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Experimental and Computational Studies on Remote #-C(sp3)H Silylation and Germanylation of Aliphatic Carboxamides Arghya Deb, Sukriti Singh, Kapileswar Seth, Sandeep Pimparkar, Bangaru Bhaskararao, Srimanta Guin, Raghavan B. Sunoj, and Debabrata Maiti ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.7b03056 • Publication Date (Web): 25 Oct 2017 Downloaded from http://pubs.acs.org on October 25, 2017
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ACS Catalysis
Experimental and Computational Studies on Remote γ-C(sp3)−H Silylation and Germanylation of Aliphatic Carboxamides Arghya Deb, Sukriti Singh, Kapileswar Seth, Sandeep Pimparkar, Bangaru Bhaskararao, Srimanta Guin, Raghavan B. Sunoj,* and Debabrata Maiti* Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India ABSTRACT: A Pd(II) catalyzed protocol for highly regioselective distal γ-C–H silylation and germanylation of aliphatic carboxylic acids has been disclosed. Bidentate 8aminoquinoline as the directing group was found to stabilize the six membered palladacycle. A variety of aliphatic carboxylic acids and amino acids were silylated and germanylated with good yield and high diasteroselectivity. Detailed mechanistic studies involving isolation of a Pd(II) intermediate, reaction rate and order determination, control experiments, isotopic labeling and DFT studies was found to be crucial for elucidating the elementary steps involved in this distal aliphatic functionalization. KEYWORDS: γ-C–H activation, silylation, germanylation, organopalladium crystal, mechanistic studies, DFT
silylation.13 In this context, earlier reports on C−H silylation of aliphatic alcohol were based on intramolecular approach.9d,9i,9j Intermolecular aliphatic silylation remained restricted to benzylic (sp3)C−H bond9a,9e or to substrates containing (sp3)C−H bonds located α to a heteroatom.9c,9h Directing group assisted approach was found to be essential for intermolecular silylation of unbiased aliphatic C−H bond.14 Kanai group first developed a palladium catalyzed intermolecular silylation protocol using aliphatic β-(sp3)C−H bond.14a An impressive procedure for β-(sp3)C−H silylation of phthalimido protected amino acids was recently reported by Zhang14b and Shi14c group. Herein we report a palladium silylation and catalyzed intermolecular (sp3)C−H germanylation15 reaction reaching at the farthest γ-position of aliphatic carboxylic acids (Scheme 1). a)
Transition
metal catalyzed selective aliphatic C−H functionalization has opened new avenues for synthesizing complex molecular scaffolds.1 Despite the challenges in sp3 C−H bond activation, a number of metal catalyzed protocols have provided avenues to controlling selectivity.2 In this regard, palladium catalyst played a pivotal role toward predictably selective C−H functionalizations.3 In the last decade, efforts for directed C(sp3)−H activation of carboxylic acid derivatives,4 imines5 and aliphatic amines6 was explored with five membered palladacycle. However, directing group assisted approaches to functionalize distal γ-C(sp3)−H bond of aliphatic carboxylic acid has remained challenging. Despite significant advances, distal C−H activation in aliphatic carboxylic acids has remained elusive.7,8 Although a variety of palladium catalyzed aliphatic functionalizations has already been reported, the scarcity of these functionalizations at distal positions may be attributed to the involvement of less favored palladacycle intermediates. The potential of C(sp3)−H activation reactions can be exploited more by introducing new functional groups at distal carbon of aliphatic acids. Driven by such motivation, we began exploring various carbon-heteroatom bond forming reactions to selectively introduce different functional groups at the distal position of aliphatic acids. Out of different carbon-heteroatom bond forming reactions, aliphatic C−H silylation9 is one of the most popular fields of research owing to the synthetic utility in addition to unique chemical and physical properties of organosilicon compounds.10 The core structural units of many important therapeutical agents contain organosilicon moieties.11 Incorporation of silyl group into α- amino acids leads to notable change in its chemical properties.12 Expectedly, transition metal catalyzed strategies have emerged as one of the most powerful tools for widening the scope of C−H silylation.9, 13 Due to the higher steric hindrance of bulky trimethylsilyl group, aliphatic (sp3)C−H silylation is even more challenging as compared to (sp2)C−H
DG
O
Me3X XMe3
PdII
Me R1
O
DG removal
R2
− −
Remote γ C H Silylation and Germanylation Detailed mechanistc and DFT studies
CCDC 1549713
H2N
COOH L valine Me
Me
H2N
COOH
COOH L isoleucine Me
H2N
XMe3
Me
H2N Me
OH γ β XMe3 R1 R2 X = Si, Ge
α
H2N L tert leucine Me
XMe3
Me
Amino acid diversification b)
Me Me c)
Me
Me Me
XMe3 Me
O Ar PdII DG Me3Si SiMe3 Ar SiMe3 − − Sequential γ C H functionalization
Ar
DG Ar
Me
O
Me Ar
PdII Me3Si SiMe3
DG
PdII D4 AcOH
− − γ C H deuteration
Me
DG DG Ar SiMe3 Me - ua ernar cen re mme r ruc uns ons o c on t ti βq t t ti f y y C O
DG
Me
COOH
O PdII Ar I
Me
Me Me
PdII Ar I
DG
O
d) O
O
DG
O
Me Me
H2N
COOH
Me
COOH
CD3 D3C
CD3
O PdII Me3Si SiMe3
DG D2 C
D3C
SiMe3 CD3
Scheme 1. Directed γ-C−H Functionalization In continuation with our efforts to promote remote (sp3)C−H functionalization, we chose 8-aminoquinolamide16 of 3,3-dimethyl-butanoic acid as the model substrate for promoting palladium catalyzed γ-(sp3)C−H silylation and germanylation of simple aliphatic carboxylic acids. To our delight, a trace amount of γ-silylated product was obtained by using Pd(OAc)2 and hexamethyldisilane (HMDS) in dioxane. Detailed optimization was resulted highly regioselectiveγ-silylated product by using Pd(OPiv)2 as the catalyst in the presence of Ag2CO3 and NaHCO3 in tBuOH or dioxane.17 Since exogenous ligands are known to facilitate C−H and accelerate the metal catalyzed sp3 functionalizations, various ligands were systematically introduced to study their effect (Scheme 2).3c,3d,17 Inclusion of
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2-chloroquinoline was found to provide the best yield under the present reaction condition (Scheme 2). 10 mol% Pd(OPiv)2 O 20 mol% Ligand R 3 equiv Ag2CO3 NHQ R1 2 equiv NaHCO3 SiMe3 R1 2 mL tBuOH, 130 °C, 24 h 2
O R R1 R1
NHQ + Me e 3Si SiM 3 e M (5 equiv) 1
a)
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+ Me3Si-SiMe3 Me (5 equiv) Me
Ar
N
3 O Me
QHN
O Me
QHN
Q
O Me
QHN
O Me
QHN
SiMe3 Ar
4
O Me
QHN SiMe3
SiMe3
SiMe3
SiMe3
O Me
QHN 10 mol% Pd(OPiv)2 20 mol% L4 3 equiv Ag2CO3 2 equiv NaHCO3 2 mL tBuOH, 130 °C, 24 h
NHQ
O
SiMe3
Br without ligand N
N Cl L2 45%
F
L1 45%
53%
N
F N L3 7%
L4 71%
O Me
QHN
F3C N
N
L6 5%
L5 19%
N
OMe
N
L7 15%
L8 25%
SiMe3
SiMe3
L9 14%
4f, 66%
b)
N
Me
4g, 72%
OMe
4h, 69%
CF3
Ar
O
Me
O
MeO2C
NHQ + Me e 3Si SiM 3 Me (5 equiv) 1
O Me
QHN
NHQ
Me 2a, 71 %
Me
NHQ , Me 2d 63 %
Me Me O
O
Me Me3Si
QHN
6a, 54%
6b, 57%
MeO
NHQ Me3Si CO2Me 6c, 65%
EtO
F3C
O
O NHQ
Me3Si
6d, 52%
O NHQ
OMe
Me3Si
O
COMe
NHQ
OEt F3C Me3Si
6e, 61%
CF3
6f, 61% CF3
SiMe3
PhthN
O
O
MeOC
Me3Si
Me3Si
10 mol% Pd(OPiv)2 O 20 mol% L4 R v u e 3 q i Ag2CO3 NHQ R1 N 2 equiv NaHCO3 SiMe3 , , ° m u R1 2 L tB OH 130 C 24 h Q 2 NPhth= N Phthalimide
DG SiMe3
Ar
NHQ
O
Ar
6 O
Table 1. Scope of Aliphatic γ-C−H Silylation17
QHN
CO2Et
Condition: same as above
+ Me3Si-SiMe3 (5 equiv)
DG
L11 14%
Scheme 2. Ligand Screening for γ-C−H Silylation17
R1
4i, 72%
OEt
O Ar
5
R
SiMe3
OH N O L10 56%
R1
O Me
QHN
Br
N
Me tBu
NO2 COMe 4d, 75% 4e, 71%
O Me
QHN
O Me
QHN SiMe3
NH2
N
OH
tBu 4c, 61%
OMe 4b, 65%
CHO
4a, 67%
Cl
PhthN Me
SiMe3
SiMe3 Me 2c, 65 %
2b, 63 %
NHQ 2e, 69 % d r 18:1 SiMe3
O PhthN 2f, 70 % d r 37:1
Me
NHQ SiMe3
Subsequently, we have explored the scope of this selective silylation protocol with various aliphatic acetamides (Table 1). Expectedly, 8-amino quinolamide of 3,5,5trimethylhexanoic acetamide (2b) and isovaleric acid (2c) gave selective mono γ-silylated product. Owing to the importance of silicon-containing amino acids in biological research,12 a number of naturally occurring α-amino acids like L-valine (2f), L-isoleucine (2g) and tert-butyl leucine (2d) have been γ-silylated by following our method. Table 2. Scope of γ-C−H Silylation Quinolamides17
with γ-Arylated
After exploring various commercially available aliphatic carboxylic acids, we further thought to explore the scope of this γ-silylation reaction by using the γ-arylated product from our earlier report.8 A number of electronically different γarylated product of 3,3-dimethyl-butanamide successfully participated in γ-silylation (Table 2a). A modified quaternary carbon centre was generated by the successful γ-C−H silylation of the γ-di-arylated carboxylic acid. To the best of our knowledge, generation of such quaternary substituted carbon centres as well as desymmetrization of aliphatic system by iterative γ-C−H activation is unprecedented in literature. Accessing these quaternary γ-silylated molecules by this protocol is, therefore, expected to enhance the significance of the current method. Table 3. Scope of Aliphatic γ-C−H Germanylation17 NHQ
O
Me
R
+ Me3Ge GeMe3 (5 equiv)
R1 R2 7 QHN
10 mol% Pd(OPiv)2 R 20 mol% L4 R v u 1 3 eq i Ag2CO3 R1 2 equiv NaHCO3 , , ° 2 mL tBuOH 130 C 24 h
QHN
O Me GeMe3 Me 8a, 61 %
Me
Me Me3Ge
Me Me
O PhthN
O
O NHQ GeMe3 8 O
QHN GeMe3
GeMe3 Me , c 8 51 %
8b, 57 %
O
O NHQ
Me
8d, 63 %
PhthN Me
NHQ 8e, 69 % d r 19:1
GeMe3
PhthN 8f, 59 % d r 20:1
Me
NHQ GeMe3
Owing to the closely similar reactivites of silicon and germanium15, a further extension of the present γ-C−H functionalization protocol was carried out with
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hexamethyldigermane. Aliphatic carboxylic acids and amino acids resulted in the γ-germanylated product with high diastereoselectivity. This exemplary set of γ-germanylated products represents new chemical entities as well as reflects the generality of the present protocol (Table 3). Removal of 8-aminoquinoline directing group by acid calalyzed hydrodrolysis resulted 90% yield of silylated aliphatic ester.17
considered as the starting point of the catalytic cycle (Scheme 4). 2-chloro quinolone acts as an effective ligand in the active catalyst and in the formation of catalyst-substrate complex. N
O N Pd II
O
Me
Me
CCDC 1549713
1
PivO
O NPhth
QHN
SiMe3 Me isolated yield 65%
Oxidation
O
2
Pd(0)
Ag
O D 20% D D3C
NH CD3 CD3
10 mol% Pd(OPiv)2 D N 20 mol% L4 100% NH O Me3Si SiMe3 v u e 3 q i Ag2CO3 D (5 equiv) CD3 2 equiv NaHCO3 20% D 2 mL tBuOH, 130 °C, time D2C CD3
D 100%
NH O 20% D CD3 D 91% D3C CD3 D1
. kH/kD = 1 07
− C H Activation
HN O N
8
S
SiMe3
Scheme 3. Mechanistic studies for γ-C−H silylation17 A stoichiometric reaction of valine quinolamide and Pd(OAc)2 resulted a 6-membered palladacycle intermediate via γ-C−H activation which was confirmed by X-ray crystallography (Scheme 3). The organopalladium species (9) was found to be chemically and kinetically competent with Kinetic studies revealed first order rate Pd(OPiv)2. dependency of the substrate for this γ-silylation reaction. Yield of the product was monitored by gas chromatography and was plotted against time. Due to the excess use (5 equiv) of HMDS, steady state approximation was considered for the same. For intermolecular KIE experiment, gram scale synthesis of D1-quinolamide (D1-1) was carried out by treating quinolamide with Pd(OAc)2 and D4-AcOH at 100 oC. A 91% deuterium incorporation in each γ-methyl group hypothesized the reversibility of this γ-C−H activation process. A small KIE value of 1.07 further supported our hypothesis (Scheme 3). To develop a better understanding on the mechanism of this catalytic transformation, we have performed density functional theory computations at the SMD/M06/6-31G**, SDD (Pd, Ag) level of theory.18a The key intermediates and transition states of the catalytic cycle were fully optimized in condensed phase using tert-butanol as the solvent continuum. A Pd(II) species with two 2-chloro quinoline ligands and two pivalate groups trans to each other Pd(OPiv)2L2 (1) is noted as energetically most favorable active species (4.2 kcal/mol).18b Out of different possibilities, the substrate binds as an amidate to the pre-catalyst 1 to form a catalyst-substrate chelate complex (2)18c which is
- ‡ e [3 4] M
N Pd
S O
Ag
4
Me Me Me
S Me Me
L
O Me Me
N Pd
7
N
O
O
Ag
O
Me
PivOH
O
PivOH + Ag CO 2 3
N
N
Pd L
Me Me
Me Me
O N Pd N
6 SiMe3
75% D
Me Me Me
H O
Me3Si
75% D 61% D
N
O
3
S
- ‡ [6 7]
91%
O
Ag O
Reductive Elimination
D1
Pd
S
O
Pd
Me3Si
Me3Si
D 100%
N
H
O
Me3Si
N
O
L
N
Me Me
Me3Si
D 75%
d) KIE experiment with labeled D 1 61% D 75% D 75% D N
L
N
S
10 mol% Pd(OAc)2 . 2 equiv Na2CO3 2 mL D4 AcOH, 120oC, 72 h
Me
Ag2CO3
Pd
3
61% D
NH
N H
Piv
N
N
PivO
+ PivOSiMe
b) Chemical and kinetic competence studies O 10 mol% Intermediate 9 NPhth 20 mol% L4 QHN + Me3Si-SiMe3 3 equiv Ag2CO3 v u e Me Me (5 q i ) 2 equiv NaHCO3 2 mL tBuOH 130 °C, 24 h c) Preparation of D 1 D 75%
O
(2b) NaOPiv + L
O
Me3Si
O
N
O Me Me
Me O Intermediate 9 [X Ray]
N
1
+ OPiv
N
N Me
Cl
O Na
L Pd
L
S = t BuOH (solvent)
a) Crystal structure of 6-membered palladacycle
N
PivO
L=
N
Oxidative e Addition M 3Si
- ‡ [5 6]
O
N L
4a
Me3Si SiMe3
Pd N Si Me3
5
Scheme 4. Mechanistic Cycle for Palladium Catalyzed γSilylation and Germanylation A concerted metalation deprotonation (CMD) in 3 takes place to form a six-membered palladacycle intermediate 4. We note that the carbonate ligand is involved in the ligandassisted C−H activation (free energy 19.2 kcal/mol for [3-4]‡). A direct pivalate-assisted CMD is found to be 4.3 kcal/mol higher in energy.18d In 4, ligand (L) can replace the labile pivalic acid and silver carbonate (formed by combining silver pivalate and silver bicarbonate), to give another intermediate 4a. Interestingly, we could characterize a palladacycle intermediate (9, Scheme 3a) similar to 4a by using X-ray crystallography. Independent geometry optimization of 9 revealed very good agreement with the experimental structure (A root mean square deviation (RMSD) of only 1.274 Å is noted between the computed and X-ray structures for 9; See Figure S5 in the Supporting Information). The second substrate, (SiMe3)2 (or (GeMe3)2) can now displace ligand (L) from 4a and bind to the Pd(II) center through a weak interaction with the two silyl atoms in disilane (or Ge) (intermediate 5). It is important to note that the structure and energetics of transition states for the insertion of disilane derivatives to a palladium center is seldom reported.19 Two possible modes of silylation were considered, namely, (i) a lower energy oxidative addition, and (ii) a higher energy transmetallation.18e In the crucial step, an oxidative addition of Pd(II) to the disilane bond in HMDS takes place via [5-6]‡ to form 6 (23.0 kcal/mol).18e, 20 The intermediate 6 can now undergo reductive elimination via [6-7]‡ to give the silylated intermediate 7 (20.5 kcal/mol). The PivOH formed during the C−H activation step may interact with intermediate 7, initially through a hydrogen-bonding and subsequently transfer its proton to the amidate nitrogen to form productcatalyst complex 8. Thus, the computed energetics reveal that the silylation/germanylation mechanism involves a Pd(II)/Pd(IV) redox cycle.18
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Certain vital insights emerged through our computational study and its relevance to the experimental observations are worth considering at this juncture. It can be noted (Figure 1) that the highest energy point on the potential energy profiles for silylation (blue) and germanylation (green) are respectively the oxidative addition and reductive elimination TSs.18f This prediction is in concert with our low KIE values for silylation (1.07) and germanylation (1.27). A closer look at the energy profile reveals that the oxidative addition is the rate-determining step for silylation while it is the reductive elimination in germanylation reaction.
Figure 1. Gibbs free energy profile (kcal/mol) of the γC(sp3)−H silylation and germanylation obtained at the SMD/M06/6-31G**, SDD(Pd) level of theory. In summary, we have developed a novel method for distal γ-C(sp3)−H silylation and germanylation of aliphatic acids. Preliminary mechanistic studies with organopalladium intermediate suggested a facile γ-C−H activation process with subsequent silylation. Detailed studies and further development towards the stereoselective silylation by rational design of directing groups is currently underway in our laboratory. ACKNOWLEDGEMENT This research was supported by SERB(EMR/2015/000164). Fellowships from CSIR-India (AD), UGC-India (BB), IITB (SS), SERB (KS and SG) and SpaceTime supercomputing facility are gratefully acknowledged. AUTHOR INFORMATION Corresponding Authors:
[email protected] (experimental studies),
[email protected] (computational studies) Supporting Information Available: Experimental details, computational methods and characterization data. This material is available free of charge via the Internet at http://pubs.acs.org
REFERENCES 1.
For selected examples, see: (a) Feng, Y.; Chen, G. Angew. Chem., Int. Ed. 2010, 49, 958-961. (b) Miao, J.; Ge, H. Eur. J. Org. Chem. 2015, 2015, 7859-7868. (c) Topczewski, J. J.; Cabrera, P. J.; Saper, N. I.; Sanford, M. S. Nature 2016, 531, 220-224. (d) Chapman, L. M.; Beck, J. C.; Wu, L.; Reisman, S. E. J. Am. Chem. Soc. 2016, 138, 9803-9806. (e) Gemoets, H. P. L.; Kalvet, I.; Nyuchev, A. V.; Erdmann, N.; Hessel, V.; Schoenebeck, F.; Noël, T. Chem. Sci. 2017, 8, 1046-1055. (f) Gemoets, H. P. L.; Laudadio, G.; Verstraete,
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K.; Hessel, V.; Noël, T. Angew. Chem., Int. Ed., 2017, 56, 71617165. 2. For selected examples, see: (a) Jazzar, R.; Hitce, J.; Renaudat, A.; Sofack-Kreutzer, J.; Baudoin, O. Chem. -Eur. J. 2010, 16, 26542672. (b) Baudoin, O. Chem. Soc. Rev. 2011, 40, 4902-4911. 3. For selected examples, see: (a) Dastbaravardeh, N.; Christakakou, M.; Haider, M.; Schnürch, M. Synthesis 2014, 46, 1421-1439. (b) Pedroni, J.; Cramer, N. Chem. Commun. 2015, 51, 17647-17657. (c) He, J.; Wasa, M.; Chan, S. L. K.; Shao, Q.; Yu, J.-Q. Chem. Rev. 2017, 117, 8754-8786. (d) Kapdi, A.; Maiti, D. Strategies for Palladium-Catalyzed Non-directed and Directed C−H Bond Functionalization 2017, ISBN: 9780128052549. 4. For selected examples see: (a) Shabashov, D.; Daugulis, O. J. Am. Chem. Soc. 2010, 132, 3965-3972. (b) Ano, Y.; Tobisu, M.; Chatani, N. J. Am. Chem. Soc. 2011, 133, 12984-12986. (c) Hoshiya, N.; Kobayashi, T.; Arisawa, M.; Shuto, S. Org. Lett. 2013, 15, 62026205. (d) Zhang, S.-Y.; Li, Q.; He, G.; Nack, W. A.; Chen, G. J. Am. Chem. Soc. 2013, 135, 12135-12141.(e)Yan, S.-B.; Zhang, S.; Duan, W.-L. Org. Lett. 2015, 17, 2458-2461. (f) Shan, G.; Huang, G.; Rao, Y. Org. Biomol. Chem. 2015, 13, 697-701. (g) Gopalakrishnan, B.; Mohan, S.; Parella, R.; Babu, S. A. J. Org. Chem. 2016, 81, 89889005. 5. For selected examples, see: (a) Desai, L. V.; Hull, K. L.; Sanford, M. S. J. Am. Chem. Soc. 2004, 126, 9542-9543. (b) Thu, H.-Y.; Yu, W.Y.; Che, C.-M. J. Am. Chem. Soc. 2006, 128, 9048-9049. (c) Ren, Z.; Mo, F.; Dong, G. J. Am. Chem. Soc. 2012, 134, 16991-16994. (d) Sharpe, R. J.; Johnson, J. S. J. Am. Chem. Soc. 2015, 137, 49684971. 6. For selected examples, see: (a) Zaitsev, V. G.; Shabashov, D.; Daugulis, O. J. Am. Chem. Soc. 2005, 127, 13154-13155. (b) Zhang, S.-Y.; He, G.; Nack, W. A.; Zhao, Y.; Li, Q.; Chen, G. J. Am. Chem. Soc. 2013, 135, 2124-2127. 7. For selected examples, see: (a) Reddy, B. V. S.; Reddy, L. R.; Corey, E. J. Org. Lett. 2006, 8, 3391-3394. (b) Rodriguez, N.; Romero-Revilla, J. A.; Fernandez-Ibanez, M. A.; Carretero, J. C. Chem. Sci. 2013, 4, 175-179. (c) He, G.; Zhang, S.-Y.; Nack, W. A.; Li, Q.; Chen, G. Angew. Chem., Int. Ed. 2013, 52, 11124-11128. (d) He, G.; Zhang, S.-Y.; Nack, W. A.; Pearson, R.; Rabb-Lynch, J.; Chen, G. Org. Lett. 2014, 16, 6488-6491. (e) Li, S.; Chen, G.; Feng, C.-G.; Gong, W.; Yu, J.-Q. J. Am. Chem. Soc. 2014, 136, 52675270. (f) Li, S.; Zhu, R.-Y.; Xiao, K.-J.; Yu, J.-Q. Angew. Chem., Int. Ed. 2016, 55, 4317-4321. (g) Xu, J.-W.; Zhang, Z.-Z.; Rao, W.H.; Shi, B.-F. J. Am. Chem. Soc. 2016, 138, 10750-10753. (h) Liu, B.; Shi, B.-F. Synlett, 2016, 27, 2396-2400. (i) Ling, P.-X.; Fang, S.L.; Yin, X.-S.; Zhang, Q.; Chen, K.; Shi, B.-F. Chem. Commun. 2017, 53, 6351-6454. (j) We are involved in developing distal C-H functionalization of aliphatic substrates. For example, remote γ-sp3 C−H thioarylation and selenoarylation were successfully developed in our laboratory. 8. Dey, A.; Pimparkar, S.; Deb, A.; Guin, S.; Maiti, D. Adv. Synth. Catal. 2017, 359, 1301-1307. 9. (a) Kakiuchi, F.; Tsuchiya, K.; Matsumoto, M.; Mizushima, E.; Chatani, N. J. Am. Chem. Soc. 2004, 126, 12792-12793. (b) Larsson, J. M.; Zhao, T. S. N.; Szabó, K. J. Org. Lett. 2011, 13, 1888-1891. (c) Ihara, H.; Ueda, A.; Suginome, M. Chem. Lett. 2011, 40, 916918. (d) Simmons, E. M.; Hartwig, J. F. Nature, 2012, 483, 70-73. (e) Mita, T.; Michigami, K.; Sato, Y. Org. Lett. 2012, 14, 34623465. (f) Frihed, T. G.; Heuckendorff, M.; Pedersen, C. M.; Bols, M. Angew. Chem., Int. Ed. 2012, 51, 12285-12288. (g) Kuninobu, Y.; Nakahara, T.; Takeshima, H.; Takai, K. Org. Lett. 2013, 15, 426428. (h) Mita, T.; Michigami, K.; Sato, Y. Chem.−Asian J. 2013, 8, 2970-2973. (i) Ghavtadze, N.; Melkonyan, F. S.; Gulevich, A. V.; Huang, C.; Gevorgyan, V. Nat. Chem. 2014, 6, 122-125. (j) Li, B.; Driess, M.; Hartwig, J. F. J. Am. Chem. Soc. 2014, 136, 6586-6589. (k) Li, Q.; Driess, M.; Hartwig, J. F. Angew. Chem., Int. Ed. 2014, 53, 8471-8474. (l) Li, W.; Huang, X.; You, J. Org. Lett. 2016, 18, 666-668. (m) Parija, A.; Sunoj, R. B. Org. Lett. 2013, 15, 40664069. 10. (a) Rappoport, Z., Apeloig, Y., Eds. Chemistry of Organosilicon Compounds; Wiley-VCH: New York, 2001; Vol. 3. 1-1172 (b) Liu, X.-M.; He, C.; Xu, J. Chem. Mater. 2005, 17, 434-441. (c) Sanchez J. C.; Trogler, W. C. Macromol. Chem. Phys. 2008, 209, 1527-1540. (d) Iida, A.; Nagura, K.; Yamaguchi, S. Chem.−Asian J. 2008, 3, 1456-1464. (e) Bai, D.; Han, S.; Lu, Z.-H.; Wang, S. Can. J. Chem.
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TOC Graphic DG
O
Me3X XMe3
PdII
Me R1
O
OH γ XMe3
R2
R1
6 Membered Palladacycle
R2
X = Si, Ge 27 examples Excellent yield and selectivity Mechanistic studies DFT calculations
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