Electronic dependence of C-O reductive elimination from palladium (aryl)neopentoxide complexes

Article abstract of DOI:10.1021/ja9806581

Thermal decomposition of the palladium (aryl)neopentoxide complexes [P-P]Pd(Ar)OCH₂CMe₃ [P-P =Tol-BINAP or BINAP; Ar p-C₆H₄CHO (1b), p-C₆H₄COPh (1c), p-C₆H₄NO₂ (1d), o-C₆H₄NO₂ (1e), o-C₆H₄CN (1F)] possessing substituents on the palladium-bound aryl group suitable for delocalization of negative charge led to quantitative (≤95%) formation of aryl ether without detectable β-hydride elimination. Thermal decomposition of 1b-f obeyed first-order kinetics, and the rate of reductive elimination decreased in the order o-NO₂ > p-NO₂ > p-CHO > p-COPh > o-CN. Conversely, thermal decomposition of the related derivatives [P-P]Pd(Ar)OCH₂CMe₃ [P-P = Tol-BINAP or BINAP; Ar p-C₆H₄Cl (1g), m-C₆H₄NO₂ (1h), m-C₆H₄CN (1i)] which did not possess a resonance stabilizing group on the palladium-bound aryl group led to no detectable formation of aryl ether. These and related data point to the buildup of negative charge in the palladium-bound aryl group in the transition state for C-O reductive elimination and are consistent with a mechanism initiated by inner-sphere nucleophilic attack of the alkoxide ligand at the ipso-carbon atom of the palladium-bound aryl group through a zwitterionic Meisenheimer-type intermediate or transition state.

Full text of DOI:10.1021/ja9806581

6504
J. Am. Chem. Soc. 1998, 120, 6504-6511
Electronic Dependence of C-O Reductive Elimination from
Palladium (Aryl)neopentoxide Complexes
Ross A. Widenhoefer1 and Stephen L. Buchwald*
Contribution from the Department of Chemistry, Massachusetts Institute of Technology,
Cambridge, Massachusetts 02139
ReceiVed February 27, 1998
Abstract: Thermal decomposition of the palladium (aryl)neopentoxide complexes [P-P]Pd(Ar)OCH2CMe3
[P-P ) Tol-BINAP or BINAP; Ar ) p-C6H4CHO (1b), p-C6H4COPh (1c), p-C6H4NO2 (1d), o-C6H4NO2
(1e), o-C6H4CN (1f)] possessing substituents on the palladium-bound aryl group suitable for delocalization of
negative charge led to quantitative (g95%) formation of aryl ether without detectable â-hydride elimination.
Thermal decomposition of 1b-f obeyed first-order kinetics, and the rate of reductive elimination decreased in
the order o-NO2 > p-NO2 > p-CHO > p-COPh > o-CN. Conversely, thermal decomposition of the related
derivatives [P-P]Pd(Ar)OCH2CMe3 [P-P ) Tol-BINAP or BINAP; Ar ) p-C6H4Cl (1g), m-C6H4NO2 (1h),
m-C6H4CN (1i)] which did not possess a resonance stabilizing group on the palladium-bound aryl group led
to no detectable formation of aryl ether. These and related data point to the buildup of negative charge in the
palladium-bound aryl group in the transition state for C-O reductive elimination and are consistent with a
mechanism initiated by inner-sphere nucleophilic attack of the alkoxide ligand at the ipso-carbon atom of the
palladium-bound aryl group through a zwitterionic Meisenheimer-type intermediate or transition state.
Introduction
Scheme 1
In conjunction with our development of catalytic C-O bond-
forming protocols,2 we recently reported some rare examples
of C-O reductive elimination from palladium alkoxide
complexes.3-5 For example, thermolysis of the palladium (p-
cyanophenyl)neopentoxide complex [Tol-BINAP]Pd(p-C6H4-
CN)(OCH2CMe3) (1a) [Tol-BINAP ) 2,2′-bis(di-p-tolyl-
phosphino)-1,1′-binaphthyl] in THF-d8 at 47 °C led to C-O
reductive elimination with formation of p-neopentoxybenzoni-
trile (85%). Thermolysis of 1a also led to formation of 4,4′-
dimethylbiphenyl (16%) via a secondary P-C bond cleavage
process. Kinetic analysis of the decomposition of 1a in the
presence of excess potassium neopentoxide was consistent with
reductive elimination via competing alkoxide-dependent and
alkoxide-independent pathways. An alkoxide-dependent path-
way, initiated by direct attack of KOCH2CMe3 at palladium,
was supported by the presence of an associative alkoxide
exchange pathway for 1a, although direct attack of the alkoxide
at the ipso-carbon atom of the palladium-bound p-cyanophenyl
group was also consistent with our kinetic data.
Several observations regarding the alkoxide-independent
reductive elimination pathway appeared inconsistent with the
concerted, symmetric three-centered mechanism6 typically
invoked for C-C7 and C-H8 reductive elimination from group
10 metal complexes (Scheme 2, path a). In particular, C-O
reductive elimination from aryl(alkoxide) complexes occurred
readily while aryl(aryloxide) derivatives were virtually resistant
to reductive elimination.3 This behavior seemed unusual for
concerted reductive elimination9 but appeared to parallel the
nucleophilicity of the corresponding OR ligand. Therefore, we
(1) Present address: Paul M. Gross Chemical Laboratories, Duke
University, Durham, NC 27708-0346.
(2) (a) Palucki, M.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc.
1996, 118, 10333. (b) Palucki, M.; Wolfe, J. P.; Buchwald, S. L. J. Am.
Chem. Soc. 1997, 119, 3395.
(3) Widenhoefer, R. A.; Zhong, H. A.; Buchwald, S. L. J. Am. Chem.
Soc. 1997, 119, 6787.
(4) For other examples of C-O reductive elimination, see: (a) Komiya,
S.; Akai, Y.; Tanaka, K.; Yamamoto, T.; Yamamoto, A. Organometallics
1985, 4, 1130. (b) Mann, G.; Hartwig, J. F. J. Am. Chem. Soc. 1996, 118,
13109. (c) Koo, K.; Hillhouse, G. L.; Rheingold, A. L. Organometallics
1995, 14, 456. (d) Matsunaga, P. T.; Mavropoulos, J. C.; Hillhouse, G. L.
Polyhedron 1995, 14, 175. (e) Han, R.; Hillhouse, G. L. J. Am. Chem. Soc.
1997, 119, 8135.
(5) (a) For examples of C-S reductive elimination, see: Baran˜ano, D.;
Hartwig, J. F. J. Am. Chem. Soc. 1995, 117, 2937. (b) For examples of
C-N reductive elimination, see: Driver, M. S.; Hartwig, J. F. J. Am. Chem.
Soc. 1997, 118, 8232.
(6) (a) Collman, J. P.; Hegedus, L. S.; Norton, J. R.; Jinke, R. G. In
Principles and Applications of Organotransition Metal Chemistry; Univer-
sity Science: Mill Valley, CA, 1987; p 322. (b) Stille, J. K. In The Chemistry
of the Metal-Carbon Bond, Vol II. The Nature and CleaVage of the Metal-
Carbon Bond; Hartley, F. R., Patai, S., Eds.; Wiley: New York, 1985; pp
625-787.
(7) (a) Stang, P. J.; Kowalski, M. H. J. Am. Chem. Soc. 1989, 111, 3356.
(b) Braterman, P. S.; Cross, R. J.; Young, G. B. J. Chem. Soc., Dalton
Trans. 1977, 1892. (c) Braterman, P. S.; Cross, R. J.; Young, G. B. J. Chem.
Soc., Dalton Trans. 1977, 1306.
(8) (a) Michelin, R. A.; Faglia, S.; Uguagliati, P. Inorg. Chem. 1983,
22, 1831. (b) Abis, L.; Sen, A.; Halpern, J. J. Am. Chem. Soc. 1978, 100,
2915.
(9) (a) Jones, W. D.; Kuykendall, V. L. Inorg. Chem. 1991, 30, 2615.
(b) Brown, J. M.; Guiry, P. J. Inorg. Chim. Acta 1994, 220, 249.
S0002-7863(98)00658-1 CCC: $15.00 © 1998 American Chemical Society
Published on Web 06/19/1998

Electronic Dependence of C-O ReductiVe Elimination
J. Am. Chem. Soc., Vol. 120, No. 26, 1998 6505
Scheme 2
Scheme 3
Scheme 4
spectroscopies.10 In addition, the m-cyanophenyl derivative 1i
was particularly stable and was isolated and characterized by
spectroscopy and elemental analysis.
Thermolysis of Palladium (Aryl)alkoxide Complexes. As
was previously observed for the p-cyanophenyl complex 1a,3
thermolysis of the p-carboxaldehyde neopentoxide complex 1b
led to C-O reductive elimination without detectable â-hydride
elimination. For example, when a THF-d8 solution of 1b was
warmed from -50 to 23 °C in an NMR probe, 1b began to
decompose. Decomposition of 1b at 23 °C obeyed first-order
kinetics to >3 half-lives with an observed rate constant of kobs
considered an alternative mechanism for C-O reductive elimi-
nation initiated by inner-sphere attack of the alkoxide ligand at
the ipso-carbon atom of the palladium-bound aryl group via a
Meisenheimer intermediate or transition state such as I (Scheme
2, path b). In an effort to further probe the intimate mechanism
of palladium-mediated C-O reductive elimination, we have
investigated the rate and efficiency of the thermal decomposition
of palladium (aryl)neopentoxide complexes as a function of the
electronic nature of the palladium-bound aryl group.
) 1.26 × 10-3 s-1 (t1/2 ) 9.2 min, ∆Gq ) 21.4 kcal mol-1
)
(Scheme 4, Figure 1, Table 1). 1H NMR and GC analysis of
the resulting black solution and comparison with authentic
sample revealed the formation of p-neopentoxybenzaldehyde
in quantitative yield (95 ( 5%). Significantly, the rate of C-O
reductive elimination from 1b was nearly an order of magnitude
faster than decomposition of p-cyanophenyl derivative 1a under
comparable conditions.3
Results
Formation of Palladium (Aryl)neopentoxide Complexes.
The palladium (aryl)neopentoxide complexes [P-P]Pd(Ar)-
OCH2CMe3 [P-P ) Tol-BINAP or BINAP; Ar ) p-C6H4CHO
(1b), p-C6H4COPh (1c), p-C6H4NO2 (1d), o-C6H4NO2 (1e),
o-C6H4CN (1f)), p-C6H4Cl (1g), m-C6H4NO2 (1h), m-C6H4CN
(1i), (dppf)Pd(p-C6H4NO2)OCH2CMe3, (2a) and (dppf)Pd(m-
C6H4CN)OCH2CMe3 (2b)] [BINAP ) 2,2′-bis(diphenylphos-
phino)-1,1′-binaphthyl; dppf ) 1,1′-bis(diphenylphosphino)-
ferrocene] were prepared from reaction of the appropriate
palladium (aryl)halide complex [P-P]Pd(Ar)X [X ) Br, I] and
1 equiv of potassium neopentoxide in THF-d8 and were
Thermolysis of related derivatives 1c-f led in each case to
first-order decay to >3 half-lives with formation of the
corresponding aryl ether in quantitative yield.11 However, the
rate of decomposition depended strongly on the nature of the
(10) 1H and 31P NMR spectra of complexes 1b-i were straightforward
and were analogous to those of 1a. However, NMR spectra of o-substituted
complexes 1e and 1f and the corresponding aryl halide complexes [(()-
BINAP]Pd(o-C6H4NO2)(I) and [(S)-Tol-BINAP]Pd(o-C6H4CN)(Br) were
complicated by the presence of two isomers in THF-d8. For example, [(()-
BINAP]Pd(o-C6H4NO2)(I) displayed a 3:2 ratio of isomers, [(S)-Tol-BINAP]-
Pd(o-C6H4CN)(Br) displayed a 2:1 ratio of isomers, 1e displayed ∼10:1
ratio of isomers at - 55 °C, and 1f displayed a 2:1 ratio of isomers at 23
°C. These isomers presumably correspond to rotamers generated by hindered
rotation of the phosphorus-bound aryl group proximal to the palladium-
bound o-substituted aryl group. However, [(()-BINAP]Pd(o-C6H4NO2)(I)
and [(S)-Tol-BINAP]Pd(o-C6H4CN)(Br) displayed a single isomer in CDCl3.
The solvent-dependence of isomer formation is not clear.
characterized without isolation by low-temperature 1H and 31
P
NMR spectroscopy (Scheme 3). In all cases, the desired
alkoxide complex was formed as the exclusive species in
1
quantitative yield (g95%) as indicated by H and 31P NMR

6506 J. Am. Chem. Soc., Vol. 120, No. 26, 1998
Widenhoefer and Buchwald
(2c) decomposed at 55 °C with formation of p-neopentoxyben-
zonitrile (46%) and pivaldehyde (36%).3 Substitution of p-
cyanophenyl with a more electron-deficient aryl group led to
dramatic rate acceleration and enhanced yields of aryl ether.
For example, when a freshly prepared solution of the p-
nitrophenyl complex 2a was warmed from -50 to 23 °C, rapid
decomposition occurred (t1/2 ) 7.1 min) with formation of
p-neopentoxynitrobenzene (81%) and pivaldehyde (12%) (Scheme
5). In contrast, thermolysis of the m-cyanophenyl derivative
2b formed pivaldehyde in 73% yield without generation of
detectable quantities m-neopentoxybenzonitrile. The strong
tendency of dppf palladium alkoxide complexes to undergo
â-hydride elimination was also noted by Hartwig in a related
study.4b
Discussion
Palladium-mediated C-O reductive elimination was facili-
tated by the presence of substituents on the palladium-bound
aryl group suitable for the delocalization of negative charge,
while simple electron-withdrawing groups failed to facilitate
reductive elimination. For example, while reductive elimination
occurred readily from the p-NO2- (σ ) 0.78) and p-CN (σ )
0.67) -substituted palladium aryl complexes 1d and 1a, the
corresponding m-nitrophenyl (1h) and m-cyanophenyl deriva-
tives (1i) were resistant toward C-O reductive elimination
despite the significant σ values for m-NO2 (σ ) 0.71) and m-CN
(σ ) 0.56).13 Likewise, despite the similar σ values for p-CHO
(σ ) 0.22) and p-Cl (σ ) 0.23), p-benzaldehyde complex 1b
underwent reductive elimination readily at room temperature,
while p-chlorophenyl derivative 1g failed to undergo C-O
reductive elimination upon extended thermolysis at 47 °C (Table
1). Consistent with this trend, the o-NO2- and o-CN-substituted
complexes 1e and 1f underwent C-O reductive elimination in
quantitative yield.12
In an effort to quantify the relationship between rate of C-O
reductive elimination and the degree of resonance stabilization
of the palladium-bound aryl group, ∆Gq was plotted versus the
parameter σ- for the substituents on the palladium-bound aryl
group (Figure 3).14 Despite a fair amount of scatter due to the
narrow range of σ- values, a linear free energy relationship was
observed between ∆Gq and σ- where F ) 6.4 ( 1.6.15 It is
noteworthy that this correlation parallels that observed in
aromatic nucleophilic substitution, which is accelerated dramati-
cally by the presence of resonance stabilizing groups.16 For
example, the rate of reaction of methoxide ion with para-
substituted o-nitrochlorobenzene derivatives displayed a linear
free energy relationship with σ- where F ) 3.90,17 while the
rate of reaction of methoxide ion with para-substituted chlo-
Figure 1. First-order plot for the thermal decomposition of 1b at 23
°C in THF-d8.
palladium-bound aryl group. For example, decomposition of
p-nitrophenyl derivative 1d at 23 °C was too fast to measure
by 1H NMR spectroscopy but occurred at a measurable rate at
-1 °C (t1/2 ) 14 min). The o-nitrophenyl complex 1e also
decomposed readily at -1 °C (t1/2 ) 9 min). In contrast,
decomposition of p-benzophenone complex 1c was sluggish at
23 °C but occurred readily at 38 °C (t1/2 ) 8.6 min). Although
o-cyanophenyl derivative 1f decomposed slowly even at 62 °C
(t1/2 ) 21 min), o-neopentoxybenzonitrile was generated in
quantitative yield (99 ( 5%), without detectable formation of
pivaldehyde. Overall, the rate of C-O reductive elimination
decreased in the order o-NO2 (1e) > p-NO2 (1d) > p-CHO
(1b) > p-COPh (1c) > p-CN (1a)3 > o-CN (1f).12
In contrast to complexes 1a-f, thermolysis of p-chlorophenyl
derivative 1g and the m-nitrophenyl and m-cyanophenyl deriva-
tives 1h and 1i led to decomposition without formation of
detectable quantities of aryl ether. Furthermore, thermolysis
of 1g-i produced kinetics consistent with auto-catalytic de-
composition. For example, heating a solution of p-chlorophenyl
complex 1g at 47 °C in THF-d8 led to no detectable decomposi-
tion (<5%) after 20 min. However, continued heating at 47
°C led to rapid decomposition over the following 20 min with
formation of chlorobenzene in 40% yield (Figure 2). Signifi-
cantly, no detectable quantities of p-neopentoxychlorobenzene
or pivaldehyde were observed. Thermolysis of the m-nitrophen-
yl derivative 1h and m-cyanophenyl complex 1i led to analogous
auto-catalytic decomposition with no detectable formation of
aryl ether. The mechanisms of these auto-catalytic decomposi-
tion pathways were not investigated further.
We also investigated briefly the electronic dependence of
C-O reductive elimination from dppf-ligated palladium neo-
pentoxide complexes. In contrast to the BINAP derivatives 1a-
f, these complexes were susceptible to â-hydride elimination,
leading to the formation of mixtures of aryl ether and pivalde-
hyde upon thermolysis. For example, we previously observed
that p-cyanophenyl derivative (dppf)Pd(p-C6H4CN)(OCH2CMe3)
(13) Ritchie, C. D.; Sager, W. F. Prog. Phys. Org. Chem. 1964, 2, 323.
(14) Lowry, T. H.; Richardson, K. S. Mechanism and Theory in Organic
Chemistry, 3rd ed.; Harper and Row: New York, 1987; pp 149-151.
(15) Free energy was employed instead of ln k in an effort to compensate
for the slightly different decomposition temperatures for the various
compounds. The σ- value for p-COPh was estimated from the σ- value
for p-COMe. Attempts to generate [BINAP]Pd(p-C6H4COMe)(OCH2CMe3)
by treatment of [BINAP]Pd(p-C6H4COMe)(Br) with KOCH2CMe3 led to
rapid decomposition without formation of the palladium (aryl)alkoxide
complex. A plot of ∆Gq versus σ- including only p-NO2, p-CN, and p-CHO
gave F ) 8.4 ( 2.0.
(11) In each case, formation of aryl ether was confirmed by 1H NMR
and GC analyses and comparison with authentic sample.
(16) (a) Ehrenson, S.; Brownlee, R. T. C.; Taft, R. W. Prog. Phys. Org.
Chem. 1973, 10, 1. (b) Wells, P. R.; Ehrenson, S.; Taft, R. W. Prog. Phys.
Org. Chem. 1968, 6, 147.
(12) Our previous results indicate that C-O reductive elimination from
palladium BINAP and palladium Tol-BINAP complexes occurs with
comparable rate and efficiency. For example, the rate of thermal decomposi-
tion of [BINAP]Pd(p-C6H4CN)(OCH2CMe3) at 47 °C was kobs ) 15.1 ×
10-4 s-1 to form aryl ether in 87% yield (NMR).2b We were unable to
isolate the complete series of palladium aryl halide derivatives with either
BINAP or Tol-BINAP due to the wide range in solubility of the complexes
as a function of phosphorous- and palladium-bound aryl groups.
(17) Miller, J. J. Chem. Soc. 1952, 3550 (b) Miller, J. Aust. J. Chem.
1956, 9, 61. (c) Miller, J. J. Am. Chem. Soc. 1954, 76, 448. (d) Heppolette,
R. L.; Miller, J. J. Chem. Soc. 1956, 2329. (e) Miller, J.; Parker, A. J.;
Bolto, B. A. J. Am. Chem. Soc. 1957, 79, 93. (f) Miller, J.; Parker, A. J.
Aust. J. Chem. 1958, 11, 302. (g) Chan, T. L.; Miller, J.; Stansfield, F. J.
Chem. Soc. 1964, 1213.

Electronic Dependence of C-O ReductiVe Elimination
J. Am. Chem. Soc., Vol. 120, No. 26, 1998 6507
Table 1. First-Order Rate Constants and Product Distribution for Thermal Decomposition of BINAP and Tol-BINAP Derivatives 1a-i and
2a-c
temp
(°C)
kobs
∆Gq
yield
yield
PdOR
Ar
σa
σ- a
(s-1 × 104)b
(kcal mol-1
)
ArOR ((5%)c
Me3CHO ((5%)c
1ad
1b
1c
1d
1e
1f
1g
1h
1i
p-CN
0.66
0.22
0.50e
0.78
0.90
1.13
0.87e
1.24
47
23
38
-1
-1
62
47
62
47
23
47
55
15.3
12.6
13.5
8.18
12.2
5.48
- -f
- -f
- -f
16.2
13.5
14.3
22.9
21.4
22.2
19.8
19.6
24.3
85
95
98
102
103
99
<2
<2
<2
81
<2
<2
<2
<2
<2
<2
24
p-CHO
p-COPh
p-NO2
o-NO2
o-CN
p-Cl
0.23
0.56
0.71
0.78
0.56
0.66
m-CN
m-NO2
p-NO2
m-CN
p-CN
2a
2b
2c
1.24
0.90
21.2
23.0
23.5
12
73
36
<2
46
1
a Hammett values taken from ref 12. b See ref 12. c Determined by H NMR spectroscopy. d Data taken from ref 2b. e σ and σ- estimated from
the respective values for p-COMe. f First-order kinetics not obeyed.
Figure 2. Plot of concentration versus time for the thermal decomposi-
tion of 1g at 47 °C in THF-d8.
Figure 3. Plot of ∆Gq versus σ- of the palladium-bound aryl
substituent for thermolysis of complexes 1a-d, where F ) 6.4 ( 1.6.
Scheme 5
state such as III followed by rapid Pd-C bond cleavage. This
concerted pathway is analogous to the insertion-type C-H19
and C-C20 reductive elimination pathways predicted by theo-
retical studies.
Although our data do not rule out a mechanism initiated by
rapid and reversible alkoxide dissociation followed by outer-
sphere attack of the alkoxide at the ipso-carbon atom, the
proposed inner-sphere mechanism is in accord with the activa-
tion parameters determined for reductive elimination from 1a
[∆Hq ) 19.8 ( 0.8 kcal mol-1, ∆Sq ) -9.3 ( 0.3 eu]2b and is
supported by the proclivity of both CO21 and isocyanides22 to
robenzenes displayed a linear free energy relationship with σ-
undergo R-migratory insertion into group 10 metal-alkoxide
bonds. The high nucleophilicity of alkoxide ligands in late
where F ) 8.47.18
The close analogy between the electronic dependence of C-O
reductive elimination and aromatic nucleophilic substitution
points to the buildup of considerable negative charge in the
palladium-bound aryl group in the transition state for C-O
reductive elimination. We propose that the accumulation of
negative charge in the palladium-bound aryl group in the
transition state for C-O reductive elimination results from inner-
sphere attack of the alkoxide oxygen atom at the ipso-carbon
atom of the palladium-bound aryl group. For example, our
kinetics are consistent with rapid and reversible generation of
intermediate I followed by rate-limiting Pd-C heterolysis to
form Pd[L-L] and aryl ether via a charge-separated transition
state such as II (Scheme 6). Alternatively, our kinetics are
consistent with rate-limiting alkoxide migration via a transition
(19) Calhorda, M. J.; Brown, J. M.; Cooley, N. A. Organometallics 1991,
10, 1431.
(20) Silvestre, J.; Calhorda, M. J.; Hoffmann, R.; Stoutland, P. O.;
Bergman, R. G. Organometallics 1986, 5, 1841.
(21) (a) Dockter, D. W.; Fanwick, P. E.; Kubiak, C. P. J. Am. Chem.
Soc. 1996, 118, 4846. (b) Bryndza, H. E.; Calabrese, J. C.; Wreford, S. S.;
Organometallics 1984, 3, 1603. (c) Bryndza, H. E.; Kretchmar, S. A.; Tulip,
T. H. J. Chem. Soc., Chem. Commun. 1985, 977. (d) Michelin, R. A.; Napoli,
M.; Ros, R. J. Organomet. Chem. 1979, 175, 239. (e) Bennett, M. A.;
Yoshida, T. J. Am. Chem. Soc. 1978, 100, 1750. (f) Arnold, D. P.; Bennett,
M. A.; Crisp, G. T.; Jeffery, J. C. AdV. Chem. Ser. 1982, 196, 195. (g)
Bennett, M. A. J. Organomet. Chem. 1986, 300, 7. (h) Bennett, M. A.;
Rokicki, A. Aust. J. Chem. 1985, 38, 1307. (i) Appleton, T. G.; Bennett,
M. A. J. Organomet. Chem. 1973, 55, C88. (j) Bennett, M. A. J. Mol. Catal.
1987, 41, 1. (k) Bennett, M. A.; Rokicki, A. J. Organomet. Chem. 1983,
244, C31. (l) Bennett, M. A.; Rokicki, A. J. Organometallics 1985, 4, 180.
(m) Bryndza, H. E. Organometallics 1985, 4, 1686.
(18) Miller, J.; Wan, K. Y. J. Chem. Soc. 1963, 3492.
(22) Michelin, R. A.; Ros, R. J. Organomet. Chem. 1979, 169, C42.

6508 J. Am. Chem. Soc., Vol. 120, No. 26, 1998
Widenhoefer and Buchwald
Scheme 6
transition metal complexes has been documented23 and is
believed responsible for the higher rates of alkoxide migratory
insertion relative to corresponding alkyl migratory insertion.24
Likewise, migratory insertion of CO into a M-C bond displays
electronic effects analogous to those observed for C-O reduc-
tive elimination. For example, addition of a Lewis acid such
as AlCl3 to a metal alkyl carbonyl complex often leads to
dramatic (108) increase in the rate of CO migratory insertion
due to polarization of the carbonyl C-O bond.25
The electronic dependence of C-O reductive elimination
differs markedly from that of C-C reductive elimination but
displays similarities with both C-S and C-N reductive
elimination.5,27 For example, both experiment27,28 and theory29
indicate that the rate of C-C reductive elimination increases
with the increasing σ-donating ability of the eliminating ligands.
In contrast, both C-S5a reductive elimination from palladium
(aryl)thiolate complexes and C-N5b,26 reductive elimination
from palladium (aryl)amido complexes were accelerated by the
presence of electron-withdrawing groups on the palladium-
bound aryl group. In both cases, the rates did not correspond
linearly to the σ values of the respective para-substituents, but
were dependent on both inductive (σ) and resonance (σ-) effects.
In addition, the rate of C-N elimination increased with the
increasing nucleophilicity of the respective amide, consistent
with reductive elimination proceeding to some degree via an
intramolecular nucleophile/electrophile pathway. However, in
contrast to these C-X reductive eliminations, the rate of C-O
reductive elimination from palladium (aryl)alkoxide complexes
depends predominantly on resonance effects and to little extent
on inductive effects.
The proposed insertion mechanism does not appear to be the
only one available for C-O reductive elimination. For example,
intramolecular C-O reductive elimination occurs readily under
both catalytic2a and stoichiometric2b conditions from palladium
complexes which do not possess resonance-stabilizing groups
on the palladium-bound aryl group. Similarly, we have previ-
ously observed catalytic cross-coupling of p-tert-butylbenzene
and sodium tert-butoxide in the presence of mixtures of
Pd2(dba)3 (dba ) trans,trans-dibenzylideneacetone) and Tol-
BINAP. These results indicate the availability, at least in some
instances, of energetically accessible alternative pathways for
the reductive elimination process to form C-O bonds.
Conclusions
C-O reductive elimination from palladium (aryl)neopentox-
ide complexes was facilitated by the presence of substituents
on the palladium-bound aryl group capable of delocalizing
negative charge. The rate data displayed a scattered yet linear
free energy relationship with σ-, generating a F value compa-
rable to that observed for uncatalyzed aromatic nucleophilic
aromatic substitution. These observations are consistent with
the buildup of negative charge in the palladium-bound aryl group
in the transition state for C-O reductive elimination. This
charge accumulation can be accounted for by a mechanism
initiated by inner-sphere nucleophilic attack of the alkoxide
ligand at the ipso-carbon atom of the palladium-bound aryl
group to form a zwitterionic Meisenheimer intermediate or
transition state. Significantly, both the electronic dependence
and mechanism of C-O reductive elimination differs markedly
from that of C-C reductive elimination. However, the proposed
mechanism does not appear to be the only mechanism available
for C-O reductive elimination.
(23) (a) Kegley, S. E.; Schaverien, C. J.; Freudenberger, J. H.; Bergman,
R. G.; Nolan, S. P.; Hoff, C. D. J. Am. Chem. Soc. 1987, 109, 6563. (b)
Osakada, K.; Kim, Y. J.; Yamamoto, A. J. Organomet. Chem. 1990, 382,
303. (c) Kim, Y. J.; Osakada, K.; Takenaka, A.; Yamamoto, A. J. Am.
Chem. Soc. 1990, 112, 1096. (d) Osakada, K.; Kim, Y. J.; Tanaka, M.;
Ishiguro, S.; Yamamoto, A. Inorg. Chem. 1991, 30, 197. (e) Shubina, E.
S.; Belkova, N. V.; Krylov, A. N.; Vorontsov, E. V.; Epstein, L. M.; Gusev,
D. G.; Niedermann, M.; Berke, H. J. Am. Chem. Soc. 1996, 118, 1105.
(24) Bryndza, H. E.; Tam, W. Chem. ReV. 1988, 88, 1163.
(25) (a) McLain, S. J. J. Am. Chem. Soc. 1983, 105, 6355. (b) Labinger,
J. A.; Bonfiglio, J. N.; Grimmet, D. L.; Masuo, S. T.; Shearin, E.; Miller,
J. S. Organometallics 1983, 2, 733. (c) Grimmett, D. L.; Labinger, J. A.;
Bonfiglio, J. N.; Masuo, S. T.; Shearin, E.; Miller, J. S. Organometallics
1983, 2, 1325. (d) Butts, S. B.; Richmond, T. G.; Shriver, D. F. Inorg.
Chem. 1981, 20, 278. (e) Grundy, K. R.; Roper, W. R. J. Organomet. Chem.
1981, 216, 255. (f) Butts, S. B.; Straus, S. H.; Holt, E. M.; Stimson, R. E.;
Alcock, N. W.; Shriver, D. F. J. Am. Chem. Soc. 1980, 102, 5093. (g)
Richmond, T. G.; Basolo, F.; Shriver, D. F. Inorg. Chem. 1982, 21, 1272.
(26) Hartwig, J. F.; Richards, S.; Baran˜ano, D.; Paul, F. J. Am. Chem.
Soc. 1996, 118, 3626.
Experimental Section
(27) Milstein, D.; Stille, J. K. J. Am. Chem. Soc. 1979, 101, 4981.
(28) Komiya, S.; Abe, Y.; Yamamoto, A.; Yamamoto, T. Organome-
tallics 1983, 2, 1466.
(29) Tatsumi, K.; Hoffmann, R.; Yamamoto, A.; Stille, J. Bull. Chem.
Soc. Jpn. 1981, 54, 7.
General Methods. All manipulations and reactions were performed
under an atmosphere of nitrogen or argon in a glovebox or by standard
Schlenk techniques. NMR spectra were recorded on a Varian XL-300

Electronic Dependence of C-O ReductiVe Elimination
J. Am. Chem. Soc., Vol. 120, No. 26, 1998 6509
spectrometer at 23 °C unless otherwise noted. Gas chromatography
was performed on a Hewlett-Packard model 5890 gas chromatograph
using a 25 m poly(dimethylsiloxane) capillary column. Elemental
analyses were performed by E+R Microanalytical Laboratories (Corona,
NY). Diethyl ether, hexane, and THF-d8 were distilled from solutions
of sodium/benzophenone ketyl under argon or nitrogen. Pd2(dba)3, P(o-
tolyl)3, (R)-Tol-BINAP, (S)-BINAP, dppf (Strem), aryl halides (Ald-
rich), and DMF (Aldrich, anhydrous) were used as received. KOCH2-
CMe3 was synthesized from reaction of anhydrous neopentanol
(Aldrich) and 1 equiv of KH in THF.
Palladium (Aryl)halide Dimers. Palladium (aryl)halide dimers
were prepared from Pd2(DBA)3 (1.0 g, 1.1 mmol), P(o-tolyl)3 (1.3 g,
4.3 mmol), and aryl halide (1.75 g) in benzene (60 mL) at room-
temperature employing procedures analogous to published protocols.30
{Pd[P(o-tolyl)3](p-C6H4NO2)(µ-I)}2. Tan solid (79%). Anal.
Calcd (found) for C54H50I2N2O4P2Pd2: C, 49.15 (48.93); H, 3.82 (4.02).
{Pd[P(o-tolyl)3](o-C6H4NO2)(µ-I)}2. Brown solid (62%). Anal.
Calcd (found) for C54H50I2N2O4P2Pd2: C, 49.15 (49.37); H, 3.82 (3.98).
{Pd[P(o-tolyl)3](m-C6H4NO2)(µ-I)}2. Tan solid (77%). Anal.
Calcd (found) for C54H50I2N2O4P2Pd2: C, 49.15 (49.26); H, 3.82 (3.85).
{Pd[P(o-tolyl)3](p-C6H4Cl)(µ-Br)}2. Bright yellow solid (71%).
Anal. Calcd (found) for C54H50Br2Cl2P2Pd2: C, 53.85 (54.04); H, 4.18
(4.44).
{Pd[P(o-tolyl)3](m-C6H4CN)(µ-Br)}2. Yellow powder (67%). Anal.
Calcd (found) for C56H50Br2O2P2Pd2: C, 56.73 (56.79); H, 4.25 (4.27).
{Pd[P(o-tolyl)3](o-C6H4CN)(µ-Br)}2. Yellow powder (72%). Anal.
Calcd (found) for C56H50Br2O2P2Pd2: C, 56.73 (56.98); H, 4.25 (4.55).
{Pd[P(o-tolyl)3](p-C6H4COPh)(µ-Br)}2. Cream-colored solid (53%).
Anal. Calcd (found) for C68H60Br2O2P2Pd2: C, 60.78 (61.00); H, 4.50
(4.75).
{Pd[P(o-tolyl)3](p-C6H4CHO)(µ-Br)}2. Bright yellow solid (64%).
Anal. Calcd (found) for C56H52Br2O2P2Pd2: C, 56.45 (56.75); H, 4.40
(4.43).
Palladium (Aryl)halide Monomers. Palladium (aryl)halide mono-
mers were prepared from the respective palladium (aryl)halide dimer
(200 mg, 0.30 mmol), BINAP (220 mg, 0.35 mmol), Tol-BINAP (240
mg, 0.35 mmol), or dppf (200 mg, 0.36 mmol) employing procedures
analogous to published protocols,2b unless otherwise noted.
[(()-BINAP]Pd(p-C6H4CHO)(Br). Pale yellow microcrystals from
ether (84%). 1H NMR (THF-d8): δ 9.71 (s, 1 H), 8.02 (t, J ) 9.1
Hz), 7.82 (m, 3 H), 7.70-7.55 (m, 6 H), 7.45 (br s, 5 H), 7.42-7.31
(m, 3 H), 7.25-7.15 (m, 3 H), 7.12-6.90 (m, 8 H), 6.78-6.50 (m, 7
H). 31P{1H}NMR: δ 27.6 (d, J ) 38.3 Hz), 12.6 (d, J ) 38.9 Hz).
Anal. Calcd (found) for C51H37BrOP2Pd: C, 67.01 (67.18); H, 4.08
(4.17).
[(S)-BINAP]Pd(p-C6H4COPh)(Br). White solid from ether (73%).
1H NMR (THF-d8): δ 8.03 (t, J ) 8.7 Hz, 1 H), 7.88-7.78 (m, 3 H),
7.70-7.50 (m, 19 H), 7.17 (t, J ) 8.6 Hz, 6 H), 7.01 (t, J ) 7.4 Hz,
5 H), 6.80-6.50 (m, 9 H). 31P{1H}NMR: δ 27.9 (d, J ) 38.6 Hz),
12.4 (d, J ) 38.7 Hz). Anal. Calcd (found) for C57H41BrOP2Pd: C,
69.14 (69.10); H, 4.17 (3.99).
[(R)-Tol-BINAP]Pd(p-C6H4NO2)(I). Tan solid from hexane/ether
(62%) which contained traces of hexane (<5% by 1H NMR). 1H NMR
(THF-d8): δ 8.01 (t, J ) 8.0 Hz, 1 H), 7.84 (d, J ) 7.1 Hz, 1 H), 7.66
(m), 7.55 (m), 7.38 (t, J ) 8.3 Hz), 7.29 (d, J ) 6.7 Hz), 7.13 (t, J )
8.3 Hz, 2 H), 6.94 (m), 6.81 (d, J ) 6.3 Hz, 2 H), 6.54 (d, J ) 8.4 Hz,
1 H), 6.45 (d, J ) 7.2 Hz, 2 H), 6.33 (d, J ) 6.7 Hz, 2 H), 2.42 (s, 3
H), 2.15 (s, 3 H), 1.96 (s, 3 H), 1.95 (s, 3 H). 31P{1H}NMR (THF-d8):
δ 26.3 (d, J ) 37.8 Hz), 11.7 (d, J ) 37.8 Hz). Anal. Calcd (found)
for C54H44INO2P2Pd: C, 62.71 (62.97); H, 4.29 (4.28).
[(R)-Tol-BINAP]Pd(m-C6H4NO2)(I)‚CH2Cl2. Brown blocks from
CH2Cl2/hexane (37%). 1H NMR (THF-d8): δ 8.13 (d, J ) 8 Hz, 1
H), 7.99 (t, J ) 9.5 Hz, 1 H), 7.79 (d, J ) 8.4 HZ, 1 H), 7.74-7.20
(m, 16 H), 7.09-6.93 (m, 4 H), 6.83-6.76 (m, 4 H), 6.54 (d, J ) 8.5
Hz, 1 H), 6.44 (d, J ) 7.3 Hz, 2 H), 6.36 (d, J ) 7.1 Hz, 2 H), 2.40
(s, 3 H), 2.14 (s, 3 H), 1.96 (s, 3 H), 1.94 (s, 3 H). 31P{1H}NMR
(CDCl3): δ 21.5 (d, J ) 38.7 Hz), 10.1 (d, J ) 38.6 Hz). Anal. Calcd
(found) for C55H46Cl2INO2P2Pd: C, 59.03 (58.15); H, 4.14 (4.23).
[(()-BINAP]Pd(o-C6H4NO2)(I). Brown needles from Et2O (81%).
1H NMR (THF-d8): δ 8.20-6.40 (m, 36 H) (resonances corresponding
to a 3:2 ratio of isomers were observed). 31P{1H}NMR (THF-d8): δ
19.4 (d, J ) 38.5 Hz), 12.6 (d, J ) 38.6 Hz) [major isomer]; δ 17.8
(d, J ) 40.1 Hz), 14.8 (d, J ) 40.0 Hz) [minor isomer]. Anal. Calcd
(found) for C51H36INO2P2Pd: C, 61.87 (61.88); H, 3.66 (3.77).
[(R)-Tol-BINAP]Pd(m-C6H4CN)(Br). Cream-colored microcrystals
from ether (84%). 1H NMR (THF-d8): δ 7.96 (t, J ) 9.6 Hz, 1 H),
7.82-7.58 (m, 7 H), 7.50-7.24 (m, 9 H), 7.16-6.94 (m, 7 H), 6.92-
6.70 (m, 4 H), 6.57 (d, J ) 8.7 Hz, 1 H), 6.45 (d, J ) 7.5 Hz, 2 H),
6.35 (d, J ) 6.9 Hz, 2 H). 31P{1H}NMR (THF-d8): δ 23.1 (d, J )
38.1 Hz), 8.6 (d, J ) 37.7 Hz). Anal. Calcd (found) for C55H44BrNP2-
Pd: C, 68.30 (68.11); H, 4.59 (4.82).
[(S)-Tol-BINAP]Pd(o-C6H4CN)(Br). Cream-colored solid from
ether (74%). 1H NMR (THF-d8): in addition to aromatic resonances
at δ 8.50-6.40 (m, 36 H), resonances corresponding to a 2:1 mixture
of isomers were observed at δ 2.42 (s, 3 H), 1.95 (s, 3 H), 1.89 (s, 3
H), 2.12 (s, 3 H) [major isomer]; 2.40 (s, 3 H), 2.14 (s, 3 H), 1.97 (s,
3 H), 1.91 (s, 3 H) [minor isomer]. 31P{1H}NMR (THF-d8): δ 26.2
(d, J ) 34.8 Hz), 11.1 (d, J ) 34.6 Hz) [major isomer]; 24.6 (d, J )
35.9 Hz), 13.3 (d, J ) 36.2 Hz) [minor isomer]. Anal. Calcd (found)
for C55H44BrNP2Pd: C, 68.30 (68.57); H, 4.59 (4.80).
[(S)-BINAP]Pd(p-C6H4Cl)(Br). Yellow microcrystals from ether
(81%), which contained traces of ether (<5% by 1H NMR). 1H NMR
(THF-d8): δ 7.97 (t, J ) 8.7 Hz, 1 H), 7.86-7.76 (m, 3 H), 7.66-
7.56 (m, 4 H), 7.50-7.30 (m, 9 H), 7.20-6.94 (m, 9 H), 6.80-6.50
(m, 8 H). 31P {1H} NMR: δ 27.9 (d, J ) 38.3 Hz), 12.5 (d, J ) 38.1
Hz). Anal. Calcd (found) for C50H36BrClP2Pd: C, 65.24 (65.23); H,
3.94 (4.03).
(dppf)Pd(p-C6H4NO2)(Br). Bright yellow solid (94%). 1H NMR
(CDCl3, 23 °C): δ 8.02 (m, 4 H), 7.48 (s, 6 H), 7.40-7.26 (m, 6 H),
7.19 (br t, J ) 7.5 Hz, 6 H), 7.10 (dt, J ) 7.2, 2.33 Hz, 6 H), 4.70 (d,
J ) 2.2 Hz, 2 H), 4.52 (s, 2 H), 4.16, (s, 2 H), 3.60 (d, J ) 2.3 Hz, 2
H). 31P {1H} NMR (CDCl3): δ 30.8 (d, J ) 31.1 Hz), 10.8 (d, J )
31.1 Hz). Anal. Calcd (found) for C40H32BrNFeO2P2Pd: C, 55.68
(55.76); H, 3.74 (3.83).
(dppf)Pd(m-C6H4CN)(Br). Bright yellow powder (90%). 1H NMR
(THF-d8): δ 8.00 (br s, 4 H), 7.48 (s, 8 H), 7.40-7.00 (m, 10 H), 6.77
(d, J ) 7.7 Hz, 1 H), 6.63 (d, J ) 7.6 Hz, 1 H), 4.77 (s, 1 H), 4.63 (s,
1 H), 4.54 (s, 1 H), 4.49 (s, 1 H), 4.15 (s, 2 H), 3.58 (br s, 2 H).
31P{1H}NMR (THF-d8): δ 31.3 (d, J ) 31.0 Hz), 10.7 (d, J ) 31.2
Hz). Anal. Calcd (found) for C41H32BrFeNP2Pd: C, 58.43 (58.71);
H, 3.83 (3.84).
Palladium (Aryl)neopentoxide Complexes. Palladium (aryl)-
neopentoxide complexes were generated in solution by addition of 1
equiv of a KOCH2CMe3 solution in THF-d8 to a THF-d8 solution (∼15
mM) of the appropriate palladium halide complex unless otherwise
noted.2b
[(()-BINAP]Pd(p-C6H4CHO)(OCH2CMe3) (1b). 1H NMR (THF-
d8, -52 °C): δ 9.70 (s, 1 H), 7.93 (t, J ) 9.6 Hz), 7.8-7.65 (m), 7.63
(t, J ) 8.7 Hz), 7.45 (br s), 7.30 (br s), 7.20-7.00 (m), 6.95-6.52
(m), 6.51 (br s), 2.79 (d, J ) 8.3 Hz, 1 H), 2.61 (d, J ) 8.3 Hz, 1 H),
0.11, (s, 9 H). 31P{1H}NMR (THF-d8, -55 °C): δ 31.8 (d, J ) 36.8
Hz), 14.7 (d, J ) 36.8 Hz).
[(S)-BINAP]Pd(p-C6H4COPh)(OCH2CMe3) (1c). 1H NMR (THF-
d8, -52 °C): δ 7.94 (t, J ) 9.0 Hz, 3 H), 7.78-6.95 (m, 30 H), 6.80-
6.50 (m, 8 H), 2.90 (d, J ) 8.5 Hz, 1 H) 2.73 (d, J ) 8.4 Hz, 1 H),
0.19 (s, 9 H). 31P{1H}NMR (THF-d8, -55 °C): δ 32.0 (d, J ) 36.7
Hz), 14.6 (d, J ) 36.8 Hz).
[(R)-Tol-BINAP]Pd(p-C6H4NO2)(OCH2CMe3) (1d). 1H NMR
(THF-d8, -54 °C): δ 7.80-6.70 (m, 36 H), 2.75 (d, J ) 8.0 Hz, 1 H),
2.66 (d, J ) 8.3 Hz, 1 H), 2.39 (s, 3 H), 2.14 (s, 3 H), 1.98 (s, 3 H),
1.96 (s, 3 H), 0.13 (s, 9 H). 31P{1H}NMR (THF-d8, -55 °C): δ 33.4
(d, J ) 36.7 Hz), 17.2 (d, J ) 36.7 Hz).
[(()-BINAP]Pd(o-C6H4NO2)(OCH2CMe3) (1e). 1H NMR (THF-
d8, -55 °C): (a ∼10:1 ratio of isomers was observed; peaks
corresponding to the major isomer are reported) δ 8.92 (m, 1 H), 8.46
(m, 1 H), 8.12-6.45 (m, 34 H), 2.60 (d, J ) 8.3 Hz, 1 H), 2.33 (d, J
) 8.3 Hz, 1 H), 0.04 (s, 9 H). 31P{1H}NMR (THF-d8, -55 °C): δ
29.7 (d, J ) 38.9 Hz), 18.4 (d, J ) 38.7 Hz).
(30) Widenhoefer, R. A.; Zhong, H. A.; Buchwald, S. L. Organometallics
1996, 15, 2745.

6510 J. Am. Chem. Soc., Vol. 120, No. 26, 1998
Widenhoefer and Buchwald
[(S)-Tol-BINAP]Pd(o-C6H4CN)(OCH2CMe3) (1f). 1H NMR (23
°C, THF-d8): (in addition to aromatic resonances at δ 9.01 (m), 8.40-
6.20 (m), and 5.60 (m), peaks corresponding to a 1:2 ratio of isomers
were observed) 2.69 (d, J ) 8.4 Hz, 1 H), 2.61 (d, J ) 9.1 Hz, 1 H),
2.39 (s, 3 H), 2.13 (s, 3 H), 1.97 (s, 3 H), 1.87 (s, 3 H), 0.09 (s, 9 H)
[major isomer]; 2.81 (br d, J ) 8.6 Hz, 1 H), 2.57 (d, J ) 8.8 Hz, 1
H), 0.09 (s, 9 H) [minor isomer]. 31P{1H}NMR (THF-d8): δ 30.0 (d,
J ) 36.7 Hz), 14.7 (d, J ) 35.4 Hz) [major isomer]; 28.3 (d, J ) 36.0
Hz), 17.4 (d, J ) 37.2 Hz) [minor isomer].
1.07 (s, 9 H). 13C{1H}NMR (THF-d8): δ 165.5, 142.5, 126.4, 114.4,
79.2, 32.5, 26.7. IR (neat, cm-1): 2960, 2871, 1607, 1514, 1366, 1336,
1260, 1173, 1111, 1041, 1006, 947, 752, 691. Anal. Calcd (found)
for C11H15NO3: C, 63.14 (63.20); H, 7.23 (7.15).
o-NO2C6H4OCH2CMe3. Reaction of 2-fluoronitrobenzene (510 mg,
3.62 mmol), neopentanol (375 mg, 4.26 mmol), and NaH (175 mg,
7.29 mmol) in DMF (15 mL) at room temperature for 15 min followed
by work up gave o-NO2C6H4OCH2CMe3 (621 mg, 82%) as a yellow
oil. 1H NMR (THF-d8) δ 7.81 (d, J ) 8.9 Hz, 1 H), 7.53 (t, J ) 7.9
Hz, 1 H), 7.21 (d, J ) 8.4 Hz, 1 H), 7.02 (t, J ) 7.7 Hz, 1 H), 3.78 (s,
2 H), 1.06 (s, 9 H). 13C{1H}NMR (THF-d8): δ 153.5, 134.7, 126.0,
125.9, 120.8, 115.3, 79.7, 32.7, 26.8. IR (neat, cm-1): 2961, 1609,
1526, 1352, 1287, 1257, 1010, 745. Anal. Calcd (found) for C11H15-
NO3: C, 63.14 (63.41); H, 7.23 (7.42).
p-PhC(O)C6H4OCH2CMe3. Reaction of 4-fluorobenzophenone
(712 mg, 3.56 mmol), neopentanol (385 mg, 4.38 mmol), and NaH
(175 mg, 7.29 mmol) in DMF (15 mL) at room temperature overnight
followed by work up gave p-COPhC6H4OCH2CMe3 (470 mg, 49%) as
a viscous, colorless oil. 1H NMR (THF-d8): δ 8.19 (d, J ) 9.2 Hz, 2
H), 7.07 (d, J ) 9.3 Hz, 2 H), 3.77 (s, 2 H), 1.07 (s, 9 H). 13C{1H}-
NMR (THF-d8): δ 194.6, 164.1, 139.7, 133.0, 132.4, 131.1, 130.4,
129.0, 114.8, 78.7, 32.5, 26.8. IR (neat, cm-1): 2942, 1654, 1601,
1508, 1477, 1317, 1281, 1247, 1171, 1149, 1047, 1016, 923, 849, 741,
637, 625. Anal. Calcd (found) for C18H20O2: C, 80.56 (80.36); H,
7.51, (7.55).
p-CNC6H4OCH2CMe3. Reaction of 4-bromobenzonitrile (1.33 g,
7.27 mmol), neopentanol (750 mg, 8.52 mmol), and NaH (350 mg,
14.6 mmol) in DMF (30 mL) at 80 °C for 2 h followed by work up
gave p-CNC6H4OCH2CMe3 (982 mg, 71%) as a colorless oil. 1H NMR
(THF-d8): δ 7.61 (d, J ) 8.1 Hz, 2 H), 7.04 (d, J ) 8.1 Hz, 2 H), 3.70
(s, 2 H), 1.05 (s, 9 H). 13C{1H}NMR (THF-d8): δ 163.7, 134.7, 119.4,
116.1, 105.1, 78.8, 32.5, 26.7. IR (neat, cm-1): 2958, 2225, 1607,
1510, 1477, 1304, 1255, 1171, 1045, 1013, 835. Anal. Calcd (found)
for C12H15NO: C, 76.16 (76.35); H, 7.99 (7.86).
p-HC(O)C6H4OCH2CMe3. p-Neopentoxybenzaldehyde was formed
via reduction of p-neopentoxybenzonitrile employing a procedure
analogous to known protocols.32 DIBAL (1.05 mL, 1.5 M, 1.58 mmol)
was added dropwise to a solution of p-CNC6H4OCH2CMe3 (262 mg,
1.38 mmol) in Et2O (10 mL) at -78 °C. The solution was stirred at
-78 °C for 30 min and then warmed to room temperature and stirred
for 1 h. After the reaction was quenched by addition of water (1 mL)
at 0 °C, 1 N HCl (25 mL) and ether (25 mL) were added, and the
resulting mixture was stirred vigorously for 15 min. The layers were
separated, and the aqueous phase was extracted with ether (3 × 20
mL). The combined organic fractions were dried (MgSO4), concen-
trated, and chromatographed (SiO2; hexane:EtOAc (12:1) to give
p-CHOC6H4OCH2CMe3 (152 mg, 58%) as a colorless oil. 1H NMR
(THF-d8): δ 9.85 (s, 1 H), 7.81 (d, J ) 8.5 Hz, 2 H), 7.06 (d, J ) 8.8
Hz, 2 H), 3.74 (s, 2 H), 1.07 (s, 9 H). 13C{1H}NMR (THF-d8): δ
190.4, 165.3, 132.3, 131.4, 115.5, 78.8, 32.5, 26.8. IR (neat, cm-1):
2957, 1690, 1604, 1576, 1510, 1477, 1365, 1313, 1256, 1216, 1160,
1046, 1014, 860, 832, 649, 616. Anal. Calcd (found) for C12H16O2:
C, 74.97 (75.05); H, 8.39 (8.49).
[(S)-BINAP]Pd(p-C6H4Cl)(OCH2CMe3) (1g). 1H NMR (23 °C,
THF-d8): δ 8.0-6.5 (m, 36 H), 2.85 (d, J ) 8.6 Hz, 1 H), 2.67 (d, J
) 8.0 Hz, 1 H), 0.18 (s, 9 H). 31P {1H} NMR (THF-d8, 23 °C): δ
30.4 (d, J ) 36.4 Hz), 14.1 (d, J ) 36.3 Hz).
[(R)-Tol-BINAP]Pd(m-C6H4NO2)(OCH2CMe3) (1h). 1H NMR (23
°C, THF-d8): δ 8.20 (d, J ) 7.3 Hz, 1 H), 7.90-7.20 (m, 17 H), 7.06
(m, 5 H), 6.81 (m, 4 H), 6.72 (d, J ) 8.6 Hz, 1 H), 6.45 (d, J ) 7.3
Hz, 2 H), 6.35 (d, J ) 7.3 Hz, 2 H), 2.80 (d, J ) 8.3 Hz, 1 H), 2.67
(d, J ) 8.4 Hz, 1 H), 2.37 (s, 3 H), 2.14 (s, 3 H), 1.98 (s, 3 H), 1.94
(s, 3 H), 0.19 (s, 9 H). 31P{1H}NMR (THF-d8, 23 °C): δ 29.6 (d, J )
37.2 Hz), 13.8 (d, J ) 37.3 Hz).
[(R)-Tol-BINAP]Pd(m-C6H4CN)(OCH2CMe3) (1i). A suspension
of Pd[(R)-Tol-BINAP](m-C6H4CN)Br (100 mg, 0.103 mmol) and
potassium neopentoxide (13 mg, 0.103 mmol) in Et2O (7 mL) was
stirred at room temperature for 5 min. The resulting orange suspension
was filtered through Celite, concentrated to ∼1 mL under vacuum, and
diluted with hexane (10 mL). The precipitate which formed over 2 h
was collected, washed with pentane, and dried under vacuum to give
1i (72 mg, 72%) as yellow microcrystals. 1H NMR (THF-d8): δ 7.84-
7.22 (m, 17 H), 7.18-6.64 (m, 11 H), 6.45 (d, J ) 7.3 Hz, 2 H), 6.33
(d, J ) 7.3 Hz, 2 H), 2.78 (d, J ) 8.6 Hz, 1 H), 2.65 (d, J ) 8.6 Hz,
1 H), 2.38 (s, 3 H), 2.20 (s, 3 H), 1.98 (s, 3 H), 1.95 (s, 3 H), 0.20 (s,
9 H). 31P{1H}NMR (THF-d8): δ 29.6 (d, J ) 36.8 Hz), 13.7 (d, J )
36.7 Hz). Anal. Calcd (found) for C60H55NOP2Pd: C, 73.69 (73.66);
H, 5.69 (5.97).
(dppf)Pd(p-C6H4NO2)(OCH2CMe2) (2a). 1H NMR (23 °C, THF-
d8): δ 8.21 (m, 4 H), 7.50-7.00 (m, 20 H), 4.86 (s, 2 H), 4.59 (s, 2
H), 4.21 (s, 2 H), 3.56 (s, 2 H, Cp), 2.70 (s, 2 H), 0.26 (s, 9 H). 31P-
{1H}NMR (THF-d8, 23 °C): δ 30.3 (d, J ) 31.8 Hz), 11.8 (d, J )
31.9 Hz).
1
(dppf)Pd(m-C6H4CN)(OCH2CMe3) (2b): H NMR (23 °C, THF-
d8): δ 8.21 (m, 4 H), 7.50-7.10 (m, 18 H), 6.79-6.63 (m, 2 H), 4.84
(s, 2 H), 4.58 (s, 2 H), 4.20 (s, 2 H), 3.55 (s, 2 H) 2.66 (s, 2 H), 0.22
(s, 9 H). 31P{1H} NMR (THF-d8, 23 °C): δ 32.4 (d, J ) 31.4 Hz),
13.2 (d, J ) 31.7 Hz).
Aryl Neopentyl Ethers. o-CNC6H4OCH2CMe3. A mixture of
2-bromobenzonitrile (500 mg, 2.73 mmol), neopentanol (289 mg, 3.3
mmol), and sodium hydride (131 mg, 5.5 mmol) in DMF (10 mL) was
stirred at 80 °C for 30 min. After the resulting dark brown suspension
was cooled to room temperature, ether (20 mL) and water (20 mL)
were added and the layers were separated. The aqueous layer was
extracted with Et2O (3 × 20 mL), and the combined organic layers
were washed with brine (30 mL), dried (MgSO4), and concentrated
using a rotary evaporator. The yellow residue was chromatographed
[SiO2; hexanes:EtOAc (12:1)]. The first band to elute was collected
and concentrated under vacuum to give o-CNC6H4OCH2CMe3 (199
mg, 31%) as a colorless oil which solidified on standing. 1H NMR
(THF-d8): δ 7.60-7.52 (m, 2 H), 7.11 (d, J ) 8.6 Hz, 1 H), 7.01 (t,
J ) 7.6 Hz, 1 H), 3.77 (s, 2 H), 1.05 (s, 9 H). 13C{1H}NMR (THF-
d8): δ 162.1, 135.1, 134.5, 121.6, 116.6, 113.6, 103.4, 79.5, 32.8, 27.0.
IR (neat, cm-1): 2960, 2223, 1598, 1478, 1478, 1402, 1364, 1297,
1260, 1164, 112, 1048, 1012, 842, 746. Anal. Calcd (found) for
C12H15NO: C, 76.16 (76.29); H, 7.99 (8.18).
Kinetic Measurements. Samples for kinetic analysis were prepared
from stock solutions of the appropriate palladium (aryl)halide complex
and were performed in oven-dried 5 mm thin-walled NMR tubes capped
with rubber septa. Solvent volume in the NMR tubes was calculated
from the solvent height measured at 25 °C according to the relationship
V (mL) ) H (mm) × 0.01384-0.006754. Kinetic data was obtained
1
by H NMR spectroscopy in the heated probe of a Varian XL-300
spectrometer. Probe temperatures were measured with an ethylene
glycol thermometer and were maintained at (0.5 °C throughout data
acquisition. Syringes employed in measuring liquids for kinetic
measurements were calibrated by mercury displacement and were
accurate to >95%. Error limits for rate constants refer to the standard
deviation of the corresponding least-squares-fit line or to the standard
deviation of two or more separate experiments.
p-NO2C6H4OCH2CMe3.31 Reaction of 4-fluoronitrobenzene (514
mg, 3.65 mmol), neopentanol (385 mg, 4.38 mmol), and NaH (175
mg, 7.29 mmol) in DMF (15 mL) at room temperature for 15 min
followed by work up gave p-NO2C6H4OCH2CMe3 (582 mg, 77%) as
a pale yellow oil which solidified on standing. 1H NMR (THF-d8) δ
8.19 (d, J ) 9.2 Hz, 2 H), 7.07 (d, J ) 9.3 Hz, 2 H), 3.77 (s, 2 H),
(31) (a) Sakai, T.; Yasuoka, N.; Minato, H.; Kobasashi, M. Chem. Lett.
1976, 1203. (b) Downie, I. M.; Heaney, H.; Kemp, G. Angew. Chem. 1975,
87, 357. (c) Danree, B.; Seyden-Penne, J. Bull. Soc. Chim. Fr. 1967, 415.
(32) (a) Proudfoot, J. R.; Li, X.; Djerassi, C. J. Org. Chem. 1985, 50,
2026. (b) Reitz, A. B.; Nortey, S. O.; Maryanoff, B. E.; Liotta, D.; Monahan,
R. J. Org. Chem. 1987, 52, 4191.

Electronic Dependence of C-O ReductiVe Elimination
J. Am. Chem. Soc., Vol. 120, No. 26, 1998 6511
Thermolysis of 1b. An NMR tube containing a freshly prepared
solution of 1b (12 mg, 1.2 × 10-2 mmol) and PhSiMe3 (0.70 mg, 4.6
× 10-2 mmol) in THF-d8 (0.70 mL) was placed in the probe of an
NMR spectrometer at 23 °C. The concentrations of 1b and p-
neopentoxybenzaldehyde were determined by integrating the tert-butyl
resonances for 1b (δ 0.17) and p-neopentoxybenzaldehyde (δ 1.06)
versus the trimethylsilyl resonance of PhSiMe3 (δ 0.25) in the 1H NMR
spectrum. The first-order rate constant for disappearance of 1b was
determined from a plot of ln{[1b]t/[1b]0} versus time (Figure 1). The
presence of p-HC(O)C6H4OCH2CMe3 was confirmed by GC analysis
and comparison to authentic sample. Kinetics and product analysis
for thermolysis of complexes 1c-h were performed analogously.
Acknowledgment. We thank the National Science Founda-
tion, Dow Chemical, and Pfizer for their support of this work.
R.W. was an NCI Postdoctoral Trainee supported by NIH
Cancer Training Grant CI T32CA09112.
JA9806581