (d, 1H), 7.21–7.42 (m, 7H), 7.49–
7.57 (m, 1H). 13C NMR (75 MHz) d: 22.1, 22.5, 25.7, 37.2,
43.2, 73.1, 125.8, 126.0, 127.1, 128.0, 129.4, 129.9, 137.5,
138.4, 141.2, 146.0, 153.0.
O-2-Trimethylsilylphenyl N-isopropylcarbamate (13ba): 10b
(0.179 g) was protected with TMSOTf (1.05 mmol) and the
lower phase was removed via a syringe. Reaction with n-
BuLi (1.20 mmol) and TMSCl (0.20 mL, 1.5 mmol, 1 h) af-
forded 13ba (0.207 g, 0.823 mmol, 82%) as a white solid,
mp 92°C (Et2O–PE). IR (KBr) ꢀ (cm–1): 3329, 1703, 1532,
3
3
d: 0.81/1.08 (d, J = 6.7 Hz, 6H), 0.99/1.05 (d, J = 6.5 Hz,
3
6H), 2.09 (m, 1H), 2.42 (s, 1H), 3.67 (m, 1H), 4.47 (d, J =
7.9 Hz, 1H), 4.66 (d, 1H), 7.23–7.40 (m, 7H), 7.48 (dd, 1H).
13C NMR (75 MHz) d: 18.7/19.4, 22.6, 33.5, 43.3, 74.2,
126.1, 127.0, 127.2, 128.1, 129.1, 129.7, 135.8, 137.5,
138.2, 145.6, 153.9. Anal. calcd.: C 76.29, H 7.47, N 4.94;
found: C 76.11, H 7.17, N 4.85.
1
3
841, 736. H NMR (300 MHz) d: 0.28 (s, 9H), 1.24 (d, J =
6.4 Hz, 6H), 3.91 (m, 1H), 4.77 (s, 1H), 7.09–7.20 (m, 2H),
7.34–7.46 (m, 2H). 13C NMR (75 MHz) d: –0.9, 22.9, 43.4,
122.2, 124.9, 130.3, 131.6, 134.8, 153.8, 155.7. Anal. calcd.
for C13H21NO2Si (251.40): C 62.11, H 8.42, N 5.57; found:
C 62.01, H 8.63, N 5.21.
O-3-(Hydroxydiphenylmethyl)-2-biphenylyl N-isopropylcarba-
mate (13am): Reaction of 10a (0.255 g) with TMSOTf
(1.05 mmol), n-BuLi, and Ph2CO (0.456 g in 3 mL of Et2O,
2.5 mmol, 1 h) afforded 13am (0.370 g, 0.846 mmol, 85%)
as a white solid, mp 150°C dec (Et2O–PE). IR (KBr) ꢀ (cm–1):
3589, 3409, 1738, 1513, 780, 752, 699. 1H NMR
O-2-Tributylstannylphenyl N-isopropylcarbamate (13bb):
Reaction of 10b (0.179 g) with TMSOTf (1.10 mmol), s-
BuLi, and Bu3SnCl (0.68 mL, 2.5 mmol, 1 h) gave 13bb
(0.396 g, 0.846 mmol, 85%) as a colourless oil. IR (film) ꢀ
3
(300 MHz) d: 0.74 (d, J = 6.5 Hz, 6H), 3.24 (m, 1H), 4.10
1
(d, 1H), 4.54 (s, 1H), 6.77 (dd, 1H), 7.13 (t, 1H), 7.17–7.45
(cm–1): 3335, 1716, 1532, 736. H NMR (300 MHz) d: 0.88
(m, 16H). 13C NMR (75 MHz) d: 22.2, 43.0, 81.1, 125.2,
(t, 3J = 7.4 Hz, 9H), 1.07 (t, 3J = 8.2 Hz, 6H), 1.24 (d, J =
3
© 2001 NRC Canada

Kauch and Hoppe
1743
6.8, Hz, 6H), 1.26–1.38 (m, 6H), 1.47–1.58 (m, 6H), 3.91
(m, 1H), 4.67 (s, 1H), 7.13–7.18 (m, 2H), 7.28–7.34 (m,
1H), 7.40–7.43 (m, 1H). 13C NMR (75 MHz) d: 9.8, 13.6,
23.0, 27.3, 29.1, 43.3, 121.4, 125.0, 129.4, 133.6, 136.9,
153.8, 156.1. Anal. calcd. for C22H39NO2Sn (468.25):
C 56.43, H 8.39, N 2.99; found: C 56.62, H 8.55, N 3.07.
6.6 Hz, 6H), 1.25–1.40 (m, 6H), 1.46–1.59 (m, 6H), 3.90
(m, 1H), 4.83 (d, 1H), 7.11 (t, 1H), 7.30 (dd, 1H), 7.34 (dd,
1H). 13C NMR (75 MHz) d: 10.0, 13.6, 22.9, 27.3, 29.0,
43.5, 126.6, 127.6, 130.4, 135.1, 137.9, 151.6, 152.6. Anal.
calcd. for C22H37ClNO2Sn (502.70): C 52.27, H 7.62,
N 2.79; found: C 52.68, H 7.91, N 2.82.
O-2-Methylphenyl N-isopropylcarbamate (13bc) (16): 10b
(0.179 g) reacted with TMSOTf (1.10 mmol), s-BuLi, and
MeI (0.20 mL, 2.5 mmol, 1 h) to give 13bc (0.160 g,
0.827 mmol, 83%) as a white solid, mp 57°C (Et2O–PE) (lit.
(16) mp 48 to 49°C). IR (KBr) ꢀ (cm–1): 3301, 1705, 1545,
O-2-Chloro-6-iodophenyl N-isopropylcarbamate (13cc):
10c (0.214 g) reacted with TMSOTf (1.05 mmol), n-BuLi,
and I2 (0.761 g in 3 mL of Et2O, 3.0 mmol, 1 h) to yield
13cc (0.291 g, 0.857 mmol, 86%) as a white solid, mp
118°C (Et2O–PE). IR (KBr) ꢀ (cm–1): 3303, 1726, 1530,
774. 1H NMR (300 MHz) d: 1.27 (d, 3J = 6.5 Hz, 6H), 3.92
(m, 1H), 5.02 (s, 1H), 6.88 (t, 1H), 7.39 (dd, 1H), 7.69 (dd,
1H). 13C NMR (75 MHz) d: 22.8, 43.8, 92.9, 127.9, 130.3,
137.5, 147.8, 151.2, 152.4. Anal. calcd. for C10H11ClINO2
(339.56): C 35.37, H 3.27, N 4.12; found: C 35.51, H 3.49,
N 4.01.
3
730. 1H NMR (300 MHz) d: 1.23 (d, J = 6.5 Hz, 6H), 2.21
(s, 3H), 3.89 (m, 1H), 4.86 (s, 1H), 6.99–7.22 (m, 4H). 13C
NMR (75 MHz) d: 16.0, 22.9, 43.4, 122.2, 125.5, 126.7,
130.6, 130.9, 149.6, 153.6. Anal. calcd. for C11H15NO2
(193.25): C 68.37, H 7.82, N 7.25; found: C 68.77, H 7.96,
N 7.39.
O-2-(Hydroxyphenylmethyl)phenyl N-isopropylcarbamate
(13bd): Reaction of 10b (0.179 g), with TMSOTf
(1.10 mmol), s-BuLi, and PhCHO (0.26 mL, 2.5 mmol, 1 h)
furnished 13bd (0.230 g, 0.806 mmol, 81%) as a white
solid, mp 100°C (Et2O–PE). IR (KBr) ꢀ (cm–1): 3423, 3359,
1714, 1519, 756, 744, 705. 1H NMR (300 MHz) d: 1.19/1.20
O-2-Chloro-6-(phenylsulfanyl)phenyl N-isopropylcarbamate
(13cd): Reaction of 10c (0.214 g) with TMSOTf
(1.05 mmol), n-BuLi, and (PhS)2 (0.546 g in 3 mL of Et2O,
2.5 mmol, 1 h) gave 13cd (0.276 g, 0.858 mmol, 86%) as a
white solid, mp 113°C (Et2O–PE). IR (KBr) ꢀ (cm–1): 3270,
1
1729, 1537, 786, 751, 689. H NMR (300 MHz) d: 1.24 (d,
3
(d, J = 6.5 Hz, 6H), 2.91 (s, 1H), 3.82 (m, 1H), 4.81 (s,
3J = 6.4 Hz, 6H), 3.89 (m, 1H), 4.94 (s, 1H), 6.95–7.06 (m,
2H), 7.20–7.44 (m, 6H). 13C NMR (75 MHz) d: 22.8, 43.8,
126.7, 127.9, 128.4, 129.0, 129.4, 129.6, 132.6, 133.5,
135.4, 145.4, 151.7. Anal. calcd. for C16H16ClNO2S
(321.83): C 59.71, H 5.01, N 4.35; found: C 59.98, H 5.18,
N 4.44.
1H), 5.99 (s, 1H), 7.09 (dd, 1H), 7.14–7.40 (m, 8H). 13C
NMR (75 MHz) d: 22.7, 43.5, 70.5, 122.6, 126.0, 126.3,
127.2, 128.2, 128.7, 128.7, 136.5, 142.7, 148.3, 154.0. Anal.
calcd. for C17H19NO3 (285.34): C 71.56, H 6.71, N 4.91;
found: C 71.45, H 6.61, N 4.89.
O-2-(Hydroxydiphenylmethyl)phenyl N-isopropylcarbamate
(13be): Reaction of 10b (0.179 g) with TMSOTf
(1.05 mmol), n-BuLi, and Ph2CO (0.456 g in 3 mL of Et2O,
2.5 mmol, 1 h) afforded 13be (0.302g, 0.836 mmol, 84%) as
a white solid, mp 115°C (Et2O–PE). IR (KBr) ꢀ (cm–1):
O-2-Chloro-6-methylphenyl N-isopropylcarbamate (13ce):
Reaction of 10c (0.214 g) with TMSOTf (1.05 mmol), n-
BuLi, and MeI (0.20 mL, 2.5 mmol, 1 h) afforded 13ce
(0.204 g, 0.895 mmol, 90%) as a white solid, mp 94°C
1
(Et2O–PE). IR (KBr) ꢀ (cm–1): 3282, 1708, 1535, 771. H
1
3
3535, 3349, 1752, 1522, 766, 704. H NMR (300 MHz) d:
NMR (300 MHz) d: 1.24 (d, J = 6.7 Hz, 6H), 2.23 (s, 6H),
3
0.95 (d, J = 6.4 Hz, 6H), 3.52 (m, 1H), 4.14 (s, 1H), 4.25
3.89 (m, 1H), 4.96 (s, 1H), 6.86–7.09 (m, 3H). 13C NMR
(75 MHz) d: 16.3, 22.7, 43.5, 126.0, 127.5, 128.0, 129.1,
133.5, 145.8, 152.3. Anal. calcd. for C11H14ClNO2 (227.89):
C 58.03, H 6.20, N 6.15; found: C 57.98, H 6.29, N 6.00.
(d, 1H), 6.73 (dd, 1H), 6.99–7.08 (m, 1H), 7.18–7.36 (m,
12H). 13C NMR (75 MHz) d: 22.5, 43.3, 81.0, 124.3, 124.8,
127.0, 127.4, 127.9, 128.8, 130.2, 138.9, 146.1, 149.0,
152.3. Anal. calcd. for C23H23NO3 (361.44): C 76.43,
H 6.41, N 3.88; found: C 76.21, H 6.54, N 3.80.
O-2-Chloro-6-(hydroxyphenylmethyl)phenyl N-isopropylcarba-
mate (13cf): Reaction of 10c (0.214 g) with TMSOTf
(1.05 mmol), n-BuLi, and PhCHO (0.26 mL, 2.5 mmol, 1 h)
afforded 13cf (0.270 g, 0.844 mmol, 84%) as a white solid,
mp 125°C (Et2O–PE). IR (KBr) ꢀ (cm–1): 3429, 3257, 1731,
O-2-Chloro-6-trimethylsilylphenyl N-isopropylcarbamate
(13ca): Reaction of 10c (0.214 g) with TMSOTf
(1.05 mmol), n-BuLi, and TMSCl (0.32 mL, 2.5 mmol, 1 h)
gave 13ca (0.260 g, 0.910 mmol, 91%) as a white solid, mp
102°C (Et2O–PE). IR (KBr) ꢀ (cm–1): 3310, 1714, 1532,
1
1529, 775, 758, 703. H NMR (300 MHz) d: 1.21/1.22 (d,
3J = 6.4 Hz, 6H), 3.11 (s, 1H), 3.84 (m, 1H), 5.05 (d, 1H),
5.97 (s, 1H), 7.13 (t, 1H), 7.20–7.39 (m, 7H). 13C NMR
(75 MHz) d: 22.7, 43.8, 70.6, 126.4, 126.9, 127.1, 127.4,
128.3, 129.4, 139.6, 142.1, 142.1, 144.8, 152.9. Anal. calcd.
for C17H18ClNO3 (319.79): C 63.85, H 5.67, N 4.38; found:
C 63.60, H 5.89, N 4.26.
3
844, 753. 1H NMR (300 MHz) d: 0.28 (s, 9H), 1.24 (d, J =
6.7 Hz, 6H), 3.91 (m, 1H), 4.92 (s, 1H), 7.14 (t, 1H), 7.33
(dd, 1H), 7.41 (dd, 1H). 13C NMR (75 MHz) d: –0.9, 22.9,
43.6, 126.4, 128.0, 131.2, 133.1, 135.4, 151.3, 152.5. Anal.
calcd. for C13H20ClNO2Si (285.84): C 54.62, H 7.05, N
4.90; found: C 54.67, H 7.16, N 5.00.
O-2-Chloro-6-(hydroxydiphenylmethyl)phenyl N-isopropylcarb-
amate (13cg): Reaction of 10c (0.214 g) with TMSOTf
(1.05 mmol), n-BuLi, and Ph2CO (0.456 g in 3 mL of Et2O,
2.5 mmol, 1 h) provided 13cg (0.325 g, 0.821 mmol, 82%)
as a white solid, mp 82°C (Et2O–PE). IR (KBr) ꢀ (cm–1):
3425, 3346, 1727, 1523, 774, 735, 700. 1H NMR (300 MHz)
O-2-Tributylstannyl-6-chlorophenyl N-isopropylcarbamate
(13cb): Reaction of 10c (0.214 g) with TMSOTf
(1.05 mmol), n-BuLi, and Bu3SnCl (0.68 mL, 2.5 mmol,
1 h) afforded 13cb (0.439 g, 0.873 mmol, 87%) as a colour-
1
less oil. IR (film) ꢀ (cm–1): 3336, 1723, 1521, 773. H NMR
3
3
(300 MHz) d: 0.89 (t, 9H), 1.04–1.14 (m, 6H), 1.30 (d, J =
d: 1.03 (d, J = 6.5 Hz, 6H), 3.59 (m, 1H), 4.25 (s, 1H), 4.51
© 2001 NRC Canada

1744
Can. J. Chem. Vol. 79, 2001
(d, 1H), 6.65–6.73 (m, 1H), 7.00 (t, 1H), 7.17–7.43 (m,
11H). 13C NMR (75 MHz) d: 22.5, 43.6, 81.0, 125.7, 127.1,
127.4, 127.7, 127.8, 128.1, 129.0, 130.0, 142.2, 145.6,
151.5. Anal. calcd. for C23H22ClNO3 (395.89): C 69.78,
H 5.60, N 3.54; found: C 69.65, H 5.77, N 3.23.
a white solid, mp 117°C dec (Et2O–PE). IR (KBr) ꢀ (cm–1):
3411, 3343, 1706, 1525, 765, 746, 711. 1H NMR (300 MHz)
d: 1.05 (d, 3J = 6.5 Hz, 6H), 3.61 (m, 1H), 4.51 (d, 1H), 4.58
(s, 1H), 6.97 (d, 1H), 7.18–7.33 (m, 6H), 7.40–7.52 (m, 6H),
7.57 (d, 1H), 7.73–7.84 (m, 2H). 13C NMR (75 MHz) d:
22.6, 43.5, 80.9, 121.9, 125.3, 126.6, 126.6, 126.8, 127.3,
127.7, 127.8, 128.8, 129.8, 134.3, 135.8, 144.5, 146.6,
153.5. Anal. calcd. for C27H25NO3 (411.49): C 78.81, H
6.12, N 3.40; found: C 78.53, H 5.99, N 3.21.
O-2-Trimethylsilyl-1-naphthyl N-isopropylcarbamate (16a):
Reaction of 15 (0.229 g) with TMSOTf (1.10 mmol), s-
BuLi, and TMSCl (0.32 mL, 2.5 mmol, 1 h) gave 16a
(0.273 g, 0.906 mmol, 91%) as a white solid, mp 185°C
(Et2O–PE). IR (KBr) ꢀ (cm–1): 3348, 1710, 1532, 848, 762.
General procedure for deprotection of N-isopropylcarbamates
13a and 13c
3
1H NMR (300 MHz) d: 0.36 (s, 9H), 1.27 (d, J = 6.3 Hz,
6H), 3.95 (m, 1H), 5.02 (s, 1H), 7.44–7.59 (m, 3H), 7.68–
7.83 (m, 3H). 13C NMR (75 MHz) d: –0.7, 23.0, 43.5, 121.5,
125.4, 126.3, 126.5, 127.6, 127.8, 128.4, 130.2, 135.5,
152.1, 153.9. Anal. calcd. for C17H23NO2Si (301.46):
C 67.73, H 7.69, N 4.65; found: C 67.40, H 7.58, N 4.62.
To a solution of the N-isopropylcarbamate 13 (0.50 mmol)
in EtOH (5 mL) under Ar in a flask was added at rt 2 M
NaOH (1.0 mL, 2.0 mmol, 4.0 equiv). The resulting reaction
mixture was stirred for 2 h. Then, 2 mL of 2 M HCl and
10 mL of Et2O were added, the phases were separated, and
the aqueous layer was extracted with Et2O (3 × 10 mL). The
combined organic phases were washed with saturated NaCl
solution (5 mL), dried over MgSO4, and filtered. Evapora-
tion of the solvents provided the crude product. Flash chro-
matography on silica gel (Et2O–PE mixtures) afforded the
free phenol 14.
O-2-Tributylstannyl-1-naphthyl N-isopropylcarbamate (16b):
Reaction of 15 (0.229 g) with TMSOTf (1.10 mmol), s-
BuLi, and Bu3SnCl (0.68 mL, 2.5 mmol, 1 h) afforded 16b
(0.438 g, 0.845 mmol, 85%) as a white solid, mp 80°C
(Et2O–PE). IR (KBr) ꢀ (cm–1): 3305, 1703, 1525, 814, 744.
1H NMR (300 MHz) d: 0.89 (t, 3J = 7.3 Hz, 9H), 1.11–1.19
3
(m, 6H), 1.28 (d, J = 6.5, Hz, 6H), 1.27–1.41 (m, 6H),
2-Hydroxy-3-trimethylsilylbiphenyl (14aa): 13aa (0.164 g)
was deprotected to yield 14aa (0.120 g, 0.495 mmol, 99%) as
a colourless oil, which solidifies after a few days to give a
white solid, mp 39°C (Et2O–PE). IR (KBr) ꢀ (cm–1): 3531,
841, 763, 708. 1H NMR (300 MHz) d: 0.32 (s, 9H), 5.39 (s,
1H), 6.98 (t, 1H), 7.21–7.24 (m, 1H), 7.35–7.52 (m, 6H). 13C
NMR (75 MHz) d: –0.9, 120.4, 125.8, 127.2, 127.9, 129.2,
129.5, 131.3, 134.8, 137.3, 157.0. Anal. calcd. for C15H18OSi
(242.39): C 74.33, H 7.48; found: C 74.39, H 7.72.
1.48–1.63 (m, 6H), 3.94 (m, 1H), 4.93 (d, 1H), 7.39–7.52
(m, 3H), 7.63–7.84 (m, 3H). 13C NMR (75 MHz) d: 9.9,
13.7, 23.1, 27.4, 29.1, 43.5, 121.4, 125.5, 126.0, 126.2,
127.5, 127.9, 131.4, 132.5, 135.2, 152.2, 154.0. Anal. calcd.
for C26H41NO2Sn (518.32): C 60.25, H 7.97, N 2.70; found:
C 60.20, H 8.04, N 2.51.
O-2-Methyl-1-naphthyl N-isopropylcarbamate (16c): Reaction
of 15 (0.229 g) with TMSOTf (1.10 mmol), s-BuLi, and MeI
(0.20 mL, 2.5 mmol, 1 h) afforded 16c (0.209 g,
0.860 mmol, 86%) as a white solid, mp 129°C (Et2O–PE).
2-Hydroxy-3-iodobiphenyl (14ab): 13ac (0.191 g) was depro-
tected to give 14ab (0.145 g, 0.490 mmol, 98%) as a white
solid, mp 42°C (Et2O–PE). IR (KBr) ꢀ (cm–1): 3452, 756,
735, 700. 1H NMR (300 MHz) d: 5.54 (s, 1H), 6.74 (t, 1H),
7.21–7.25 (m, 1H), 7.34–7.50 (m, 5H), 7.67 (dd, 1H). 13C
NMR (75 MHz) d: 85.8, 122.5, 128.0, 128.8, 129.1, 129.1,
131.0, 137.3, 138.1, 151.6. Anal. calcd. for C12H9IO
(296.10): C 48.68, H 3.06; found: C 48.75, H 3.18.
1
IR (KBr) ꢀ (cm–1): 3286, 1705, 1538, 818, 770, 747. H
3
NMR (300 MHz) d: 1.22 (d, J = 6.4 Hz, 6H), 2.36 (s, 3H),
3.91 (m, 1H), 5.09 (s, 1H), 7.30 (d, 1H), 7.36–7.50 (m, 2H),
7.62 (d, 1H), 7.74–7.87 (m, 2H). 13C NMR (75 MHz) d:
16.2, 22.8, 43.5, 120.9, 125.3, 125.4, 126.3, 127.2, 127.7,
128.1, 128.7, 132.2, 144.3, 153.3. Anal. calcd. for
C15H17NO2 (243.13): C 74.05, H 7.04, N 5.76; found:
C 73.82, H 7.07, N 5.51.
3-Bromo-2-hydroxybiphenyl (14ac) (17): 13ad (0.167 g) was
deprotected to yield 14ac (0.123 g, 0.494 mmol, 99%) as a
white solid, mp 59°C (Et2O–PE) (lit. (17) mp 38 to 39°C). IR
(KBr) ꢀ (cm–1): 3498, 759, 733, 701. 1H NMR (300 MHz) d:
5.65 (s, 1H), 6.87 (t, 1H), 7.22–7.26 (m, 1H), 7.33–7.54 (m,
6H). 13C NMR (75 MHz) d: 111.0, 121.7, 127.8, 128.5, 129.2,
129.7, 130.1, 131.5, 137.2, 149.3. Anal. calcd. for C12H9BrO
(249.10): C 57.86, H 3.64; found: C 58.08, H 3.46.
O-2-(Hydroxyphenylmethyl)-1-naphthyl N-isopropylcarba-
mate (16d): 15 (0.229 g) reacted with TMSOTf
(1.10 mmol), s-BuLi, and PhCHO (0.26 mL, 2.5 mmol, 1 h)
to give 16d (0.277 g, 0.826 mmol, 83%) as a white solid, mp
174°C dec (Et2O–PE). IR (KBr) ꢀ (cm–1): 3564, 3310, 1698,
1
1533, 757, 727, 700. H NMR (300 MHz) d: 1.29/1.28 (d,
3J = 6.4 Hz, 6H), 3.16 (s, 1H), 3.93 (m, 1H), 5.18 (d, 1H),
6.20 (s, 1H), 7.20–7.38 (m, 4H), 7.39–7.56 (m, 4H), 7.67 (d,
1H), 7.77–7.84 (m, 1H), 7.87–7.94 (m, 1H). 13C NMR
(75 MHz) d: 22.8, 43.9, 69.8, 121.5, 125.7, 126.3, 126.4,
126.5, 126.7, 127.1, 127.8, 127.9, 128.2, 133.2, 134.2,
142.5, 143.7, 154.4. Anal. calcd. for C21H21NO3 (335.40): C
75.20, H 6.31, N 4.18; found: C 75.10, H 6.01, N 3.88.
2-Hydroxy-3-phenylsulfanylbiphenyl (14ad): Deprotection of
13af (0.182 g) gave 14ad (0.138 g, 0.496 mmol, 99%) as a
colourless oil, which solidifies after a few days to give a
white solid, mp 71°C (Et2O–PE). HRMS calcd. for
C18H14OS (278.37): 278.0765; found: 278.0759. IR (KBr) ꢀ
1
O-2-(Hydroxydiphenylmethyl)-1-naphthyl N-isopropylcarba-
mate (16e): Reaction of 15 (0.229 g) with TMSOTf
(1.05 mmol), n-BuLi, and Ph2CO (0.456 g in 3 mL of Et2O,
2.5 mmol, 1 h) afforded 16e (0.357 g, 0.868 mmol, 87%) as
(cm–1): 3394, 761, 741, 701, 690. H NMR (300 MHz) d:
6.67 (s, 1H), 6.92 (t, 1H), 7.03–7.54 (m, 12H). 13C NMR
(75 MHz) d: 117.7, 121.1, 126.4, 127.4, 127.5, 127.6, 128.2,
128.9, 129.2, 133.0, 135.6, 135.7, 137.6, 154.0.
© 2001 NRC Canada

Kauch and Hoppe
1745
2-Hydroxy-3-(hydroxydiphenylmethyl)biphenyl (14ae):
13am (0.219 g) was deprotected to yield 14ae (0.169 g,
0.480 mmol, 96%) as a colourless oil, which solidifies after
a few days to give a white solid, mp 129°C dec (Et2O–PE).
IR (KBr) ꢀ (cm–1): 3471, 803, 760, 701. 1H NMR (300 MHz)
d: 4.17 (s, 1H), 6.52 (dd, 1H), 6.80 (t, 1H), 7.22–7.52 (m,
17H). 13C NMR (75 MHz) d: 83.9, 119.3, 127.4, 127.7,
127.8, 128.1, 128.5, 129.5, 129.7, 129.9, 130.5, 131.4,
137.6, 145.4, 152.1. Anal. calcd. for C25H20O2 (352.43):
C 85.20, H 5.72; found: C 84.85, H 5.50.
158.9, 169.5. Anal. calcd. for C16H17NO2 (255.32): C 75.27,
H 6.71, N 5.49; found: C 75.37, H 6.79, N 5.35.
Conclusions
In summary, we found a simple protocol for the electro-
philic ortho-substitution of phenols. The in situ generated N-
alkyl-N-silylcarbamoyl group serves as a powerful DMG for
lithiation reactions. Several silyl sources could be used for in
situ silyl protection and complete metalation could be
achieved by means of n-BuLi–TMEDA at low temperatures.
The deprotection of the N-monoalkylcarbamates to phenols
proceeds quantitatively under mild basic conditions.
2-Chloro-6-trimethylsilylphenol (14ca): Deprotection of 13ca
(0.143 g, 0.500 mmol) furnished 14ca (0.099 g, 0.493 mmol,
99%) as a colourless liquid. HRMS calcd. for C9H13ClOSi
(200.74): 200.0424; found: 200.0388. IR (film) ꢀ (cm–1):
3539, 842, 759. 1H NMR (300 MHz) d: 0.31 (s, 9H), 5.72 (s,
1H), 6.84 (dd, 1H), 7.25 (dd, 1H), 7.30 (dd, 1H). 13C NMR
(75 MHz) d: –1.1, 119.5, 121.1, 127.1, 129.8, 133.7, 155.3.
Anal. calcd.: C 53.85, H 6.53; found: C 54.14, H 6.71.
Acknowledgements
This work was supported by the Deutsche
Forschungsgemeinschaft, the Fonds der Chemischen
Industrie, and the Alexander von Humboldt foundation.
M.K. gratefully acknowledges a fellowship of the Fonds der
Chemischen Industrie. The authors wish to thank Mr.
Thomas Vatheuer for his engaged work on the O-2-chlorophenyl
carbamate series during his “Staatsexamensarbeit für
Lehramtskandidaten”. M.K. thanks Professor Victor
Snieckus and his group for the warm welcome at Queen’s
University during a collaboration stay.
2-Chloro-6-iodophenol (14cb) (18): 13cc (0.170 g) was
deprotected to yield 14cb (0.119 g, 0.468 mmol, 94%) as a
white solid, mp 59°C (Et2O–PE) (lit. (18) mp 38 to 39°C).
1
IR (KBr) ꢀ (cm–1): 3433, 760. H NMR (300 MHz) d: 5.91
(s, 1H), 6.62 (t, 1H), 7.30 (dd, 1H), 7.61 (dd, 1H). 13C NMR
(75 MHz) d: 83.5, 119.3, 122.8, 129.6, 137.8, 150.9. Anal.
calcd. for C6H4ClI (254.45): C 28.32, H 1.58; found:
C 28.31, H 1.82.
References
2-Chloro-6-phenylsulfanylphenol (14cc): 13cd (0.161 g) was
deprotected to afford 14cc (0.108 g, 0.456 mmol, 91%) as a
white solid, mp 67°C (Et2O–PE). HRMS calcd. for
C12H9ClOS (263.72): 236.0063; found: 236.0051. IR (KBr)
1. (a) V. Snieckus. Chem. Rev. 90, 879 (1990); (b) M. Gray, M.
Tinkl, and V. Snieckus. In Comprehensive organometallic
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Appl. Chem. 71, 1521 (1999).
1
ꢀ (cm–1): 3408, 774, 739, 690. H NMR (300 MHz) d: 6.59
(s, 1H), 6.86 (t, 1H), 7.13–7.30 (m, 5H), 7.32–7.40 (m, 2H).
13C NMR (75 MHz) d: 119.8, 120.8, 121.3, 126.9, 128.5,
129.4, 131.5, 134.1, 134.7, 152.5.
2. S.T. Chadwick, R.A. Rennels, J.L. Rutherford, and D.B.
Collum. J. Am. Chem. Soc. 122, 8640 (2000).
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Brönneke, and F. Lichtenberg. Angew. Chem. Int. Ed. Engl.
20, 1024 (1981); (c) D. Hoppe and A. Brönneke. Synthesis,
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1183 (1999).
N-Isopropyl-2-hydroxybiphenyl-3-carboxamide (12) (19):
10a (0.255 g) was N-trimethylsilyl-protected according to
the general procedure described above. The resulting mixture
was cooled to 0°C and LDA solution (2.50 mmol, 2.50 equiv;
prepared by stirring a 1:1 mixture of diisopropylamine
(0.253 g) and n-BuLi in 2 mL of Et2O at 0°C for 30 min)
was added slowly. The resulting mixture was stirred at 0°C
for 4 h and warmed to rt. After an additional stirring for 2 h,
5 mL of 2 M HCl was added, the phases were separated, and
the aqueous layer was extracted with Et2O (3 × 20 mL). The
combined organic phases were washed with saturated NaCl
solution (10 mL), dried over MgSO4, filtered, and evapo-
rated in vacuo. Purification of the crude product by flash
chromatography on silica gel (Et2O–PE gradient) gave 12
(0.201 g, 0.787 mmol, 79%) as a white solid, along with
13aa (0.052 g, 0.159 mmol, 16%), mp 119°C (Et2O–PE) (lit.
(19) mp 118 to 119°C). IR (KBr) ꢀ (cm–1): 3399, 1642,
1
1585, 1540, 766, 752, 700. H NMR (300 MHz) d: 1.27 (d,
9. D. Hoppe and T. Hense. Angew. Chem. Int. Ed. Engl. 36, 2282
(1997), and refs. cited therein.
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