Substitution of hydroxybiaryls via directed ortho-lithiation of N-silylated O-aryl N-isopropylcarbamates

Article abstract of DOI:10.1021/jo0506938

Herein we report regioselective substitution reactions of a series of 2- and 3-hydroxybiaryls including BINOL via a new directed ortho-metalation procedure. O-Aryl N-isopropylcarbamates, conveniently prepared from phenols and isopropyl isocyanate, are tem

Full text of DOI:10.1021/jo0506938

Substitution of Hydroxybiaryls via Directed ortho-Lithiation of
N-Silylated O-Aryl N-Isopropylcarbamates
Matthias Kauch,† Victor Snieckus,‡ and Dieter Hoppe*,†
Westfa¨lische Wilhelms-Universita¨t Mu¨nster, Organisch-Chemisches Institut, Corrensstrasse 40,
D-48149 Mu¨nster, Germany, and Queen’s University, Department of Chemistry, Kingston,
Ontario, K7L 3N6, Canada
dhoppe@uni-muenster.de
Received April 7, 2005
Herein we report regioselective substitution reactions of a series of 2- and 3-hydroxybiaryls including
BINOL via a new directed ortho-metalation procedure. O-Aryl N-isopropylcarbamates, conveniently
prepared from phenols and isopropyl isocyanate, are temporarily and in situ N-protected by means
of silyl triflates to form stable intermediates for low temperature lithiation reactions using
butyllithium/TMEDA in diethyl ether. The resulting aryllithiums are efficiently substituted by a
wide range of electrophilic reagents to afford functionalized biaryls in high yields. N-Desilylation
already occurs during aqueous workup. The following deprotection of the urethanes to the
corresponding phenols proceeds rapidly and in quantitative yields. Even sensitive substituents (e.g.,
CO2Me, CHO, SiMe3, I) in the products are preserved under mild alkaline conditions which have
been established for carbamate ester cleavage. Furthermore, applications of ortho-substituted
products in common cross-coupling reactions for further C-C bond formations are demonstrated.
Introduction
1).4 Frequently, migration of the carbamoyl group in the
ortho-lithiated intermediate (“anionic ortho-Fries rear-
rangement”)4 complicates efficient quench with electro-
philes,5 although the migration reaction is useful in its
own right.1b,6 In addition, harsh conditions which are
required for liberating the free hydroxyl group under
basic conditions have to be taken into account.7 To
The Directed ortho-Metalation (DoM reaction) allows
the efficient introduction of substituents into aromatic
and heteroaromatic substrates adjacent to a Lewis-basic
substituent via preceding coordination and regioselective
deprotonation.1 For phenols, besides the weakly directing
methoxy group2 and the modest but synthetically useful
methoxymethoxy group (MOM),3 the very powerful N,N-
diethyl O-carbamoyl-directed metalation group (DMG)
was introduced in 1983 by Sibi and Snieckus (Scheme
(3) Christensen, H. Synth. Commun. 1975, 5, 65-78. For further
examples, see ref 2.
(4) Sibi, M. P.; Snieckus, V. J. Org. Chem. 1983, 48, 1935-1937.
(5) Side product formation by this rearrangement may be avoided
in certain cases by using lower reaction temperatures; for an example,
see: (a) Wang, W.; Snieckus, V. J. Org. Chem. 1992, 57, 424-426. (b)
van Doorn, A. R.; Bos, M.; Harkema, S.; van Eerden, J.; Verboom, W.;
Reinhoudt, D. N. J. Org. Chem. 1991, 56, 2371-2380.
† Westfa¨lische Wilhelms-Universita¨t Mu¨nster.
‡ Queen’s University.
(1) For reviews, see: (a) Snieckus, V. Chem. Rev. 1990, 90, 879-
933. (b) Hartung, C. G.; Snieckus, V. In Modern Arene Chemistry;
Astruc, D., Ed.; Wiley-VCH: Weinheim, Germany, 2002; pp 330-367.
(c) Clayden, J. In The Chemistry of Organolithium Compounds;
Rappoport, Z., Marek, I., Eds.; Wiley: Chichester, U.K., 2004; pp 495-
646. For mechanistic aspects, especially related to the influence of the
Complex Induced Proximity Effect (CIPE), see: (d) Whisler, M. C.;
MacNeil, S.; Snieckus, V.; Beak, P. Angew. Chem., Int. Ed. 2004, 43,
2206-2225.
(6) For synthetic applications of the anionic ortho-Fries rearrange-
ment and other O f C carbamoyl transfer reactions, see ref 5a and:
(a) Kalinin, A. V.; Miah, M. A. J.; Chattopadhyay, S.; Tsukazaki, M.;
Wicki, M.; Nguen, T.; Coelho, A. L.; Kerr, M.; Snieckus, V. Synlett 1997,
839-841. (b) Mohri, S.-i.; Stefinovic, M.; Snieckus, V. J. Org. Chem.
1997, 62, 7072-7073. (c) Kalinin, A. V.; da Silva, A. J. M.; Lopes, C.
C.; Lopes, R. S. C.; Snieckus, V. Tetrahedron Lett. 1998, 39, 4995-
4998. (d) Kalinin, A. V.; Snieckus, V. Tetrahedron Lett. 1998, 39, 4999-
5002. (e) Chauder, B. A.; Kalinin, A. V.; Taylor, N. J.; Snieckus, V.
Angew. Chem., Int. Ed. 1999, 38, 1435-1438. (f) Reed, M. A.; Chang,
M. T.; Snieckus, V. Org. Lett. 2004, 6, 2297-2300.
(2) For tabulated lists, see: (a) Gschwend, H. W.; Rodriguez, H. R.
Org. React. 1979, 26, 1-360. (b) Schlosser, M. In Organometallics in
Synthesis, 2nd ed.; Schlosser, M., Ed.; Wiley: Chichester, U.K., 2002;
pp 1-352. See also ref 1c.
10.1021/jo0506938 CCC: $30.25 © 2005 American Chemical Society
Published on Web 07/28/2005
J. Org. Chem. 2005, 70, 7149-7158
7149

Kauch et al.
SCHEME 1. Substitution of Phenols by the
Directed ortho-Lithiation
SCHEME 3. Directed ortho-Lithiation of
O-2-Biphenylyl Carbamate 8
reported,12 in this case, the solution of 3 is directly treated
with 2 equivalents of n- or s-butyllithium/ TMEDA,13 and
the lithium chelate 4 is subsequently trapped by suitable
electrophiles EX. During the aqueous workup, the silyl
group in the initial product 5 is lost and in most cases,
the crystalline urethane 6 is isolated in high yield.
The removal of the carbamoyl group for the formation
of phenol 7 proceeds smoothly and quantitatively by
treatment with aqueous NaOH or solid K2CO3 in ethanol
at room temperature. Herein we report the utilization
of this new method for the regioselective synthesis of
substituted hydroxybiaryls.
SCHEME 2. Directed ortho-Lithiation of in Situ
N-Silylated O-Aryl N-Isopropylcarbamates
Results and Discussion
O-2- and O-3-Biphenylyl N-Isopropylcarbamates.
The directed ortho-lithiation of 8 and subsequent sub-
stitution by some carbo- and hetero-electrophiles have
been reported9 previously to proceed smoothly in high
yield (Scheme 3). In continuation of this study, we find
that reactions with allyl and benzyl bromide proceed only
slowly (Table 1, entries 1 and 2) and require large excess
of the alkylation agent in order to achieve good yields of
9a and 9b. Formation of ketones or esters by use of acid
chlorides (entries 3 and 4) may be followed by further
attack by the aryllithium on the incipient carbonyl group;
hence, use of excess reagent was found to be advanta-
geous. The same was also found in formylation by means
of DMF (entry 5). In this reaction, aldehyde-carbamate
cyclization during workup was observed.14 Boronation by
means of triisopropyl borate proceeded smoothly, but for
facile purification by liquid chromatography, re-esterifi-
cation of the crude arylboronic acid with pinacol to form
the more hydrolytically stable 1,3,2-dioxaborolane 9f was
carried out.15
overcome this deficiency, Snieckus introduced the N-
cumyl-N-methyl O-carbamoyl group, which can be re-
moved under mild acidic conditions.8
Kauch and Hoppe found9 that the N-isopropyl-N-
trimethylsilylcarbamoyl DMG10 provides the following
advantages (Scheme 2): the O-aryl N-isopropylcarbamate
2 is conveniently produced from phenol 1 by treatment
with isopropyl isocyanate.11 Furthermore, steps 2 f 6 of
the standard sequence are carried out in a one-flask
operation, beginning with the reaction of 2 with tri-
methylsilyl triflate in the presence of N,N,N′,N′-tetra-
methylethylenediamine (TMEDA) in diethyl ether to
form the N-silyl derivative 3. Although the isolation and
characterization of similar N-benzyl carbamates has been
In contrast to observations of the analogous N,N-
diethyl carbamate,5 in all reactions of 8 with electro-
(7) The hydrolysis of tertiary N,N-diethyl O-aryl carbamates to
phenols normally requires vigorous basic conditions utilizing NaOH
(MeOH/H2O or ethylene glycol, reflux; see ref 4), LAH (THF, reflux;
see ref 4), or MeLi (Et2O, rt; see ref 24a). Recently, a new method using
Cp2Zr(H)Cl has been developed: Morin, J.; Snieckus, V. Unpublished
results.
(12) (a) Roby, J.; Voyer, N. Tetrahedron Lett. 1997, 38, 191-194.
(b) Barberis, C.; Voyer, N. Synlett 1999, 1106-1108. (c) Barberis, C.;
Voyer, N.; Roby, J.; Che´nard, S.; Tremblay, M.; Labrie, P. Tetrahedron
2001, 57, 2965-2972.
(13) Normally, the salt TMEDA‚HOTf precipitates as an oil, which
solidifies on cooling to -78 °C. Due to its consistency, it undergoes
reaction more slowly than 3 with the alkyllithium reagent. As a result,
even when applying only 1.1 equiv of butyllithium, high yields of 6
are achieved (see ref 9).
(14) The oxazinone byproduct 10 reacted under deprotection condi-
tions C (see Table 2, entry 3) as well as carbamate 9e to the
corresponding salicylic aldehyde 15c, so that a high overall yield was
obtained.
(15) The purification and analysis of organoboronic acids are gener-
ally difficult due to their spontaneous condensation to various degrees
to boroxines; for a discussion of possibilities for their derivatization
and isolation, see: (a) Miyaura, N. In Metal-Catalyzed Cross-Coupling
Reactions, 2nd ed.; de Meijere, A., Diederich, F., Eds.; Wiley-VCH:
Weinheim, Germany, 2004; pp 41-123. See also ref 26c. For a general
review on organoboronic acids and their esters, see: (b) Ko¨ster, R. In
Methoden der Organischen Chemie (Houben-Weyl), 4th ed.; Ko¨ster, R.,
Ed.; Thieme: Stuttgart, Germany, 1982; Vol. 13/3a, pp 489-852.
(8) Metallinos, C.; Nerdinger, S.; Snieckus, V. Org. Lett. 1999, 1,
1183-1186.
(9) Kauch, M.; Hoppe, D. Can. J. Chem. 2001, 79, 1736-1746.
(10) Direct N,C-dilithiation of O-aryl N-monoalkylcarbamates cannot
be achieved due to an irreversible cleavage reaction of the initial formed
N-lithiated intermediate (see ref 9). In contrast to this observation,
the analogues O-allyl and S-allyl carbamates can be converted to the
dianionic species, see: (a) Hanko, R.; Hoppe, D. Angew. Chem., Int.
Ed. Engl. 1981, 20, 127-128. (b) Marr, F.; Fro¨hlich, R.; Hoppe, D. Org.
Lett. 1999, 1, 2081-2083. (c) Marr, F.; Fro¨hlich, R.; Wibbeling, B.;
Diedrich, C.; Hoppe, D. Eur. J. Org. Chem. 2002, 2970-2988.
(11) (a) Petersen, S. In Methoden der Organischen Chemie (Houben-
Weyl), 4th ed.; Mu¨ller, E., Ed.; Thieme: Stuttgart, Germany, 1956;
Vol. VIII, pp 137-149. The N-monoalkylcarbamoyl group has been
used as protecting group for phenols of tyrosine derivatives: (b) Ja¨ger,
G.; Geiger, R.; Siedel, W. Chem. Ber. 1968, 101, 2762-2770.
7150 J. Org. Chem., Vol. 70, No. 18, 2005

Substitution of Hydroxybiaryls by ortho-Lithiation
TABLE 1. Directed ortho-Lithiation and Substitution of O-Biphenylyl N-Isopropylcarbamates 8, 11, and 13
entry
substrate
electrophile EX (equiv)
reaction time
product
E
yield (%)
1
2
3
4
5
6
8
8
8
8
8
8
CH2dCHCH2Br (10)
PhCH2Br (10)
t-BuC(O)Cl (6)
MeOC(O)Cl (6)
DMF (10)
6 h
6 h
1 h
1 h
1 h
2 h
9a
9b
9c
9d
9e
9f
CH2CHdCH2
CH2Ph
C(O)t-Bu
C(O)OMe
CHO
85a
80b
90c
82
77d,e
66f
B(Oi-Pr)3 (4)
7
11
11
11
11
11
11
11
11
13
13
13
Me3SiCl (2.5)
Bu3SnCl (2.5)
ICH2CH2I (2.5)
C2Cl6 (2.5)
PhSSPh (2.5)
MeI (2.5)
1 h
1 h
1 h
1 h
1 h
1 h
1 h
1 h
1 h
1 h
1 h
12a
12b
12c
12d
12e
12f
12g
12h
14a
14b
14c
SiMe3
SnBu3
I
96g (64)h
90g (70)h
89g (64)h
85g
8
9
10
11
12
13
14
15
16
17
Cl
SPh
Me
95g
92g (78)h
88g (74)h
94g (67)h
97g
PhCHO (2.5)
Ph2CO (2.5)
Me3SiCl (2.5)
C2Cl6 (2.5)
CH(OH)Ph
C(OH)Ph2
SiMe3
Cl
94g
MeSSMe (2.5)
SMe
93g
a 2.5 equiv of allyl bromide, 1 h: 63%; see ref 9. b 2.5 equiv of benzyl bromide, 2 h: 75%; see ref 9. c 2.5 equiv of acid chloride, 2 h: 48%.
d 11% of 3,4-dihydro-4-hydroxy-3-isopropyl-8-phenylbenzo[e]-[1,3]-oxazin-2-one (10) was also isolated. e 2.5 equiv of DMF: 35% of 9e and
31% of 10 were isolated. f After re-esterification with pinacol. g TBDMSOTf and s-BuLi/TMEDA were used. h TMSOTf and n-BuLi/TMEDA
were used.
TABLE 2. Deprotection of O-Isopropylcarbamoyl-
SCHEME 4. Directed ortho-Lithiation of
O-3-Biphenylyl Carbamates 11 and 13
Substituted Hydroxybiaryls 9 and 12a
yield
(%)
entry substrate method product R1
R2
15ab OH CH2Ph
15b OH CO2Me
15cb OH CHO
R3
1
2
3
4
5
6
7
8
9b
A
B
C
D
D
C
C
C
H
H
H
98
96
89c
9d
9e
12a
12c
12d
12e
12f
15d
15e
15f
H
H
H
H
H
OH
OH
OH
OH
OH
SiMe3 98
I
99
98
97
99
philes, the carboxamide, which may be formed by com-
peting anionic Fries rearrangement, was not detected;
such products were observed only at elevated tempera-
tures.9
Cl
SPh
Me
15g
15hb
a Conditions A: cyclohexylamine (10 equiv), THF, reflux, 6 h.
Conditions B: Bu4NF (1.5 equiv), THF, rt, 2 h. Conditions C: 2
M NaOH (4 equiv), EtOH, rt, 2 h. Conditions D: K2CO3 (10 equiv),
EtOH, rt, 12 h. b Known compounds, see: refs 18 (for 15a), 5b and
19 (for 15c), and 20 (for 15h). c Crude 9e was used, yield based
on 8.
3-Hydroxybiphenyl (11, H for CbH) was prepared by
Suzuki-Miyaura coupling of 3-bromophenol with phenyl-
boronic acid,16 and converted into the urethane 11 with
isopropyl isocyanate in 96% yield. Application of the
standard sequence (TMSOTf and n-BuLi/TMEDA) in
diethyl ether provided, after trapping with different
electrophiles, the 4-substituted products 12 (Scheme 4,
Table 1, entries 7-14). Although no 2-substituted regio-
isomers were isolated, the yields (64-78%) were unusu-
ally low. Since 3-hydroxybiphenyl was found along with
recovered starting material 11, we suspected that, to
some extent, attack of n-BuLi at the carbamoyl group
was a competitive reaction. Indeed, after having ex-
changed TMSOTf for the bulkier TBDMSOTf and n-BuLi
for s-BuLi, the usual high yields of 12 (85-96%) were
achieved.
the other aryl substituent does not play a contributing
DMG role.
As we have shown previously,9 cleavage of the N-
isopropylcarbamates to form the corresponding phenols
is a very facile process under basic conditions (Scheme
2, Table 2). Surprisingly, the silicophilic tetrabutylam-
monium fluoride is a suitable reagent for decarbamoy-
lation, leaving the methoxycarbonyl group in ester 9d
untouched.
(17) Carbamate 13 was prepared via Suzuki-Miyaura coupling of
1-bromo-3-isopropoxybenzene with (2-methoxy-2,4-dimethylphenyl)-
boronic acid pinacol ester (95%) and subsequent O-deisopropylation
with AlCl3 (94%) and treatment of the resulting phenol with isopropyl
isocyanate (95%). The exact procedure will be published elsewhere,
see ref 22.
(18) Factor, A.; Finkbeiner, H.; Jerussi, R. A.; White, D. M. J. Org.
Chem. 1970, 35, 57-62.
(19) (a) Van Veldhuizen, J. J.; Gillingham, D. G.; Garber, S. B.;
Kataoka, O.; Hoveyda, A. H. J. Am. Chem. Soc. 2003, 125, 12502-
12508. (b) Antonisse, M. M. G.; Snellink-Rue¨l, B. H. M.; Ion, A. C.;
Engbersen, J. F. J.; Reinhoudt, D. N. J. Chem. Soc., Perkin Trans. 2
1999, 1211-1218.
Equally smoothly proceeded the 4-lithio-deprotonation
of the 2′,4′,6′-trisubstituted O-3-biphenylyl carbamate 13
by application of the TBDMS method (Table 1, entries
15-17).17 From these results, we conclude that the 4-H
in 3-hydroxybiphenyls is much more readily removed
than the 2-H, presumably due to steric shielding and that
(16) Bumagin, N. A.; Bykov, V. V. J. Gen. Chem. USSR 1996, 66,
1925-1938.
J. Org. Chem, Vol. 70, No. 18, 2005 7151

Kauch et al.
TABLE 4. Deprotection of Carbamates 17, 19 and 23a
TABLE 3. C2-Lithiation and Silylation of
O-4-Methoxy-3-biphenylyl N-Isopropylcarbamatesa
entry
substrate
R1
R2
product
yield (%)
1
2
3
17
19
23
H
OMe
OMe
H
24a
24b
24c
97
96
98
Me
entry substrate
R1
R2
R3
R4
silane yield (%)
t-Bu
1b
2
16
18
20
22
H
OMe
OMe Me
OMe
H
H
H
Me
H
H
17
19
21
23
80
90
85
91
a Conditions: 2 M NaOH (4 equiv), EtOH, rt, 2 h.
Me
3
i-Pr
4
H
t-Bu t-Bu
SCHEME 5. Bis-silylation of BINOL by Directed
ortho-Lithiation
a Conditions: (i) TBDMSOTf, TMEDA, Et2O; (ii) s-BuLi/TMEDA
(4.0 equiv), -60 °C, 4 h; (iii) TMSCl. b Reaction time: 2 h.
O-4-Methoxy-3-biphenylyl N-Isopropylcarbamates.
To achieve 2-deprotonation of O-3-biphenylyl carbamates,
blocking of the 4-position is necessary. Synthesis of
3-hydroxy-4-methoxybiphenyl (16, H for CbH) was ac-
complished in 81-90% yield by ortho-deprotonation of
commercially available 4-methoxybiphenyl by means of
s-BuLi/TMEDA, boronation with trimethyl borate, fol-
lowed by oxidative workup with H2O2.21 The carbamate
16 was then prepared in 96% yield by the usual treat-
ment with isopropyl isocyanate. The higher substituted
biphenylols, corresponding to carbamates 18 (95%), 20
(85%), and 22 (96%), were prepared by carefully opti-
mized Suzuki-Miyaura protocols.22 By applying the stan-
dard method (TMSOTf and 2 equiv of s-BuLi/TMEDA,
Et2O, -78 °C, 1 h; EX ) Me3SiCl), none or only trace
amounts of the expected silanes 17, 19, 21, or 23 (Table
3) were detected, indicating low reactivity of these
substrates.
However, by applying TBDMSOTf as the N-silylating
reagent, s-BuLi/TMEDA in large excess (4.0 equiv), and
higher reaction temperatures (-60 °C), the resulting
2-silylated biphenyls were isolated in good yields (80-
91%). The urethanes 17, 19, and 23 were cleaved by
aqueous NaOH in ethanol to give the free phenols 24a-c
in nearly quantitative yields (Table 4).
1,1′-Binaphthyl-2,2′-diyl Dicarbamates. 3,3′-Disub-
stituted 2,2′-dihydroxy-1,1′-binaphthyls are frequently
used as chiral ligands in enantioselective catalysis.23 The
possible access, starting from BINOL (25), via didepro-
tonation of the bis(N,N-diethyl O-carbamate), has already
been demonstrated by Snieckus24 and their deprotection
to the corresponding BINOL derivatives was described
for the 3,3′-dimethylated product (10 equiv of MeLi, Et2O,
rt). In the present work, the dicarbamate (R)-26 was
deprotonated after conversion into the N,N′-bis(trimeth-
ylsilyl)diurethane under standard conditions and then
excess trimethylsilyl chloride was added to form (R)-27
in essentially quantitative yield (Scheme 5). Carbamate
cleavage using aqueous NaOH gave the bis-silylated
BINOL derivative (R)-2825 in 99% yield. As expected from
lithiation-electrophile quench reactions of the MOM-
BINOL series,24a all three steps proceeded without race-
mization of the chiral axis.26 The same sequence, car-
bamoylation (93%), bis-silylation (97%), and deprotection
(99%), was performed on racemic material to furnish rac-
28 with comparable high yield. It is quite likely that, in
view of the mild conditions, other electrophiles may also
be introduced into (R)- or (S)-25 with similar efficiency
without racemization.
Pd-catalyzed Cross-coupling Reactions of O-Ha-
loaryl N-Isopropylcarbamates. The combination of
directed ortho-lithiation and cross-coupling reactions
provides a useful synthetic tool for introduction of further
aryl, vinyl, or alkynyl substituents.27 The ortho-metalated
N-isopropylurethanes produced by the method described
above are suitable substrates for Pd-catalyzed coupling
reactions. For instance, the intermediate lithium com-
pound 29 (Scheme 6), after addition of ZnCl2, underwent
smooth Negishi coupling28 with iodobenzene to form
m-terphenyl-2′-yl N-isopropylcarbamate (30). The same
compound is accessible by Stille coupling29 of stannane
9g.9 Furthermore, o-iodoaryl carbamates, as exemplified
(24) (a) Cox, P. J.; Wang, W.; Snieckus, V. Tetrahedron Lett. 1992,
33, 2253-2256. For lithiation reactions of the corresponding biphenyl-
2,2′-diol system, see: (b) Parsons, A. S.; Garcia, J. M.; Snieckus, V. A.
Tetrahedron Lett. 1994, 35, 7537-7540.
(25) (a) Buisman, G. J. H.; van der Veen, L. A.; Klootwijk, A.; de
Lange, W. G. J.; Kamer, P. C. J.; van Leeuwen, P. W. N. M.; Vogt, D.
Organometallics 1997, 16, 2929-2939. For the synthesis of (R)-28, see
also: (b) Maruoka, K.; Itoh, T.; Araki, Y.; Shirasaka, T.; Yamamoto,
H. Bull. Chem. Soc. Jpn. 1988, 61, 2975-2976.
(20) Wessely, F.; Holzer, L.; Vilcsek, H. Monatsh. Chem. 1952, 83,
1253-1273.
(21) (a) Ainley, A. D.; Challenger, F. J. Chem. Soc. 1930, 2171-
2180. For illustration of the boronation-oxidation of aryllithiums to
introduce an OH+ synthon, see: (b) Brandsma, L. In Methoden der
Organischen Chemie (Houben-Weyl), 4th ed.; Hanack, M., Ed.; Thi-
eme: Stuttgart, Germany, 1993; Vol. E19d, pp 369-447. See also ref
1a.
(26) The complete retention of chirality (g99% ee) during the BINOL
substitution was proved by HPLC analysis of (R)-25 and (R)-28, see
Experimental Section.
(27) (a) Chauder, B.; Green, L.; Snieckus, V. Pure Appl. Chem. 1999,
71, 1521-1529. (b) Anctil, E. J.-G.; Snieckus, V. J. Organomet. Chem.
2002, 653, 150-160. (c) Anctil, E. J.-G.; Snieckus, V. In Metal-
Catalyzed Cross-Coupling Reactions, 2nd ed.; de Meijere, A., Diederich,
F., Eds.; Wiley-VCH: Weinheim, Germany, 2004; pp 761-813.
(22) Kauch, M.; Hoppe, D. Synthesis, manuscript in preparation.
(23) For reviews of 1,1′-binaphthyl systems, including BINOL
derivatives, see: (a) Pu, L. Chem. Rev. 1998, 98, 2405-2494. (b) Chen,
Y.; Yekta, S.; Yudin, A. K. Chem. Rev. 2003, 103, 3155-3211.
7152 J. Org. Chem., Vol. 70, No. 18, 2005

Substitution of Hydroxybiaryls by ortho-Lithiation
SCHEME 6. Negishi and Stille Couplings of
Carbamate 8
methods. N-Desilylation already occurs during aqueous
workup. Liberation of the free phenols may be ac-
complished quantitatively under mild basic conditions.
Even highly substituted biphenylols and binaphthols may
be further readily functionalized.
Experimental Section
All reactions were run in flame-dried glassware under an
atmosphere of dry argon using syringe-septum cap techniques.
Et2O was dried extensively over sodium/benzophenone ketyl
and then distilled prior to use. Pentane and TMEDA were
refluxed and distilled from CaH2 before use. The commercial
solution of s-BuLi (1.3 M in cyclohexane/hexane, 92:8) was
filtered using Celite and titrated against diphenylacetic acid;
n-BuLi (1.6 M in hexane), TMSOTf, and TBDMSOTf were used
without further purification. NMR spectra were recorded in
CDCl3 with TMS as the internal reference. Melting points are
uncorrected. For TLC, Merck precoated plates (silica gel 60
F
254) were used. Flash column chromatography (FCC) was
performed on Merck silica gel 60 (0.040-0.063 mm) using
Et2O/PET mixtures; PET ) light petroleum ether, bp 36-46
°C.
SCHEME 7. Heck and Sonogashira Couplings of
Carbamate 31
Directed ortho-Lithiation and Substitution of Carb-
amate 8. General Procedure A: O-3-Allylbiphenyl-2-yl
N-Isopropylcarbamate (9a).9 A solution of carbamate 8
(0.255 g, 1.0 mmol) in 10 mL of Et2O at room temperature
under Ar was sequentially treated with TMEDA (0.128 g, 1.1
mmol) and dropwise with TMSOTf (1.05 mmol, 1.1-1.4 M
solution in pentane), and the reaction mixture was stirred for
30 min. The resulting mixture was cooled to -78 °C and
TMEDA (0.233 g, 2.0 mmol) and s-BuLi (2.0 mmol) were added
consecutively. The yellow solution was stirred for 1 h and
treated with allyl bromide (0.87 mL, 10.0 mmol). After an
additional stirring for 6 h, 0.1 mL of MeOH and 5 mL of 2 M
HCl were added, and the mixture was allowed to warm to room
temperature. The aqueous phase was extracted with Et2O and
the combined organic extracts were washed with saturated
NaHCO3 solution, dried with MgSO4, and concentrated in
vacuo. The crude residue was purified by FCC (Et2O/PET, 1:10
to 1:5) to yield 9a (0.252 g, 0.853 mmol, 85%) as a colorless
solid.
for the parent compound 31 (Scheme 7), behave well in
Heck30 and Sonogashira31 reactions.
Conclusions
Directed ortho-lithiation of simple O-2-biaryl N-iso-
propylcarbamate 8 proceeds smoothly after in situ N-
silylation by means of TMSOTf with n- or s-BuLi/TMEDA
at -78 °C to give 9 in good to excellent yields. O-3-Biaryl
carbamates 11 and 13 are metalated with complete
regioselectivity at the 4-position to afford products 12 and
14. For the removal of the 2-proton in biaryl substrates
16, 18, 20, or 22, higher temperatures (-60 °C) and
excess s-BuLi are required; here N-protection with the
more robust TBDMS-group is essential to obtain good
yields (∼90%) of substituted products 17, 19, 21, and 23.
A wide range of electrophiles may be introduced by these
O-3-Benzylbiphenyl-2-yl N-Isopropylcarbamate (9b).9
According to General Procedure A, reaction of 8 (0.255 g, 1.0
mmol) with TMEDA, TMSOTf, s-BuLi/TMEDA, and benzyl
bromide (1.19 mL, 10.0 mmol, 6 h), and purification of the
crude product (FCC, Et2O/PET, 1:10 to 1:5) gave 9b (0.277 g,
0.802 mmol, 80%) as a colorless solid.
O-3-(2,2-Dimethylpropionyl)biphenyl-2-yl N-Isopro-
pylcarbamate (9c). Following the General Procedure A,
reaction of 8 (0.255 g, 1.0 mmol) with TMEDA, TMSOTf,
s-BuLi/TMEDA, and pivaloyl chloride (0.74 mL, 6.0 mmol, 1
h), and purification of the crude product (FCC, Et2O/PET, 1:5
to 1:2) gave 9c (0.305 g, 0.899 mmol, 90%) as a colorless solid:
mp 118-119 °C; IR (KBr) ν 3333, 3054, 2972, 2931, 1722, 1699,
1533, 1202, 1171, 1029, 974, 940, 783, 763, 706 cm-1; 1H NMR
(300 MHz, CDCl3) δ 0.96 (d, J ) 6.5 Hz, 6H), 1.28 (s, 9H),
(28) For reviews of coupling reactions with organozinc reagents,
see: (a) Negishi, E.-i.; Zeng, X.; Tan, Z.; Qian, M.; Hu, Q.; Huang, Z.
In Metal-Catalyzed Cross-Coupling Reactions, 2nd ed.; de Meijere, A.,
Diederich, F., Eds.; Wiley-VCH: Weinheim, Germany, 2004; pp 815-
889. (b) Erdik, E. Tetrahedron 1992, 48, 9577-9648.
(29) For reviews of the Stille reaction, see: (a) Farina, V.; Krish-
namurthy, V.; Scott, W. J. Org. React. 1997, 50, 1-652. (b) Mitchell,
T. N. In Metal-Catalyzed Cross-Coupling Reactions, 2nd ed.; de Meijere,
A., Diederich, F., Eds.; Wiley-VCH: Weinheim, Germany, 2004; pp
125-161. (c) Fugami, K.; Kosugi, M. Top. Curr. Chem. 2002, 219, 87-
130.
3.57 (m, 1H), 4.61 (br d, 1H, NH), 7.19-7.45 (m, 8H) ppm; 13
C
NMR (75 MHz, CDCl3) δ 22.5 (CH3), 27.4 (CH3), 43.2 (CH),
44.9 (C), 125.0 (CH), 125.3 (CH), 127.4 (CH), 128.2 (CH), 128.9
(CH), 131.4 (CH), 135.4 (C), 136.8 (C), 137.6 (C), 143.9 (C),
152.3 (C), 211.0 (C) ppm; TLC Rf ) 0.33 (Et2O/PET, 1:2). Anal.
Calcd for C21H25NO3: C, 74.31; H, 7.42; N, 4.13. Found: C,
74.21; H, 7.46; N, 4.10.
2-(Isopropylcarbamoyloxy)biphenyl-3-carboxylic Acid
Methyl Ester (9d). Following the General Procedure A,
reaction of 8 (0.255 g, 1.0 mmol) with TMEDA, TMSOTf,
s-BuLi/TMEDA, and methyl chloroformate (0.92 mL, 10.0
mmol, 1 h), and purification of the crude product (FCC, Et2O/
PET, 1:5 to 1:2) afforded 9d (0.256 g, 0.817 mmol, 82%) as a
colorless solid: mp 107-108 °C; IR (KBr) ν 3397, 3058, 2973,
1740, 1531, 1429, 1309, 1286, 1206, 1022, 935, 788, 749, 707
(30) For reviews of the Heck reaction, see: (a) Bra¨se, S.; de Meijere,
A. In Metal-Catalyzed Cross-Coupling Reactions, 2nd ed.; de Meijere,
A., Diederich, F., Eds.; Wiley-VCH: Weinheim, Germany, 2004; pp
217-315. (b) Beletskaya, I. P.; Cheprakov, A. V. Chem. Rev. 2000, 100,
3009-3066. (c) Link, J. T. Org. React. 2002, 60, 157-534.
(31) Recent reviews: (a) Marsden, J. A.; Haley, M. M. In Metal-
Catalyzed Cross-Coupling Reactions, 2nd ed.; de Meijere, A., Diederich,
F., Eds.; Wiley-VCH: Weinheim, Germany, 2004; pp 317-394. (b)
Sonogashira, K. J. Organomet. Chem. 2002, 653, 46-49.
J. Org. Chem, Vol. 70, No. 18, 2005 7153

Kauch et al.
1
cm-1; H NMR (300 MHz, CDCl3) δ 1.10 (d, J ) 6.4 Hz, 6H),
7.46 (m, 5H), 7.51 (d, J ) 7.7 Hz, 1H), 7.56-7.62 (m, 2H) ppm;
13C NMR (75 MHz, CDCl3) δ -0.8 (CH3), 23.0 (CH3), 43.5 (CH),
121.0 (CH), 123.8 (CH), 127.2 (CH), 127.5 (CH), 128.7 (CH),
130.3 (C), 135.2 (CH), 140.3 (C), 143.6 (C), 153.8 (C), 156.1
(C) ppm; TLC Rf ) 0.35 (Et2O/PET, 1:5). Anal. Calcd for C19H25-
NO2Si: C, 69.68; H, 7.69; N, 4.28. Found: C, 69.45; H, 7.64;
N, 4.11.
3.76 (m, 1H), 3.87 (s, 3H), 4.77 (br s, 1H, NH), 7.21-7.46 (m,
6H), 7.53 (dd, J ) 7.6, 1.7 Hz, 1H), 7.96 (dd, J ) 7.8, 1.7 Hz,
1H) ppm; 13C NMR (100 MHz, CDCl3) δ 22.7 (CH3), 43.4 (CH),
52.1 (CH3), 124.9 (C), 125.4 (CH), 127.5 (CH), 128.1 (CH), 129.1
(CH), 130.7 (CH), 134.9 (CH), 137.2 (C), 137.3 (C); 147.6 (C),
153.3 (C), 165.5 (C) ppm; TLC Rf ) 0.38 (Et2O/PET, 1:2). Anal.
Calcd for C18H19NO4: C, 68.99; H, 6.11; N, 4.47. Found: C,
69.34; H, 6.25; N, 4.34.
O-4-(Tributylstannyl)biphenyl-3-yl N-Isopropylcarb-
amate (12b). According to General Procedure B, reaction of
11 (0.128 g, 0.5 mmol) with TMEDA, TBDMSOTf, s-BuLi/
TMEDA, and tributyltin chloride (0.41 mL, 1.25 mmol, 1 h),
and purification of the crude product (FCC, Et2O/PET, 1:20
to 1:10) afforded 12b (0.246 g, 0.452 mmol, 90%) as a colorless
solid: mp 76-77 °C; IR (KBr) ν 3316, 3061, 2959, 1705, 1594,
1526, 1467, 1240, 1065, 1167, 881, 827, 761, 697 cm-1; 1H NMR
(300 MHz, CDCl3) δ 0.90 (t, J ) 7.3 Hz, 9H), 1.04-1.14 (m,
6H), 1.25 (d, J ) 6.5 Hz, 6H), 1.28-1.41 (m, 6H), 1.49-1.62
(m, 6H), 3.93 (m, 1H), 4.70 (br s, 1H, NH), 7.28-7.35 (m, 1H),
7.36-7.44 (m, 4H), 7.47 (d, 1H), 7.56-7.62 (m, 2H) ppm; 13C
NMR (75 MHz, CDCl3) δ 9.9 (CH2), 13.6 (CH3), 23.0 (CH3),
27.4 (CH2), 29.1 (CH2), 43.4 (CH), 120.2 (CH), 123.9 (CH), 127.2
(CH), 127.4 (CH), 128.6 (CH), 132.4 (C), 137.2 (CH), 140.6 (C),
142.7 (C), 153.8 (C), 156.6 (C) ppm; TLC Rf ) 0.43 (Et2O/PET,
1:5). Anal. Calcd for C28H43NO2Sn: C, 61.78; H, 7.96; N, 2.57.
Found: C, 61.83; H, 7.79; N, 2.47.
O-3-Formylbiphenyl-2-yl N-Isopropylcarbamate (9e).
According to General Procedure A, reaction of 8 (0.255 g, 1.0
mmol) with TMEDA, TMSOTf, s-BuLi/ TMEDA, and DMF
(0.77 mL, 10.0 mmol, 1 h), and purification of the crude residue
(FCC, Et2O/PET, 1:5 to 1:1) gave oxazinone 10 (0.032 g, 0.113
mmol, 11%) as a colorless solid and aldehyde 9e (0.217 g, 0.766
mmol, 77%) as a colorless solid: mp 118-119 °C; IR (KBr) ν
3334, 3067, 2973, 2877, 1716, 1686, 1531, 1254, 1209, 1082,
1023, 791, 761, 704 cm-1; H NMR (300 MHz, CDCl3) δ 1.06
1
(d, J ) 6.5 Hz, 6H), 3.70 (m, 1H), 4.86 (br d, 1H, NH), 7.32-
7.45 (m, 6H), 7.60 (dd, J ) 7.5, 1.8 Hz, 1H), 7.88 (dd, J ) 7.6,
1.8 Hz, 1H), 10.20 (s, 1H) ppm; 13C NMR (75 MHz, CDCl3) δ
22.6 (CH3), 43.5 (CH), 126.1 (CH), 127.8 (CH), 128.3 (CH),
128.7 (CH), 129.0 (CH), 129.9 (C), 136.5 (CH), 136.6 (C), 137.1
(C), 149.7 (C), 153.0 (C), 188.9 (C) ppm; TLC Rf ) 0.19 (Et2O/
PET, 1:5). Anal. Calcd for C17H17NO3: C, 72.07; H, 6.05; N,
4.94. Found: C, 72.09; H, 6.15; N, 4.92.
O-4-Iodobiphenyl-3-yl N-Isopropylcarbamate (12c). Ac-
cording to General Procedure B, reaction of 11 (0.255 g, 1.0
mmol) with TMEDA, TBDMSOTf, s-BuLi/TMEDA, and 1,2-
diiodoethane (0.705 g in 3 mL of Et2O, 2.5 mmol, 1 h), and
purification of the residue (FCC, Et2O/PET, 1:5 to 1:2) yielded
12c (0.328 g, 0.887 mmol, 89%) as a colorless solid: mp 116-
117 °C; IR (KBr) ν 3314, 3049, 2974, 1710, 1535, 1254, 1021,
3,4-Dihydro-4-hydroxy-3-isopropyl-8-phenylbenzo[e]-
[1,3]-oxazin-2-one (10): mp 160-161 °C; IR (KBr) ν 3323,
3027, 2986, 1698, 1432, 1216, 798, 756, 702 cm-1 1H NMR
;
(300 MHz, CDCl3) δ 1.40/1.45 (d, J ) 6.8 Hz, 6H), 2.00 (s, 1H,
OH), 4.32 (septet, J ) 6.8 Hz, 1H), 5.86 (s, 1H), 7.24 (t, J )
7.6 Hz, 1H), 7.32-7.38 (m, 2H), 7.38-7.46 (m, 3H), 7.52-7.57
(m, 2H); 13C NMR (75 MHz, CDCl3) δ 19.9/21.3 (CH3), 50.3
(CH), 76.5 (CH), 121.6 (C), 124.4 (CH), 125.9 (CH), 127.7 (CH),
128.3 (CH), 129.3 (CH), 129.5 (C), 131.3 (CH), 135.9 (C), 145.7
(C), 149.5 (C) ppm; TLC Rf ) 0.09 (Et2O/PET, 1:2). Anal. Calcd
for C17H17NO3: C, 72.07; H, 6.05; N, 4.94. Found: C, 72.01;
H, 5.98; N, 4.78.
1
1057, 890, 819, 760, 697 cm-1; H NMR (400 MHz, CDCl3) δ
1.27 (d, J ) 6.5 Hz, 6H), 3.93 (m, 1H), 5.01 (br s, 1H, NH),
7.16 (dd, J ) 8.2, 2.1 Hz, 1H), 7.31-7.46 (m, 4H), 7.51-7.57
(m, 2H), 7.83 (d, J ) 8.2 Hz, 1H) ppm; 13C NMR (100 MHz,
CDCl3) δ 22.9 (CH3), 43.7 (CH), 89.4 (C), 122.0 (CH), 125.8
(CH), 127.0 (CH), 127.9 (CH), 128.8 (CH), 129.8 (CH), 139.3
(C), 142.9 (C), 151.5 (C), 152.6 (C) ppm; TLC Rf ) 0.22 (Et2O/
PET, 1:5). Anal. Calcd for C16H16INO2: C, 50.41; H, 4.23; N,
3.67. Found: C, 50.72; H, 4.09; N, 3.54.
O-3-(4,4,5,5-Tetramethyl-[1,3,2]-dioxaborolan-2-yl)bi-
phenyl-2-yl N-Isopropylcarbamate (9f). Following the
General Procedure A, reaction of 8 (0.255 g, 1.0 mmol) with
TMEDA, TMSOTf, s-BuLi/TMEDA, and triisopropyl borate
(0.92 mL, 4.0 mmol, 2 h) yielded the crude product, which was
stirred with pinacol (0.591 g, 5.0 mmol) and MgSO4 (0.5 g) in
5 mL of CH2Cl2 for 18 h. The reaction mixture was subjected
to filtration, the filtrate was concentrated and the residue was
purified by FCC (Et2O/PET, 1:5 to 1:2) to afford 9f (0.251 g,
0.658 mmol, 66%) as a colorless solid: mp 130-131 °C; IR
(KBr) ν 3296, 3056, 2984, 1705, 1543, 1365, 1210, 1135, 862,
793, 762, 707 cm-1; 1H NMR (300 MHz, CDCl3) δ 1.09 (d, J )
6.5 Hz, 6H), 1.32 (s, 12H), 3.77 (m, 1H), 4.65 (br s, 1H, NH),
7.24-7.47 (m, 7H), 7.77 (dd, J ) 7.3, 1.8 Hz, 1H) ppm; 13C
NMR (100 MHz, CDCl3) δ 23.0 (CH3), 24.8 (CH3), 43.1 (CH),
83.6 (C), 125.3 (CH), 127.0 (CH), 128.0 (CH), 129.1 (CH), 133.6
(CH), 135.5 (CH), 135.4 (C), 138.2 (C), 137.9 (C), 152.2 (C),
154.1 (C) ppm; TLC Rf ) 0.23 (Et2O/PET, 1:2). Anal. Calcd
for C22H28BNO4: C, 69.30; H, 7.40; N, 3.67. Found: C, 69.39;
H, 7.38; N, 3.60.
Directed ortho-Lithiation and Substitution of Carb-
amates 11, 13, 16, 18, 20, and 22. General Procedure B:
O-4-(Trimethylsilyl)biphenyl-3-yl N-Isopropylcarbamate
(12a). The General Procedure A described above was used,
but the protecting reagent TMSOTf was exchanged for TB-
DMSOTf. Reaction of carbamate 11 (0.255 g, 1.0 mmol) with
TMEDA, TBDMSOTf, s-BuLi/TMEDA, and trimethylsilyl
chloride (0.32 mL, 2.5 mmol, 1 h), and purification of the crude
product by FCC (Et2O/PET, 1:5 to 1:2) gave 12a (0.315 g, 0.962
mmol, 96%) as a colorless solid: mp 137.5-138.5 °C; IR (KBr)
ν 3332, 3063, 2963, 1712, 1607, 1526, 1244, 1086, 886, 837,
751, 704 cm-1; 1H NMR (300 MHz, CDCl3) δ 0.31 (s, 9H), 1.25
(d, J ) 6.5 Hz, 6H), 3.94 (m, 1H), 4.80 (br s, 1H, NH), 7.29-
O-4-Chlorobiphenyl-3-yl N-Isopropylcarbamate (12d).
According to General Procedure B, reaction of 11 (0.255 g, 1.0
mmol) with TMEDA, TBDMSOTf, s-BuLi/TMEDA, and
hexachloroethane (0.710 g in 3 mL of Et2O, 3.0 mmol, 1 h),
and purification of the crude product (FCC, Et2O/PET, 1:10
to 1:5) afforded 12d (0.246 g, 0.849 mmol, 85%) as a colorless
solid: mp 128-129 °C; IR (KBr) ν 3326, 3033, 2981, 1710,
1528, 1473, 1250, 1036, 1073, 886, 822, 764, 699 cm-1; 1H NMR
(300 MHz, CDCl3) δ 1.25 (d, J ) 6.5 Hz, 6H), 3.91 (m, 1H),
5.01 (br d, 1H, NH), 7.30-7.48 (m, 6H), 7.51-7.56 (m, 2H)
ppm; 13C NMR (75 MHz, CDCl3) δ 22.8 (CH3), 43.7 (CH), 122.7
(CH), 125.0 (CH), 126.3 (C), 127.0 (CH), 127.8 (CH), 128.8
(CH), 130.3 (CH), 139.3 (C), 141.2 (C), 147.4 (C), 152.6 (C) ppm;
TLC Rf ) 0.21 (Et2O/PET, 1:5). Anal. Calcd for C16H16ClNO2:
C, 66.32; H, 5.57; N, 4.83. Found: C, 66.62; H, 5.84; N, 4.71.
O-4-(Phenylsulfanyl)biphenyl-3-yl N-Isopropylcarba-
mate (12e). According to General Procedure B, reaction of 11
(0.255 g, 1.0 mmol) with TMEDA, TBDMSOTf, s-BuLi/
TMEDA, and diphenyl disulfide (0.546 g in 3 mL of Et2O, 2.5
mmol, 1 h), and purification of the crude product (FCC, Et2O/
PET, 1:10 to 1:5) gave 12e (0.346 g, 0.952 mmol, 95%) as a
colorless solid: mp 99-100 °C; IR (KBr) ν 3355, 3066, 2972,
1709, 1526, 1471, 1074, 941, 885, 823, 762, 690 cm-1; 1H NMR
(300 MHz, CDCl3) δ 1.19 (d, J ) 6.5 Hz, 6H), 3.85 (m, 1H),
4.84 (br d, 1H, NH), 7.20-7.46 (m, 11H), 7.53-7.59 (m, 2H)
ppm; 13C NMR (75 MHz, CDCl3) δ 22.8 (CH3), 43.5 (CH), 120.4
(C), 122.0 (CH), 124.7 (CH), 127.0 (CH), 127.1 (CH), 127.7
(CH), 128.8 (CH), 129.2 (CH), 131.1 (CH), 132.8 (CH), 134.9
(C), 139.6 (C), 141.7 (C), 150.1 (C), 152.9 (C) ppm; TLC Rf )
0.15 (Et2O/PET, 1:5). Anal. Calcd for C22H21NO2S: C, 72.70;
H, 5.82; N, 3.85. Found: C, 72.32; H, 5.87; N, 3.68.
7154 J. Org. Chem., Vol. 70, No. 18, 2005

Substitution of Hydroxybiaryls by ortho-Lithiation
O-4-Methylbiphenyl-3-yl N-Isopropylcarbamate (12f).
According to General Procedure B, reaction of 11 (0.128 g, 0.5
mmol) with TMEDA, TBDMSOTf, s-BuLi/TMEDA, and methyl
iodide (0.08 mL, 1.25 mmol, 1 h), and purification of the crude
residue (FCC, Et2O/PET, 1:5 to 1:2) yielded 12f (0.124 g, 0.460
mmol, 92%) as a colorless solid: mp 103-104 °C; IR (KBr) ν
3324, 3060, 2976, 1703, 1532, 1249, 1045, 1126, 880, 828, 761,
of Et2O, 1.25 mmol, 1 h), and purification of the crude product
(FCC, Et2O/PET, 1:5 to 1:1) gave 14b (0.163 g, 0.469 mmol,
94%) as a colorless solid: mp 108-109 °C; IR (KBr) ν 3336,
3065, 2977, 1729, 1536, 1466, 1240, 1200, 1094, 1022, 937, 835,
1
753, 711 cm-1; H NMR (300 MHz, CDCl3) δ 1.23 (d, J ) 6.5
Hz, 6H), 2.06 (s, 3H), 2.34 (s, 3H), 3.67 (s, 3H), 3.89 (m, 1H),
4.99 (br d, 1H, NH), 6.61 (s, 1H), 6.70 (s, 1H), 6.99 (dd, J )
8.2, 1.8 Hz, 1H), 7.07 (d, J ) 1.8 Hz, 1H), 7.40 (d, J ) 8.2 Hz,
1H) ppm; 13C NMR (75 MHz, CDCl3) δ 20.3 (CH3), 21.5 (CH3),
22.8 (CH3), 43.6 (CH), 55.6 (CH3), 109.3 (CH), 123.2 (CH), 126.1
(CH), 126.2 (CH), 128.5 (C), 128.5 (CH), 129.5 (CH), 137.3 (C),
137.5 (C), 138.3 (C), 146.7 (C), 152.7 (C), 156.7 (C) ppm; TLC
Rf ) 0.41 (Et2O/PET, 1:2). Anal. Calcd for C19H22ClNO3: C,
65.61; H, 6.38; N, 4.03. Found: C, 65.92; H, 6.15; N, 3.70.
1
700 cm-1; H NMR (300 MHz, CDCl3) δ 1.23 (d, J ) 6.5 Hz,
6H), 2.25 (s, 3H), 3.91 (m, 1H), 4.92 (br s, 1H, NH), 7.35-7.44
(m, 6H), 7.53-7.59 (m, 2H) ppm; 13C NMR (75 MHz, CDCl3) δ
15.8 (CH3), 22.9 (CH3), 43.5 (CH), 120.9 (CH), 124.1 (CH), 127.0
(CH), 127.2 (CH), 128.6 (CH), 129.5 (C), 131.2 (CH), 140.2 (C),
140.3 (C), 149.8 (C), 153.5 (C) ppm; TLC Rf ) 0.35 (Et2O/PET,
1:2). Anal. Calcd for C17H19NO2: C, 75.81; H, 7.11; N, 5.20.
Found: C, 75.54; H, 6.93; N, 5.11.
O-4-(Hydroxyphenylmethyl)biphenyl-3-yl N-Isopro-
pylcarbamate (12g). According to General Procedure B,
reaction of 11 (0.128 g, 0.5 mmol) with TMEDA, TBDMSOTf,
s-BuLi/TMEDA, and benzaldehyde (0.13 mL, 1.25 mmol, 1 h),
and purification of the crude product (FCC, Et2O/PET, 1:2 to
2:1) gave 12g (0.159 g, 0.440 mmol, 88%) as a colorless solid:
mp 118-119 °C; IR (KBr) ν 3568, 3335, 3064, 2971, 1704, 1524,
1241, 1018, 1124, 879, 837, 763, 698 cm-1; 1H NMR (300 MHz,
CDCl3) δ 1.19/1.20 (d, J ) 6.5 Hz, 6H), 3.09 (br s, 1H, OH),
3.83 (m, 1H), 4.90 (br s, 1H, NH), 6.01 (s, 1H), 7.21-7.45 (m,
11H), 7.52-7.58 (m, 2H) ppm; 13C NMR (75 MHz, CDCl3) δ
22.8 (CH3), 43.6 (CH), 70.5 (CH), 121.3 (CH), 124.7 (CH), 126.4
(CH), 127.1 (CH), 128.3 (CH), 128.7 (CH), 127.3 (CH), 127.6
(CH), 129.1 (CH), 135.4 (C), 139.9 (C), 142.1 (C), 142.7 (C),
148.7 (C), 154.0 (C) ppm; TLC Rf ) 0.09 (Et2O/PET, 1:2). Anal.
Calcd for C23H23NO3: C, 76.43; H, 6.41; N, 3.88. Found: C,
76.17; H, 6.45; N, 3.75.
O-2′-Methoxy-4′,6′-dimethyl-4-(methylsulfanyl)biphe-
nyl-3-yl N-Isopropylcarbamate (14c). Following the Gen-
eral Procedure B, reaction of 13 (0.157 g, 0.5 mmol) with
TMEDA, TBDMSOTf, s-BuLi/TMEDA, and dimethyl disulfide
(0.12 mL, 1.25 mmol, 1 h), and purification of the crude product
(FCC, Et2O/PET, 1:5 to 2:1) gave 14a (0.167 g, 0.465 mmol,
93%) as a colorless solid: mp 86-87 °C; IR (KBr) ν 3325, 3052,
2972, 1732, 1516, 1466, 1316, 1235, 1076, 1019, 828, 756, 713
1
cm-1; H NMR (300 MHz, CDCl3) δ 1.23 (d, J ) 6.5 Hz, 6H),
2.08 (s, 3H), 2.34 (s, 3H), 2.46 (s, 3H), 3.68 (s, 3H), 3.89 (m,
1H), 4.94 (br s, 1H, NH), 6.61 (s, 1H), 6.70 (s, 1H), 6.99 (d, J
) 1.7 Hz, 1H), 7.04 (dd, J ) 8.0, 1.7 Hz, 1H), 7.26 (d, J ) 8.0
Hz, 1H) ppm; 13C NMR (75 MHz, CDCl3) δ 15.2 (CH3), 20.4
(CH3), 21.5 (CH3), 22.9 (CH3), 43.5 (CH), 55.7 (CH3), 109.4
(CH), 123.2 (CH), 124.8 (CH), 126.4 (CH), 126.8 (C), 128.0
(CH), 129.6 (C), 135.7 (C), 137.6 (C), 138.0 (C), 147.9 (C), 153.1
(C), 156.9 (C) ppm; TLC Rf ) 0.23 (Et2O/PET, 1:2). Anal. Calcd
for C20H25NO3S: C, 66.82; H, 7.01; N, 3.90. Found: C, 66.53;
H, 6.90; N, 3.78.
O-4-(Hydroxydiphenylmethyl)biphenyl-3-yl N-Isopro-
pylcarbamate (12h). According to General Procedure B,
reaction of 11 (0.128 g, 0.5 mmol) with TMEDA, TBDMSOTf,
s-BuLi/TMEDA, and benzophenone (0.228 g in 2 mL of Et2O,
1.25 mmol, 1 h), and purification of the crude product (FCC,
Et2O/PET, 1:5 to 1:2) gave 12h (0.205 g, 0.469 mmol, 94%) as
a colorless solid: mp 100-102 °C (dec); IR (KBr) ν 3418, 3335,
O-4-Methoxy-2-(trimethylsilyl)biphenyl-3-yl N-Isopro-
pylcarbamate (17). Following the General Procedure B,
carbamate 16 (0.114 g, 0.4 mmol) was dissolved in 10 mL of
Et2O and treated sequentially with TMEDA, TBDMSOTf,
s-BuLi/TMEDA (1.6 mmol, -60 °C, 2 h), and trimethylsilyl
chloride (0.23 mL, 1.8 mmol, -60 °C, 1 h). Workup and
purification of the crude product by FCC (Et2O/PET, 1:5 to
1:1) afforded silane 17 (0.114 g, 0.319 mmol, 80%) as a colorless
solid: mp 141-142 °C; IR (KBr) ν 3365, 3058, 2972, 1734,
1523, 1462, 1392, 1285, 1249, 1160, 1088, 1038, 1022, 868, 847,
3061, 2970, 1715, 1532, 1019, 1120, 886, 833, 763, 701 cm-1
;
1H NMR (400 MHz, CDCl3) δ 0.99 (d, J ) 6.5 Hz, 6H), 3.56
(m, 1H, CH), 4.19 (br d, 1H, NH), 4.29 (br s, 1H, OH), 6.81 (d,
J ) 8.2 Hz, 1H), 7.23-7.51 (m, 15H), 7.55-7.60 (m, 2H) ppm;
13C NMR (75 MHz, CDCl3) δ 22.5 (CH3), 43.4 (CH), 80.9 (C),
123.0 (CH), 123.3 (CH), 127.1 (CH), 127.3 (CH), 127.6 (CH),
127.7 (CH), 127.9 (CH), 128.7 (CH), 129.1 (CH), 139.7 (C),
141.4 (C), 142.1 (C), 146.1 (C), 149.2 (C), 152.3 (C) ppm; TLC
Rf ) 0.26 (Et2O/PET, 1:2). Anal. Calcd for C29H27NO3: C, 79.61;
H, 6.22; N, 3.20. Found: C, 79.48; H, 6.25; N, 2.94.
819, 766, 700 cm-1 1H NMR (400 MHz, CDCl3) δ -0.04 (s,
;
9H), 1.24 (d, J ) 6.5 Hz, 6H), 3.85 (s, 3H), 3.93 (m, 1H), 4.88
(br d, 1H, NH), 6.95 (d, J ) 8.3 Hz, 1H), 7.01 (d, J ) 8.3 Hz,
1H), 7.22-7.27 (m, 2H), 7.29-7.34 (m, 3H) ppm; 13C NMR (100
MHz, CDCl3) δ 1.2 (CH3), 22.9 (CH3), 43.4 (CH), 56.0 (CH3),
112.5 (CH), 126.8 (CH), 127.6 (CH), 128.1 (CH), 129.7 (CH),
131.8 (C), 141.7 (C), 144.1 (C), 145.0 (C), 150.3 (C), 153.3 (C)
ppm; TLC Rf ) 0.20 (Et2O/PET, 1:2). Anal. Calcd for C20H27-
NO3Si: C, 67.19; H, 7.61; N, 3.92. Found: C, 67.10; H, 7.53;
N, 3.78.
O-2′-Methoxy-4′,6′-dimethyl-4-(trimethylsilyl)biphenyl-
3-yl N-Isopropylcarbamate (14a). Following the General
Procedure B, reaction of 13 (0.157 g, 0.5 mmol) with TMEDA,
TBDMSOTf, s-BuLi/TMEDA, and trimethylsilyl chloride (0.16
mL, 1.25 mmol, 1 h), and purification of the crude product
(FCC, Et2O/PET, 1:5 to 1:2) gave 14a (0.187 g, 0.485 mmol,
97%) as a colorless solid: mp 118-119 °C; IR (KBr) ν 3341,
3063, 2976, 1705, 1517, 1465, 1237, 1170, 1084, 1023, 842, 751,
O-2′,4-Dimethoxy-4′,6′-dimethyl-2-(trimethylsilyl)bi-
phenyl-3-yl N-Isopropylcarbamate (19). Following the
General Procedure B, carbamate 18 (0.103 g, 0.3 mmol) was
dissolved in 7 mL of Et2O and treated sequentially with
TMEDA, TBDMSOTf, s-BuLi/TMEDA (1.2 mmol, -60 °C, 4
h), and trimethylsilyl chloride (0.17 mL, 1.35 mmol, -60 °C,
1 h). Workup and purification of the crude product by FCC
(Et2O/PET, 1:5 to 1:1) yielded silane 19 (0.112 g, 0.270 mmol,
90%) as a colorless solid: mp 154-155 °C; IR (KBr) ν 3324,
3012, 2966, 1715, 1523, 1467, 1283, 1240, 1161, 1099, 1081,
1024, 938, 866, 841, 759, 727 cm-1; 1H NMR (300 MHz, CDCl3)
δ -0.10 (s, 9H), 1.24 (d, J ) 6.5 Hz, 6H), 1.93 (s, 3H), 2.43 (s,
3H), 3.65 (s, 3H), 3.84 (s, 3H), 3.91 (m, 1H), 4.82 (br d, 1H,
NH), 6.53 (br s, 1H), 6.65 (br s, 1H), 6.81 (d, J ) 8.3 Hz, 1H),
6.97 (d, J ) 8.3 Hz, 1H) ppm; 13C NMR (75 MHz, CDCl3) δ 0.4
(CH3), 20.4 (CH3), 21.6 (CH3), 22.9 (CH3), 43.4 (CH), 55.2 (CH3),
55.8 (CH3), 108.6 (CH), 113.2 (CH), 122.6 (CH), 128.3 (C), 129.3
(C), 132.9 (C), 136.0 (C), 137.6 (C), 138.0 (C), 145.3 (C), 149.9
(C), 153.3 (C), 157.5 (C) ppm; TLC Rf ) 0.27 (Et2O/PET, 1:1).
1
719 cm-1; H NMR (300 MHz, CDCl3) δ 0.31 (s, 9H), 1.21 (d,
J ) 6.5 Hz, 6H), 2.09 (s, 3H), 2.34 (s, 3H), 3.68 (s, 3H), 3.89
(m, 1H), 4.74 (br d, 1H, NH), 6.62 (s, 1H), 6.70 (s, 1H), 6.97 (d,
J ) 1.3 Hz, 1H), 7.04 (dd, J ) 7.5, 1.3 Hz, 1H), 7.45 (d, J )
7.5 Hz, 1H) ppm; 13C NMR (75 MHz, CDCl3) δ -0.8 (CH3),
20.4 (CH3), 21.5 (CH3), 22.9 (CH3), 43.4 (CH), 55.8 (CH3), 109.4
(CH), 123.2 (CH), 124.1 (CH), 126.9 (CH), 127.2 (C), 129.3 (C),
134.2 (CH), 137.6 (C), 137.9 (C), 140.0 (C), 153.8 (C), 155.5
(C), 156.8 (C) ppm; TLC Rf ) 0.47 (Et2O/PET, 1:2). Anal. Calcd
for C22H31NO3Si: C, 68.53; H, 8.10; N, 3.63. Found: C, 68.42;
H, 7.95; N, 3.41.
O-4-Chloro-2′-methoxy-4′,6′-dimethylbiphenyl-3-yl N-
Isopropylcarbamate (14b). Following the General Procedure
B, reaction of 13 (0.157 g, 0.5 mmol) with TMEDA, TBDM-
SOTf, s-BuLi/TMEDA, and hexachloroethane (0.296 g in 2 mL
J. Org. Chem, Vol. 70, No. 18, 2005 7155

Kauch et al.
Anal. Calcd for C23H33NO4Si: C, 66.47; H, 8.00; N, 3.37.
Found: C, 66.44; H, 7.81; N, 3.21.
vacuum. Purification of the resulting residue was performed
by FCC (Et2O/PET, 1:20) to give phenol 15b (0.109 g, 0.478
mmol, 96%) as a colorless oil: IR (film) ν 3088, 2952, 1672,
1612, 1430, 1329, 1286, 1247, 1200, 1149, 971, 835, 758, 699
cm-1; 1H NMR (300 MHz, CDCl3) δ 3.96 (s, 3H), 6.94 (dd, J )
8.0, 7.5 Hz, 1H), 7.34 (m, 1H), 7.39-7.46 (m, 2H), 7.51 (dd, J
) 7.5, 1.8 Hz, 1H), 7.55-7.60 (m, 2H), 7.85 (dd, J ) 8.0, 1.8
Hz, 1H), 11.27 (s, 1H, OH) ppm; 13C NMR (75 MHz, CDCl3) δ
52.4 (CH3), 112.6 (C), 119.0 (CH), 127.4 (CH), 128.1 (CH), 129.2
(CH), 129.3 (CH), 130.5 (C), 136.6 (CH), 137.2 (C), 159.0 (C),
171.0 (C) ppm; TLC Rf ) 0.48 (Et2O/PET, 1:10). Anal. Calcd
for C14H12O3: C, 73.67; H, 5.30. Found: C, 73.78; H, 5.60.
O-6′-Isopropyl-2′,4-dimethoxy-3′-methyl-2-(trimethyl-
silyl)biphenyl-3-yl N-Isopropylcarbamate (21). Following
the General Procedure B, carbamate 20 (0.111 g, 0.3 mmol)
was dissolved in 5 mL of Et2O and treated sequentially with
TMEDA, TBDMSOTf, s-BuLi/TMEDA (1.2 mmol, -60 °C, 4
h), and trimethylsilyl chloride (0.17 mL, 1.35 mmol, -60 °C,
1 h). The crude product was purified by FCC (Et2O/PET, 1:10
to 1:5) to give silane 21 (0.113 g, 0.255 mmol, 85%) as a
colorless solid: mp 155-156 °C; IR (KBr) ν 3353, 3016, 2960,
1715, 1521, 1466, 1286, 1248, 1156, 1048, 936, 869, 839, 760
1
cm-1; H NMR (400 MHz, CDCl3) δ -0.08 (s, 9H), 1.06/1.08
Method C: 4-Chlorobiphenyl-3-ol (15f). To a solution of
carbamate 12d (0.145 g, 0.5 mmol) in 5 mL of EtOH and 1
mL of THF was added at room temperature 2 M NaOH (1.0
mL, 2.0 mmol), and the resulting reaction mixture was stirred
for 2 h. Then 3 mL of 2 M HCl and 10 mL of Et2O were added,
the aqueous layer was extracted with Et2O, and the combined
organic phases were washed with brine, dried over MgSO4,
and the solvent was removed under reduced pressure. FCC
(Et2O/PET, 1:20 to 1:10) of the residue afforded phenol 15f
(0.100 g, 0.489 mmol, 98%) as a colorless oil which solidified
on standing to give a colorless solid: mp 51-52 °C; IR (KBr)
ν 3251, 3030, 1420, 1310, 1219, 1042, 1068, 897, 817, 866, 764,
(d, J ) 6.5 Hz, 6H), 1.25 (d, J ) 6.1 Hz, 6H), 2.25 (s, 3H), 2.75
(septet, 1H), 3.29 (s, 3H), 3.87 (s, 3H), 3.92 (m, 1H), 4.85 (br s,
1H, NH), 6.89-7.03 (m, 3H), 7.12 (d, J ) 7.9 Hz, 1H) ppm;
13C NMR (100 MHz, CDCl3) δ 0.3 (CH3), 16.0 (CH3), 22.9/23.1
(CH3), 24.7 (CH3), 29.3 (CH), 43.4 (CH), 55.8 (CH3), 59.2 (CH3),
112.2 (CH), 120.5 (CH), 127.7 (C), 128.8 (CH), 130.1 (CH),
133.4 (C), 135.0 (C), 135.7 (C), 145.1 (C), 146.3 (C), 149.9 (C),
153.2 (C), 156.0 (C) ppm; TLC Rf ) 0.34 (Et2O/PET, 1:1). Anal.
Calcd for C25H37NO4Si: C, 67.68; H, 8.41; N, 3.16. Found: C,
67.50; H, 8.28; N, 2.99.
O-2′,4′-Di-tert-butyl-4,6′-dimethoxy-2-(trimethylsilyl)-
biphenyl-3-yl N-Isopropylcarbamate (23). Following the
General Procedure B, carbamate 22 (0.128 g, 0.3 mmol) was
dissolved in 6 mL of Et2O and treated sequentially with
TMEDA, TBDMSOTf, s-BuLi/TMEDA (1.2 mmol, -60 °C, 4
h), and trimethylsilyl chloride (0.17 mL, 1.35 mmol, -60 °C,
1 h). The crude product was purified by FCC (Et2O/PET, 1:10
to 1:5) to afford silane 23 (0.136 g, 0.272 mmol, 91%) as a
colorless solid: mp 177-178 °C; IR (KBr) ν 3444, 2960, 1731,
1
701 cm-1; H NMR (300 MHz, CDCl3) δ 5.58 (br s, 1H, OH),
7.09 (dd, J ) 8.3, 2.2 Hz, 1H), 7.25 (d, J ) 2.2 Hz, 1H), 7.31-
7.37 (m, 1H), 7.35 (d, J ) 8.3 Hz, 1H), 7.38-7.45 (m, 2H),
7.51-7.56 (m, 2H) ppm; 13C NMR (75 MHz, CDCl3) δ 114.8
(CH), 119.0 (C), 120.1 (CH), 127.0 (CH), 127.7 (CH), 128.8
(CH), 129.1 (CH), 139.8 (C), 141.9 (C), 151.5 (C) ppm; TLC Rf
) 0.31 (Et2O/PET, 1:5). Anal. Calcd for C12H9ClO: C, 70.43;
H, 4.43. Found: C, 70.39; H, 4.47.
1462, 1284, 1231, 1156, 1064, 1026, 938, 868, 840, 758 cm-1
;
Method D: 4-(Trimethylsilyl)biphenyl-3-ol (15d). To a
stirred solution of carbamate 12a (0.196 g, 0.6 mmol) in 12
mL of EtOH was added at room temperature K2CO3 (0.829 g,
6.0 mmol) in one portion, and stirring was continued for 12 h.
Then the reaction mixture was quenched with 9 mL of 2 M
HCl, the aqueous phase was extracted with Et2O, and the
combined organic phases were washed with brine, dried over
MgSO4, and concentrated in vacuo. FCC (Et2O/PET, 1:20 to
1:5) of the residue yielded phenol 15d (0.143 g, 0.590 mmol,
98%) as a colorless solid: mp 123-124 °C; IR (KBr) ν 3488,
3048, 2953, 1546, 1391, 1084, 838, 758, 719, 692 cm-1; 1H NMR
(300 MHz, CDCl3) δ 0.34 (s, 9H), 4.82 (s, 1H, OH), 6.87 (d, J
) 1.5 Hz, 1H), 7.16 (dd, J ) 7.5, 1.5 Hz, 1H), 7.29-7.45 (m,
4H), 7.51-7.58 (m, 1H) ppm; 13C NMR (75 MHz, CDCl3) δ -0.9
(CH3), 113.2 (CH), 119.5 (CH), 124.1 (C), 127.1 (CH), 127.5
(CH), 128.8 (CH), 135.8 (CH), 140.7 (C), 144.0 (C), 160.7 (C)
ppm; TLC Rf ) 0.47 (Et2O/PET, 1:5). Anal. Calcd for C15H18-
OSi: C, 74.33; H, 7.49. Found: C, 74.43; H, 7.63.
1H NMR (300 MHz, CDCl3) δ -0.12 (s, 9H), 1.15 (s, 9H), 1.35
(s, 9H), 1.23 (d, J ) 6.5 Hz, 6H), 3.62 (s, 3H), 3.85 (s, 3H),
3.91 (m, 1H), 4.80 (br d, 1H, NH), 6.72 (d, J ) 1.6 Hz, 1H),
6.88 (d, J ) 8.4 Hz, 1H), 6.91 (d, J ) 8.4 Hz, 1H), 7.15 (d, J )
1.6 Hz, 1H) ppm; 13C NMR (75 MHz, CDCl3) δ 0.2 (CH3), 22.9
(CH3), 31.5 (CH3), 33.0 (CH3), 35.0 (C), 37.2 (C), 43.4 (CH),
55.4 (CH3), 55.7 (CH3), 105.0 (CH), 111.6 (CH), 116.6 (CH),
128.6 (C), 129.2 (CH), 134.4 (C), 137.3 (C), 144.8 (C), 148.2
(C), 149.7 (C), 150.5 (C), 153.3 (C), 157.8 (C) ppm; TLC Rf )
0.30 (Et2O/PET, 1:1). Anal. Calcd for C29H45NO4Si: C, 69.70;
H, 9.08; N, 2.80. Found: C, 69.63; H, 9.01; N, 2.79.
Deprotection of O-Isopropylcarbamoyl-Substituted
Hydroxybiaryls. Method A: 3-Benzylbiphenyl-2-ol (15a).18
A solution of carbamate 9b (0.173 g, 0.5 mmol), DMAP (6 mg,
0.05 mmol), and cyclohexylamine (0.57 mL, 5.0 mmol) in 2 mL
of THF was heated at reflux for 6 h. After cooling, 3 mL of 2
M HCl was added and the aqueous layer was extracted with
Et2O. The combined organic phases were washed with brine,
dried over MgSO4, and concentrated under reduced pressure.
The residue was purified by FCC (Et2O/PET, 1:10 to 1:5) to
yield phenol 15a (0.127 g, 0.488 mmol, 98%) as a colorless oil:
IR (film) ν 3543, 3060, 3021, 2924, 1599, 1492, 1453, 1431,
4-Iodobiphenyl-3-ol (15e). According to Method D, 12c
(0.229 g, 0.6 mmol) was stirred with K2CO3 in EtOH. Standard
workup and FCC (Et2O/PET, 1:20 to 1:5) afforded 15e (0.176
g, 0.594 mmol, 99%) as a colorless solid: mp 80-81 °C; IR
(KBr) ν 3247, 1562, 1399, 1205, 892, 859, 814, 758, 699 cm-1
;
1
1323, 1222, 1078, 760, 700 cm-1; H NMR (300 MHz, CDCl3)
1H NMR (300 MHz, CDCl3) δ 5.31 (br s, 1H, OH), 6.91 (dd, J
) 8.2, 2.1 Hz, 1H), 7.22 (d, J ) 2.1 Hz, 1H), 7.31-7.46 (m,
3H), 7.51-7.58 (m, 2H), 7.69 (d, J ) 8.2 Hz, 1H) ppm; 13C NMR
(75 MHz, CDCl3) δ 84.3 (C), 113.7 (CH), 121.3 (CH), 126.9
(CH), 127.9 (CH), 128.9 (CH), 138.4 (CH), 139.8 (C), 143.8 (C),
155.1 (C) ppm; TLC Rf ) 0.23 (Et2O/PET, 1:5). Anal. Calcd
for C12H9IO: C, 48.67; H, 3.06. Found: C, 48.69; H, 3.08.
δ 4.04 (s, 2H), 5.25 (br s, 1H, OH), 6.90 (t, J ) 7.5 Hz, 1H),
7.06-7.12 (m, 2H), 7.14-7.31 (m, 5H), 7.32-7.40 (m, 1H),
7.40-7.50 (m, 4H) ppm; 13C NMR (75 MHz, CDCl3) δ 36.3
(CH2), 120.4 (CH), 126.0 (CH), 127.8 (C), 127.8 (CH), 128.2
(C), 128.3 (CH), 128.4 (CH), 128.9 (CH), 129.2 (CH), 129.3
(CH), 130.3 (CH), 137.3 (C), 140.6 (C), 150.4 (C) ppm; TLC Rf
) 0.58 (Et2O/PET, 1:5). Anal. Calcd for C19H16O: C, 87.66; H,
6.19. Found: C, 87.49; H, 6.22.
4-(Phenylsulfanyl)biphenyl-3-ol (15g). According to
Method C, 12e (0.182 g, 0.5 mmol) was treated with 2 M NaOH
in 5 mL of EtOH and 1 mL of THF, and the crude product
was purified after workup by FCC (Et2O/PET, 1:20 to 1:10) to
afford 15g (0.135 g, 0.485 mmol, 97%) as a colorless oil: IR
(film) ν 3430, 3062, 1601, 1583, 1555, 1476, 1191, 1024, 900,
878, 760, 696 cm-1; 1H NMR (300 MHz, CDCl3) δ 6.53 (s, 1H,
OH), 7.31 (d, J ) 2.0 Hz, 1H), 7.10-7.27 (m, 5H), 7.18 (dd, J
) 8.0, 2.0 Hz, 1H), 7.33-7.39 (m, 1H), 7.40-7.47 (m, 2H), 7.57
(d, J ) 8.0 Hz, 1H), 7.57-7.63 (m, 2H) ppm; 13C NMR (75 MHz,
Method B: 2-Hydroxybiphenyl-3-carboxylic Acid Meth-
yl Ester (15b). Tetrabutylammonium fluoride (0.75 mL, 1.0
M in THF, 0.75 mmol) was added at room temperature to a
solution of carbamate 9d (0.157 g, 0.5 mmol) in 5 mL of THF,
and stirring was continued for 2 h. The reaction was quenched
with 2 mL of saturated NH4Cl solution, and the aqueous phase
was extracted with Et2O. The combined organic phases were
washed with brine, dried over MgSO4, and concentrated under
7156 J. Org. Chem., Vol. 70, No. 18, 2005

Substitution of Hydroxybiaryls by ortho-Lithiation
CDCl3) δ 114.0 (CH), 115.3 (C), 120.1 (CH), 126.2 (CH), 127.0
(CH), 127.1 (CH), 128.0 (CH), 128.8 (CH), 129.2 (CH), 135.9
(C), 137.1 (CH), 140.0 (C), 145.7 (C), 157.4 (C) ppm; TLC Rf )
0.51 (Et2O/PET, 1:5). Anal. Calcd for C18H14OS: C, 77.66; H,
5.07. Found: C, 77.51; H, 5.06.
1.15 (s, 9H), 1.35 (s, 9H), 3.64 (s, 3H), 3.89 (s, 3H), 5.90 (br s,
1H, OH), 6.58 (d, J ) 8.1 Hz, 1H), 6.72 (d, J ) 1.7 Hz, 1H),
6.80 (d, J ) 8.1 Hz, 1H), 7.15 (d, J ) 1.7 Hz, 1H) ppm; 13C
NMR (75 MHz, CDCl3) δ -0.1 (CH3), 31.5 (CH3), 33.1 (CH3),
35.0 (C), 37.2 (C), 55.5 (CH3), 55.5 (CH3), 105.0 (CH), 109.6
(CH), 116.6 (CH), 123.2 (CH), 125.7 (C), 129.1 (C), 137.8 (C),
144.2 (C), 147.9 (C), 149.7 (C), 150.3 (C), 157.8 (C) ppm; TLC
Rf ) 0.60 (Et2O/PET, 1:2). Anal. Calcd for C25H38O3Si: C,
72.41; H, 9.24. Found: C, 72.66; H, 9.37.
4-Methylbiphenyl-3-ol (15h).20 Following Method C, 12f
(0.135 g, 0.5 mmol) was stirred with 2 M NaOH in 5 mL of
EtOH, and the crude product was purified after workup by
FCC (Et2O/PET, 1:10 to 1:5) to afford 15h (0.091 g, 0.494 mmol,
99%) as a colorless solid: mp 78-79 °C; IR (KBr) ν 3528, 3031,
2945, 1409, 1305, 1239, 1123, 899, 823, 762, 691 cm-1; 1H NMR
(300 MHz, CDCl3) δ 2.27 (s, 3H), 4.84 (br s, 1H, OH), 6.98 (d,
J ) 1.8 Hz, 1H), 7.07 (dd, J ) 7.8, 1.8 Hz, 1H), 7.16 (d, J )
7.8 Hz, 1H), 7.23 (m, 1H), 7.35-7.42 (m, 2H), 7.50-7.55 (m,
2H) ppm; 13C NMR (100 MHz, CDCl3) δ 15.4 (CH3), 113.6 (CH),
119.5 (CH), 122.8 (C), 126.9 (CH), 127.2 (CH), 128.7 (CH),
131.3 (CH), 140.5 (C), 140.7 (C), 154.0 (C) ppm; TLC Rf ) 0.28
(Et2O/PET, 1:5). Anal. Calcd for C13H12O: C, 84.75; H, 6.57.
Found: C, 84.75; H, 6.43.
2-Hydroxybiphenyl-3-carbaldehyde (15c).5b,19 Following
the procedure for the synthesis of 9e, reaction of 8 (0.255 g,
1.0 mmol) with DMF and standard workup gave the crude
product, which was treated according to Method C with 2 M
NaOH in 10 mL of EtOH. Workup and FCC (Et2O/PET, 1:20
to 1:5) afforded salicylic aldehyde 15c (0.176 g, 0.888 mmol,
89%) as a light yellow oil which solidified on standing to give
a pale yellow solid: mp 41-42 °C; IR (film) ν 3058, 2849, 2745,
1656, 1451, 1430, 1386, 1279, 917, 832, 760, 695 cm-1; 1H NMR
(300 MHz, CDCl3) δ 7.08 (t, J ) 7.6 Hz, 1H), 7.31-7.64 (m,
7H), 9.92 (s, 1H), 11.51 (s, 1H, OH) ppm; 13C NMR (75 MHz,
CDCl3) δ 119.9 (CH), 120.9 (C), 127.6 (CH), 128.2 (CH), 129.2
(CH), 130.5 (C), 133.1 (CH), 136.1 (C), 137.7 (CH), 158.9 (C),
196.7 (CH) ppm; TLC Rf ) 0.45 (Et2O/PET, 1:5). Anal. Calcd
for C13H10O2: C, 78.77; H, 5.09. Found: C, 78.85; H, 5.20.
Bis-silylation of BINOL by Directed ortho-Lithiation.
rac-O,O′-[1,1′]-Binaphthyl-2,2′-diyl Di(N-isopropylcarb-
amate)(rac-26). A solution of rac-BINOL (rac-25) (2.291 g,
8.0 mmol) and DMAP (0.098 g, 0.8 mmol) in 5 mL of THF and
5 mL of CH2Cl2 was treated with isopropyl isocyanate (1.89
mL, 19.2 mmol). The reaction mixture was stirred at 60 °C
for 2 d, cooled to room temperature, and quenched with 8 mL
of 2 M HCl. The aqueous layer was extracted with Et2O and
the organic extracts were washed with saturated NaHCO3
solution, dried over MgSO4, and concentrated in vacuo. The
residue was subjected to FCC (Et2O/PET, 1:5 to 1:2) to afford
rac-26 (3.347 g, 7.331 mmol, 92%) as a colorless solid: mp
161-162 °C; IR (KBr) ν 3347, 3055, 2967, 1698, 1522, 1454,
1363, 1314, 1224, 1076, 1042, 934, 832, 818, 788, 770, 753
1
cm-1; H NMR (300 MHz, CDCl3) δ 0.75/1.01 (d, J ) 5.8 Hz,
12H), 3.52 (m, 2H), 4.84 (br d, 2H, NH), 7.14-7.30 (m, 4H),
7.37-7.44 (m, 2H), 7.51 (d, J ) 8.8 Hz, 2H), 7.88 (d, J ) 8.2
Hz, 2H), 7.95 (d, J ) 8.8 Hz, 2H) ppm; 13C NMR (100 MHz,
CDCl3) δ 22.2/22.5 (CH3), 43.0 (CH), 122.4 (CH), 123.5 (C),
125.3 (CH), 126.4, (CH), 126.5 (CH), 127.8 (CH), 129.2 (CH),
131.4 (C), 133.4 (C), 147.4 (C), 153.8 (C) ppm; TLC Rf ) 0.15
(Et2O/PET, 1:2). Anal. Calcd for C28H28N2O4: C, 73.66; H, 6.18;
N, 6.14. Found: C, 73.30; H, 6.04; N, 5.98.
(R)-O,O′-[1,1′]-Binaphthyl-2,2′-diyl Di(N-isopropylcarb-
amate) ((R)-26). Following the procedure described for rac-
26, a solution of (R)-BINOL ((R)-25) (4.295 g, 15.0 mmol, g99%
ee),32 DMAP (0.367 g, 3.0 mmol), and isopropyl isocyanate (3.83
mL, 39.0 mmol) in 30 mL THF was stirred at 60 °C for 2 d.
(R)-26 (6.701 g, 14.68 mmol, 98%) was obtained as a colorless
4-Methoxy-2-(trimethylsilyl)biphenyl-3-ol (24a). Fol-
lowing Method C, 17 (0.143 g, 0.4 mmol) was stirred with 2 M
NaOH in 8 mL of EtOH and 2 mL of THF. The crude product
was purified after workup by FCC (Et2O/PET, 1:10) to yield
24a (0.106 g, 0.389 mmol, 97%) as a colorless oil: IR (film) ν
3530, 3057, 2952, 1602, 1566, 1457, 1263, 1226, 1152, 1049,
20
foam: mp 64-66 °C; [R]D -21 (c ) 1.01, THF, g99% ee).
rac-O,O′-3,3′-Bis(trimethylsilyl)-[1,1′]-binaphthyl-2,2′-
diyl Di(N-isopropylcarbamate (rac-27). Following the
General Procedure A, a solution of rac-26 (0.137 g, 0.3 mmol)
in 10 mL of Et2O was sequentially treated with TMEDA (0.077
g, 0.66 mmol), TMSOTf (0.63 mmol), s-BuLi/TMEDA (1.5
mmol, -78 °C, 1.5 h), and trimethylsilyl chloride (0.23 mL,
1.8 mmol, -78 °C, 1 h). Standard workup and purification of
the residue (FCC, Et2O/PET, 1:5) afforded rac-27 (0.175 g,
0.291 mmol, 97%) as a colorless solid: mp 158-159 °C; IR
(KBr) ν 3311, 3047, 2967, 1711, 1533, 1394, 1252, 1202, 1144,
863, 840, 808, 764, 698 cm-1 1H NMR (300 MHz, CDCl3) δ
;
0.00 (s, 9H), 3.91 (s, 3H), 6.03 (br s, 1H, OH), 6.70 (d, J ) 8.2
Hz, 1H), 6.85 (d, J ) 8.2 Hz, 1H), 7.22-7.27 (m, 2H), 7.28-
7.35 (m, 3H) ppm; 13C NMR (75 MHz, CDCl3) δ 1.0 (CH3), 55.9
(CH3), 110.5 (CH), 121.7 (CH), 123.1 (C), 126.7 (CH), 127.5
(CH), 129.6 (CH), 142.4 (C), 144.7 (C), 144.8 (C), 150.7 (C) ppm;
TLC Rf ) 0.59 (Et2O/PET, 1:5). Anal. Calcd for C16H20O2Si:
C, 70.54; H, 7.40. Found: C, 70.87; H, 7.44.
2′,4-Dimethoxy-4′,6′-dimethyl-2-(trimethylsilyl)biphe-
nyl-3-ol (24b). Following Method C, 19 (0.481 g, 1.157 mmol)
was treated with 2 M NaOH in 12 mL of EtOH and 3 mL of
THF. The crude product was purified after workup by FCC
(Et2O/PET, 1:10) to afford 24b (0.367 g, 1.110 mmol, 96%) as
a colorless solid: mp 104-105 °C; IR (KBr) ν 3508, 3068, 2949,
1599, 1571, 1463, 1421, 1314, 1282, 1236, 1162, 1092, 865, 842,
808, 757 cm-1; 1H NMR (400 MHz, CDCl3) δ 0.02 (s, 9H), 2.02
(s, 3H), 2.43 (s, 3H), 3.76 (s, 3H), 3.97 (s, 3H), 6.04 (s, 1H, OH),
6.59 (d, J ) 8.2 Hz, 1H), 6.63 (s, 1H), 6.73 (s, 1H), 6.96 (d, J
) 8.2 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3) δ 0.1 (CH3),
20.2 (CH3), 21.6 (CH3), 55.4 (CH3), 55.6 (CH3), 108.6 (CH),
111.0 (CH), 121.9 (CH), 122.5 (CH), 124.1 (C), 129.9 (C), 136.4
(C), 137.4 (C), 137.8 (C), 144.3 (C), 150.5 (C), 157.5 (C) ppm;
TLC Rf ) 0.64 (Et2O/PET, 1:2). Anal. Calcd for C19H26O3Si:
C, 69.05; H, 7.93. Found: C, 69.11; H, 7.98.
1093, 1056, 961, 848, 744, 698 cm-1 1H NMR (400 MHz,
;
CDCl3) δ 0.38 (s, 18H), 0.52/0.91 (d, J ) 6.5 Hz, 12H), 3.26
(m, 2H), 4.66 (br d, 2H, NH), 7.13 (d, J ) 8.5 Hz, 2H), 7.20-
7.26 (m, 2H), 7.35-7.42 (m, 2H), 7.85 (d, J ) 8.1 Hz, 2H), 8.07
(s, 2H) ppm; 13C NMR (100 MHz, CDCl3) δ -0.4 (CH3), 22.1/
22.5 (CH3), 42.8 (CH), 124.1 (C), 125.1 (CH), 126.5 (CH), 126.9
(CH), 127.6 (CH), 131.3 (C), 133.3 (C), 134.4 (C), 136.5 (CH),
151.4 (C), 153.4 (C) ppm; TLC Rf ) 0.58 (Et2O/PET, 1:2). Anal.
Calcd for C34H44N2O4Si2: C, 67.96; H, 7.38; N, 4.66. Found:
C, 67.95; H, 7.40; N, 4.42.
(R)-O,O′-3,3′-Bis(trimethylsilyl)-[1,1′]-binaphthyl-2,2′-
diyl Di(N-isopropylcarbamate ((R)-27). The reaction was
carried out according to the procedure described for rac-27
using (R)-26 (0.137 g, 0.3 mmol). (R)-27 (0.173 g, 0.288 mmol,
20
96%) was obtained as a colorless solid: mp 175-177 °C; [R]D
-77 (c ) 1.00, THF, g99% ee).
2′,4′-Di-tert-butyl-4,6′-dimethoxy-2-(trimethylsilyl)bi-
phenyl-3-ol (24c). Following method C, 23 (0.165 g, 0.33
mmol) was stirred with 2 M NaOH in 5 mL of EtOH and 2
mL of THF. Workup and purification the crude product by FCC
(Et2O/PET, 1:20) gave 24c (0.134 g, 0.323 mmol, 98%) as a
colorless solid: mp 137-138 °C; IR (KBr) ν 3512, 3066, 2964,
1602, 1558, 1455, 1402, 1300, 1269, 1231, 1206, 1064, 926, 862,
(32) (R)-BINOL ((R)-25) (g99% ee) was purchased from Merck. The
enantiomeric purity was checked by HPLC analysis (CHIRA GROM 1
column, 60 × 2 mm, 2-propanol/hexane, 1:100, flow rate 3.0 mL/min,
tR ) 25.6 min for (S)-25, tR ) 35.4 min for (R)-25).
(33) (a) M´ınguez, J. M.; Castellote, M. I.; Vaquero, J. J.; Garcı´a-
Navio, J. L.; Alvarez-Builla, J.; Castano, O.; Andre´s, J. L. J. Org. Chem.
1996, 61, 4655-4665. (b) Terrian, D. L.; Mohammad, T.; Morrison, H.
J. Org. Chem. 1995, 60, 1981-1984.
836, 757 cm-1 1H NMR (300 MHz, CDCl3) δ -0.09 (s, 9H),
;
J. Org. Chem, Vol. 70, No. 18, 2005 7157

Kauch et al.
rac-3,3′-Bis(trimethylsilyl)-[1,1′]-binaphthyl-2,2′-diol
(rac-28).25a According to Method C, rac-27 (0.180 g, 0.3 mmol)
was stirred with 2 M NaOH (0.75 mL, 1.5 mmol, rt, 2.5 h) in
10 mL of EtOH. The crude product was purified after workup
by FCC (Et2O/PET, 1:20) to yield rac-28 (0.128 g, 0.297 mmol,
99%) as a colorless solid: mp 153-154 °C; IR (KBr) ν 3520,
3041, 2947, 1581, 1413, 1246, 1179, 1042, 997, 848, 749, 702
Heck Coupling of Carbamate 31:9 (E)-3-(2-Hydroxy-
phenyl)acrylic Acid Methyl Ester (32).33 A mixture of Bu4-
NCl (0.278 g, 1.0 mmol), KOAc (0.245 g, 2.5 mmol), Pd(OAc)2
(7 mg, 0.03 mmol), and acrylic acid methyl ester (0.065 g, 0.75
mmol) in 2 mL of DMF was stirred at room temperature for
10 min. Then, a solution of carbamate 31 (0.153 g, 0.5 mmol)
in 2 mL of DMF was added, and the whole was heated to 80
°C for 16 h. After cooling, quenching was effected with 5 mL
of 2 M HCl and 20 mL of Et2O. The aqueous layer was then
extracted with Et2O, and the combined organic phases were
washed with brine, dried over MgSO4, and concentrated under
vacuum. FCC (Et2O/PET, 1:5 to 1:1) provided 32 (0.082 g, 0.460
mmol, 92%) as a colorless solid: mp 135 °C; IR (KBr) ν 3383,
3033, 2957, 1695, 1628, 1461, 1330, 1199, 1176, 993, 871, 804,
1
cm-1; H NMR (300 MHz, CDCl3) δ 0.41 (s, 18H), 5.22 (br s,
2H, OH), 7.05-7.12 (m, 2H), 7.23-7.38 (m, 4H), 7.85-7.91 (m,
2H), 8.07 (s, 2H) ppm; 13C NMR (75 MHz, CDCl3) δ -0.9 (CH3),
109.6 (C), 123.7 (CH), 124.6 (CH), 127.6 (CH), 128.5 (CH),
129.0 (C), 129.3 (C), 134.3 (C), 137.8 (CH), 156.9 (C) ppm; TLC
Rf ) 0.78 (Et2O/PET, 1:10). Anal. Calcd for C26H30O2Si2: C,
72.51; H, 7.02. Found: C, 72.84; H, 7.09.
(R)-3,3′-Bis(trimethylsilyl)-[1,1′]-binaphthyl-2,2′-diol ((R)-
28).25 According to the procedure described for rac-28, (R)-27
(0.150 g, 0.25 mmol) was deprotected with 2 M NaOH (0.63
mL, 1.25 mmol, rt, 4 h) in 5 mL EtOH to furnish (R)-28 (0.107
1
765 cm-1; H NMR (300 MHz, CDCl3) δ 2.42 (br s, 1H, OH),
3.80 (s, 3H), 6.57 (d, J ) 16.1 Hz, 1H), 6.80-6.91 (m, 2H),
7.21 (ddd, J ) 8.1, 7.7, 1.7 Hz, 1H), 7.45 (dd, J ) 7.7, 1.7 Hz,
1H), 7.99 (d, J ) 16.1 Hz, 1H) ppm; 13C NMR (75 MHz, CDCl3)
δ 51.4 (CH3), 116.0 (CH), 117.3 (CH), 119.7 (CH), 121.4 (C),
128.9 (CH), 131.3 (CH), 141.0 (CH), 156.4 (C), 168.6 (C) ppm;
TLC Rf ) 0.37 (Et2O/PET, 1:1). Anal. Calcd for C10H10O3: C,
67.41; H, 5.66. Found: C, 67.28; H, 5.74.
20
g, 0.248 mmol, 99%) as a colorless foam: mp 71-73 °C; [R]D
+139 (c ) 1.00, THF, g99% ee) (lit.25a [R]D +142 (c ) 0.52,
20
THF), lit.25b [R]D +143 (c ) 0.985, THF)). The enantiomeric
excess was determined by HPLC analysis (CHIRA GROM 2
column, 250 × 2 mm, pentane, flow rate 3.0 mL/min, tR ) 6.4
min for (S)-28, tR ) 7.3 min for (R)-28).
Sonogashira Coupling of Carbamate 31:9 O-2-(Phenyl-
ethynyl)phenyl N-Isopropylcarbamate (33). To a stirred
solution of carbamate 31 (0.153 g, 0.5 mmol) and phenylacety-
lene (0.11 mL, 1.0 mmol) in 3 mL of NEt3 were added
Pd(PPh3)2Cl2 (14 mg, 0.02 mmol) and CuI (2 mg, 0.01 mmol)
in one portion. The dark reaction mixture was stirred at room
temperature for 4 h and quenched with 5 mL of saturated NH4-
Cl solution and 5 mL of 2 M HCl. The aqueous phase was
extracted with Et2O, and the combined organic layers were
washed with 5 M HCl, saturated NaHCO3 solution, dried over
MgSO4, and concentrated under reduced pressure. The result-
ing residue was subjected to FCC (Et2O/PET, 1:5 to 1:2) to
give 33 (0.138 g, 0.494 mmol, 99%) as a colorless solid: mp
126 °C; IR (KBr) ν 3364, 3061, 2970, 2218, 1712, 1523, 1493,
1209, 1021, 782, 756, 692 cm-1; 1H NMR (300 MHz, CDCl3) δ
1.19 (d, J ) 6.5 Hz, 6H), 3.90 (m, 1H), 5.01 (br s, 1H, NH),
7.13-7.22 (m, 2H), 7.27-7.38 (m, 4H), 7.45-7.58 (m, 3H) ppm;
13C NMR (75 MHz, CDCl3) δ 22.8 (CH3), 43.5 (CH), 84.6 (C),
93.6 (C), 117.7 (C), 122.7 (CH), 123.2 (C), 125.4 (CH), 128.2
(CH), 128.4 (CH), 129.3 (CH), 131.6 (CH), 132.9 (CH), 151.7
(C), 153.2 (C) ppm; TLC Rf ) 0.09 (Et2O/PET, 1:5). Anal. Calcd
for C18H17NO2: C, 77.40; H, 6.13; N, 5.01. Found: C, 77.13;
H, 6.02; N, 4.84.
Pd-catalyzed Cross-coupling Reactions. Negishi Coup-
ling of Carbamate 8: O-[1,1′:3′,1′′]-Terphenyl-2′-yl N-Iso-
propylcarbamate (30). Following the General Procedure A,
a solution of carbamate 8 (0.128 g, 0.5 mmol) in 5 mL of THF
was sequentially treated with TMEDA (0.064 g, 1.1 mmol),
TBDMSOTf (1.05 mmol), s-BuLi/TMEDA (1.25 mmol, -78 °C,
1 h), and zinc(II) chloride (2.63 mL, 0.5 M in THF, 1.31 mmol,
-78 °C, 15 min). The reaction mixture was allowed to warm
to room temperature and stirring was continued for 45 min.
The mixture was then transferred into a solution of iodoben-
zene (0.17 mL, 1.5 mmol) and Pd(PPh3)4 (29 mg, 0.025 mmol)
in 1 mL of THF and the whole was heated at reflux for 6 h.
Quenching was effected at room temperature with 5 mL of 2
M HCl, the aqueous phase was then extracted with Et2O, and
the combined organic layers were washed with saturated
NaHCO3 solution, dried over MgSO4 and concentrated in
vacuo. The resulting residue was purified by FCC (Et2O/PET,
1:10 to 1:2) to yield starting material 8 (0.027 g, 0.106 mmol,
21%) and 30 (0.120 g, 0.362 mmol, 72%) as a colorless solid:
mp 163-164 °C; IR (KBr) ν 3327, 3060, 2977, 1703, 1527, 1421,
1257, 1212, 1172, 1039, 786, 767, 705 cm-1; 1H NMR (300 MHz,
CDCl3) δ 0.84 (d, J ) 6.5 Hz, 6H), 3.49 (m, 1H), 4.40 (br s, 1H,
NH), 7.26-7.50 (m, 13H) ppm; 13C NMR (75 MHz, CDCl3) δ
22.5 (CH3), 43.0 (CH), 125.9 (CH), 127.2 (CH), 128.1 (CH),
129.1 (CH), 130.0 (CH), 136.4 (C), 138.2 (C), 145.2 (C), 153.0
(C) ppm; TLC Rf ) 0.12 (Et2O/PET, 1:2). Anal. Calcd for C22H21-
NO2: C, 79.73; H, 6.39; N, 4.23. Found: C, 79.72; H, 6.42; N,
4.14.
Acknowledgment. This work was supported by the
Deutsche Forschungsgemeinschaft, the Fonds der Che-
mischen Industrie, the Alexander von Humboldt foun-
dation, and the NSERC Canada. M.K. gratefully ac-
knowledges a fellowship of the Fonds der Chemischen
Industrie. We thank Ms. Astrid Bru¨ns for her engaged
work on the O-3-biphenylyl N-isopropylcarbamate se-
ries. V.S. thanks NSERC Canada for continuing support
of synthetic programs.
Stille Coupling of Carbamate 9g.9 Following the General
Procedure B, stannane 9g (0.109 g, 0.2 mmol) was N-silylated
with i-Pr2NEt (0.054 g, 0.42 mmol) and TBDMSOTf (0.21
mmol) in 2 mL of THF. The mixture was then transferred into
a solution of iodobenzene (0.04 mL, 0.3 mmol) and Pd(PPh3)4
(12 mg, 0.01 mmol) in 2 mL of THF, and the whole was stirred
at 60 °C for 2 d. Workup and purification was performed as
described for the Negishi coupling to give 30 (0.037 g, 0.112
mmol, 56%) along with starting material 9g (0.038 g, 0.070
mmol, 35%).
JO0506938
7158 J. Org. Chem., Vol. 70, No. 18, 2005