Palladacyclic imidazoline-naphthalene complexes: Synthesis and catalytic performance in Pd(II)-catalyzed enantioselective reactions of allylic trichloroacetimidates

Article abstract of DOI:10.1021/jo2025724

A new family of air- and moisture-stable enantiopure C,N-palladacycles (PIN-acac complexes) were prepared in good overall yield in three steps from 2-iodo-1-naphthoic acid and enantiopure β-amino alcohols. Three of these PIN complexes were characterized by single-crystal X-ray analysis. As anticipated, the naphthalene and imidazoline rings of PIN-acac complexes 18a and 18b were canted significantly from planarity and projected the imidazoline substituents R¹ and R² on opposite faces of the palladium square plane. Fifteen PIN complexes were evaluated as catalysts for the rearrangement of prochiral (E)-allylic trichloroacetimidate 19 (eq 2) and the S_N2′ allylic substitution of acetic acid with prochiral (Z)-allylic trichloroacetimidate 23. Although these complexes were kinetically poor catalysts for the Overman rearrangement, they were good catalysts for the allylic substitution reaction, providing branched allylic esters in high yield. However, enantioselectivities were low to moderate and significantly less than that realized with palladacyclic complexes of the COP family. Computational studies support an anti-acetoxypalladation/syn-deoxypalladation mechanism analogous to that observed with COP catalysts. The computational study further suggests that optimizing steric influence in the vicinity of the carbon ligand of a chiral C,N-palladacycle, rather than near the nitrogen heterocycle, is the direction to pursue in future development of improved enantioselective catalysts of this motif.

Full text of DOI:10.1021/jo2025724

Article
pubs.acs.org/joc
Palladacyclic Imidazoline−Naphthalene Complexes: Synthesis and
Catalytic Performance in Pd(II)-Catalyzed Enantioselective Reactions
of Allylic Trichloroacetimidates
Jeffrey S. Cannon, James H. Frederich,† and Larry E. Overman*
Department of Chemistry, 1102 Natural Sciences II, University of California, Irvine, California 92697-2025, United States
S
* Supporting Information
ABSTRACT: A new family of air- and moisture-stable enantiopure C,N-
palladacycles (PIN-acac complexes) were prepared in good overall yield in
three steps from 2-iodo-1-naphthoic acid and enantiopure β-amino
alcohols. Three of these PIN complexes were characterized by single-
crystal X-ray analysis. As anticipated, the naphthalene and imidazoline rings
of PIN-acac complexes 18a and 18b were canted significantly from
planarity and projected the imidazoline substituents R1 and R2 on opposite
faces of the palladium square plane. Fifteen PIN complexes were evaluated
as catalysts for the rearrangement of prochiral (E)-allylic trichloroacetimidate 19 (eq 2) and the SN2′ allylic substitution of acetic
acid with prochiral (Z)-allylic trichloroacetimidate 23. Although these complexes were kinetically poor catalysts for the Overman
rearrangement, they were good catalysts for the allylic substitution reaction, providing branched allylic esters in high yield.
However, enantioselectivities were low to moderate and significantly less than that realized with palladacyclic complexes of the
COP family. Computational studies support an anti-acetoxypalladation/syn-deoxypalladation mechanism analogous to that
observed with COP catalysts. The computational study further suggests that optimizing steric influence in the vicinity of the
carbon ligand of a chiral C,N-palladacycle, rather than near the nitrogen heterocycle, is the direction to pursue in future
development of improved enantioselective catalysts of this motif.
of particular value. A structural feature of the C,N-palladacycle
catalyst motifs 5−8 that is believed to be important for
achieving high levels of enantioselectivity is the projection of
steric bulk both above and below the palladium square-plane
coordination sphere. Sterically differentiating the faces of the
palladium square plane is thought to control which prochiral
face of the coordinated alkene is activated in the enantiode-
termining step. As a result, most enantioselective palladacycle
catalysts rely on a planar chiral design to place steric elements
perpendicular to the cyclopalladated ring.11 However, methods
for preparing nonracemic planar-chiral palladacycles are
multistep, typically requiring diastereoselective cyclopalladation
of an auxiliary-appended metallocene or resolution of a racemic
complex.12 Consequently, this structural moiety adds complex-
ity to catalyst synthesis and limits the accessibility of analogues.
With the aforementioned considerations in mind, we have
explored the C,N-palladacyclic imidazoline naphthalene (PIN)
catalyst motif 9 (Figure 2). The modular nature of this
bidentate palladacycle, derived from a naphthalene and an
easily modified imidazoline ring, should allow rapid access to an
array of catalyst structures. Moreover, both the steric and
electronic environment around the metal center can be
systemically altered by variation of the imidazoline substituents
(R1, R2, and R3), the aromatic carbon ligand, and the ancillary
ligands (L) on palladium. Of central importance, we envisioned
INTRODUCTION
■
Enantioselective allylic substitution reactions are an essential
class of catalytic asymmetric processes that are used to prepare
a wide variety of enantioenriched chiral organic molecules.1 For
a number of years, we have been engaged in the development
of catalytic enantioselective transformations of allylic substrates
that employ palladium(II) complexes.2 Among these are allylic
alkylation reactions of trichloroacetimidate derivatives of
prochiral 2-alken-1-ols with carboxylic acid3 and phenol3c,4
nucleophiles (Figure 1). These reactions take place with
extraordinarily high branched-to-linear ratios (>100:1) and
have been shown to not proceed via η3-allylpalladium(0)
intermediates.3c Of the many palladium(II) complexes
investigated for the reaction of (Z)-allylic trichloroacetimidates
1 with carboxylic acids and phenols, the commercially available
5
catalysts [(Rp,S and Sp,R)-COP-OAc]2 (5 and ent-5) were
found to be optimal. For the transformation of (E)-allylic
trichloroacetimidates 4 to branched allylic phenols 3, the di-μ-
amidate dipalladium complexes [(Rp,S and Sp,R)-COP-
NHCOCCl3]2 (6 and ent-6) are preferred because they are
kinetically poor catalysts for the competing allylic rearrange-
ment to form 3-trichloroacetamido-1-alkenes.4b
Since our initial disclosure in 1997,6 a wide variety of
palladium(II) complexes have been evaluated as catalysts for
various transformations of allylic imidates.7 Among these,
palladacyclic catalysts,8 in particular C,N-palladacycles such as
the COP (5 and 6)5 and FOP complexes (e.g., 7)9 and related
complexes such as 8 developed by Peters10 have proven to be
Received: December 14, 2011
Published: January 30, 2012
© 2012 American Chemical Society
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adjustment of the electronic properties of the palladium
center.13 In this article, we report the preparation and structural
characterization of a family of PIN complexes 9 and an
evaluation of their performance as catalysts for the
enantioselective transformation of (Z)-allylic trichloroacetimi-
dates 1 to branched allylic esters 2 and phenols 3.
RESULTS AND DISCUSSION
■
Synthesis of PIN Complexes. Nitrogen-directed carbo-
palladation of an aromatic ring is the most direct route to C,N-
palladacycles;8,14 therefore, we began our investigation by
exploring the C−H activation of imidazoline 12 with various
Pd(II) electrophiles (Scheme 1). Starting from (S)-valinol-
Scheme 1. Attempted Synthesis of PIN Complexes by Direct
Cyclopalladation
Figure 1. Enantioselective reactions of allylic trichloroacetimidates
catalyzed by COP complexes 5 and 6.
derived β-hydroxyamide 10, enantiopure 1-naphthylimidazoline
12 was prepared by a conventional sequence that began by the
conversion of amide 10 to imidoyl chloride 11 by reaction with
SOCl2 at 85 °C.15 After evaporation of excess SOCl2 under
reduced pressure, crude 11 was allowed to react with 1.1 equiv
of isopropylamine in 5:1 CH2Cl2−Et3N at room temperature.
This two-step sequence provided imidazoline 12 in 70% yield
and >98% ee.16 However, attempted reaction of 12 with
stoichiometric amounts of various Pd(II) electrophiles under
common cyclopalladation conditions did not generate pallada-
cycle 13.8 For example, attempted cyclopalladation of 12 with
Pd(OAc)2 in refluxing acetic acid5 resulted in decomposition of
the imidazoline and formation of palladium black, whereas
attempted reaction at ambient temperature afforded a dark,
intractable reaction mixture. Attempted cyclopalladation of
imidazoline 12 using Pd(OAc)2, Na2PdCl4, or PdCl2(MeCN)2
under both neutral and basic reaction conditions either
returned 12 or resulted in decomposition. We reasoned that
the desired cyclopalladation reaction was complicated by the
steric strain associated with bringing the naphthyl and
imidazoline rings into the near coplanar orientation required
to promote C−H activation.
The inability to cyclopalladate imidazoline 12 led us to
explore forming palladacyclic PIN complexes by the oxidative
addition of Pd(0) with halogen-containing precursors. Accord-
ingly, 1-cyanonaphthalene (14) was deprotonated at low
temperature with lithium 2,2,6,6-tetramethylpiperide and the
resultant aryllithium species was quenched with I2 as reported
by Fraser to give 1-cyano-2-iodonaphthalene (Scheme 2).17
Hydrolysis of this crude product in refluxing HOAc containing
concentrated H2SO4 yielded the primary aryl amide, which was
Figure 2. Design of the palladacycle imidazoline−naphthalene (PIN)
catalyst motif.
creating an adjustable element of chirality by perturbation of
the steric interaction between the naphthalene ring and
imidazoline substituent R2. This approach would capitalize on
two potential steric contacts: (1) the interaction between R1
and R3 and the ancillary palladium ligands L and (2) the
interaction between R2 and the peri-C−H bond of the
naphthalene ring. When R1 and R2 are large (and R3 small),
these steric interactions should result in the cyclopalladated
complex being nonplanar, with the naphthalene and imidazo-
line rings canted out of plane and the substituents R1 and R2
oriented in an anti fashion. Furthermore, we anticipated that
the nitrogen substituent R2 would provide a handle to tune the
basicity of the donating nitrogen atom, allowing easy
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Scheme 2. Synthesis of (S)-PIN-acac Complexes 18
Table 1. Prepartion of (S)-PIN-acac Complexes 18 from
Imidazoline Precursors 17
a
entry
17
R1
R2
18
yield (%)
1
2
17a
17b
17c
17d
17e
17f
i-Pr
t-Bu
i-Pr
i-Pr
i-Pr
i-Pr
t-Bu
t-Bu
i-Pr
t-Bu
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
18a
18b
18c
18d
18e
18f
70
68
53
62
57
68
41
63
72
52
54
58
65
64
50
b
3
CH2Ph
CH(Ph)2
Cy
b
4
b
5
6
t-Bu
b
7
17g
17h
17i
t-Bu
18g
18h
18i
8
9
1-adamantyl
Ph
b
10
17j
Ph
18j
b
11
17k
17l
p-OMeC6H4
p-CF3C6H4
mesityl
Ts
18k
18l
b
12
b
13
17m
17o
17p
18m
18o
18p
14
15
C(O)t-Bu
a
b
Isolated yield. Prepared directly from amides 16a,b without
purification of the imidazoline intermediate. Reflects overall isolated
yield (3 steps).
overall yields directly from amides 16a,b without purification of
the labile imidazoline ligand. These monomeric complexes
displayed a high degree of stability, withstanding silica gel
chromatography and prolonged exposure to air and moisture at
room temperature. Palladacycles 18 were generally more
soluble in common organic solvents such as Et2O and toluene
than COP complexes 5 and 6. Analysis of the NMR spectra of
(S)-PIN-acac complexes 18 revealed that most were produced
as single stereoisomers; the exception was (S)-PIN-acac
complex 18h (R2 = 1-adamantyl), which was isolated in 41%
yield as a ∼1:1 mixture of inseparable stereoisomers.
Structural Properties of PIN-acac Complexes. Two
PIN-acac complexes having alkyl substituents, 18a (R1 = R2 = i-
Pr) and 18b (R1 = t-Bu, R2 = i-Pr), provided single crystals
suitable for X-ray diffraction by slow evaporation from solutions
of 10% CH2Cl2−cyclohexane. Palladacycle 18a crystallizes in
the orthorhombic space group P212121, whereas palladacycle
18b crystallizes in the monoclinic space group P21.
Representations of their X-ray models are shown in Figure 3.
The bond lengths and angles involving the atoms coordinated
to palladium are nearly identical in the two complexes, with the
ligands about palladium being approximately square-planar
(Table 2). Bond lengths and angles involving Pd, the
coordinated imidazoline nitrogen atom N(1), and the cyclo-
metalated carbon C(1) are similar to those found in other C,N-
palladacycles.8b The Pd−O bond lengths of the acetylacetonate
ligand are longer for the bond trans to carbon [Pd−O(2) bond
length: 18a, 2.0796(11) Å; 18b, 2.0848(13) Å] than that trans
to nitrogen [Pd−O(1) bond length: 18a, 2.0122(11) Å; 18b,
2.0050(14) Å], consistent with a larger trans influence for the
anionic naphthyl ligand.
subsequently dissolved in MeCN and treated with excess
NaNO2 and 70% H2SO4 at room temperature to provide 2-
iodo-1-naphthoic acid (15).18 This three step sequence was
preformed routinely on 5−10 g scales without purification of
intermediates to give iodoacid 15 in 65% overall yield after
recrystallization. Conversion of 15 to the corresponding acid
chloride and subsequent reaction with either (S)-valinol or (S)-
tert-leucinol gave respectively β-hydroxyamides 16a (R1 = i-Pr)
and 16b (R1 = t-Bu) in high yields as colorless solids after
recrystallization.
Hydroxy amides 16a,b were converted in 43−76% yield to
imidazolines 17a−m by the two-step sequence utilized to
prepare imidazoline 12 (Scheme 2, Table 1). In addition,
imidazolines 17o (R2 = Ts) and 17p (R2 = COt-Bu) were
prepared in good yield from N−H imidazoline 17n by reaction
with TsCl or pivaloyl chloride at room temperature. With the
exception of imidazoline 17n, these products were 1:1 mixtures
of atropisomers.19
Having developed an efficient route to imidazolines 17,
several conditions for promoting their conversion to pallada-
cycles were explored. The optimal condition was found to be
reaction of the imidazoline with 0.5 equiv of Pd2dba3 in
refluxing toluene,20 which furnished iodide-bridged palladacy-
clic products as yellow-orange solids. NMR analysis showed
that these products were mixtures of head-to-head and head-to-
tail isomers. Separation of these dimeric complexes was
complicated by their decomposition upon exposure to silica
gel. As a result, the crude mixtures of iodide-bridged dimers
were allowed to react with silver acetylacetonate in CH2Cl2 at
room temperature to give (S)-PIN-acac complexes 18a−m,o−p
as pale yellow solids in 41−68% yield (Table 1). Alternatively,
the acetylacetonate complexes could be prepared in comparable
As we had anticipated, the imidazoline and naphthalene
fragments are twisted out of plane in the X-ray models of PIN-
acac complexes 18a and 18b, with the two alkyl substituents on
opposite sides of the palladium square plane. The torsion
angles around the C(2)−C(3) bond provide a measure of the
degree to which the imidazoline substituents would be expected
to influence coordination of an alkene π-bond to the Pd(II)
center. This angle is 18.1° for diisopropyl complex 18a and
slightly larger, 24.6°, for the isopropyl/tert-butyl complex 18b.
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Scheme 3. Nitrogen Inversion of PIN Complexes
(b3-lyp/def2-TZVP) that estimate the barrier to be <15 kcal/
mol,22,23 are consistent with the N(2) nitrogen stereocenter
undergoing rapid inversion at room temperature.
The structural features and catalytic properties of PIN-acac
complex 18i in which R2 is phenyl and R1 isopropyl are quite
different than those of complexes 18a and 18b. The X-ray
model of complex 18i (Figure 4) shows that the geometry
Figure 4. X-ray structure of (S)-PIN-acac complex 18i.
around the palladium center is approximately square planar
with the bond lengths and angles involving the palladium atom
being quite similar to those of complexes 18a and 18b (Table
2). However, the imidazoline substituents reside on the same
face of the palladium coordination sphere and N(2) is nearly
sp3 hybridized. The overall shape of this complex is quite flat,
with the torsion angle around the C(2)−C(3) bond being
−5.9°.24 The phenyl substituent is twisted perpendicular to the
imidazoline ring, thus minimizing destabilizing steric inter-
actions when the naphthalene and imidazoline fragments are
oriented nearly coplanar.22
Catalytic Performance of PIN-acac Complexes. (S)-
PIN-acac complexes 18 were examined as enantioselective
catalysts for the [3,3]-rearrangement and allylic substitution
reactions of allylic trichloroacetimidates. Initial investigations
were carried out with complex 18a, which was found to be a
poor catalyst for the rearrangement of (E)-allylic imidate 19.
Figure 3. X-ray models of (S)-PIN-acac complexes 18a and 18b.
Although the imidazoline substituents of PIN-acac complexes
18a and 18b reside on opposite sides of the palladium square
plane in the solid state, the configurational stability of the N-
isopropyl substituent in solution was less certain (Scheme 3).
Inversion at this site, which would require bringing the bulky
isopropyl substituent into an unfavorable coplanar orientation
with the naphthalene ring, could result in both alkyl
substituents residing on the same face of the palladium square
plane. The configurational stability of 18a in solution was
1
examined by variable temperature H NMR from −80 to 110
°C.21 Within this temperature range, the 1H NMR spectrum of
18a was unchanged. This observation, and DFT calculations
Table 2. Selected Bond Lengths and Bond Angles for Three PIN-acac Complexes and COP-hexafluoroacetylacetonate
bond length (Å)
bond angle (deg)
dihedral angle (deg)
a
b
c
complex
Pd−C
Pd−N
Pd−O(1)
Pd−O(2)
C−Pd−N
O−Pd−O
τ
18a
18b
18i
1.9800(16)
1.9693(16)
1.964(2)
1.962
1.9970(13)
2.0262(16)
1.9817(18)
2.0122(11)
2.0050(14)
2.0186(16)
2.020
2.0769(11)
2.0848(13)
2.0791(17)
2.102
80.74(6)
80.97(7)
79.65(8)
92.48(5)
92.72(5)
91.55(7)
92.76
18.11(18)
24.6(3)
−5.9(4)
n/a
d
(Rp,S)-COP-hfacac
2.026
80.78
a
b
c
The Pd−O(1) bond is trans to the Pd−N bond. The Pd−O(2) bond is trans to the Pd−C bond. The dihedral angle C(1)−C(2)−C(3)−N(1).
d
Crystalographic data for the COP hexafluoroacetylacetonate complex (COD 4021070) is available from the Crystallographic Open Database.
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For example, after 24 h, allylic trichloroacetamide 20 was
formed in only 10% yield when 19 was exposed to 10 mol % of
18a (1.0 M substrate concentration) at 38 °C, with the bulk of
the starting allylic imidate remaining unchanged (eq 1).
be improved by modification of the imidazoline substituents.
Accordingly, our small library of PIN catalysts was surveyed for
the enantioselective conversion of (Z)-allylic trichloroacetimi-
date 23 to 3-acetoxy-5-phenyl-1-pentene (24) (Table 3).
Several trends in the data summarized in Table 3 are
apparent. Palladacycles containing bulky alkyl substituents on
the imidazoline nitrogen (18a−h) provided 3-acetoxy-1-
pentene (24) in excellent yields (70−95%) and moderate
enantioselectivities (25−57% ee). Increasing the size of the R1
substituent from i-Pr to t-Bu translated into only a marginal
increase in enantioselectivity (Table 3, entries 1 and 2),
whereas increasing the size of the imidazoline nitrogen
substituent R2 proved to be more critical to the stereochemical
outcome (Table 3, entries 3−7). The most effective R2
substituent was t-Bu, with PIN catalysts 18f and 18g providing
acetate 24 in 48% and 57% ee, respectively (Table 3, entries 6
and 7). Notably, catalyst 18g (R1 = t-Bu, R2 = t-Bu), which is
expected to have the largest degree of angular torsion around
the C(2)−C(3) bond, provided the highest level of
enantioselectivity among the PIN complexes screened (Table
3, entry 7). However, catalytic rate was somewhat lower with
this catalyst, with a reaction time of 48 h being required to give
acetate 24 in high yield. It is not surprising that complex 18h,
which was used as a 1:1 mixture of atropisomers, provided
acetate 24 in low ee only (Table 3, entry 8). PIN complexes
having N-aryl substituents (Table 3, entries 9−13) displayed
useful catalytic activity but provided the allylic acetate product
in low to moderate ee. The most enantioselective N-aryl PIN
variant was 18m (R1 = t-Bu, R2 = Mes), which gave allylic
acetate 24 in 90% yield and 42% ee (Table 3, entry 13). PIN
catalysts 18o−p, bearing an electron-withdrawing substituent
on the imidazoline nitrogen, gave product 24 in low ee and
exhibited only marginal improvement in reaction rate relative to
18a−m (Table 3, entries 14 and 15).
In contrast, PIN-acac complexes proved to be kinetically
excellent catalysts for the allylic esterification reaction. Initial
experiments were again conducted with complex 18a, which at
10 mol % transformed (Z)-allylic trichloroacetimidate 21
cleanly to branched allylic acetate 22 within 8 h at room
temperature (eq 2). This reaction proceeded with no detectable
formation of rearrangement product 20; however, allylic acetate
22 was produced in only 21% ee. Attempts to improve
enantioselectivity by carrying out the reaction at 0 °C resulted
only in prolonged reaction times without any improvement in
enantioselectivity. In addition, changes in the solvent had only a
small influence on catalytic efficiency or enantioselectivity
(yield of 22, reaction time at 23 °C, ee): CH2Cl2 (95%, 8 h,
21%) ≈ MeCN (92%, 8 h, 20%) > toluene (88%, 10 h, 10%) >
Et2O (94%, 16 h, 20%) ≈ THF (94%, 18 h, 18%).
These initial experiments indicated that PIN-acac complexes
might be useful catalysts for enantioselective allylic esterifica-
tion of (Z)-allylic trichloroacetimidates if stereoinduction could
This catalyst survey showed that PIN-acac complexes are
useful catalysts for the addition of carboxylic acid nucleophiles
Table 3. Survey of (S)-PIN-acac Complexes for the Catalytic Asymmetric Synthesis of Branched Allylic Acetates
a
b
entry
catalyst
R1
R2
time (h)
yield (%)
ee (%)
1
2
3
4
5
6
7
18a
18b
18c
18d
18e
18f
i-Pr
t-Bu
i-Pr
i-Pr
i-Pr
i-Pr
t-Bu
t-Bu
i-Pr
t-Bu
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
18
18
18
18
18
24
48
18
18
18
18
18
36
12
18
95
96
93
90
95
96
95
65
97
96
94
96
90
90
91
88
28
34
30
38
25
48
57
28
20
23
18
21
42
16
10
91
CH2Ph
CH(Ph)2
Cy
t-Bu
18g
18h
18i
t-Bu
cd
,
8
9
1-adamantyl
Ph
10
11
12
13
14
15
16
18j
Ph
18k
18l
p-OMeC6H4
p-CF3C6H4
mesityl
Ts
18m
18o
18p
C(O)t-Bu
e
[COP-OAc]2 (5)
16
a
b
c
Duplicate experiments ( 3%). Determined by GC analysis of duplicate experiments ( 2%). Complex 18h was used as a 1:1 mixture of
d
e
atropisomers. The remaining mass was imidate 23. Catalyst loading of 5 was 1.5 mol % (3 mol % Pd).
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to allylic trichloroacetimidates, with catalytic rates being similar
to those of COP catalyst 5 (Table 3, entry 16). Unfortunately,
the enantioselectivity achieved with PIN catalysts 18 is
significantly lower than that realized with COP catalyst 5.
Computational Modeling. To gain insight into what
features of the PIN complex architecture might be modified to
increase enantioselectivity of these catalysts, computational
modeling was undertaken. The structural relationship between
the C,N-palladacycle portions of the PIN and COP catalyst
structures and their comparable reactivity suggests that they
might operate by a common mechanism. We have recently
reported a detailed computational study of the addition of
carboxylic acid nucleophiles to (Z)-allylic trichloroacetimidates
using COP catalyst 5.3c The proposed catalytic cycle, which
involves antarafacial SN2′ addition of acetic acid to the double
bond, is summarized in Scheme 4.25 On the basis of
of acetic acid with (Z)-2-butenyl trichloroacetimidate catalyzed
by COP complex 5 was used as the starting geometry for
calculations of PIN transition-state structures 29−32.3c The
results of this computational study are depicted in Figure 5. In
transition-state structures 29 and 30, the reacting allylic C−C
π-bond is positioned cis to the Pd−C(1) bond, consistent with
the predicted preferred coordination geometry of the imidate
(e.g., 26, Scheme 4). Conversely, in transition-state structures
31 and 32, the C−C π-bond is coordinated trans to the
palladacycle Pd−C(1) bond. Transition-state structures 29 and
31 would afford the observed major R-enantiomer of the allylic
acetate product, whereas the transition-state structures 30 and
32 would produce the minor S-enantiomer. Of the four
transition structures, 29 was found to have both the lowest
activation energy (ΔE‡ = 4.2 kcal/mol) and the lowest relative
energy (ΔΔE‡). Structures 31 and 32 having the C−C π-bond
coordinated trans to the carbon of the palladacycle are
calculated to be 4.0 and 5.4 kcal/mol higher in energy than
the corresponding cis complexes. Transition-state structure 30,
which has the imidate nitrogen coordinated trans to the Pd−
C(1) bond and leads to the formation of the minor enantiomer,
is calculated to be only 0.2 kcal/mol higher in energy than the
low energy transition-state structure 29.
Scheme 4. Proposed Catalytic Cycle for the Pd(II)-Catalyzed
Conversion of (Z)-Allylic Trichloroacetimidates (1) to
Enantioenriched Allylic Esters (2)
Several additional observations from the computational study
warrant comment. In low energy transition-state structures 29
and 30, nucleophilic attack on the activated C−C double bond
takes place next to C(19) of the naphthalene ligand. Thus, the
enantiodetermining event is occurring relatively far away from
the chiral environment provided by the imidazoline sub-
stituents R1 and R2. The small energy difference (ΔΔE‡ = 0.2
kcal/mol) between the transition-state structures 29 (Re face
addition) and 30 (Si face addition) is consistent with the
observed low level of enantioselectivity realized with PIN
complex 18a. Although variation of R1 and R2 can undoubtedly
lead to increased torsion around the C(2)−C(3) bond, which
would place these groups in somewhat closer proximity to the
reacting C−C π-system, it is doubtful that the N(2) substituent
could be positioned in a way to effect a high degree of energy
separation between transition-state structures 29 and 30. Our
computational analysis suggests that the most useful approach
to optimizing the PIN catalyst structure would be by appending
functionality at C(19) of the naphthalene backbone.
experimental observations and computational experiments,
this earlier study concluded that (1) oxypalladation (26 →
27) is the rate- and enantio-determining step; (2) bidentate
coordination of the allylic trichloroacetimidate to the pallada-
cycle catalyst (e.g., intermediate 26) is favored over other
coordination modes; and (3) there is a preference for the
alkene π-bond to coordinate cis to the Pd−C σ-bond of the
palladacycle.3c This latter observation is consistent with our
mechanistic investigations of the COP-catalyzed [3,3]-rear-
rangement of (E)-allylic trichloroacetimidates26 and with the
strong trans influence observed for d8 square-planar Pd(II)
complexes.27 The current analysis thus focused on the
interactions between the imidate substrate, acetate nucleophile,
and C,N-palladacycle framework in the oxypalladation step.
In order to gain a better understanding of diastereoselection
induced by the chiral PIN catalyst architecture, the oxy-
palladation step (Scheme 4, 26 → 27) was studied computa-
tionally. Calculations modeled the addition of HOAc to the
trichloroacetimidate derivative of (Z)-2-butene-1-ol using
complex 18a as a catalyst.28−31 The previously reported
enantiodetermining transition-state structure for the reaction
CONCLUSION
■
In summary, a new family of enantiopure C,N-palladacycles
(PIN-acac complexes 18) were developed and evaluated as
asymmetric catalysts for the reaction of allylic trichloroaceti-
midates with external nonmetal bound nucleophiles. These air-
and moisture-stable complexes were formed in good overall
yield in three steps from 2-iodo-1-naphthoic acid (15) and β-
amino alcohols. Three PIN complexes were characterized by
single-crystal X-ray analysis. As anticipated, the naphthalene
and imidazoline rings of PIN-acac complexes 18a and 18b were
canted significantly from planarity and projected the imidazo-
line substituents R1 and R2 on opposite faces of the palladium
square plane. Although these PIN palladacycles displayed useful
levels of catalytic activity for the allylic substitution of prochiral
allylic trichloroacetimidates with carboxylic acid nucleophiles
and exclusively provided branched allylic esters in high yield,
enantioselectivities were low to moderate. Nonetheless, the
accessible and easily varied naphthalene−imidazoline ligands
described here may be useful for the synthesis of related
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Figure 5. Relative energies of four isomeric transition-state structures for oxypalladation using PIN complex 18a.
(approximately 2 h). The reaction mixture was then concentrated
under reduced pressure, and the resulting yellow residue was dissolved
in CH2Cl2 (50 mL) and transferred by cannula to a solution of (S)-
valinol (2.07 g, 21.1 mmol) and Et3N (8.5 mL, 61 mmol) in CH2Cl2
(150 mL) maintained at 0 °C. The reaction mixture was allowed to
warm to rt over 16 h. The reaction then was diluted with CH2Cl2 (150
mL) and washed successively with 1 M HCl (2 × 250 mL), 1 M
NaOH (2 × 250 mL), and brine. The organic layer was dried with
anhydrous MgSO4, filtered, and concentrated under reduced pressure.
The resulting brown residue was recrystallized from CHCl3 to afford
enantiopure axial chiral cyclometalated complexes that might
find future applications in asymmetric catalysis.
The experimental and computational results presented here
reinforce our previous conclusions with COP catalysts that the
alkene π-bond of an allylic imidate substrate is preferentially
coordinated cis to the carbon ligand of the palladacycle3c,26
with attack of an external nucleophile occurring from the least-
sterically hindered face in this quadrant. This study further
suggests that optimizing steric influence in the vicinity of the
carbon ligand of a chiral C,N-palladacycle, rather than near the
nitrogen heterocycle, is the direction to pursue in future
development of improved enantioselective catalysts in this area.
24
16a (6.55 g, 17.1 mmol, 85%) as a tan solid: mp 132−136 °C; [α]D
24
= +11.2, [α]57724 = +12.1, [α]54624 = +12.9, [α]43524 = +15.3, [α]405
=
1
+17.4, (c = 0.2, CHCl3); H NMR (500 MHz, CDCl3, 298 K) δ 7.87
(q, J = 3.0, 1H), 7.80−7.76 (m, 2H), 7.52−7.47 (m, 3H), 6.07 (d, J =
8.3, 1H), 4.07−4.01 (m, 1H), 3.93−3.91 (m, 1H), 3.81−3.79 (m, 1H),
2.50 (br s, 1H), 1.97 (octet, J = 6.8, 1H), 1.04 (d, J = 6.8, 3H), 1.03 (d,
J = 6.8, 3H); 13C NMR (125 MHz, CDCl3, 298 K) δ 170.3 (C), 141.0
(C), 135.2 (CH), 132.5 (C), 131.2 (C), 130.4 (CH), 128.2 (CH),
127.9 (CH), 127.0 (CH), 125.2 (CH), 91.2 (C), 63.6 (CH2), 57.8
(CH), 29.0 (CH), 19.8 (CH3), 19.3 (CH3); IR (thin film) 3406, 2960,
1732, 1076 cm−1; HRMS (ESI) m/z, 406.0271 (406.0280 calcd for
C16H18NINaO2, (M + Na)+).
EXPERIMENTAL SECTION
■
General Procedure for the Synthesis of β-Hydroxyamides.
Preparation of (S)-N-(1-Hydroxy-3-methylbutan-2-yl)-2-iodo-
naphthalene-1-carboxamide (16a). Carboxylic acid 15 (6.00 g,
20.1 mmol) was suspended in CH2Cl2 (100 mL) and rapidly stirred.
Oxalyl chloride (3.6 mL, 40 mmol) and a catalytic amount of DMF (∼
0.02 mL) were added dropwise at rt (Caution! Gas evolved), and the
resultant suspension was stirred until it became homogeneous
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(S)-N-(1-Hydroxy-3,3-dimethyl-2-yl)-2-iodonaphthalene-1-
carboxamide (16b). Prepared following the general procedure used
to prepare 16a. The crude residue was recrystallized from CHCl3 to
afford amide 16b (2.48 g, 6.24 mmol, 93%) as a light brown solid: mp
crude residue was purified by column chromatography (silica gel, 7:2:1
hexane/Et2O/Et3N) to afford 17b (0.379 g, 0.902 mmol, 43%) as an
orange film. The product was characterized as a 1:1 mixture of
1
atropisomers: H NMR (500 MHz, CDCl3, 298 K) δ 7.92−7.89 (m,
23
71−75 °C; [α]D23 = −10.3, [α]57723 = −11.2, [α]54623 = −13.3, [α]435
2H), 7.86 (app dd, J = 8.7, 2.8, 2H), 7.80−7.77 (m, 2H), 7.55 (app dd,
J = 8.7, 2.6, 2H), 7.50−7.46 (m, 4H), 4.08 (t, J = 11.4, 2H), 3.54 (dt, J
= 9.5, 4.3, 2H), 3.42−3.36 (m, 2H), 3.19 (sextet, J = 6.4, 2H), 1.22−
1.21 (m, 6H), 1.10 (s, 9H), 1.09 (s, 9H), 0.96 (d, J = 6.6, 3H), 0.92 (d,
J = 6.5, 3H); 13C NMR (125 MHz, CDCl3, 298 K) δ 163.43 (C),
163.41 (C), 135.82 (C), 135.80 (C), 135.7 (CH), 135.6 (CH), 133.1
(C), 132.8 (C), 132.6 (C), 132.5 (C), 130.14 (CH), 130.11 (CH),
128.13 (CH), 128.0 (CH), 127.3 (CH), 127.1 (CH), 126.7 (CH),
126.6 (CH), 126.0 (CH), 125.9 (CH), 96.6 (C), 95.6 (C), 74.88
(CH), 74.86 (CH), 46.42 (CH), 46.36 (CH), 43.7 (CH2), 43.5
(CH2), 34.7 (C), 34.3 (C), 27.2 (CH3), 26.6 (CH3), 22.1 (CH3), 21.7
(CH3), 20.5 (CH3), 20.4 (CH3); IR (thin film) 3051, 2990, 1661,
1235, cm−1; HRMS (ESI) m/z, 443.0970 (443.0960 calcd for
C20H25IN2Na, (M + Na)+)
1
= −24.6, (c = 0.83, CH2Cl2); H NMR (500 MHz, CDCl3, 298 K) δ
8.01 (br s, 1H), 7.83 (d, J = 8.5, 2H), 7.58 (d, J = 8.4, 1H), 7.55−7.53
(m, 2H), 6.02 (d, J = 8.2, 1H), 4.22 (ddd, J = 9.8, 6.8, 3.0, 1H), 4.10
(dd, J = 11.0, 2.4, 1H), 5.38 (m, 1H), 2.48 (br s, 1H), 1.10 (s, 9H);
13C NMR (125 MHz, CDCl3, 298 K) δ 170.6 (C), 141.2 (C), 135.2
(CH), 132.5 (C), 131.3 (C), 130.4 (CH), 128.2 (CH), 127.9 (CH),
127.0 (CH), 125.3 (CH), 91.2 (C), 63.1 (CH), 60.5 (CH2), 33.8 (C),
27.5 (CH3); IR (thin film) 3395, 3278, 3058, 2960, 1746 cm−1; HRMS
(ESI) m/z, 398.0625 (398.0619 calcd for C17H21INO2, (M + H)+).
General Procedure for the Synthesis of Imidazolines.32
Preparation of (S)-1,4-Diisopropyl-2-(naphthalene-1-yl)-4,5-
dihydro-1H-imidazole (12). Amide 10 (0.518 g, 2.00 mmol) was
dissolved in freshly distilled SOCl2 (0.73 mL, 10 mmol), and the
solution was warmed to 85 °C. After 5 h, the reaction was cooled to rt,
diluted with toluene (10 mL), and concentrated under reduced
pressure. The unpurified chloroalkylimidoyl chloride was dissolved in
CH2Cl2 (5 mL), and any insoluble impurities were removed by
filtration. The resulting solution was treated with a solution of Et3N
(0.83 mL, 6.0 mmol) and isopropylamine (0.18 mL, 2.2 mmol) in
CH2Cl2 (2 mL) at rt. The reaction mixture was maintained at rt for 12
h, then stirred with 2 M NaOH (20 mL) for 30 min. The organic layer
was separated, and the aqueous layer was extracted with EtOAc (3 ×
10 mL). The combined organics were dried with anhydrous MgSO4,
filtered, and concentrated under reduced pressure. The resulting
yellow residue was purified by column chromatography (silica gel,
8:1:1 hexanes/Et2O/Et3N)33 to afford imidazoline 12 (0.392 g, 1.40
(S)-1-tert-Butyl-2-(2-iodonaphthalen-1-yl)-4-isopropyl-4,5-
dihydro-1H-imidazole (17f). Following the general procedure, the
crude residue was purified by column chromatography (silica gel, 8:1:1
hexane/Et2O/Et3N) to afford 17f (0.274 g, 0.652 mmol, 71%) as a
yellow paste. The product was characterized as a 1:1 mixture of
1
atropisomers: H NMR (500 MHz, CDCl3, 298 K) δ 7.88−7.86 (m,
2H), 7.80 (d, J = 5.3, 1H), 7.78 (d, J = 5.4, 1H), 7.75−7.71 (m, 2H),
7.49−7.43 (m, 6H), 3.96 (dt, J = 11.0, 6.3, 1H), 3.86 (dt, J = 10.8, 7.3,
1H), 3.74 (app ddd, J = 11.0, 9.3, 6.3, 2H), 3.45 (app q, J = 9.3, 2H),
1.97 (m, 2H), 1.12 (d, J = 6.7, 3H), 1.07 (d, J = 6.8, 3H), 1.04−1.02
(m, 24H); 13C NMR (125 MHz, CDCl3, 298 K) δ 162.8 (C), 162.6
(C), 139.0 (C), 138.98 (C), 135.7 (CH), 135.6 (CH), 133.5 (C),
132.8 (C), 132.5 (C), 132.4 (C), 129.6 (CH), 128.0 (CH), 127.9
(CH), 127.0 (CH), 126.9 (CH), 126.7 (CH), 126.4 (CH), 97.8 (C),
96.7 (C), 69.9 (CH), 69.7 (CH), 54.5 (C), 50.6 (CH2), 50.0 (CH2),
33.6 (CH), 33.4 (CH), 29.4 (CH3), 29.2 (CH3), 19.9 (CH3), 19.5
(CH3), 19.4 (CH3), 18.8 (CH3); IR (thin film) 3059, 2980, 1655,
1241 cm−1; HRMS (ESI) m/z, 421.1143 (421.1141 calcd for
C20H26IN2, (M + H)+).
24
24
mmol, 70%) as a colorless foam: [α]D = −37.0, [α]577 = −38.9,
[α]54624 = −42.6, [α]43524 = −72.4, [α]40524 = −85.7, (c = 1.0, CHCl3);
1H NMR (500 MHz, CDCl3, 298 K) δ 8.34 (d, J = 8.3, 1H), 7.95 (d, J
= 8.0, 1H), 7.88 (d, J = 7.9, 1H), 7.65 (d, J = 7.9, 1H), 7.56−7.54 (m,
2H), 7.48 (dd, J = 8.0, 7.3, 1H), 6.18 (d, J = 8.7, 1H), 4.11−4.08 (m,
1H), 3.94−3.91 (m, 1H), 3.86 (m, 1H), 2.51 (br s, 1H), 2.05 (septet, J
= 7.0, 1H), 1.10 (d, J = 6.8, 3H), 1.09 (d, J = 6.8, 3H); 13C NMR (125
MHz, CDCl3, 298 K) δ 170.6 (C), 134.7 (CH), 133.7 (CH), 130.6
(C), 130.1 (CH), 128.3 (CH), 127.2 (C), 126.5 (CH), 125.4 (CH),
124.8 (C), 124.7 (CH), 64.0 (CH), 57.6 (CH2), 29.2 (CH), 19.7
(CH3), 19.0 (CH3); IR (thin film) 3296, 3060, 3051, 2931, 1623 cm−1;
HRMS (ESI) m/z, 281.2021 (281.2018 calcd for C19H25N2, (M +
H)+).
(S)-1,4-Di-tert-butyl-2-(2-iodonaphthalen-1-yl)-4,5-dihydro-
1H-imidazole (17g). Following the general procedure, the crude
residue was purified by column chromatography (silica gel, 8:2:1
hexane/Et2O/Et3N) to afford 17g (0.504 g, 1.16 mmol, 75%) as a
yellow film. The product was characterized as a 1:1 mixture of
1
atropisomers: H NMR (500 MHz, CDCl3, 298 K) δ 7.89−7.88 (m,
2H), 7.79 (t, J = 8.5, 2H), 7.72 (m, 1H), 7.71 (d, J = 9.0, 1H), 7.49−
7.43 (m, 6H), 3.93 (t, J = 11.8, 2H), 3.68 (t, J = 9.3, 1H), 3.66 (t, J =
8.7, 1H), 3.51−3.47 (m, 2H), 1.10 (s, 9H), 1.04 (s, 9H), 1.03 (s, 9H),
1.01 (s, 9H); 13C NMR (125 MHz, CDCl3, 298 K) δ 163.0 (C), 162.9
(C), 139.13 (C), 139.08 (C), 135.9 (CH), 135.6 (CH), 133.9 (C),
132.7 (C), 132.6 (C), 132.4 (C), 129.7 (CH), 129.6 (CH), 128.1
(CH), 127.8 (CH), 127.0 (CH), 126.84 (CH), 126.80 (CH), 126.7
(CH), 126.5 (CH), 98.3 (C), 96.1 (C), 73.5 (CH), 73.5 (CH), 54.7
(C), 54.6 (C), 48.8 (CH2), 48.6 (CH2), 34.7 (C), 34.3 (C), 29.5
(CH3), 29.1 (CH3), 27.2 (CH3), 26.6 (CH3); IR (thin film) 2989,
2908, 1648, 1211, 1023 cm−1; HRMS (ESI) m/z, 435.1294 (435.1297
calcd for C21H28IN2, (M + H)+).
The following compounds were prepared in identical fashion from
16a or 16b employing 1.1 equiv of the appropriate alkyl/aryl primary
amine.
(S)-2-(2-Iodonaphthalen-1-yl)-1,4-diisopropyl-4,5-dihydro-
1H-imidazole (17a). Following the general procedure, the crude
residue was purified by column chromatography (silica gel, 6:3:1
hexane/Et2O/Et3N) to afford 17a (0.463 g, 1.14 mmol, 76%) as a
yellow foam. The product was characterized as a 1:1 mixture of
1
atropisomers: H NMR (500 MHz, CDCl3, 298 K) δ 7.90−7.89 (m,
2H), 7.87 (dd, J = 8.7, 1.7, 2H), 7.80−7.78 (m, 2H), 7.56 (d, J = 8.7,
2H), 7.52−7.47 (m, 4H), 4.13 (dt, J = 11.0, 6.3, 1H), 4.05 (dt, J =
10.6, 3.1, 1H), 3.65−3.60 (m, 2H), 3.35−3.31 (m, 2H), 3.18 (sextet, J
= 6.7, 2H), 2.00 (sextet, J = 6.5, 2H), 1.24 (d, J = 6.6, 3H), 1.23 (d, J =
6.6, 3H), 1.16 (d, J = 6.7, 3H), 1.13 (d, J = 6.7, 3H), 1.08 (d, J = 6.6,
3H), 1.07 (d, J = 6.7, 3H), 0.96 (d, J = 6.6, 3H), 0.93 (d, J = 6.6, 3H);
13C NMR (125 MHz, CDCl3, 298 K) δ 163.30 (C), 163.26 (C), 135.7
(S)-4-tert-Butyl-2-(2-iodonaphthalen-1-yl)-1-(1-adamantyl)-
4,5-dihydro-1H-imidazole (17h). Following the general procedure,
the crude residue was purified by column chromatography (silica gel,
8:1:1 hexane/Et2O/Et3N) to afford 17h (0.155 g, 0.302 mmol, 60%)
as a colorless foam. The product was characterized as a 1:1 mixture of
1
atropisomers: H NMR (500 MHz, CDCl3, 298 K) δ 7.93−7.89 (m,
(CH), 135.6 (CH), 132.9 (C), 132.7 (C), 132.6 (C), 132.5 (C), 130.2
(CH), 128.1 (CH), 128.0 (CH), 127.3 (CH), 127.2 (CH), 126.7
(CH), 126.6 (CH), 125.8 (CH), 96.3 (C), 95.9 (C), 71.2 (CH), 70.9
(CH), 46.34 (CH), 46.31 (CH), 45.6 (CH2), 45.1 (CH2), 33.8 (CH),
33.7 (CH), 21.7 (CH3), 21.5 (CH3), 20.8 (CH3), 20.7 (CH3), 19.9
(CH3), 19.4 (CH3), 18.9 (CH3); IR (thin film) 3040, 2952, 1712,
1624, cm−1; HRMS (ESI) m/z, 429.0811 (429.0804 calcd for
C19H23IN2Na, (M + Na)+).
2H), 7.81 (t, J = 8.6, 2H), 7.79−7.76 (m, 2H), 7.50−7.46 (m, 6H),
3.93 (t, J = 11.8, 1H), 3.92 (t, J = 11.6, 1H), 3.75−3.69 (m, 2H),
3.60−3.56 (m, 2H), 1.85−1.84 (m, 6H), 1.73−1.67 (m, 12H), 1.50−
1.38 (m, 8H), 1.09 (s, 9H), 1.06 (s, 9H); 13C NMR (125 MHz,
CDCl3, 298 K) δ 162.48 (C), 139.7 (C), 135.8 (CH), 135.6 (CH),
134.0 (C), 132.9 (C), 132.6 (C), 132.4 (C), 129.53 (CH), 129.50
(CH), 128.0 (CH), 127.8 (CH), 127.0 (CH), 126.9 (CH), 126.82
(CH), 126.80 (CH), 126.41 (CH), 126.39 (CH), 98.2 (C), 96.2 (C),
73.30 (CH), 73.28 (CH), 55.74 (C), 55.69 (C), 41.5 (CH2), 41.1
(S)-4-tert-Butyl-2-(2-iodonaphthalen-1-yl)-1-isopropyl-4,5-
dihydro-1H-imidazole (17b). Following the general procedure, the
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(CH2), 36.07 (CH2), 36.06 (CH2), 34.8 (C), 34.4 (C), 27.2 (CH3),
26.6 (CH3); IR (thin film) 3056, 2994, 2852, 1590, 1260, 1242 cm−1;
HRMS (ESI) m/z, 513.1748 (513.1767 calcd for C27H34IN2, (M +
H)+).
(S)-1-(2-(2-Iodonaphthalen-1-yl)-4-isopropyl-4,5-1H-imida-
zol-1-yl)-2,2-dimethylpropan-1-one (17p). Prepared by the
procedure used to prepare 17o using 1.1 equiv of pivaloyl chloride
as the electrophile. The crude residue was purified by column
chromatography (silica gel, 9:1:1 hexane/Et2O/Et3N) to furnish 17p
(0.182 g, 0.406 mmol, 92%) as a yellow foam. The product was
(S)-2-(2-Iodonaphthalen-1-yl)-4-isopropyl-1-phenyl-4,5-di-
hydro-1H-imidazole (17i). Following the general procedure, the
crude residue was purified by column chromatography (silica gel, 8:1:1
hexane/Et2O/Et3N) to afford 17i (0.355 g, 0.806 mmol, 69%) as an
orange foam. The product was characterized as a ∼1.4:1 mixture of
atropisomers. The compound contains some minor impurities but was
used directly in the next step, as decomposition was observed during
purification attempts: 1H NMR (500 MHz, CDCl3, 298 K) δ 8.02 (dd,
J = 8.0, 2.8, 1H), 7.83−7.80 (m, 5H), 7.79 (d, J = 8.3, 1H), 7.73−7.53
(m, 4H), 7.01−6.96 (m, 3H), 6.83−6.80 (m, 3H), 6.62 (d, J = 8.4,
1H), 6.57−6.55 (m, 3H), 4.26−4.20 (m, 2H), 4.05−4.00 (m, 2H),
3.91 (d, J = 6.2, 1H), 2.17 (septet, J = 6.8, 1H), 2.12 (septet, J = 6.5,
1H), 1.16 (d, J = 6.7, 3H), 1.15 (d, J = 6.7, 3H), 1.12 (d, J = 6.5, 3H),
1.11 (d, J = 6.5, 3H); 13C NMR (125 MHz, CDCl3, 298 K) δ 160.3
(C), 160.2 (C), 140.4 (C), 140.2 (C), 135.7 (CH), 135.6 (CH), 135.5
(C), 135.2 (C), 133.6 (C), 132.9 (CH), 132.7 (CH), 132.5 (C), 130.1
(CH), 129.5 (CH), 128.7 (CH), 128.1 (CH), 128.0 (CH), 127.9
(CH), 127.3 (CH), 127.2 (CH), 126.7 (CH), 126.6 (CH), 125.9
(CH), 125.3 (CH), 122.3 (CH), 122.2 (CH), 118.3 (CH), 118.2
(CH), 97.0 (C), 96.4 (C), 70.8 (CH), 70.6 (CH), 53.4 (CH2), 53.1
(CH2), 33.2 (CH), 33.0 (CH), 20.0 (CH3), 19.4 (CH3), 19.2 (CH3),
19.1 (CH3); IR (thin film) 3061, 2995, 1675, 1238 cm−1; HRMS (ESI)
m/z, 463.0650 (463.0647 calcd for C22H21IN2Na, (M + Na)+).
(S)-2-(2-Iodonaphthalen-1-yl)-4-isopropyl-4,5-dihydro-1H-
imidazole (17n). The general procedure was followed with the
exception that the unpurified chloroalkylimidoyl chloride was
suspended in a saturated solution of NH3 in CHCl3 (15 mL) at rt.
The crude residue was purified by column chromatography (silica gel,
6:3:1 hexane/Et2O/Et3N) to afford 17n (0.379 g, 1.04 mmol, 90%) as
1
characterized as a 1:1 mixture of atropisomers: H NMR (500 MHz,
CDCl3, 298 K) δ 7.80−7.77 (m, 4H), 7.75−7.73 (m, 2H), 7.53 (d, J =
8.6, 2H), 7.48−7.46 (m, 2H), 4.33−4.21 (m, 4H), 4.07 (dd, J = 8.6,
5.6, 1H), 3.94 (t, J = 9.4, 1H), 2.14−2.06 (m, 2H), 1.31−1.30 (m,
18H), 1.81 (app t, J = 6.9, 6H), 1.14−1.20 (m, 6H); 13C NMR (125
MHz, CDCl3, 298 K) δ 174.8 (C), 174.7 (C), 160.8 (C), 160.7 (C),
137.9 (C), 137.7 (C), 135.0 (CH), 134.9 (CH), 132.7 (C), 132.6 (C),
132.5 (C), 132.4 (C), 129.74 (CH), 129.67 (CH), 128.4 (CH), 128.3
(CH), 127.3 (CH), 127.2 (CH), 126.4 (CH), 126.3 (CH), 125.7
(CH), 125.4 (CH), 94.1 (C), 93.5 (C), 73.6 (CH), 73.4 (CH), 50.7
(CH2), 50.2 (CH2), 40.4 (C), 33.0 (CH), 32.7 (CH), 27.6 (CH3),
27.5 (CH3), 19.7 (CH3), 19.3 (CH3), 19.2 (CH3); IR (thin film) 3056,
2960, 2872, 1668, 1334 cm−1; HRMS (ESI) m/z, 449.1089 (449.1092
calcd for C21H26IN2O, (M + H)+).
General Procedure for the Synthesis of (S)-PIN-acac
Complexes from Imidazolines 17. Preparation of
Acetylacetonato{(S)-2-[2-(1-isopropyl)-4-isopropyl)-4,5-dihy-
dro-1H-imidazyl]-naphthyl-C,N}palladium(II) (18a). Imidazoline
17a (0.406 g, 1.00 mmol) and Pd2dba3 (0.458 g, 0.500 mmol) were
dissolved in toluene (3 mL), and the resulting dark red solution was
heated to 120 °C. After 12 h, the reaction mixture was concentrated
under reduced pressure to furnish a labile mixture of iodine-bridged
palladacycle dimers, as a dark brown residue.
The residue prepared above was dissolved in CH2Cl2 (5 mL), and
silver acetylacetonate (0.217 g, 1.05 mmol) was added in a single
portion. The resulting black suspension was stirred at rt for 4 h, then
filtered through a pad of Celite. The filter cake was washed with
CH2Cl2 (50 mL), and the filtrate was concentrated to afford a yellow
residue. The crude product was purified by column chromatography
(silica gel, 10:1 hexanes/acetone) to afford palladacycle 18a (0.339 g,
24
24
a colorless solid: mp 159−163 °C; [α]D = −12.8, [α]577 = −13.6,
24
24
24
[α]546 = −15.9, [α]435 = −30.4, [α]405 = −36.9, (c = 1.0,
CH2Cl2); H NMR (500 MHz, CDCl3, 330 K) δ 7.96 (m, 1H), 7.84
1
24
0.70 mmol, 70%) as a yellow solid: mp 150−152 °C; [α]D +22.7,
(d, J = 8.6, 1 H), 7.87 (m, 1H), 7.55 (d, J = 8.6, 1H), 7.41−7.40 (m,
2H), 4.82 (br s, 1H), 3.97 (m, 2 H), 3.66 (br s, 1H), 2.00−1.99 (m,
1H), 1.10 (d, J = 6.0, 3H), 1.05 (d, J = 6.3, 3H); 13C NMR (125 MHz,
CDCl3, 298 K) δ 164.3 (C), 136.0 (C), 135.2, (CH), 132.6 (C), 132.5
(C), 130.4 (CH), 127.9 (CH), 127.5 (CH), 126.8 (CH), 125.8 (CH),
94.8 (C), 33.1 (CH), 29.8 (CH2), 19.7 (CH3), 19.1 (CH3); IR (thin
film) 3142, 3064, 2955, 2869, 1610, 1504 cm−1; HRMS (ESI) m/z,
365.0511 (365.0515 calcd for C16H18IN2, (M + H)+).
24
24
24
24
[α]577 +23.1, [α]546 +24.2, [α]435 +25.5, [α]435 +28.1 (c = 0.2,
CHCl3); 1H NMR (500 MHz, CDCl3, 298 K) δ 7.85 (d, J = 8.4, 2H),
7.77 (d, J = 8.0, 1H), 7.63 (d, J = 8.4, 1H), 7.39 (t, J = 7.4, 1H), 7.30
(t, J = 7.4, 1H), 5.35 (s, 1H), 4.34 (septet, J = 6.6, 1H), 4.12 (ddd, J =
10.5, 8.0, 5.1, 1H), 3.59 (t, J = 10.5, 1H), 3.36 (dd, J = 10.5, 8.0, 1H),
2.50−2.49 (m, 1H), 2.07 (s, 3H), 1.95 (s, 3H), 1.25 (d, J = 6.7, 3H),
1.01 (d, J = 6.7, 3H), 0.95 (d, J = 7.0, 3H), 0.91 (d, J = 7.0, 3H); 13C
NMR (125 MHz, CDCl3, 298 K) δ 188.0 (C), 186.1 (C), 176.8 (C),
156.0 (C), 132.0 (C), 129.7 (C), 129.6 (C), 129.1 (CH), 129.0 (CH),
128.8 (CH), 125.7 (CH), 123.6 (CH), 123.5 (CH), 100.3 (CH), 67.5
(CH), 50.5 (CH2), 43.9 (CH), 30.9 (CH), 29.8 (CH3), 27.9 (CH3),
27.7 (CH3), 21.0 (CH3), 18.9 (CH3), 18.7 (CH3), 15.8 (CH3); IR
(thin film) 3053, 2960, 1572, 1514, 1263 cm−1; HRMS (ESI) m/z,
507.1242 (507.1249 calcd for C24H30N2O2PdNa, (M + Na)+). Anal.
Calcd for C24H30N2O2Pd: C, 59.44; H, 6.24; N, 5.78. Found: C, 59.29;
H, 6.22; N, 5.76.
Preparation of (S)-2-(2-Iodonaphthalen-1-yl)-4-isopropyl-1-
tosyl-4,5-dihydro-1H-imidazole (17o). A solution of 17n (0.150 g,
0.441 mmol) and Et3N (0.18 mL, 1.3 mmol) in CH2Cl2 (2 mL) was
cooled to 0 °C. A solution of TsCl (0.100 g, 0.534 mmol) in CH2Cl2
(1 mL) was added, and the reaction was allowed to warm to rt. After
16 h, the reaction was diluted with CH2Cl2 (25 mL) and washed with
saturated aqueous NaHCO3 (2 × 20 mL). The organic layer was
separated, dried with anhydrous MgSO4, filtered, and concentrated
under reduced pressure to afford 17o (0.217 g, 0.419 mmol, 95%) as a
colorless foam. No purification was necessary. The product was
The following compounds were prepared in identical fashion from
the corresponding imidazoline.
1
characterized as a 1:1 mixture of atropisomers: H NMR (500 MHz,
CDCl3, 298 K) δ 7.87−7.79 (m, 4H), 7.63 (d, J = 8.7, 2H), 7.57−7.54
(m, 2H), 7.50−7.46 (m, 2H), 7.35 (app t, J = 7.6, 2 H), 7.30−7.25 (m,
4H), 7.19−7.14 (m, 1H), 7.08 (app d, J = 8.0, 3H), 4.23−4.09 (m,
4H), 3.89−3.85 (m, 2H), 2.38 (s, 3H), 2.37 (s, 3H), 2.06 (septet, J =
6.7, 1H), 2.02 (septet, J = 6.9, 1H), 1.16 (d, J = 6.7, 3H), 1.16−1.05
(m, 9H); 13C NMR (125 MHz, CDCl3, 298 K) δ 156.1 (C), 156.0
(C), 144.4 (C), 144.3 (C), 135.5 (C), 135.3 (C), 135.2 (CH), 135.2
(CH), 133.8 (C), 133.7 (C), 133.0 (C), 132.8 (C), 132.2 (C), 132.2
(C), 130.9 (CH), 129.5 (CH), 129.5 (CH), 129.1 (CH), 128.3 (CH),
128.2 (CH), 128.1 (CH), 127.8 (CH), 127.7 (CH), 127.2 (CH),
126.52 (CH), 126.49 (CH), 125.6 (CH), 125.5 (CH), 97.6 (C), 97.2
(C), 71.7 (CH), 71.4 (CH), 51.4 (CH2), 50.9 (CH2), 33.2 (CH), 33.0
(CH), 21.7 (CH3), 21.6 (CH3), 19.7 (CH3), 19.4 (CH3), 19.1 (CH3),
18.9 (CH3); IR (thin film) 3058, 2959, 2872, 1640, 1360 cm−1; HRMS
(ESI) m/z, 519.0610 (519.0605 calcd for C23H24IN2O2S, (M + H)+).
Acetylacetonato{(S)-2-[2-(1-isopropyl)-4-tert-butyl-4,5,-dihy-
dro-1H-imidazyl]-naphthyl-C,N}palladium(II) (18b). Following
the general procedure, the crude product was purified by column
chromatography (silica gel, 10:1 hexanes/acetone) to afford pallada-
cycle 18b (0.220 g, 0.441 mmol, 68%) as a yellow solid: mp 123−126
°C; [α]D −22.6, [α]577 −22.9, [α]546 −24.7, [α]435 −30.1,
[α]43524 −36.3 (c = 1.0, CHCl3); 1H NMR (500 MHz, CDCl3, 298 K)
δ 7.86 (d, J = 8.4, 1H), 7.81 (d, J = 8.1, 1H), 7.72 (d, J = 8.4, 1H), 7.65
(d, J = 8.1, 1H), 7.41 (dt, J = 6.8, 1.2, 1H), 7.35 (dt, J = 6.8, 1.2, 1H),
5.38 (s, 1H), 4.47 (septet, J = 6.6, 1H), 3.84 (dd, J = 10.6, 3.8, 1H),
3.73 (t, J = 10.6, 1H), 3.49 (dd, J = 10.6, 3.8, 1H), 2.10 (s, 3H), 2.00
(s, 1H), 2.06 (s, 3H), 1.34 (d, J = 6.6, 3H), 1.01 (s, 9H), 0.99 (d, J =
6.6, 3H); 13C NMR (125 MHz, CDCl3, 298 K) δ 187.9 (C), 185.9
(C), 176.5 (C), 153.6 (C), 132.0 (C), 130.2 (C), 129.4 (C), 129.2
(CH), 128.6 (CH), 128.5 (CH), 125.7 (CH), 123.7 (CH), 123.5
24
24
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24
1947
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The Journal of Organic Chemistry
Article
(CH), 100.2 (CH), 69.6 (CH), 49.7 (CH), 45.3 (CH2), 36.1 (C), 28.0
(CH3), 27.6 (CH3), 25.7 (CH3), 21.1 (CH3), 18.3 (CH3); IR (thin
film) 3111, 2901, 2780, 1761, 1654, 1031 cm−1; HRMS (ESI) m/z,
521.1405 (521.1406 calcd for C25H32N2O2PdNa, (M + Na)+). Anal.
Calcd for C25H32N2O2Pd: C, 60.18; H, 6.46; N, 5.61. Found: C, 59.98;
H, 6.48; N, 5.59.
(CH3); IR (thin film) 3434, 3053, 2960, 1572, 1514, 1263 cm−1;
HRMS (ESI) m/z, 541.1080 (541.1083 calcd for C27H28N2O2PdNa,
(M + Na)+). Anal. Calcd for C27H28N2O2Pd: C, 62.49; H, 5.44; N,
5.40. Found: C, 62.33; H, 5.42; N, 5.42.
Acetylacetonato{(S)-2-[2-(1-tosyl)-4-isopropyl-4,5,-dihydro-
1H-imidazyl]-naphthyl-C,N}palladium(II) (18o). Following the
general procedure, the crude product was purified by column
chromatography (silica gel, 5:1 hexanes/acetone) to afford pallada-
cycle 18o (0.184 g, 0.309 mmol, 64%) as a orange solid: mp 162−166
Acetylacetonato{(S)-2-[2-(1-tert-butyl)-4-isopropyl-4,5,-dihy-
dro-1H-imidazyl]-naphthyl-C,N}palladium(II) (18f). Following
the general procedure, the crude product was purified by column
chromatography (silica gel, 9:1 hexanes/acetone) to afford pallada-
cycle 18f (0.230 g, 0.461 mmol, 68%) as a yellow solid: mp 148−151
24
24
24
24
°C; [α]D +41.2, [α]577 +43.4, [α]546 +56.7, [α]435 +64.3 (c =
1.1, CH2Cl2); 1H NMR (500 MHz, CDCl3, 298 K) δ 8.62 (d, J = 8.5,
1H), 7.88 (d, J = 8.4, 1H), 7.76 (d, J = 8.1, 1H), 7.74 (d, J = 8.4, 3H),
7.47 (t, J = 8.1, 1H), 7.39−7.36 (m, 3H), 5.40 (s, 1H), 3.95 (dd, J =
12.6, 7.7, 1H), 3.18−3.13 (m, 1H), 2.50−2.47 (m, 1H), 2.15 (s, 3H),
2.08 (s, 3H), 1.92 (s, 3H), 0.78 (d, J = 6.8, 6H); 13C NMR (125 MHz,
CDCl3, 298 K) δ 188.1 (C), 186.2 (C), 171.6 (C), 158.2 (C), 145.6
(C), 133.1 (C), 132.2 (C), 131.8 (C), 131.0 (CH), 130.0 (C), 128.6
(CH), 128.5 (CH), 127.8 (CH), 125.8 (CH), 125.6 (CH), 124.3
(CH), 100.4 (CH), 67.1 (CH), 49.0 (CH2), 28.8 (CH3), 27.7 (CH),
27.6 (CH3), 21.9 (CH3), 18.7 (CH3), 14.8 (CH3); IR (thin film) 3061,
2944, 1642, 1579, 1241 cm−1; HRMS (ESI) m/z, 619.0857 (619.0859
calcd for C28H30N2O4PdSNa, (M + Na)+). Anal. Calcd for
C28H30N2O4PdS: C, 56.33; H, 5.06; N, 4.69. Found: C, 56.55; H,
5.04; N, 4.68.
24
24
24
24
°C; [α]D +43.7, [α]577 +44.1, [α]546 +44.8, [α]435 +47.5,
[α]43524 +51.2 (c = 0.1, CHCl3); 1H NMR (500 MHz, CDCl3, 298 K)
δ 8.64 (d, J = 8.4, 1H), 7.99 (d, J = 8.4, 1H), 7.79 (d, J = 8.2, 1H), 7.66
(d, J = 8.4, 1H), 7.41 (t, J = 8.2, 1H), 7.35 (d, J = 8.2, 1H), 5.54 (s,
1H), 4.20 (ddd, J = 12.1, 7.4, 4.8, 1H), 3.67 (dd, J = 12.7, 7.5, 1H),
3.42 (t, J = 12.1, 1H), 2.98−2.96 (m, 1H), 2.12 (s, 3H), 2.04 (s, 3H),
1.35 (s, 9H), 1.01 (d, J = 7.1, 3H), 0.89 (d, J = 7.1, 3H); 13C NMR
(125 MHz, CDCl3, 298 K) δ 188.1 (C), 186.0 (C), 179.7 (C), 154.8
(C), 133.7 (C), 132.0 (C), 131.7 (C), 128.6 (CH), 128.5 (CH), 128.4
(CH), 125.4 (CH), 124.7 (CH), 123.5 (CH), 100.3 (CH), 67.9 (CH),
61.6 (CH2), 47.4 (C), 28.9 (CH3), 28.4 (CH), 27.9 (CH3), 27.7
(CH3), 19.1 (CH3), 15.3 (CH3); IR (thin film) 3051, 2968, 2933,
1729, 1582, 1264 cm−1; HRMS (ESI) m/z, 499.1582 (499.1578 calcd
for C25H33N2O2Pd, (M + H)+). Anal. Calcd for C25H32N2O2Pd: C,
60.18; H, 6.46; N, 5.61. Found: C, 60.09; H, 6.47; N, 5.60.
Acetylacetonato{(S)-2-[2-(1-pivoloyl)-4-isopropyl-4,5,-dihy-
dro-1H-imidazyl]-naphthyl-C,N}palladium(II) (18p). Following
the general procedure, the crude product was purified by column
chromatography (silica gel, 19:1→5:1 hexanes/acetone) to afford
palladacycle 18p (0.147 g, 0.279 mmol, 50%) as a yellow solid: mp
Acetylacetonato{(S)-2-[2-(1-1-adamantyl)-4-tert-butyl-4,5,-
dihydro-1H-imidazyl]-naphthyl-C,N}palladium(II) (18h). Follow-
ing the general procedure, the crude product was purified by column
chromatography (silica gel, 15:1 hexanes/acetone) to afford pallada-
cycle 18h (0.186 g, 0.315 mmol, 63%) as a yellow solid. The resulting
compound was an inseparable 1:1 mixture of isomers: mp 89−92 °C;
1H NMR (500 MHz, toluene-d8, 298 K) δ 9.09 (d, J = 8.4, 1H), 8.51
24
24
24
131−136 °C (decomp); [α]D +111.2, [α]577 +112.4, [α]546
24
+115.2, [α]435 +118.8 (c = 1.5, CH2Cl2); 1H NMR (500 MHz,
CDCl3, 298 K) δ 7.90 (d, J = 8.3, 1H), 7.81 (br s, 1H), 7.74 (d, J = 8.4,
1H), 7.61 (d, J = 4.3, 1H), 7.34−7.28 (m, 2H), 5.41 (s, 1H), 4.14 (br
s, 1H), 4.08−4.06 (m, 2H), 2.29 (br s, 1H), 2.12 (s, 3H), 2.00 (s, 3H),
1.44 (s, 9H), 1.04 (d, J = 6.7, 3H), 0.83 (d, J = 5.2, 3H); 13C NMR
(125 MHz, CDCl3, 298 K) δ 187.9 (C), 186.4 (C), 180.3 (C), 173.7
(C), 131.9 (C), 130.1 (C), 130.0 (CH), 129.8 (C), 129.0 (CH), 128.8
(C), 128.2 (CH), 125.4 (CH), 123.5 (CH), 100.3 (CH), 47.8 (CH),
40.8 (CH2), 28.7 (C), 28.2 (CH3), 27.8 (CH3), 27.7 (CH3), 25.4
(CH), 19.6 (CH3), 15.1 (CH3); IR (thin film) 3072, 2955, 1729, 1629,
1252 cm−1; HRMS (ESI) m/z, 549.1352 (549.1345 calcd for
C26H32N2O3PdNa, (M + Na)+). Anal. Calcd for C26H32N2O3Pd: C,
59.26; H, 6.12; N, 5.32. Found: C, 59.33; H, 6.14; N, 5.31.
(d, J = 8.4, 1H), 8.23 (d, J = 8.3, 1H), 8.13 (d, J = 8.5, 1H), 7.61 (d, J =
8.2, 1H), 7.54 (d, J = 8.3, 1H), 7.53 (d, J = 8.4, 1H), 7.52 (d, J = 8.3,
1H), 7.47 (t, J = 7.0, 1H), 7.39−7.36 (m, 2H), 7.20 (m, 1H), 5.24 (s,
1H), 5.21 (s, 1H), 4.01 (dd, J = 10.1, 7.0, 1H), 3.95 (t, J = 9.3, 1H),
3.86 (dd, J = 13.0, 10.3, 1H), 3.77 (dd, J = 13.0, 7.0, 1H), 3.51 (app t, J
= 11.4, 1H), 3.12 (dd, J = 11.5, 8.3, 1H), 2.16−2.06 (m, 8H), 1.98−
1.95 (m, 2H), 1.94−1.91 (m, 4H), 1.90−1.84 (m, 13H), 1.78−1.74
(m, 2H), 1.73 (s, 1H), 1.67 (s, 3H), 1.60 (s, 3H), 1.00 (s, 9H), 0.99 (s,
9H); 13C NMR (125 MHz, CDCl3, 298 K) δ 188.1 (C), 188.0 (C),
185.9 (C), 185.7 (C), 177.6 (C), 165.4 (C), 151.5 (C), 147.3 (C),
134.8 (C), 132.4 (C), 131.9 (C), 131.8 (C), 131.7 (C), 129.0 (C),
128.4 (CH), 127.9 (CH), 127.7 (CH), 127.3 (CH), 127.1 (CH),
126.4 (CH), 125.7 (CH), 125.6 (CH), 124.9 (CH), 124.4 (CH),
124.3 (CH), 123.4 (CH), 78.8 (CH), 70.3 (CH), 67.9 (CH2), 62.5
(CH2), 53.0 (CH2), 47.1 (CH2), 42.3 (CH2), 40.5 (CH2), 35.95
(CH2), 35.90 (CH2), 34.4 (C), 30.2 (CH3), 29.81 (CH3), 29.77 (C),
28.3 (CH), 28.0 (CH), 27.62 (CH), 27.55 (CH), 26.5 (CH3), 26.2
(CH3); IR (thin film) 3092, 2898, 1701, 1594, 1234 cm−1; HRMS
(ESI) m/z, 591.2197 (591.2203 calcd for C32H41N2O2Pd, (M + H)+).
Anal. Calcd for C32H40N2O2Pd: C, 65.02; H, 6.82; N, 4.74. Found: C,
65.18; H, 6.81; N, 4.73.
General Procedure for the Synthesis of (S)-PIN-acac
Complexes Directly from Amide 16. Preparation of
Acetylacetonato{(S)-2-[2-(1-benzyl)-4-isopropyl-4,5,-dihydro-
1H-imidazyl]-naphthyl-C,N}palladium(II) (18c). Amide 16a (0.350
g, 0.913 mmol) was dissolved in freshly distilled SOCl2 (0.33 mL, 4.6
mmol), and the resulting solution was heated to 85 °C. After 5 h, the
reaction was diluted with toluene (15 mL) and concentrated under
reduced pressure to afford the crude chloroalkylimidoyl chloride. The
residue was dissolved in CH2Cl2 (2 mL) and treated with a solution of
benzylamine (0.11 mL, 1.0 mmol) and Et3N (0.38 mL, 2.7 mmol) in
CH2Cl2 (2 mL). The reaction was maintained at rt for 6 h and then
stirred with 2 M NaOH (10 mL) for 20 min. The organic layer was
separated and flushed through a small pad of silica gel. The filter cake
was washed with 1:1 Et2O/hexane (50 mL), and the combined
organics were concentrated under reduced pressure to afford the
corresponding imidazoline as an orange foam of sufficient purity to be
used in the next step.
The imidazoline ligand prepared above was dissolved in toluene (2
mL), and Pd2dba3 (0.418 g, 0.457 mmol) was added in a single
portion. The resulting red solution was heated to 120 °C. After 16 h,
the reaction was concentrated under reduced pressure. The resulting
solid was immediately dissolved in CH2Cl2 (4 mL), and silver
acetylacetonate (0.207 g, 1.00 mmol) was added in a single portion.
The resulting black suspension was stirred at rt overnight then filtered
through a pad of Celite. The filter cake was washed with CH2Cl2 (50
mL), and the filtrate was concentrated to afford a yellow residue. The
crude product was purified by column chromatography (silica gel, 10:1
Acetylacetonato{(S)-2-[2-(1-phenyl)-4-isopropyl-4,5,-dihy-
dro-1H-imidazyl]-naphthyl-C,N}palladium(II) (18i). Following the
general procedure, the crude product was purified by column
chromatography (silica gel, 9:1 hexanes/acetone) to afford pallada-
cycle 18i (0.618 g, 1.19 mmol, 72%) as a yellow solid: mp 182−185
°C; [α]D24 +96.6, [α]57724 +102.7, [α]54624 +109.8, [α]43524 +114.3 (c =
1
1.0, CHCl3); H NMR (500 MHz, CDCl3, 298 K) δ 7.91 (d, J = 8.4,
1H), 7.65−7.62 (m, 2H), 7.35 (d, J = 8.6, 1H), 7.11−7.07 (m, 3H),
6.98 (t, J = 7.4, 1H), 6.87 (d, J = 7.4, 2H), 6.82 (t, J = 7.4, 1H), 5.39 (s,
1H), 4.28−4.22 (m, 2H), 3.92 (app d, J = 5.9, 1H), 2.63−2.59 (m,
1H), 2.10 (s, 3H), 1.98 (s, 3H), 0.92 (d, J = 7.1, 3H), 0.84 (d, J = 7.1,
3H); 13C NMR (125 MHz, CDCl3, 298 K) δ 188.0 (C), 186.4 (C),
172.4 (C), 157.9 (C), 144.7 (C), 132.0 (C), 130.0 (CH), 129.5 (C),
129.2 (CH), 128.9 (C), 128.7 (CH), 128.6 (CH), 125.1 (CH), 124.6
(CH), 124.2 (CH), 123.3 (CH), 122.8 (CH), 100.4 (CH), 66.3 (CH),
55.0 (CH2), 29.3 (CH), 27.9 (CH3), 27.8 (CH)3, 18.9 (CH3), 15.3
1948
dx.doi.org/10.1021/jo2025724 | J. Org. Chem. 2012, 77, 1939−1951

The Journal of Organic Chemistry
Article
hexanes/acetone) to afford palladacycle 18c (0.258 g, 0.484 mmol,
cycle 18g (72 mg, 0.14 mmol, 41%) as a yellow film: mp 123−126 °C;
24
24
24
24
24
53%) as a yellow solid: mp 122−128 °C (decomp); [α]D −110.3,
[α]D −82.4, [α]577 −83.3, [α]546 −85.1, [α]435 −89.6 (c = 0.5,
[α]57724 −110.9, [α]54624 −112.7, [α]43524 −114.4, [α]43524 −118.6 (c =
CH2Cl2); H NMR (500 MHz, toluene-d8, 298 K) δ 8.36 (d, J = 8.4,
1
1
1.2, CH2Cl2); H NMR (500 MHz, toluene-d8, 298 K) δ 8.20 (d, J =
1H), 8.23 (d, J = 8.4, 1H), 7.53 (d, J = 8.4, 1H), 7.47 (d, J = 8.4, 1H),
7.18 (t, J = 7.0, 1H), 7.10 (t, J = 7.0, 1H), 5.24 (s, 1H), 3.91 (dd, J =
9.6, 7.8, 1H), 3.28 (dd, J = 11.4, 9.6, 1H), 3.15 (dd, J = 11.4, 7.8, 1H),
1.92 (s, 3H), 1.87 (s, 3H), 0.97 (s, 9H), 0.95 (s, 9H); 13C NMR (125
MHz, CDCl3, 298 K) δ 188.0 (C), 185.7 (C), 177.8 (C), 151.5 (C),
134.3 (C), 131.8 (C), 131.6 (C), 128.5 (CH), 127.9 (CH), 127.7
(CH), 125.6 (CH), 124.5 (CH), 123.4 (CH), 100.2 (CH), 70.0 (CH),
61.1 (C), 49.1 (CH2), 35.8 (C), 29.8 (CH3), 28.9 (CH3), 27.5 (CH3),
26.0 (CH3); IR (thin film) 3101, 2979, 1690, 1584 cm−1; HRMS (ESI)
m/z, 535.1549 (535.1553 calcd for C26H34N2O2PdNa, (M + Na)+).
Anal. Calcd for C26H34N2O2Pd: C, 60.88; H, 6.68; N, 5.46. Found: C,
60.84; H, 6.70; N, 5.45.
8.4, 1H), 7.89 (d, J = 8.1, 1H), 7.56 (d, J = 7.8, 1H), 7.51 (d, J = 8.4,
1H), 7.11−7.08 (m, 5H), 7.07−7.01 (m, 2H), 5.24 (s, 1H), 4.39 (d, J
= 16.3, 1H), 4.11 (d, J = 16.3, 1H), 4.02−4.00 (m, 1H), 3.22−3.19 (m,
1H), 3.09 (t, J = 10.8, 1H), 2.54−2.51 (m, 1H), 1.92 (s, 3H), 1.84 (s,
3H), 0.88 (d, J = 6.8, 3H), 0.83 (d, J = 7.0, 3H); 13C NMR (125 MHz,
CDCl3, 298 K) δ 188.0 (C), 186.2 (C), 177.0 (C), 157.0 (C), 136.9
(C), 132.0 (C), 129.6 (C), 129.3 (CH), 129.2 (CH), 129.0 (CH),
128.9 (CH), 127.6 (CH), 127.1 (CH), 125.9 (CH), 123.6 (CH),
100.3 (CH), 67.1 (CH), 56.5 (CH2), 52.2 (CH2), 30.4 (CH), 27.9
(CH3), 27.7 (CH3), 18.7 (CH3), 15.8 (CH3); IR (thin film) 3072,
3019, 2951, 1668, 1592, 1255 cm−1; HRMS (ESI) m/z, 555.1236
(555.1251 calcd for C28H30N2O2PdNa, (M + Na)+). Anal. Calcd for
C28H30N2O2Pd: C, 63.10; H, 5.67; N, 5.26. Found: C, 62.90; H, 5.68;
N, 5.27.
Acetylacetonato{(S)-2-[2-(1-phenyl)-4-tert-butyl-4,5,-dihy-
dro-1H-imidazyl]-naphthyl-C,N}palladium(II) (18j). Following the
general procedure, the crude product was purified by column
chromatography (silica gel, 10:1 hexanes/acetone) to afford pallada-
cycle 18j (0.119 g, 0.223 mmol, 52%) as a yellow film: mp 98−101 °C
The following compounds were prepared in identical fashion from
amides 16a or 16b without purification of the intermediate
imidazoline.
24
24
24
24
(decomp); [α]D −8.4, [α]577 −8.9, [α]546 −10.7, [α]435 −15.3,
[α]40524 −17.7 (c = 1.9, CH2Cl2); 1H NMR (500 MHz, CDCl3, 298 K)
δ 7.92 (d, J = 8.3, 1H), 7.65 (t, J = 8.8, 2H), 7.30 (d, J = 8.3, 1H),
7.11−7.09 (m, 3H), 7.04 (t, J = 8.1, 2H), 7.02 (br s, 1H), 6.84 (t, J =
6.84, 1H), 5.41 (s, 1H), 4.31 (dd, J = 10.1, 3.0, 1H), 4.04 (dd, J = 10.6,
3.0, 1H), 3.92 (t, J = 10.1, 1H), 2.13 (s, 3H), 2.01 (s, 3H), 1.10 (s,
9H); 13C NMR (125 MHz, CDCl3, 298 K) δ 187.9 (C), 186.1 (C),
173.4 (C), 156.2 (C), 144.4 (C), 131.9 (C), 129.8 (C), 129.5 (CH),
129.3 (C), 128.7 (CH), 128.6 (CH), 128.4 (CH), 125.5 (CH), 125.0
(CH), 124.4 (CH), 123.9 (CH), 123.3 (CH), 100.3 (CH), 69.1 (CH),
57.5 (CH2), 36.1 (C), 28.0 (CH3), 27.7 (CH3), 26.0 (CH3); IR (thin
film) 3444, 3063, 2961, 1562, 1513, 1260 cm−1; HRMS (ESI) m/z,
533.1423 (533.1420 calcd for C28H31N2O2Pd, (M + H)+). Anal. Calcd
for C28H30N2O2Pd: C, 63.10; H, 5.67; N, 5.26. Found: C, 63.19; H,
5.68; N, 5.26.
Acetylacetonato{(S)-2-[2-(1-benzhydryl)-4-isopropyl-4,5,-di-
hydro-1H-imidazyl]-naphthyl-C,N}palladium(II) (18d). Following
the general procedure, the crude product was purified by column
chromatography (silica gel, 12:1 hexanes/acetone) to afford pallada-
cycle 18d (0.195 g, 0.320 mmol, 62%) as a yellow solid: mp 197−201
24
24
24
24
°C; [α]D +12.7, [α]577 +12.9, [α]546 +14.1, [α]435 +18.6,
[α]43524 +19.9 (c = 1.3, CH2Cl2); 1H NMR (500 MHz, CDCl3, 298 K)
δ 8.02 (d, J = 8.3, 1H), 7.84 (d, J = 8.1, 1H), 7.81 (d, J = 8.6, 1H), 7.77
(d, J = 8.4, 1H), 7.52−7.49 (m, 2H), 7.45 (d, J = 7.1, 1H), 7.37−7.32
(m, 4H), 7.26 (t, J = 8.1, 1H), 7.03−7.01 (m, 2H), 6.97 (t, J = 7.1,
1H), 6.61 (s, 1H), 5.44 (s, 1H), 3.85−3.81 (m, 1H), 3.65 (dd, J = 10.5,
7.9, 1H), 3.84 (t, J = 10.5, 1H), 2.59−2.55 (m, 1H), 2.18 (s, 3H), 2.00
(s, 3H), 0.93−0.89 (m, 6H); 13C NMR (125 MHz, CDCl3, 298 K) δ
188.1 (C), 186.1 (C), 176.8 (C), 156.9 (C), 139.1 (C), 138.9 (C),
131.9 (C), 129.8 (C), 129.5 (CH), 129.4 (C), 129.1 (CH), 128.8
(CH), 128.7 (CH), 128.6 (CH), 128.3 (CH), 128.0 (CH), 127.5
(CH), 125.8 (CH), 124.0 (CH), 123.7 (CH), 100.3 (CH), 67.6 (CH),
67.2 (CH), 46.4 (CH2), 30.0 (CH), 27.9 (CH3), 27.7 (CH3), 18.7
(CH3), 15.5 (CH3); IR (thin film) 3058, 3029, 2960, 1768, 1582, 1264
cm−1; HRMS (ESI) m/z, 609.1740 (609.1733 calcd for
C34H35N2O2Pd, (M + H)+). Anal. Calcd for C34H34N2O2Pd: C,
67.05; H, 5.63; N, 4.60. Found: C, 66.89; H, 5.64; N, 4.59.
Acetylacetonato{(S)-2-[2-(1-(4-methoxyphenyl))-4-isoprop-
yl-4,5,-dihydro-1H-imidazyl]-naphthyl-C,N}palladium(II) (18k).
Following the general procedure, the crude product was purified by
column chromatography (silica gel, 5:1 toluene/CH2Cl2) to afford
24
palladacycle 18k (51 mg, 0.09 mmol, 54%) as a yellow film: [α]D
+34.4, [α]57724 +35.1, [α]54624 +35.9, [α]43524 +42.3, [α]40524 +45.1 (c =
0.9, CH2Cl2); 1H NMR (500 MHz, CDCl3, 298 K) δ 7.92 (d, J = 8.4,
1H), 7.66 (t, J = 8.6, 2H), 7.42 (d, J = 8.8, 1H), 7.11 (t, J = 7.4, 1H),
6.90−6.85 (m, 3H), 6.66 (d, J = 8.8, 1H), 5.41 (s, 1H), 4.24−4.20 (m,
2H), 3.89 (dd, J = 9.5, 4.2, 1H), 3.70 (s, 3H), 2.66−2.58 (m, 1H), 2.13
(s, 3H), 2.00 (s, 3H), 0.95 (d, J = 7.0, 3H), 0.90 (d, J = 7.0, 3H); 13C
NMR (125 MHz, CDCl3, 298 K) δ 188.0 (C), 186.3 (C), 172.7 (C),
157.7 (C), 156.7 (C), 138.1 (C), 131.9 (C), 129.8 (CH), 129.5 (C),
129.0 (C), 128.8 (CH), 128.7 (CH), 128.5 (CH), 128.5 (CH), 125.1
(CH), 124.3 (CH), 124.2 (CH), 123.3 (CH), 114.4 (CH), 100.3
(CH), 66.3 (CH), 55.5 (CH3), 29.5 (CH2), 27.9 (CH3), 27.8 (CH3),
18.9 (CH3), 15.4 (CH3); IR (thin film) 3092, 2958, 1662, 1510, 1248
Acetylacetonato{(S)-2-[2-(1-cyclohexyl)-4-isopropyl-4,5,-di-
hydro-1H-imidazyl]-naphthyl-C,N}palladium(II) (18e). Following
the general procedure, the crude product was purified by column
chromatography (silica gel, 15:1 hexanes/acetone) to afford pallada-
cycle 18e (0.134 g, 0.255 mmol, 57%) as a orange solid: mp 187−190
24
24
24
24
°C; [α]D −71.7, [α]577 −72.9, [α]546 −74.1, [α]435 −78.6,
[α]43524 −82.4 (c = 1.5, CH2Cl2); 1H NMR (500 MHz, CDCl3, 298 K)
δ 7.89 (d, J = 8.5, 1H), 7.85 (d, J = 8.5, 1H), 7.80 (d, J = 7.7, 1H), 7.64
(d, J = 8.3, 1H), 7.40 (dt, J = 6.8, 1.3, 1H), 7.33 (dt, J = 6.9, 1.1, 1H),
5.37 (s, 1H), 4.13 (ddd, J = 8.0, 4.5, 1.3, 1H), 3.96−3.90 (m, 1H), 3.67
(t, J = 10.6, 1H), 3.42 (dd, J = 10.6, 8.0, 1H), 2.57−2.51 (m, 1H), 2.09
(s, 3H), 1.98 (s, 3H), 1.85−1.80 (m, 1H), 1.66−1.63 (m, 1H), 1.56−
1.47 (m, 5H), 1.23−1.14 (m, 2H), 0.97 (d, J = 7.0, 3H), 0.93 (d, J =
6.8, 3H); 13C NMR (125 MHz, CDCl3, 298 K) δ 187.9 (C), 186.1
(C), 176.5 (C), 155.9 (C), 132.1 (C), 129.8 (C), 129.6 (C), 129.1
(CH), 128.9 (CH), 128.8 (CH), 125.5 (CH), 123.6 (CH), 123.5
(CH), 100.2 (CH), 67.6 (CH), 58.7 (CH), 45.2 (CH2), 31.9 (CH2),
30.8 (CH), 29.5 (CH2), 27.9 (CH3), 27.7 (CH3), 25.9 (CH2), 25.4
(CH2), 25.3 (CH2), 18.7 (CH3), 15.8 (CH3); IR (thin film) 3045,
2950, 1718, 1612, 1258 cm−1; HRMS (ESI) m/z, 547.1568 (547.1564
calcd for C27H34N2O2PdNa, (M + Na)+). Anal. Calcd for
C27H34N2O2Pd: C, 61.77; H, 6.53; N, 5.34. Found: C, 61.84; H,
6.54; N, 5.33.
cm−1
; HRMS (ESI) m/z, 549.1376 (549.1370 calcd for
C28H31N2O3Pd, (M + H)+). Anal. Calcd for C28H30N2O3Pd: C,
61.26; H, 5.51; N, 5.10. Found: C, 61.21; H, 5.49; N, 5.10.
Acetylacetonato{(S)-2-[2-(1-(3,4,5-trifluorophenyl))-4-iso-
propyl-4,5,-dihydro-1H-imidazyl]-naphthyl-C,N}palladium(II)
(18l). Following the general procedure, the crude product was purified
by column chromatography (silica gel, 8:1 toluene/CH2Cl2) to afford
palladacycle 18l (0.107 g, 0.187 mmol, 58%) as a colorless solid: mp
24
24
24
24
210−214 °C; [α]D +68.4, [α]577 +69.1, [α]546 +71.3, [α]435
+78.9, [α]40524 +83.2 (c = 1.5, CH2Cl2); 1H NMR (500 MHz, CDCl3,
298 K) δ 7.94 (d, J = 8.4, 1H), 7.73 (d, J = 8.3, 1H), 7.70 (d, J = 8.4,
1H), 7.35 (d, J = 8.6, 1H), 7.21 (t, J = 7.6, 1H), 7.03 (t, J = 8.0, 1H),
6.55−6.52 (m, 2H), 5.42 (s, 1H), 4.31−4.28 (m, 1H), 4.23 (t, J = 10.8,
1H), 3.87 (dd, J = 9.6, 4.3, 1H), 2.69−2.64 (m, 1H), 2.14 (s, 3H), 2.01
(s, 3H), 0.96 (d, J = 7.0, 3H), 0.84 (d, J = 6.8, 3H); 13C NMR (125
MHz, CDCl3, 298 K) δ 188.1 (C), 186.4 (C), 171.5 (C), 158.9 (C),
151.2 (d, J = 249 Hz, C), 140.3 (app s, C), 136.8 (d, J = 248 Hz, C),
132.1 (C), 130.6 (CH), 129.2 (CH), 128.8 (C), 128.7 (CH), 128.4
Acetylacetonato{(S)-2-[2-(1-tert-butyl)-4-tert-butyl-4,5,-dihy-
dro-1H-imidazyl]-naphthyl-C,N}palladium(II) (18g). Following
the general procedure, the crude product was purified by column
chromatography (silica gel, 10:1 hexanes/acetone) to afford pallada-
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The Journal of Organic Chemistry
Article
(C), 125.8 (CH), 123.7 (CH), 123.4 (CH), 107.2 (CH), 107.0 (CH),
100.5 (CH), 66.5 (CH), 55.0 (CH2), 29.0 (CH), 27.9 (CH3), 27.7
(CH3), 19.0 (CH3), 15.2 (CH3); IR (thin film) 3071, 2955, 1622,
1533, 1241 cm−1; HRMS (ESI) m/z, 595.0801 (595.0811 calcd for
C27H25F3N2O2PdNa, (M + Na)+). Anal. Calcd for C27H25F3N2O2Pd:
C, 56.60; H, 4.40; N, 4.89. Found: C, 56.71; H, 4.41; N, 4.88.
Acetylacetonato{(S)-2-[2-(1-mesityl)-4-isopropyl-4,5,-dihy-
dro-1H-imidazyl]-naphthyl-C,N}palladium(II) (18m). Following
the general procedure, the crude product was purified by column
chromatography (silica gel, 10:1 hexanes/acetone) to afford pallada-
cycle 18m (0.190 g, 0.339 mmol, 65%) as a yellow solid: mp 134−139
washed with 3 M NaOH (3 × 150 mL). The organic layer was dried
over MgSO4, filtered, and concentrated under reduced pressure to
afford a brown paste. The residue was digested in toluene (300 mL)
and concentrated under reduced pressure to remove residual AcOH
and water. This process was repeated (1−3 times) until a light brown
solid formed. The crude solid was recrystallized from MeCN to afford
2-iodonaphthalene-1-carboxamide (5.05 g, 17.0 mmol, 95%) as a tan
solid in sufficient purity to be used in the next step. This solid (5.05 g,
17.0 mmol) was dissolved in MeCN (10.0 mL) with external heating.
A chilled solution of aqueous H2SO4 (70% (w/w), 100 mL) was
added, and the resulting solution was maintained at rt. NaNO2 (11.7 g,
170 mmol) was added to the reaction mixture in five equal portions
over 1 h. Gas evolution and a color change to red-brown were
accompanied by the formation of a precipitate. The resulting
suspension was protected from light and stirred at rt. After 16 h, the
mixture was diluted with water (100 mL) and extracted with CH2Cl2
(3 × 100 mL). The combined organic extracts were washed with 2 M
NaOH (3 × 100 mL). The pH of the combined aqueous extracts was
adjusted to ∼3 with 2 M HCl. The resulting cloudy suspension was
extracted with CH2Cl2 (3 × 50 mL). The combined organics were
dried over Na2SO4, filtered, and concentrated under reduced pressure
to afford 15 (3.90 g, 13.1 mmol, 77%) as a tan solid. Spectral data was
identical in all respects to previously reported values.18
24
24
24
23
°C; [α]D +32.6, [α]577 +32.9, [α]546 +33.7, [α]435 +38.9 (c =
1
0.1, CHCl3); H NMR (500 MHz, CDCl3, 298 K) δ 7.88 (d, J = 8.4,
1H), 7.59 (d, J = 8.1, 1H), 7.57 (d, J = 8.4, 1H), 7.05−7.02 (m, 2H),
6.94 (s, 1H), 6.74 (t, J = 8.1, 1H), 6.54 (s, 1H), 5.38 (s, 1H), 4.28 (dt,
J = 10.4, 5.5, 1H), 3.95 (dd, J = 10.4, 5.7, 1H), 3.63 (t, J = 10.4, 1H),
2.54−2.48 (m, 1H), 2.44 (s, 3H), 2.17 (s, 3H), 2.09 (s, 3H), 1.98 (s,
3H), 1.79 (s, 3H), 1.03 (d, J = 6.8, 3H), 1.00 (d, J = 6.8, 3H); 13C
NMR (125 MHz, CDCl3, 298 K) δ 188.1 (C), 186.3 (C), 174.8 (C),
138.7 (C), 137.4 (C), 135.40 (C), 135.36 (C), 131.8 (C), 130.8 (C),
130.4 (CH), 129.6 (CH), 129.4 (CH), 128.73 (C), 128.70 (CH),
128.4 (CH), 124.2 (CH), 123.3 (CH), 123.1 (CH), 100.4 (C), 66.2
(CH), 54.4 (CH2), 30.9 (CH), 28.0 (CH3), 27.8 (CH3), 20.9 (CH3),
18.9 (CH3), 18.7 (CH3), 18.3 (CH3), 15.9 (CH3); IR (thin film) 2958,
2920, 1584, 1398, 1264 cm−1; HRMS (ESI) m/z, 583.1560 (583.1564
calcd for C30H34N2O2PdNa, (M + Na)+). Anal. Calcd for
C30H34N2O2Pd: C, 64.23; H, 6.11; N, 4.99. Found: C, 64.30; H,
6.13; N, 4.98.
General Procedure for the PIN-Catalyzed Synthesis of
Enantiomerically Enriched 3-Acyloxy-1-alkenes. Preparation
of 3-Acetoxy-5-phenyl-1-pentene (24). Palladacycle 18a (0.9 mg,
0.02 mmol, 3 mol %) was added in a single portion to a solution of
allylic trichloroacetimidate 23 (0.200 g, 0.652 mmol), acetic acid (0.11
mL, 2.0 mmol), in CH2Cl2 (0.65 mL). The reaction was sealed under
an inert atmosphere (N2 or Ar) and maintained at rt. After 18 h, the
reaction mixture was concentrated under reduced pressure and
purified by chromatography (silica gel, 95:5 pentane/Et2O) to afford
allylic acetate 24 (0.126 g, 0.619 mmol, 95%) as a colorless oil.
Enantiomeric excess was determined by GC using a chiral stationary
phase [T = 130 °C, hold 40 min; ramp 5 to 180 °C, hold 40 min; S
(minor) enantiomer tR = 28.12 min, R (major) enantiomer tR = 30.09
min; 28% ee]. Spectral data was identical in all respects to previously
reported values.8c
ASSOCIATED CONTENT
* Supporting Information
VT-NMR experiments for PIN complexes 18a and 18i, details
■
S
1
of computational studies, X-ray data for 18a, 18b, and 18i, H
and 13C NMR data for new compounds, and copies of
enantioselective GC traces used to determine enantiomeric
purity (77 pages). This material is available free of charge via
the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: leoverma@uci.edu.
■
Present Address
†Department of Chemistry and Biochemistry, UCLA, 607
Charles E. Young Drive East, Box 951569, Los Angeles,
California 90095-1569, United States.
Preparation of 2-Iodo-1-naphthoic Acid (15).17,18 A solution
of n-BuLi (2.5 M, hexane, 34.5 mL) was added dropwise over 1 h to a
solution of 2,2,6,6-tetramethylpiperidine (12.20 g, 86.35 mmol) in
THF (300 mL) maintained at 0 °C. After 30 min, the reaction mixture
was cooled to −78 °C, and a solution of 1-cyanonaphthalene (14,
12.57 g, 82.03 mmol) in THF (25 mL) was added dropwise over 30
min. The resulting dark solution was maintained at −78 °C for 2 h. A
solution of I2 (21.92 g, 86.35 mmol) in THF (250 mL) was added
dropwise via addition funnel over 2 h. The reaction mixture was
maintained at −78 °C for 2 h and then allowed warm to rt overnight.
The reaction mixture was quenched with H2O (400 mL), and the
resulting mixture was extracted with EtOAc (2 × 250 mL). The
combined organics were washed successively with saturated aqueous
Na2S2O3 (3 × 300 mL), 1 M HCl (3 × 300 mL), and brine (1 × 300
mL). The organic layer was dried over MgSO4, filtered, and
concentrated under reduced pressure. The crude residue was
recrystallized from CHCl3/heptane to afford 2-iodo-1-cyanonaphtha-
lene (21.45 g, 76.85 mmol, 89%) as a tan solid. Spectral data was
identical in all respects to previously reported values.17
2-Iodo-1-cyanonaphthalene (5.00 g, 17.9 mmol) was suspended in a
solution of water (60 mL) and glacial acetic acid (120 mL). The
suspension was cooled to 0 °C, and concentrated H2SO4 (100 mL)
was slowly added dropwise such that the internal temperature was
maintained between 45−50 °C. The resulting brown solution was
heated to 120 °C. After 16 h, the reaction mixture was cooled to rt and
poured into ice water (300 mL). The resulting slurry was extracted
with EtOAc (3 × 100 mL), and the combined organic extracts were
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This research was supported by NSF (CHE-9726471) and
NIGMS (GM-30859). We thank Dr. Joe Ziller for his help
obtaining crystallographic data for 18a, 18b, and 18i.
Computational studies were performed on hardware purchased
with funding from CRIF (CHE-0840513); NMR and mass
spectra were obtained with instruments acquired with the
assistance of NSF and NIH shared instrumentation grants. 3D
renderings were generated using the program CYLview (www.
cylview.org).
REFERENCES
■
(1) For a recent review of enantioselective allylation reactions, see:
Lu, Z.; Ma, S. Angew. Chem., Int. Ed. 2008, 47, 258−297.
(2) For recent reviews of the important use of palladium(II)
complexes for catalytic enantioselective [3,3]-rearrangement of allylic
imidates to form enantioenriched chiral allylic amides, see: (a) Over-
man, L. E.; Carpenter, N. E. Org. React. 2005, 66, 1−107. (b) Nomura,
H.; Richards, C. J. Chem.Asian J. 2010, 5, 1726−1740.
(3) (a) Kirsch, S. F.; Overman, L. E.; Sneddon, H. F. J. Am. Chem.
Soc. 2005, 127, 2866−2867. (b) Cannon, J. S.; Kirsch, S. F.; Overman,
L. E. J. Am. Chem. Soc. 2010, 132, 15185−15191. (c) Cannon, J. S.;
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Kirsch, S. F.; Overman, L. E.; Sneddon, H. F. J. Am. Chem. Soc. 2010,
132, 15192−15203.
(4) (a) Kirsch, S. F.; Overman, L. E.; White, N. S. Org. Lett. 2007, 9,
911−913. (b) Olson, A.; Overman, L. E.; Sneddon, H. F.; Ziller, J. W.
Adv. Synth. Catal. 2009, 351, 3186−3192.
(20) Palladacycle formation is not observed in toluene at ambient
temperature.
(21) No broadening or coalescence of the proton signals was
observed for complex 18a, whereas complex 18i showed sharp signals
at room temperature, some of which broadened upon cooling to −78
°C. See the Supporting Information for details.
(22) The process of inversion at N(2) was studied by DFT
computational studies (B3-LYP/def2-TZVP, vacuum) for complexes
18a and 18i. Optimized starting geometries were derived from X-ray
crystal structure data. The energy barrier for inversion of the nitrogen
substituent in 18a (R2 = i-Pr) was 12.2 kcal/mol, whereas a much
lower barrier of 6.7 kcal/mol was observed for 18i. See the Supporting
Information for details.
(23) (a) TURBOMOLE V6.2, Turbomole GmbH: Karlsruhe,
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(24) A negative value for dihedral angle τ corresponds to C(2)−C(3)
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solvent.31 Full geometry optimization and numerical frequency
calculations were performed on all structures. Transition-state
structures were characterized by exactly one imaginary vibrational
mode along the reaction pathway (formation of the C−O bond), and
intermediates were confirmed by the absence of imaginary vibrational
modes.
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799−805.
(32) This procedure was adapted from one published by Casey and
co-workers.15
(15) Boland, N. A.; Casey, M.; Hynes, S. J.; Matthews, J. W.; Smyth,
M. P. J. Org. Chem. 2002, 67, 3919−3922.
(16) Imidazolines produced by this method were purified by column
chromatography on silica gel using 10% Et3N as a cosolvent to prevent
decomposition.
(33) The imidazolines described here displayed significant sensitivity
to mild acid. The addition of Et3N was necessary to prevent
decomposition of the product on silica gel.
(17) 1-Cyano-2-iodonaphthalene[103408-15-7] has been reported,
see: Fraser, R. R.; Savard, S. Can. J. Chem. 1986, 60, 621−628.
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previously on a small scale, see: (a) Tilly, D.; Castanct, A.-S.; Mortier,
J. Chem. Lett. 2005, 34, 446−447. (b) Moss, R. A.; Zhang, H.;
Caterjee, S.; Krogh-Jespersen, K. Tetrahedron Lett. 1993, 34, 1729−
1732.
(19) Isomeric mixtures of imidazolines 17a−m,o−p could not be
separated using conventional column chromatography employing
either silica or neutral alumina as a stationary phase.
1951
dx.doi.org/10.1021/jo2025724 | J. Org. Chem. 2012, 77, 1939−1951