Difference in Energy between Two Distinct Types of Chalcogen Bonds Drives Regioisomerization of Binuclear (Diaminocarbene)PdII Complexes

Article abstract of DOI:10.1021/jacs.6b09133

The reaction of cis-[PdCl₂(CNXyl)₂] (Xyl = 2,6-Me₂C₆H₃) with various 1,3-thiazol- and 1,3,4-thiadiazol-2-amines in chloroform gives a mixture of two regioisomeric binuclear diaminocarbene complexes. For 1,3-thiazol-2-amines the isomeric ratio depends on the reaction conditions and kinetically (KRs) or thermodynamically (TRs) controlled regioisomers were obtained at room temperature and on heating, respectively. In CHCl₃ solutions, the isomers are subject to reversible isomerization accompanied by the cleavage of Pd-N and C-N bonds in the carbene fragment XylNCN(R)Xyl. Results of DFT calculations followed by the topological analysis of the electron density distribution within the formalism of Bader's theory (AIM method) reveal that in CHCl₃ solution the relative stability of the regioisomers (ΔG_exp = 1.2 kcal/mol; ΔG_calcd = 3.2 kcal/mol) is determined by the energy difference between two types of the intramolecular chalcogen bonds, viz. S?Cl in KRs (2.8-3.0 kcal/mol) and S?N in TRs (4.6-5.3 kcal/mol). In the case of the 1,3,4-thiadiazol-2-amines, the regioisomers are formed in approximately equal amounts and, accordingly, the energy difference between these species is only 0.1 kcal/mol in terms of ΔG_exp (ΔG_calcd = 2.1 kcal/mol). The regioisomers were characterized by elemental analyses (C, H, N), HRESI⁺-MS and FTIR, 1D (¹H, ¹³C{¹H}) and 2D (¹H,¹H-COSY, ¹H,¹H-NOESY, ¹H,¹³C-HSQC, ¹H,¹³C-HMBC) NMR spectroscopies, and structures of six complexes (three KRs and three TRs) were elucidated by single-crystal X-ray diffraction.

Full text of DOI:10.1021/jacs.6b09133

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Article
Difference in Energy between Two Distinct Types of Chalcogen Bonds
II
Drives Regioisomerization of Binuclear (Diaminocarbene)Pd Complexes
Alexander S. Mikherdov, Mikhail A. Kinzhalov, Alexander S. Novikov, Vadim P. Boyarskiy,
Irina A. Boyarskaya, Dmitry V. Dar'in, Galina L. Starova, and Vadim Yu. Kukushkin
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.6b09133 • Publication Date (Web): 04 Oct 2016
Downloaded from http://pubs.acs.org on October 6, 2016
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Journal of the American Chemical Society
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Difference in Energy between Two Distinct Types of Chalcogen
Bonds Drives Regioisomerization of Binuclear (Diaminocarbene)PdII
Complexes
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Alexander S. Mikherdov, Mikhail A. Kinzhalov, Alexander S. Novikov, Vadim P. Boyarskiy*,
Irina A. Boyarskaya, Dmitry V. Dar'in, Galina L. Starova, Vadim Yu. Kukushkin*
Saint Petersburg State University, Saint Petersburg State University, 7/9 Universitetskaya Nab., Saint Petersburg, 199034
Russian Federation
ABSTRACT: The reaction of cisꢀ[PdCl2(CNXyl)2] (Xyl = 2,6ꢀMe2C6H3) with various 1,3ꢀthiazolꢀ and 1,3,4ꢀthiadiazolꢀ2ꢀamines in
chloroform gives a mixture of two regioisomeric binuclear diaminocarbene complexes. For 1,3ꢀthiazolꢀ2ꢀamines the isomeric ratio
depends on the reaction conditions and kinetically (KRs) or thermodynamically (TRs) controlled regioisomers were obtained at
room temperature and on heating, respectively. In CHCl3 solutions, the isomers are subject to reversible isomerization accompanied
with the cleavage of Pd–N and С–N bonds in the carbene fragment XylNCN(R)Xyl. Results of DFT calculations followed by the
topological analysis of the electron density distribution within the formalism of Bader's theory (AIM method) reveal that in CHCl3
solution the relative stability of the regioisomers (∆Gexp = 1.2 kcal/mol; ∆Gcalcd = 3.2 kcal/mol) is determined by the energy differꢀ
ence between two types of the intramolecular chalcogen bonds, viz. S•••Cl in KRs (2.8–3.0 kcal/mol) and S•••N in TRs (4.6–5.3
kcal/mol). In the case of the 1,3,4ꢀthiadiazolꢀ2ꢀamines, the regioisomers are formed in approximately equal amounts and, accordꢀ
ingly, the energy difference between these species is only 0.1 kcal/mol in terms of ∆Gexp (∆Gcalcd = 2.1 kcal/mol). The regioisomers
1
were characterized by elemental analyses (C, H, N), HRESI+ꢀMS and FTIR, 1D (1H, 13C) and 2D (1H,1HꢀCOSY, H,1HꢀNOESY,
1H,13CꢀHSQC, 1H,13CꢀHMBC) NMR spectroscopies, and structures of six complexes (three KRs and three TRs) were elucidated by
singleꢀcrystal Xꢀray diffraction.
that act via formation of intramolecular S•••O CB in the inꢀ
termediate,[14] stabilization of an intermediate in Pummerer
reaction by interꢀ and intramolecular S•••O contacts,[15] faciliꢀ
tation of the intramolecular redox cyclization of Sꢀcontaining
diazene,[16] the photochromic cyclization of 2,3ꢀ
dithiazolylbenzothiophene,[17] and the bondꢀswitch rearrangeꢀ
ment of substituted isothiadiazoles and isothiazoles[18] by forꢀ
mation in both cases intramolecular S•••N CBs in the starting
compounds. The other reports disclose electronic effects of
CB on the reaction center, viz. facilitation of the S–S bond
cleavage in benzoꢀ1,2ꢀdithiolanꢀ3ꢀoneꢀ1ꢀoxides by formation
of either S•••O, or S•••Cl contacts,[19] the protodeboronation of
5ꢀthiazolylꢀboronic acid[20] and the Mann–Pope reaction[21]
which are driven by intramolecular S•••O interactions. Thus,
only one example when the reactivity is affected by S•••Cl CB
is known.
INTRODUCTION
Chalcogen bonding (CB) is usually defined as nonꢀcovalent
interaction between a localized positive region on a chalcogen
atom in the extension of the covalent bonds (σꢀhole) and elecꢀ
tron donor species serving as CB acceptors.[1] The phenomeꢀ
non of CB currently attracts great attention due to applicability
of CB in biochemistry,[2] drug design,[2d, 3] polymer science,[4]
crystal engineering,[5] and supramolecular chemistry.[6] Altꢀ
hough heavier chalcogens, Se[7] and Te,[6f, 8] are better CB doꢀ
nors because of their higher polarizability,[1bꢀd] the majority of
recent reports deal with CBs involving more abundant S cenꢀ
ters. Most common types of CB with S atoms are S•••S, S•••O,
and S•••N interactions that are widely available in proteins[2aꢀc]
and also in some organic compounds.[6b, 6e, 6g, 9] The CBs of
sulfur with halogens (particularly with Cl centers in both orꢀ
ganic species[10] and metal complexes[11]) are also known, albeꢀ
it still unusual.
In this work, we continued our project focused on the ligand
reactivity of acyclic diaminocarbenes giving, after the couꢀ
pling with the isocyanide species, the binuclear palladium(II)
complexes.[22] When 1,3ꢀthiazolꢀ and 1,3,4ꢀthiadiazolꢀ2ꢀ
amines were applied as reactivity partners, we have now found
that the reaction of cisꢀ[PdCl2(CNXyl)2] (Xyl = 2,6ꢀMe2C6H3)
and these heterocycles leads to a mixture of two regioisomeric
binuclear diaminocarbene species. In the case of 1,3ꢀthiazolꢀ2ꢀ
amines, the two structures are held by intramolecular S•••Cl
(for kinetically controlled isomers) or S•••N (for thermodyꢀ
namically controlled isomers) CBs and the energy difference
between these nonꢀcovalent interactions drives the regioisomꢀ
The ability of CB to control the structures of Sꢀcontaining
compounds (e.g., conformational stabilization),[3c,
their
3f, 12]
molecular assembly,[6] protein folding,[2aꢀc,
and molecular
13]
recognition[2e] was repeatedly reported, whereas the effect of
CB on reactivity was exceptionally rarely verified. The domiꢀ
nant part of the published examples deals with stabilization
through CB of certain conformation either in starting comꢀ
pounds or in intermediates. These works include the applicaꢀ
tion of the chiral isothiourea derivatives as organocatalysts
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erization. The most relevant example is the reversible bondꢀ to isolate isomerically pure KR6 and TR7 failed and these
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switch rearrangement of substituted isothiadiazoles and isothiꢀ
azoles,[18b, 18c] where the products and the starting compounds
are involved in the identical S•••N interactions; these CBs led
to stabilization of the synꢀconformation required for occurꢀ
rence of the reaction.
species were obtained only in a mixture with the other regioiꢀ
somer.
S
+
R1
H
N
Xyl
R1
N
N
S
N
Cl
Cl
C
C
C
Y
NH
Xyl
N
To the best of our knowledge, this work is the first example
of a system where the chemical reactivity (regioisomerization)
mainly depends on the energy difference between two distincꢀ
tive types of CB, viz. S•••Cl and S•••N.
NH2
+
Pd
Pd
Y
Cl
C
1–9 (Y = CR2, N
R1 = H, Me, Ph, Cl, Br, I
R2 = H, Ph)
N
PC
MNC
Xyl
9
Xyl
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Xyl
Xyl
Xyl
N
N
N
Cl
RESULTS AND DISCUSSION
C
Xyl
C
Pd
R1
R1
S
S
N
Pd
N
N
N
Cl
+
N
Y
C
Y
C
N
N
Generation of binuclear aminocarbenes. The treatment of
the palladium(II) complex cisꢀ[PdCl2(CNXyl)2] (PC) with 1,3ꢀ
thiazolꢀ2ꢀamines (1–6; Figure 1) in a molar ratio 1:1.5 in
CDCl3 at RT in each case gives a mixture of two binuclear
aminocarbene products (Scheme 1) corresponding to kineticalꢀ
ly (KR1–6) and thermodynamically (TR1–6) controlled regiꢀ
oisomers formed in (3–7):1 ratios depending on the nature of
the 1,3ꢀthiazoles (Table S1, Supporting Information).
Pd
Pd
Xyl
Xyl
Cl
C
C
Cl
N
N
TR1–9
KR1–9
Xyl
Xyl
Scheme 1. Reaction between PC and 1–9.
We believe that the generation of isomers KR and TR proꢀ
ceeds by deprotonation of the initially formed mononuclear
aminocarbene complex (MNC; Scheme 1) followed by its
coupling with a XylNC in PC. The deprotonation increases the
nucleophilic activity of the NCN group and, subsequently,
provides its addition to two electrophilic centers (at a ligated
isocyanide carbon and at the metal center) of another molecule
of the starting palladium(II) isocyanide complex as we sugꢀ
gested earlier for the adduct with pyridinꢀ2ꢀamine.[22] In this
work, MNCs were not obtained directly even on slow addition
of a suspension of PC in CDCl3 to 3ꢀ or 4ꢀfold molar excess of
any one of 1–9 in CDCl3 at either RT, or upon reflux. This
could be due to the electron withdrawing character of the 1,3ꢀ
thiazole and 1,3,4ꢀthiadiazole rings (e.g., pKa 5.32 for 1,3ꢀ
thiazolꢀ2ꢀamine[23] vs. 6.71 for pyridinꢀ2ꢀamine[24]), which
facilitates the deprotonation of MNC. By contrast, the reaction
with pyridinꢀ2ꢀamine requires the presence of a base.[22] The
appearance of MNC and its deprotonated form in the reaction
between PC and 1 was confirmed by HRESI+ꢀMS (calcd for
C21H22ClN4PdS+ 503.0284, found m/z 503.0280 [M – Cl]+ and
calcd for C21H21N4PdS+ 467.0517, found m/z 467.0520 [M –
Cl – HCl]+).
Cl
S
S
S
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
N
N
N
1
2
3
Br
I
S
S
S
N
N
N
Ph
Ph
4
5
6
S
S
S
N
N
N
N
N
N
7
8
9
Figure 1. The heterocycles employed for the reactivity study.
When this reaction was conducted upon reflux, an isomeric
ratio KR/TR1–6 was 1:(3–7) thus indicating predominant
generation of thermodynamically controlled product (Table
S1).
Characterization of the regioisomers. All solid isomeric
mixtures gave satisfactory microanalyses (C, H, N). Pure
complexes were obtained as yellow solids and characterized
by high resolution ESI+ꢀMS, FTIR, 1D (1H, 13C{1H}) and 2D
The isomeric ratio is different in the reaction of PC with
1,3,4ꢀthiadiazolꢀ2ꢀamines (7–9; Figure 1). At room temperaꢀ
ture an isomeric ratio was (2–3):1 for KR/TR7–8, whereas
upon reflux it was ca. 13:10 for KR/TR7 and ca. 10:11 for
KR/TR8. In the reaction with 9, isomeric ratio KR/TR9 is
almost independent on the synthesis temperature, viz. ca. 11:9
at RT and ca. 10:11 upon reflux (Table S1).
1
1
1
(1H,1HꢀCOSY, H,1HꢀNOESY, H,13CꢀHSQC, H,13CꢀHMBC)
NMR spectroscopies (Supporting Information). Complexes
KR6 and TR7 were characterized only by H NMR spectrosꢀ
copy in the isomeric mixtures (see above). In addition, the
solid state structures of KR1, KR7, KR9, TR1, TR7 and TR8
were elucidated by singleꢀcrystal Xꢀray diffraction.
For all complexes the HRESI+ mass spectra display a fragꢀ
mentation pattern corresponding to [M – Cl]+ with the characꢀ
teristic isotopic distribution. The FTIR spectra for KRs and
TRs exhibit one or two strong and broad ν(C≡N) bands in the
range 2215–2190 cm–1 from both RNC ligands in each speꢀ
cies. In addition, KRs demonstrate three ν(C=N) strong bands
near 1635, 1470, and 1430 cm–1 in contrast to three ν(C=N)
bands at ca. 1620, 1550, and 1470 cm–1 observed for TRs.
1
Kinetically controlled complexes KR1–5 and KR7–9 were
isolated from the reaction mixtures that were obtained at RT,
whereas TR1–4, TR6, TR8, and TR9 were isolated from the
mixtures formed upon reflux (Table S1). Procedure of isolaꢀ
tion of pure TR5 is different due to instability of 5 under reꢀ
flux conditions (the KR/TR5 yield was only 30%) and TR5
was isolated from the equilibrium mixture obtained at 45 °C
(Table 1). In all cases, the appropriate mixtures were evapoꢀ
rated to dryness in air and then the residue was redissolved in
a CH2Cl2–Me2CO system and the solution was subjected to
fractional crystallization on slow evaporation. All our attempts
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The 1H NMR spectra of KRs and TRs display a set of overꢀ
The crystal data, data collection parameters, and structure
refinement data of KR1, KR7, KR9, TR1, TR7 and TR8 are
given in Table S2 (Supporting Information). The plots of the
structures with selected bond lengths and angles are given in
Figures 2–4.
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8
lapped and individual signals in the δ 7.25–6.05 range asꢀ
signed to the twelve aromatic C–H protons in the metaꢀ and
paraꢀpositions of the xylyl groups and the individual group of
signals of the thiaazaheterocyclic fragment in the δ 8.65–6.75
range. Signals of the Me groups were observed in δ 2.50–2.00
interval as four resolved singlets for KRs and as two resolved
and two overlapped singlets for TRs.
Generally, the molecules lie in one slightly distorted plane
with an exception of the xylyl groups. In KRs and TRs, both
metal centers adopt a distorted square planar geometry. The
isocyanide ligands are in the cisꢀposition to the NCN fragꢀ
ments. In each complex, the bond lengths of the two coordiꢀ
nated CN groups fall in the interval of 1.144–1.155 Å that is
typical for the common range of the CN triple bonds in the
related isocyanide palladium complexes, e.g., [PdХ2(CNXyl)2]
(1.145–1.156 Å; X = Cl[26], Br[27]).
The 13C NMR spectra of all KRs and TRs exhibit two sigꢀ
nals of carbons in the NCN fragments near δ 195 and 165 for
KRs and near δ 180 and 160 for TRs. These resonances beꢀ
long to the range specific for Pd–Ccarbene (δC 160–224) in acyꢀ
clic diaminocarbenes.[22, 25] Remarkable that the NCN carbon
signals of KRs and TRs are different. The assignments of the
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1H and 13C signals were performed by H,1HꢀCOSY, H,1Hꢀ
NOESY, 1H,13CꢀHSQC, 1H,13CꢀHMBC NMR methods (See
Supporting Information).
Figure 2. Views of KR1 (left) and TR1 (right) with the atomic numbering scheme. Thermal ellipsoids are drawn at the 50% probability
level. Dotted lines indicate the S•••Cl and S•••N contacts. Selected bond distances (Å) and angles (°) for KR1: Pd1–C4 2.024(6), N2–C4
1.365(8), N3–C4 1.312(9), Pd2–C5 1.991(6), N3–C5 1.451(9), N4–C5 1.260(9), N5–C6 1.155(9), N6–C7 1.149(9), S1–Cl2 3.097(2), C2–
S1–Cl2 172.0(3). Selected bond distances (Å) and angles (°) for TR1: Pd1–C4 2.018(3), N2–C4 1.407(5), N3–C4 1.280(5), Pd2–C5
1.990(4), N2–C5 1.427(4), N4–C5 1.267(5), N5–C6 1.152(4), N6–C7 1.144(5), S1–N4 2.672(3), C2–S1–N4 160.65(16).
Figure 3. Views of KR7 (left) and TR7 (right) with the atomic numbering scheme. Thermal ellipsoids are drawn at the 50% probability
level. Dotted lines indicate the S•••Cl and S•••N contacts. Selected bond distances (Å) and angles (°) for KR7: Pd1–C3 2.016(2), N3–C3
1.363(3), N4–C3 1.328(3), Pd2–C4 1.985(2), N4–C4 1.471(3), N5–C4 1.258(3), N6–C5 1.145(4), N7–C6 1.152(4), S1–Cl2 3.0927(9),
Cl2–S1–C2 172.79(12). Selected bond distances (Å) and angles (°) for TR7: Pd1–C3 2.016(2), N3–C3 1.412(4), N4–C3 1.285(4), Pd2–C4
1.955(3), N3–C4 1.477(4), N5–C4 1.268(4), N6–C5 1.151(4), N7–C6 1.148(4), S1–N5 2.702(3), C2–S1–N5 157.45(13).
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Figure 4. Views of TR8 (left) and KR9 (right) with the atomic numbering scheme. Thermal ellipsoids are drawn at the 50% probability
level. Dotted lines indicate the S•••Cl and S•••N contacts. Selected bond distances (Å) and angles (°) for TR8: Pd1–C4 2.003(4), N4–C4
1.288(5), N3–C4 1.415(5), N3–C5 1.444(6), N5–C5 1.258(5), Pd2–C5 1.995(4), N6–C6 1.145(5), N7–C7 1.155(6), S1–N5 2.740(4), C2–
S1–N5 156.89(17). Selected bond distances (Å) and angles (°) for KR9: Pd1–C9 2.009(3), N4–C9 1.331(4), N3–C9 1.357(4), N4–C10
1.465(4), N5–C10 1.259(4), Pd2–C10 1.985(3), C11–N6 1.149(4), C12–N7 1.145(4), S1–Cl2 3.0511(10), C2–S1–Cl2 177.90(11).
The structure of KRs is similar to that for the relevant binuꢀ
clear aminocarbene complexes also bearing four adjacent xyꢀ
lyl substituents.[22] In the metallacycles of KRs, the angles
around the palladium(II) centers are within the 78.25(9)–
80.78(11)° range being slightly larger to those previously obꢀ
served in the similar pyridinꢀ2ꢀamine based binuclear amiꢀ
nocarbene complex [78.73(9)–79.36(8)°].[22] In TRs, these
angles are larger than in KRs (79.93–81.70°). The Pd–C disꢀ
tances (KR1: Pd1–C4 2.024(6), Pd2–C5 1.991(6); KR7: Pd1–
C3 2.016(2), Pd2–C4 1.985(2); KR9: Pd1–C9 2.009(3), Pd2–
C10 1.985(3); TR1 Pd1–C4 2.018(3), Pd2–C5 1.990(3); TR7:
Pd1–C3 2.016(2), Pd2–C4 1.955(3); TR8: Pd1–C4 2.003(4),
Pd2–C5 1.995(4) Å) are longer than those reported for the
previously observed for the pyridinꢀ2ꢀamine based binuclear
aminocarbene complex (1.988(2) and 1.977(2) Å).[22]
r(S + N) = 3.35 Å)) and the angles C2–S1–X (X = Cl for KRs
or N for TRs) are within the 156.89(17)–177.90(11)° range
and this suggests the presence of chalcogen bonding[1d, 1e, 31]
between the S and Cl centers in KRs and between the S and N
atoms in TRs. Both the S•••Cl and S•••N contacts are among
short CBs reported (the shortest S•••Cl is 2.982 Å[10a] and
S•••N is 2.324 Å[32]).
All other bond lengths in KRs and TRs are typical, and
their values agree with those reported for related palladium(II)
carbene and isocyanide complexes.[26, 33]
The regioisomerization. The isomerization of KR1 into
TR1 at 45 °С was monitored by IR spectroscopy in CHCl3 and
by NMR in CDCl3 (Figure 5). In the IR spectra, each isomer
has a specific band used for monitoring, viz. 1431 cm–1 (KR1)
that losses its intensity upon isomerization and 1556 cm–1
(TR1) that increasing in time; two isosbestic points at 1458
cm–1 and at 1349 cm–1 were observed indicating the presence
of two interconvertible forms. However, insofar as the isomerꢀ
ization is very slow, monitoring by NMR is much simpler and
we used this method to achieve and to characterize the equilibꢀ
rium.
In KRs, the lengths of the C–N bonds in the NCN fragment
connected to Pd1 are close (KR1: C4–N3 1.312(9), C4–N2
1.365(9); KR7: C3–N3 1.363(3), C3–N4 1.328(3); KR9: C9–
N3 1.357(4) Å, C9–N4 1.331(4) Å) and they are intermediate
between the typical double and single bonds reflecting the
diaminocarbene nature. In the other NCN fragment connected
to Pd2, one bond (KR1: N3–C5 1.451(9); KR9: N4–C4
1.471(3); KR6: N4–C10 1.465(4) Å) is a single bond
(1.452(8) Å),[28] while the other bond (KR1: N4–C5 1.260(9);
KR7: N5–C4 1.258(3); KR9: N5–C10 1.259(4) Å) is a typical
double bond (1.260(9) Å).[28] In TRs, one C–N bond in each
NCN fragment is single (TR1: C4–N2 1.407(4), C5–N2
1.427(4); TR7: N3–C3 1.412(4), N3–C4 1.477(4); TR8: N3–
C4 1.415(5), N3–C5 1.444(6) Å) and another one is closer to
the double bond (TR1: C4–N3 1.280(5), C5–N4 1.2677(5);
TR7: N4–C3 1.285(4), N5–C4 1.268(4); TR8: N4–C4
1.288(5), N5–C5 1.258(5) Å).
When pure isomers KR1 and TR1 were dissolved in CDCl3
and both solutions were kept at RT, in their NMR spectra we
observed appearance of signals of the other isomer. The isomꢀ
erization is slow and at 45 °С the equilibrium (1:7, respectiveꢀ
ly; obtained by 1H NMR integration; Figure 5: blue ovals indiꢀ
cate selected signals of KR1, whereas red ovals – selected
signals of TR1) was reached after 13 days.
The isomerization of other complexes was also studied by
NMR in CDCl3 at 45 °С (Table 1). For all studied complexes
with 7–9 (KR/TR7–9) the equilibrium ratio between KRs and
TRs is close 9:11 compared to 1:(5–7) for the studied 1,3ꢀ
thiazolꢀ2ꢀamines adducts (KR/TR1–6). As can be inferred
from the obtained data, the substitution in a heterocycle does
not significantly affect the equilibrium ratio, whereas the addiꢀ
tion of one more nitrogen atom in the heterocycle lead to subꢀ
stantial change of relative stability of the regioisomers.
Xꢀray diffraction data also indicate that the S•••Cl (KR1:
S1•••Cl2 3.097(2); KR7: S1•••Cl2 3.0927(9); KR9: S1•••Cl2
3.0511(10) Å) distances in KRs and S•••N (TR1: S1•••N4
2.672(3); TR7: S1•••N5 2.702(3); TR8: S1•••N5 2.740(4) Å)
in TRs are less than the sum of Rowland’s van der Waals raꢀ
dii[29] of these atoms (vdw r(S + Cl) = 3.57, vdw r(S + N) =
3.45 Å and even Bondi’s[30] vdw separations (r(S + Cl) = 3.55,
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1
Ph
Table 1. Equilibrium Ratios and Constants based on H
NMR monitoring at 45 °С.
1
NH
Ph
Ph
Ph
R
2
3
4
5
6
7
8
9
N
N
N
Equilibrium
ratios
Equilibrium
constant
N
Mixture
R
R
R
C
C
C
C
N
H
N
N
Pd
Pd
H
H
KR/TR1
KR/TR2
KR/TR3
KR/TR4
KR/TR5
KR/TR6
KR/TR7
KR/TR8
KR/TR9
13:87
17:83
15:85
14:86
15:85
14:86
46:54
48:52
45:55
6.7
4.9
5.7
6.1
5.7
6.1
1.2
1.1
1.2
Cl
Cl
Cl
Cl
Scheme 2. Reversible ring opening.[34]
Theoretical consideration of the effect of CB on the
isomerization. Inspection of the crystallographic data sugꢀ
gests the presence of the chalcogen bonds S•••Cl and S•••N in
all KRs and TRs. In order to confirm or deny the hypothesis
on the existence of these nonꢀcovalent interactions and to esꢀ
timate the contribution of these weak interactions to the stabiꢀ
lization of regioisomers in a CHCl3 solution, we carried out
DFT calculations and performed topological analysis of the
electron density distribution within the formalism of Bader's
theory (AIM method)[35] for two isomeric pairs of the simplest
studied 1,3ꢀthiazoleꢀ (KR/TR1) and 1,3,4ꢀthiadiazoleꢀ
(KR/TR7) derived complexes. We successfully used this apꢀ
proach upon studies of nonꢀcovalent interactions and properꢀ
ties of coordination bonds in transition metal complexes.[11b, 36]
The results are summarized in Table S3 (Supporting Inforꢀ
mation), the contour line diagrams of the Laplacian distribuꢀ
tion ∇2ρ(r), bond paths, and selected zeroꢀflux surfaces for
KR1 and TR1 are shown in Figure 6. The Poincare–Hopf
relationship in all cases is satisfied, thus all critical points have
been found.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The observed regioisomerization cannot proceed without
splitting the Pd−N and C−N bonds of the aminocarbene fragꢀ
ment.
The only known reversible formation of palladium diaꢀ
minocarbene backbone in a solution was reported by Slaughter
and coworkers for intramolecular chelate ring opening in a
palladium(II) bisꢀcarbene complex (Scheme 2).[34] To the best
of our knowledge, we found the first example of the intermoꢀ
lecular regioisomerization of palladium aminocarbene comꢀ
plexes accompanied with the splitting of the C–N bond in the
carbene fragment.
Figure 5. 1H NMR monitoring of isomerization KR1 into TR1 in CDCl3 at 45 °C.
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1
2
3
4
Table 2. Energies of CBs defined by Espinosa et al.a and
Vener et al.b approaches[37],[38] and relative stabilities of isoꢀ
mers.
5
6
∆Ecb,
kcal/mol
Ecb, kcal/mol
∆G(CHCl3), kcal/mol
7
8
9
Isomer
Experimental
Solid
state
CHCl3
solution
CHCl3
solution
Calculated
3.2
(based
Keq)
on
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3.1a;
3.2b
6.0a;
5.1b
3.1a;
3.2b
2.8a;
3.0b
5.0a;
4.6b
2.8a;
3.0b
KR1
TR1
KR7
TR7
Figure 6. Contour line diagrams of the Laplacian distribution
∇2ρ(r), bond paths and selected zeroꢀflux surfaces for KR1 (left)
and TR1 (right) in solid state. Bond critical points (3, –1) are
shown in blue, nuclear critical points (3, –3) – in pale brown, ring
critical points (3, +1) – in orange, length unit – Å.
1.2
0.1
1.8–2.0
1.6–2.5
2.1
5.3a;
4.9b
5.3a;
4.6b
The AIM analysis demonstrates the presence of bond critiꢀ
cal points (BCPs) (3, –1) for chalcogen bonding S•••Cl and
S•••N in KR1, KR7, TR1, and TR7 both in the solid state and
in CHCl3 solution (Table S3). The geometry optimization for
all these species in a CHCl3 solution leads to elongation of the
S•••Cl and S•••N contacts (by 0.045 Å for KR1, 0.038 Å for
KR7, 0.058 Å for TR1, and 0.020 Å for TR7) compared to
their solid state geometries. The low magnitude of the electron
density (0.015–0.026 Hartree), positive values of the Laplaciꢀ
an (0.051–0.080 Hartree), and close to zero energy density
(0.001–0.002 Hartree) in these BCPs are typical for nonꢀ
covalent interactions. We have defined energies for these conꢀ
tacts according to the procedures proposed by Espinosa et
al.[37] and Vener et al.[38] (Table S3). The balance between the
Lagrangian kinetic energy G(r) and potential energy density
V(r) at the bond critical points (3, –1) reveals the nature of
these interactions, if the ratio –G(r)/V(r) > 1 is satisfied, than
the nature of appropriate interaction is purely nonꢀcovalent, in
case the –G(r)/V(r) < 1 some covalent component takes
place.[39] Based on this criterion one can state that the covalent
contribution in the chalcogen bonding S•••Cl and S•••N in all
structures under study is absent both in the solid state and in
CHCl3. The negligible nonzero or zero values of the Wiberg
bond indices for the S•••Cl and S•••N contacts in the equilibriꢀ
um structures of KR1, KR7, TR1, and TR7 in CHCl3 (0.04
for KR1, 0.00 for KR7, 0.03 for TR1, and 0.05 for TR7) adꢀ
ditionally confirms the electrostatic nature of these nonꢀ
covalent interactions.
The difference in energies of S•••N contact in TR1 and
S•••Cl contact in KR1 (1.8–2.0 kcal/mol in CHCl3) correlates
well with relative stability of these isomers (∆G experimental
= 1.2 kcal/mol and ∆G calculated = 3.2 kcal/mol, Figure 7).
Thus, we assume that in this case the S•••N and S•••Cl chalcoꢀ
gen bonds make a dominant contribution to the stabilization of
isomer TR1 comparing to KR1. For TR7 and KR7, despite
the slightly greater gap in energies of S•••N and S•••Cl conꢀ
tacts (1.6–2.5 kcal/mol in CHCl3), the difference in the relative
stability of these isomers is less noticeable (∆G experimental =
0.1 kcal/mol and ∆G calculated = 2.1 kcal/mol).
S•••Cl chalcogen bond
Ecb = 2.8–3.0 kcal/mol
S•••N chalcogen bond
Ecb = 4.6–5.0 kcal/mol
∆Gcalcd = –3.2 kcal/mol
∆Ecb(CHCl3)= 1.8–2.0 kcal/mol
TR1
KR1
Figure 7. Energy difference of the equilibrium structures of TR1
and KR1 and the chalcogen bonds.
Based on the results of AIM analysis (Table S3) it is clear
that the S•••N contacts in TR1 and TR7 (4.9–6.0 kcal/mol in
the solid state and 4.6–5.3 kcal/mol in CHCl3) are stronger
than the S•••Cl contacts in KR1 and KR7 (3.1–3.2 kcal/mol in
the solid state and 2.8–3.0 kcal/mol in CHCl3), and appropriate
interaction energies are typical for CBs.[1b, 1c, 40] We also deꢀ
termined relative stability of these isomers in CHCl3 solution
(Table 2, for more details see Table S4, Supporting Inforꢀ
mation) and in both cases TR is more stable than KR. In the
case of 1,3ꢀthiazole compounds, energy difference for the
equilibrium structures of KR1 and TR1 is 3.2 kcal/mol in
terms of Gibbs free energies, whereas for 1,3,4ꢀthiadiazole
species (KR7 and TR7) it is only 2.1 kcal/mol (Table S4).
Taking into account systematic overestimation of these therꢀ
modynamic parameters[1a, 41] (approx. by 2 kcal/mol) and after
introducing the corresponding amendment, these results
agreeable with the experimental data (Table 2).
We assumed that possible reason for different behavior of
KR/TR1 and KR/TR7 is the difference in energies of the Pd–
N and C–N bonds. In order to verify this hypothesis, we evalꢀ
uated the vertical total energies of KR1, KR7, TR1, and TR7
dissociation (Ev) through the Pd–N, C–N, and S•••Cl/S•••N
contacts (Scheme 3). Calculated Ev values are 243.2 (KR1),
242.2 (KR7), 247.1 (TR1), and 243.3 (TR7) kcal/mol, and
this is agree well with Keq parameters: in the case of KR/TR1,
the thermodynamically controlled regioisomer TR1 is noticeꢀ
ably more resistant to decomposition (by 3.9 kcal/mol),
whereas for KR/TR7 both regioisomers are prone to decomꢀ
pose similarly (difference in Ev values is only 1.1 kcal/mol).
The difference of calculated vertical total energies without the
contribution of CB for KR/TR1 is 1.9–2.1 kcal/mol, and the
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thermodynamically controlled regioisomer TR1 in such case
is still more resistant to decomposition. At the same time, if
EXPERIMENTAL SECTION
1
2
3
4
5
6
7
8
we consider the calculated vertical total energies without the
contribution of CB for KR/TR7 pair, the KR7 should be more
resistant to decomposition than the TR7 (by 0.8–1.4
kcal/mol), but accounting for the CB contribution dramatically
changes the situation, and TR7 becomes more stable.
Xyl
Materials and Instrumentation. Solvents, PdCl2, heteroꢀ
cycles 1, 2, 6–9, and xylyl isocyanide were obtained from
commercial sources and used as received, apart from chloroꢀ
form, which was dried by the distillation over calcium chloꢀ
ride. Complex cisꢀ[PdCl2(CNXyl)2][42] and heterocycles 3–5[43]
were synthesized by the modified literature procedures. C, H,
and N elemental analyses were carried out on a Euro EA 3028
HT CHNSO analyzer. Massꢀspectra were obtained on a
Bruker micrOTOF spectrometer equipped with electrospray
ionization (ESI) source, a mixture of MeOH and CH2Cl2 was
used for samples dissolution. The instrument was operated at a
positive ion mode using m/z range of 50–3000. The capillary
voltage of the ion source was set at –4500 V and the capillary
exit at 50–150 V. The nebulizer gas pressure was 0.4 bar and
the drying gas flow 4.0 L/min. The most intensive peak in the
isotopic pattern is reported. Infrared spectra were recorded on
a Perkin Elmer Spectrum BX FTꢀIR spectrometer (4000–400
cm–1) in KBr pellets for solid samples and in IR cells (KBr, l =
1.05 mm) for chloroform solutions. 1D (1H, 13C{1H}) NMR
spectra were acquired on a Bruker Avance 400 spectrometer,
while 2D (1H, 1HꢀCOSY, 1H,1HꢀNOESY, 1H, 13Cꢀ
Xyl
Xyl
N
N
N
Cl
C
Xyl
C
9
S
Pd
S
N
Pd
N
N
N
Cl
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Y
N
C
N
Y
N
C
Pd
Pd
Xyl
Xyl
C
Cl
Cl
C
N
N
Xyl
Xyl
Y = CH TR1
Y = N TR7
Y = CH KR1
Y = N KR7
Scheme 3. Cleavage of the Pd–N and C–N bonds, and the
S•••Cl/S•••N contacts in KR1, KR7, TR1, and TR7.
CONCLUSIONS
The reaction between the isocyanide–palladium(II) complex
cisꢀ[PdCl2(CNXyl)2] and two classes of heterocyclic sysꢀ
tems—1,3ꢀthiazolꢀ2ꢀamines (1–6) and 1,3,4ꢀthiadiazolꢀ2ꢀ
amines (7–9)—affords binuclear complexes KR/TR1–9 as
mixtures of kinetically (KR) and thermodynamically (TR)
controlled regioisomers. The structures of all these species
featuring two fused 5ꢀmembered palladacycles were deterꢀ
1
HMQC/HSQC, and H,13CꢀHMBC) NMR correlation experiꢀ
ments were recorded on a Bruker Avance II+ 500 MHz (Ulꢀ
traShield Magnet) spectrometer. All NMR spectra were acꢀ
quired in CDCl3 at ambient temperature.
Synthetic work. A solution of any one of 1–9 (0.068 mmol)
((i) in CH2Cl2 (3 mL) or (ii) in CHCl3 (5 mL) for generation of
mixtures enriched with KR or TR, correspondingly) was addꢀ
ed to solid PC (20 mg, 0.045 mmol) placed in a 10ꢀmL roundꢀ
bottom flask. The reaction mixtures were stirred in air (i) at
RT for 24 h (48 h in the case of 6) giving KR/TR mixtures
enriched with KR or (ii) upon reflux for 12 h for the mixtures
enriched with TR. In all cases, the color of the reaction mixꢀ
tures gradually turned from pale yellow to intense lemon yelꢀ
low and solid PC was dissolved. The formed solutions were
filtered from some insoluble material and evaporated at 20–
25 °C to dryness and then the solid residues were washed with
Et2O (three 1ꢀmL portions) and dried in air at RT. The yields,
isomeric ratios, and elemental analyses data for the obtained
mixtures are given in Table S1.
1
mined by 1D (1H, 13C) and 2D (1H,1HꢀCOSY, H,1HꢀNOESY,
1
1H,13CꢀHSQC, H,13CꢀHMBC) NMR in CDCl3 solutions and
Xꢀray diffraction in the solid state (five structures). Remarkaꢀ
ble that each pair of the isomers exhibits two different types of
chalcogen bonding such as S•••Cl (KRs) and S•••N (TRs); the
presence of CBs has been proved by combined Xꢀray crystalꢀ
lographic and DFT study.
In CDCl3 solutions, we observed interconversion of KRs
and TRs giving equilibrium mixtures of both isomers. Results
of DFT calculations followed by the topological analysis of
the electron density distribution within the formalism of Baꢀ
der's theory (AIM method) revealed that in CHCl3 solution the
relative stability of the regioisomers (∆Gexp = 1.2 kcal/mol;
∆Gcalcd = 3.2 kcal/mol) is determined by the energy difference
between two types of the intramolecular chalcogen bonds, viz.
S•••Cl in KRs (2.8–3.0 kcal/mol) and S•••N in TRs (4.6–5.3
kcal/mol). In the case of the 1,3,4ꢀthiadiazolꢀ2ꢀamines, the
regioisomers are formed in approximately equal amounts and,
accordingly, the energy difference between these species is
only 0.1 kcal/mol (∆Gcalcd = 2.1 kcal/mol). The different beꢀ
havior of 1,3ꢀthiazolꢀ2ꢀamine and 1,3,4ꢀthiadiazolꢀ2ꢀamine
derivatives determined by the different strengths of the Pd–N
and C–N bonds. The studied systems provide the first example
when the chemical reaction is driven by the energy difference
between two types of CB, viz. S•••Cl and S•••N. Noteworthy
that, in principle, CB could also preꢀorganize the reactants in
preference of the kinetic regioisomer prior to bond/ring forꢀ
mation, and further studies in this direction are under way in
our group.
Pure KRs and TRs were obtained by dissolution of the isoꢀ
meric mixtures (Table S1) enriched with KR or TR (except
TR5 which was obtained from equilibrium mixture), respecꢀ
tively, in acetone (1.5 mL)/CH2Cl2 (2 mL) mixture and then
these solutions were left to evaporate at 20–25 °C to ca. 1 mL.
In case of KR9, TR8, and TR9, one additional reꢀ
crystallization from acetone/CH2Cl2 mixture was performed.
The formed crystals of pure isomers were filtered off, washed
with Et2O (three 1ꢀmL portions) and dried in air at 20–25 °C.
Pure complexes were obtained as yellow solids and characterꢀ
ized by HRESI+ꢀMS, IR, 1D (1H, 13C{1H) and 2D (1H,1Hꢀ
1
1
1
COSY, H,1HꢀNOESY, H,13CꢀHSQC, H,13CꢀHMBC) NMR
spectroscopies. Our attempts to isolate pure complexes KR6
and TR7 failed and these species were characterized only by
1H NMR as a component of certain isomeric mixture.
Characterization. Characterization data, H, 13C{1H} and
HMBC NMR spectra are included in Supporting Information.
1
Equilibrium Measurements for KR1. (i) NMR study.
Complex KR1 (9 mg, 10 ꢁmol) and CDCl3 (0.5 mL) were
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Page 8 of 22
placed into an NMR tube, which was thermostated at 45 °C.
ASSOCIATED CONTENT
Supporting Information
The 1H NMR spectra were acquired every 1–2 days until equiꢀ
librium KR1/TR1 had been reached (ca. 13 days) as judged
by integral ratios of the XylꢀH4 peaks; (ii) IR study. Complex
KR1 (5 mg, 5.5 ꢁmol) was dissolved in CHCl3 (0.5 mL) and
the solution was placed in an IR cell, which was then placed in
thermostat at 45 °C. The IR spectra were measured every 30
min for the first 6 h and then after 6 h gap every 1 h for the
next 6 h.
1
2
3
4
5
6
7
8
The Supporting Information is available free of charge on the
ACS Publications website.
Experimental details for the synthesis and characterization of the
complexes, NMR spectra, crystallographic and computational
information (PDF)
Crystal data (CIF)
Equilibrium Measurements for Other Complexes. In
case of other complexes, the mixtures of both regioisomers (9
mg in every case) and CDCl3 (0.5 mL) were placed into NMR
tubes, which were thermostated at 45 °C until the equilibrium
was established. The isomeric ratios were determined by NMR
integration of the XylꢀH4 resonances.
9
AUTHOR INFORMATION
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11
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37
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49
50
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53
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59
60
Corresponding Authors
* v.boiarskii@spbu.ru; v.kukushkin@spbu.ru
Author Contributions
All authors have given approval to the final version of the manuꢀ
script.
Notes
X-ray Structure Determinations. Singleꢀcrystals of KR1,
KR7, TR8, and KR9 were grown from acetone/CH2Cl2 mixꢀ
tures and that of TR1 and TR7 from a Et2O/CHCl3 mixture.
The Xꢀray experiments were conducted on a SuperNova, Dual,
Cu at zero, Atlas diffractometer of KR1, TR1 and on a Xcaliꢀ
bur, Eos diffractometer of KR7, TR8, TR7, and KR9. The
crystals were kept at 100(2) K during data collection. Using
Olex2,[44] the structure was solved with the Superflip[45] strucꢀ
ture solution program using Charge Flipping (KR1, TR8) and
with the ShelXS[45] using Direct Methods (TR1, KR7, TR7,
KR9) and all structures were refined with the ShelXL[45] reꢀ
finement package using Least Squares minimization. The carꢀ
bonꢀbound H atoms were placed in calculated positions and
were included in the refinement in the ‘riding’ model approxꢀ
imation, with Uiso(H) set to 1.5Ueq(C) and C–H 0.96 Å for the
CH3 groups, with Uiso(H) set to 1.2Ueq(C) and C–H 0.93 Å for
the CH groups. Empirical absorption correction was applied in
CrysAlisPro[46] program complex using spherical harmonics
implemented in SCALE3 ABSPACK scaling algorithm.
The authors declare no competing financial interest.
ACKNOWLEDGMENT
This work was supported by Russian Science Foundation (grant
14ꢀ43ꢀ00017). Physicochemical studies were performed at the
Center for Magnetic Resonance, Center for Xꢀray Diffraction
Studies, Center for Chemical Analysis and Materials Research,
and Chemistry Educational Centre (all belong to Saint Petersburg
State University). The authors declare no competing financial
interests.
REFERENCES
1.
(a) Bauza, A.; Alkorta, I.; Frontera, A.; Elguero, J. J. Chem.
Theory Comput. 2013, 9, 5201ꢀ5210; (b) Wang, W.; Ji, B.; Zhang, Y. J.
Phys. Chem. A 2009, 113, 8132ꢀ8135; (c) Bleiholder, C.; Werz, D. B.;
Koppel, H.; Gleiter, R. J. Am. Chem. Soc. 2006, 128, 2666ꢀ2674; (d) Bauꢀ
za, A.; Quinonero, D.; Deya, P. M.; Frontera, A. CrystEngComm 2013,
15, 3137ꢀ3144; (e) Cavallo, G.; Metrangolo, P.; Pilati, T.; Resnati, G.;
Terraneo, G. Cryst. Growth Des. 2014, 14, 2697ꢀ2702.
Computational Details. The full geometry optimization
and single point calculations based on the experimental Xꢀray
geometries (quasiꢀsolidꢀstate approach) have been carried out
at DFT level of theory using the M06 functional[47] (this funcꢀ
tional was specifically developed to describe weak dispersion
forces and nonꢀcovalent interactions) with the help of Gaussiꢀ
anꢀ09[48] program package. The calculations were performed
using the quasiꢀrelativistic Stuttgart pseudopotentials that deꢀ
scribed 28 core electrons and the appropriate contracted basis
sets[49] for the palladium atoms and the 6ꢀ31G* basis sets for
other atoms. No symmetry restrictions have been applied durꢀ
ing the geometry optimization. The solvent effects were taken
into account using the SMD continuum solvation model by
Truhlar et al.[50] with CHCl3 as solvent. The Hessian matrix
was calculated analytically for the optimized structures in orꢀ
der to prove the location of correct minima (no imaginary freꢀ
quencies), and to estimate the thermodynamic parameters, the
latter being calculated at 25 °C. The topological analysis of the
electron density distribution with the help of the atoms in molꢀ
ecules (AIM) method developed by Bader[35] has been perꢀ
formed by using the Multiwfn program (version 3.3.4).[51] The
Wiberg bond indices were computed by using the natural bond
orbital (NBO) partitioning scheme.[52] The Cartesian atomic
coordinates of the calculated equilibrium structures in CHCl3
solution are presented in Table S5 (Supporting Information).
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TOC graphic
1
2
S•••N chalcogen bond
Ecb = 4.6–5.0 kcal/mol
3
4
5
6
7
8
9
S•••Cl chalcogen bond
Ecb = 2.8–3.0 kcal/mol
Xyl
Xyl
Xyl
Xyl
N
N
N
Cl
C
C
Pd
S
S
N
Pd
N
N
N
Cl
N
N
C
N
C
Pd
Pd
Xyl
Xyl
∆Gcalcd = –3.2 kcal/mol
∆Ecb(CHCl3)= 1.8–2.0 kcal/mol
Cl
C
C
Cl
N
N
Xyl
kinetically
controlled regioisomer
Xyl
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thermodynamically
controlled regioisomer
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Cl
S
S
S
NH2
NH2
NH2
Journal of the American ChPeamgeic1a2l Soof c2i2ety
N
N
N
2
3
1
Br1
2
3
4
5
I
S
S
S
NH2
NH2
NH2
NH2
N
N
N
Ph
Ph
4
5
6
S
S
S
ACS Paragon Plus Environment
6
NH2
NH2
N
7N
N
N
N
N
7
8
9
8

10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34

Journal of the American Chemical Society
Page 16 of 22
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
ACS Paragon Plus Environment

16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50

S•••Cl chalcogen bond
Ecb = 2.8–3.0 kcal/mol
Journal of the American
S
C
•••N
h
c
e
ha
m
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cPaalgSeo1c8ieotyf 22
n
b
o
n
d
Ecb = 4.6–5.0 kcal/mol
1
2
3
4
5
6
7
∆Gcalcd = –3.2 kcal/mol
∆Ecb(CHCl3)= 1.8–2.0 kcal/mol
ACS Paragon Plus Environment
TR1
KR1

S
+
R1
H
N
Xyl
R1
N
S
PagJoeu1r9naolfo2f2the American Chemical Society
Cl
C
C
Y
NH
Xyl
N
NH2
+
Pd
Pd
Y
N
Cl
C
Cl
1
2
3
4
5
C
1–9 (Y = CR2, N
R1 = H, Me, Ph, Cl, Br, I
R2 = H, Ph)
N
N
PC
MNC
Xyl
Xyl
Xyl
Xyl
Xyl
N
N
N
Cl
C
Xyl
C
Pd
S
N
R1
1
S
R 6
Pd
N
N
N
Cl
+
N
C
Y
7 Y
N
C
N
ACS Paragon Plus Environment
Pd
Pd
Xyl
Xyl
8
9
Cl
C
C
Cl
N
N
TR1–9
10KR1–9
Xyl
Xyl

Ph
urnal of theNAHmericanPCaghem20icoafl 2S2oci
Ph
Ph
Ph
R
N
ACS Paragon Plus Environment
N
N
N
R
R
R
C
C
C
C
N
N
N
Pd
H
Pd
1
2
H
H
Cl
Cl
Cl
Cl

Xyl
Xyl
Xyl
N
N
ourPnaaglCeol f2t1hoefA2m2 erican ChemicNal Socie
C
Xyl
C
S
Pd
S
N
Pd
N
N
Cl
N
C
Y
N
N
C
Y1N
2
Pd
Pd
Xyl
Xyl
ACS Paragon Plus EnviroCnment
Cl
C
Cl
N
N
3
Xyl
Xyl
Y = CH TR1
Y = N TR7
Y = CH KR1
4
Y = N KR7
5

S•••N chalcogen bond
Ecb = 4.6–5.0 kcal/mol
S•••Cl chalcogen bond
Ecb = 2.8–3.0 kcal/mol
Journal of the American Chemical Society
Page 22 of 22
Xyl
Xyl
Xyl
Xyl
1
2
3
4
5
6
7
8
N
N
N
Cl
N
C
C
Pd
S
S
N
Pd
N
Cl
Xyl
N
N
C
N
C
N
Pd
Pd
Xyl
∆Gcalcd = –3.2 kcal/mol
∆Ecb(CHCl3)= 1.8–2.0 kcal/mol
Cl
C
C
Cl
9
N
N
10
11
12
13
14
15
Xyl
kinetically
controlled regioisomer
Xyl
ACS Paragon Plus Environment
thermodynamically
controlled regioisomer