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Palladium(II)-Catalyzed Stereospecific Alkenyl CH Bond Alkylation of Allylamines with Alkyl Iodides Yun-Cheng Luo, Chao Yang, Sheng-Qi Qiu, QIU-JU LIANG, Yun-He Xu, and Teck-Peng Loh ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.8b04415 • Publication Date (Web): 28 Mar 2019 Downloaded from http://pubs.acs.org on March 28, 2019
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ACS Catalysis
Palladium(II)-Catalyzed Stereospecific Alkenyl C-H Bond Alkylation of Allylamines with Alkyl Iodides Yun-Cheng Luo,† Chao Yang,† Sheng-Qi Qiu,† Qiu-Ju Liang,† Yun-He Xu,*,† and Teck-Peng Loh*, †, ‡ †Department
of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, P. R. China of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371 ‡Division
Supporting Information Placeholder
ABSTRACT: A palladium-catalyzed stereospecific alkylation of allylamines with primary and secondary alkyl iodides is described. Isoquinoline-1-carboxamide (IQA) acts as directing group to generate multi-substituted olefin products in cis configuration in moderate to good yields. Mechanistic studies suggest that alkenyl C–H bond activation is the rate-determining step.
KEYWORDS: palladium, alkylation, alkenyl C-H activation, bidentate directing group, stereospecific.
Direct transition metal-catalyzed C-H alkylation1,2 has become a popular and highly efficient method for C-C bond formation. Alkylation of aromatic C(sp2)-H2,3 and aliphatic C(sp3)-H2,4 is well documented, but direct functionalization of alkenyl C(sp2)-H2 remains relatively challenging due to competing reactions involving unsaturated π bonds in alkenes. A potentially attractive solution is stereospecific synthesis of substituted alkenes via directing group-mediated C(alkenyl)-H alkylation. This approach can generate synthetically useful multi-substituted alkenes.5 Since 19951d, numerous alkylating reagents (alkenes, alkyl electrophiles and alkyl metal reagents) have been used in C(alkenyl)-H alkylations catalyzed by Fe6, Co7, Ni8, Pd9, Re10, Ru1d,11, Rh1d,12, and Ir13. Despite impressive progress in this field, success has been limited primarily to activated alkenes such as α,β-unsaturated carbonyl compounds, vinylpyridines, α,β-unsaturated imines, enamides and enolates. In contrast, reactions with common alkenes remain largely undeveloped.14-18 Few examples have been reported of stereoselective C(alkenyl)-H functionalization of unactivated alkenes. In 2013, Li and coworkers reported Rh(III)-catalyzed alkenylation of allylamines using sulfonamide as the directing group (Scheme 1a, eq 1).14 The Zhao group later reported oxalyl amide-directed silylation of allylamines and homoallylamines (Scheme 1a, eq 2) as well as their carbonylation (Scheme 1a, eq 3).15 In 2017, Babu and co-workers used picolinamide (PA) to direct C(alkenyl)−H arylation (Scheme 1a, eq 4).16 Recently, our group reported stereoselective cross-coupling between homoallylic alcohols and electron-deficient alkenes with assistance from hydroxyl group chelation and in the presence of palladium catalyst (Scheme 1a, eq 1).17
Given our continued interest in transition metal-catalyzed oxidative alkenyl C-H functionalization,17,19 we report the palladium-catalyzed, isoquinoline-1-carboxamide (IQA)directed alkylation of allylamines with alkyl iodides.20 This reaction is more challenging than previous examples of alkenyl C-H bond functionalization, because it involves alkyl iodides that react readily with nucleophilic ligands, base and substrate, leading to the premature termination of catalytic C-H alkylation. In addition, base-promoted elimination of alkyl iodides can occur as a competing reaction, especially in the case of secondary and tertiary alkyl halides.21 a) Previous work: Chelation assisted stereoselective functionalization of alkenyl C-H bond n
R
DG H
Pd or Rh
Pd
R1
Me3Si-SiMe3
n
R
R
DG
(1)
R1
Pd
CO
R
OA N H SiMe3
N OA
Pd R
N H
PA
Ar
O
(2)
Ar-I
(3)
(4)
b) This work: Palladium-catalyzed stereospecific alkylation of allylamines R1 R
R1
O
R4
2
R3
N H H
+ N
[I, Br] R
IQA
1o and 2o
5
R2 cat. [Pd]
R3
IQA R4
R5 (Z)-isomer only
Scheme 1. Chelation assisted stereoselective functionalization of the alkenyl C-H bonds. The experiment was first tested using N-(2methylallyl)picolinamide 1a-A and n-iodobutane 2a. The
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desired (Z)-alkylation product 3a was obtained in 14% yield under previously developed reaction conditions22 (Table 1, entry 1). Removing the additive NaOTf improved yield to 29% (Table 1, entry 2). The promoters (BnO)2PO2H, PivOH, TsNH2, and Ag2CO3, which are frequently used in C-H alkylation,4b did not work efficiently in the alkylation. Further screening of additives (see Supplementary Tables S4 and S5)23 showed that 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) and 18-crown-6 (18-Cr-6) significantly improved yield (Table 1, entries 7 and 8). Next, various palladium catalysts, bases, and solvents were examined sequentially (see Supplementary Tables S1–S3), and they did not lead to better results. Screening of bidentate directing groups (see Supplementary Table S7) showed that IQA generated the desired (Z)-alkylation product 3a in 62% yield.
R1 R2
Me
DG
I
+
Me
H 1
Me
1 Me
Me
A
NaOTf (300)
14
2
A
none
29
3
A
(BnO)2PO2H (20)
11
4
A
PivOH (20)
19
5
A
TsNH2(20)
26
6
A
Ag2CO3(200)
0
yield(%)
7
A
TEMPO (30)
38
8
A
TEMPO (30), 18-Cr-6 (5)
43
9
J
TEMPO (30), 18-Cr-6 (5)
62 (61)c
10
J
18-Cr-6 (5)
54
11
J
TEMPO (30)
38
none 2
4
A
5
IQA
3d, 73%
Bu 3h, 58%
3g, 77%
Me
IQA
O
F IQA
IQA
IQA
Bu
Bu
Bu
3j, 53%
3i, 48%
IQA
IQA
Me
O N
IQA Bu
Bu
3f, 84%
3e, 88%
IQA Bu 3
Me
3c, 68%
Bu
Bu
3k, 59%
3l, 58%
IQA Bu 3n, 0%
3m, 62%
aConducted under standard conditions (Condition A): the mixture
of 1 (0.3 mmol, 1.0 equiv), 2a (0.6 mmol, 2.0 equiv), Pd(OAc)2 (10 mol %), TEMPO (30 mol %), 18-crown-6 (5 mol %), and K2CO3 (2.0 equiv) in tAmylOH (0.2 M) was heated at 130 °C for 22h under air. bIsolated yields.
Table 3. Substrate Scope of Alkylation Reagents.a,b Pd(OAc)2 (10 mol %) TEMPO (30 mol %) 18-crown-6 (5 mol %) K2CO3 (2.0 equiv)
O i
Pr
N H
N
H 1h i
IQA
IQA
Pr
i
IQA
IQA
i
Pr
IQA
4f, 76%
4e, 63% i
Pr
IQA
Pr
IQA
Ph
2
4
4h, 85%
4g, 44%
IQA
C8H17
I
4
F
Pr
4d, 84%(82%)c
4c, 81% i
4
IQA n
IQA R
i
Pr
Et
4b, 81% i
Pr
AmylOH (0.2 M) air, 130 oC, 22 h
Pr
Me
i
t
2 i
Pr
I R
+
4i, 80%
J N
i
6
Pr
i
IQA
i
Pr
IQA
aReaction
conditions: 1a (0.3 mmol, 1.0 equiv), 2a (4.0 equiv), Pd(OAc)2 (10 mol %), K2CO3 (2.0 equiv), and additive were stirred in tAmylOH (0.2 M) for 22h at 130 °C in air. bYields were determined by 1H NMR. cIsolated yields. DG = directing group.
With the optimized reaction conditions in hand, we explored the substrate scope of alkenes using n-iodobutane 2a (Table 2). Various 1,1-disubstituted aliphatic alkenes such as 1a and 1d-1i with different functionalities worked well, affording the corresponding coupling products in moderate to high yields. Aryl-substituted alkenes gave the corresponding products in moderate yields (3k-3m). Unfortunately, the mono-substituted alkene afforded the desired product 3b in poor yield, while alkylation reaction was applicable to the tri-substituted cyclic alkene such as 1d. A branched allylamine also gave the desired product 3j in moderate yield (Table 2). However, the protected homoallyamine failed to work under the standard conditions (Table 2, 3n). Table 2. Substrate Scope of Alkenes.a,b
IQA Bu
IQA
Bu
30
N H
IQA Bu 3b, 9%
3a, 62%
O
3
N 1
IQA
R3
AmylOH (0.2 M) air, 130 oC, 22 h
2a 2.0 equiv
Bu
3
1
N H
t
Bu
DG
AmylOH (0.2 M) air, 130 oC, 22 h
additive(mol %)
O
Me
IQA
Me
DG
J
N
H
R1 R2
IQA
entry
12
+ I
MeO
t
2a
Pd(OAc)2 (10 mol %) TEMPO (30 mol %) 18-crown-6 (5 mol %) K2CO3 (2.0 equiv)
O N H
R3
Table 1. Optimization of Reaction Conditions.a,b Pd(OAc)2 (10 mol %) K2CO3 (2.0 equiv) additives
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2 4j, 81% i
Pr
i
IQA
4r, 24%d
CN
5 4o, 85% i
Pr
IQA 3
Pr
IQA
OTBDPS
2
4l, 86%
IQA
O 4n, 75% Pr
OBn
i
Pr
O
i
Pr
4k, 77%
IQA
i
i
Pr
IQA 4
COOEt
4m, 70% Pr
IQA
NHCbz
4p, 72%
4q, 30%(53%)d
IQA
4s, 46%d
aConducted under standard conditions (Condition A): the mixture
of 1h (0.3 mmol, 1.0 equiv), 2 (0.6 mmol, 2.0 equiv), Pd(OAc)2 (10 mol %), TEMPO (30 mol %), 18-crown-6 (5 mol %), and K2CO3 (2.0 equiv) in tAmylOH (0.2 M) was heated at 130 °C for 22h under air. bIsolated yields. cCondition B: KI (2.0 equiv) and 1bromooctane were used instead of 1-iodooctane. dCondition C: 3.0 equiv 2 and 12.5 mol % Pd(OAc)2 were used.
Next, different alkyl iodides were investigated for this alkylation reaction (Table 3). Direct methylation and
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ethylation were achieved, affording the corresponding cisisomers exclusively. Primary iodoalkanes with a long carbon chain or bearing various functionalities reacted smoothly with the allylamine 1h, generating the corresponding products in high yields. This reaction did not permit appreciable β-H elimination under standard conditions, since the level of elimination side-product from iodoalkane 2k was only about 2%, based on 1HNMR. The substrates 6-iodohexene (2i) and cyclopropylmethyl iodide (2j) afforded the corresponding products in good yields, without detectable amounts of rearrangement or ring-opening products. Thus, the coupling reaction does not appear to involve radical-mediated oxidative addition. Secondary alkyl iodides were less reactive than other substrates: 2-iodopropane (1q), sec-butyl iodide (1r), and iodocyclopentane (1s) gave only low to moderate yields of the corresponding products and only after increasing the loadings of catalyst and iodoalkanes (Condition C). Moreover, in the presence of 2 equivalents of KI (Condition B), alkyl bromides were similarly efficient as alkyl iodides (Table 3, 4d).
n
C8H17
4d IQA
Pr
NH2
2-Propanol (0.2 M) 82 oC, 18 h
n
Br
C8H17
IQA
D/H
IQA
eq. 2
H/D
n
1
C8H17
t AmylOH (0.2 M) air, 60 oC, 30 min
IQA
1a
N Pd N
N
eq. 4
N
6, 92% Me X-Ray diffraction determined Pd(OAc)2 (1.0 equiv) K2CO3 (2.0 equiv) t AmylOH (0.2 M) air, 60 oC, 30 min
1a Me
11.0
10.5
10.0
9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0 5.5 f1 (ppm)
6 replace Pd(OAc)2 standard condition I nBu (4.0 equiv)
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
-0.5
-1.0
Figure 1. 1H NMR spectrum: (A) Mixture of 1a and Pd(OAc)2 in 10:1 molar ratio; (B) Pure 5; (C) Pure 1a. B
A 0.010
0.005
0.01
0.02
0.010
0.005
0.000 0.1
0.03
0.2
[Pd] (M)
D 0.010
0.005
0.000
0.2
0.4
[2d] (M)
0.3
[1a] (M)
C
O
IQA
11.5
eq. 3
O
Pd(OAc)2 (0.5 equiv) K2CO3 (2.0 equiv)
1a
Me
12.0
3ad or [D]-3ad Me
IQA
IQA
0.000 0.00
IQA
D/H
1a or [D2]-1a
Me
2
3at one step, 15% yield
Me
I nC8H17 (2.0 equiv)
N
Me
Me
C.
COOMe
KIE = 3.3 standard condition
O N Pd N O
Treating 4d with NaOH in 2-propanol at 82 oC easily removed the isoquinoline-1-carbonyl group (eq 1) to yield the (Z)-2-isopropylundec-2-en-1-amine (5) in excellent yield.24 The removable protecting group enabled this alkylation protocol to synthesize the key fragment of the nitric oxide synthase inhibitor (2S,5Z)-2-amino-6-methyl-7[(1iminoethyl)amino]-5-heptenoic acid (eq 2).25 Despite the desired product 3at was only obtained in 15% yield, the direct formation of key fragment was more atomic economy compared with previous work to access a similar allylamine motif via several steps (22% yield).25b Me
Me
N
NHBoc
NHBoc COOMe
3
B.
eq. 1
t AmylOH (0.2 M) air, 60 oC, 30 min
1a 1.0 equiv
5, 92%
Condition B Pd(OAc)2 (12.5 mol%) 2t
1a
i
NaOH (10 equiv)
Pd(OAc)2 (10 mol %) K2CO3 (2.0 equiv)
IQA
Initial Rate (M/h)
IQA
Me
Concentration of 3ad (M)
Pr
A.
Initial Rate (M/h)
i
To explore the mechanism of this alkylation, the reaction was conducted with N-(2-methylallyl)isoquinoline-1carboxamide 1a and its deuterated analogue 1a-D2 under standard conditions. A primary kinetic isotope effect of 3.3 was observed, suggesting that C-H bond cleavage is the ratedetermining step (eq 3). A palladium complex 6 chelated by two molecules of 1a was isolated in 92% yield, and the structure was characterized by X-ray diffraction analysis26 (eq 4, CCDC 1873826). Complex 6 was also detected under excess 1a (1a and Pd(OAc)2 in 10:1 molar ratio, see SI 2.8 for details) (Figure 1, A). However, when the substrate 1a reacted with Pd(OAc)2 in a 1:1 molar ratio, a messy mixture was obtained (eq 5). These results suggest that excess substrate 1a favors the formation of complex 6. Replacing the Pd(OAc)2 catalyst with complex 6 allowed smooth alkylation (eq 6).
Initial Rate (M/h)
1 2 3 4 5 6 7 8 9 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
ACS Catalysis
0.6
0.03
TEMPO, 18-Cr-6 18-Cr-6 TEMPO None
0.02
0.01
0.00
0
1
2
3
Time (h)
O Me
N Pd N X 7, Not found Messy mixture Me
IQA n
Bu
3a, 68%
eq. 5
eq. 6
Figure 2. Dependence of initial alkylation rate on (A) [Pd(OAc)2] (first order), (B) [1a] (zero order), and (C) [2a] (zero order). (D) Concentration of 3ad over time in the presence of different additives.
Next, we analyzed how initial reaction rate between 1a and 2d depends on [Pd], [1a], and [2d] (Figure 2, A-C). Dependence on amount of Pd(OAc)2 was first-order (Figure 2A), suggesting that the palladium catalyst participates in the C–H activation step. Dependence on [1a] or [2d] was zero-
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order, indicating that residual 1a and 2d might not participate in the catalytic progression from complex 6 to the rate-determing step (Figure 2B and 2C). We also cannot exclude the possibility that fast and reversible substrate binding occurs, such that complex 7 participates in the rate-determining step, in which the dissociation step might not expect to be reflected in the global rate law.27 The concentration of product 3ad over time was measured in the presence of different additives (Figure 2D). The initial rate of alkylation was similar in the presence or absence of TEMPO, suggesting that it is not involved in the catalytic cycle. Instead, it may serve to reoxidize any stray Pd(0) lost off-cycle. In contrast, the initial reaction rate was slower in the absence of 18-Cr-6 than in its presence. It is possible that its stronger coordination ability with Pd(II) allows it to inhibit formation of unreactive PdI2 species, thereby accelerating the reaction. i
I i
Pr
IQA
IQA C6H13
4u, 20% ee
2. NaBH4 3. ArCOCl, DMAP
MeO
KHCO3 + KI + 3a Ligand Exchange
O
N O
AUTHOR INFORMATION
Me 6
Corresponding Author
O H
N PdII N Bu I IV
H
O
O
N PdII N
Me or H
N Me I
N
Reductive Elimination
C-H Activation
O N PdIV N Bu I III
Supporting Information.
N PdII N N
O
Me
ASSOCIATED CONTENT The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/. Experimental procedures, characterization data for all computers (PDF)
Me Me
eq. 8
(S)-8, 15% ee
34 % yield for 3 steps
Me
K2CO3 + 1a
14% yield, 20% ee. O C6H13 O Me
1. O3
Me
eq. 7
36% yield, 5% ee;
Condition D: Pd(OAc)2 (25 mol %), 1h: Pr
IQA C6H13 Me 4u
H 1h Condition C: Pd(OAc)2 (12.5 mol %), 22h: i
Pr
2u, 94 % ee
Me
whose absolute configuration was determined. The results suggest that stereoselective coupling of iodoalkane 2u occurs via an SN2 pathway21d rather than a concerted pathway21e, in accordance with Lautens’ observation.21d On the basis of these results, we propose a plausible catalytic cycle (Scheme 2). First, the palladium complex 6 generated from Pd(OAc)2 and protected allylamine 1a isomerizes into the intermediate I or undergoes substrate dissociation to access a less-stable intermediate I’, enabling alkenyl C-H activation and subsequent concerted base-assisted metalation-deprotonation to afford an intermediate II. Oxidative addition of iodoalkane with intermediate II generates a Pd(IV) species III, which undergoes reductive elimination. The desired alkylation product 3a and catalyst 6 are generated in the presence of potassium carbonate and another molecule of allyl isoquinoline1-carboxamide 1a. In summary, we have developed a reliable method for stereospecific alkylation of allylamines via alkenyl C-H bond activation. (Z)-tri- and tetra-substituted functionalized alkenes were prepared in moderate to high yields. The isoquinoline-1carbonyl auxiliary can be removed conveniently. Detailed kinetics studies suggest that alkenyl C-H activation is the ratedetermining step.
O
H
*
[email protected]. *
[email protected].
N PdII N O OH
I'
1a
Oxidative Addition
Yun-He Xu: 0000-0001-8817-0626 Teck-Peng Loh: 0000-0002-2936-337X
Notes The authors declare no competing financial interest.
O Me
ORCID
N PdII N
ACKNOWLEDGMENT We gratefully acknowledge the funding support of the National Natural Science Foundation of China (21672198, 21871240), the State Key Program of National Natural Science Foundation of China (21432009), and the Fundamental Research Funds for the Central Universities (WK2060190082).
II Bu I
Scheme 2. Proposed Mechanistic Pathway. To gain more insights into the mechanism, we analyzed coupling between 1h and the secondary halide (R)-2iodooctane 2u (94 % ee), prepared from commercially available (S)-octan-2-ol. The alkylation product 4u was obtained with only 5% ee under slightly modified reaction conditions (eq 7, Condition C). When a higher catalyst loading of Pd(OAc)2 (25 mol %) and a short reaction time (1 h) were employed (eq 6, Condition D), 20% ee was observed. The low ee of 4u may be due to rapid racemization of 2u induced by I- anion generated during alkylation and elimination. The product 4u was derivatized into (S)-2-methyloctyl 4-methoxybenzoate 8 (eq 8),
REFERENCES (1) (a) Ackermann, L. Metal-Catalyzed Direct Alkylations of (Hetero)Arenes via C-H Bond Cleavages with Unactivated Alkyl Halides. Chem. Commun. 2010, 46, 4866-4877. (b) Schoenherr, H.; Cernak, T. Profound Methyl Effects in Drug Discovery and a Call for New C-H Methylation Reactions. Angew. Chem., Int. Ed. 2013, 52, 12256-12267. (c) Dong, Z.; Ren, Z.; Thompson, S. J.; Xu, Y.; Dong, G. Transition-Metal-Catalyzed C-H Alkylation Using Alkenes. Chem. Rev. 2017, 117, 9333-9403. (d) Mishra, N. K.; Sharma, S.; Park, J.; Han, S.; Kim, I. S. Recent Advances in Catalytic C(sp2)–H Allylation Reactions. ACS Catal. 2017, 7, 2821-2847.
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(2) (a) Lyons, T. W.; Sanford, M. S. Palladium-Catalyzed LigandDirected C-H Functionalization Reactions. Chem. Rev. 2010, 110, 1147-1169. (b) Colby, D. A.; Tsai, A. S.; Bergman, R. G.; Ellman, J. A. Rhodium Catalyzed Chelation-Assisted C-H Bond Functionalization Reactions. Acc. Chem. Res. 2012, 45, 814-825. (c) Arockiam, P. B.; Bruneau, C.; Dixneuf, P. H. Ruthenium(II)-Catalyzed C−H Bond Activation and Functionalization. Chem. Rev. 2012, 112, 5879-5918. (d) Chen, Z.; Wang, B.; Zhang, J.; Yu, W.; Liu, Z.; Zhang, Y. Transition Metal-Catalyzed C–H Bond Functionalizations by the Use of Diverse Directing Groups. Org. Chem. Front. 2015, 2, 1107-1295. (e) Moselage, M.; Li, J.; Ackermann, L. Cobalt-Catalyzed C–H Activation. ACS Catal. 2015, 6, 498-525. (f) Zhu, R.-Y.; Farmer, M. E.; Chen, Y.-Q.; Yu, J.-Q. A Simple and Versatile Amide Directing Group for C-H Functionalizations. Angew. Chem., Int. Ed. 2016, 55, 10578-10599. (3) (a) Sandtorv, A. H. Transition Metal-Catalyzed C-H Activation of Indoles. Adv. Synth. Catal. 2015, 357, 2403-2435. (b) Della Ca, N.; Fontana, M.; Motti, E.; Catellani, M. Pd/Norbornene: A Winning Combination for Selective Aromatic Functionalization via C-H Bond Activation. Acc. Chem. Res. 2016, 49, 1389-1400. (4) (a) He, J.; Wasa, M.; Chan, K. S. L.; Shao, Q.; Yu, J.-Q. PalladiumCatalyzed Transformations of Alkyl C-H Bonds. Chem. Rev. 2017, 117, 8754−8786. (b) Neufeldt, S. R.; Seigerman, C. K.; Sanford, M. S. Mild Palladium-Catalyzed C-H Alkylation Using Potassium Alkyltrifluoroborates in Combination with MnF3. Org. Lett. 2013, 15, 2302-2305. (c) Qiu, G.; Wu, J. Transition Metal-Catalyzed Direct Remote C-H Functionalization of Alkyl Groupsvia C(sp3)-H Bond Activation. Org. Chem. Front. 2015, 2, 169-178. (5) Selective examples see: (a) Qin, L.; Ren, X.; Lu, Y.; Li, Y.; Zhou, J. Intermolecular Mizoroki-Heck Reaction of Aliphatic Olefins with High Selectivity for Substitution at the Internal Position. Angew. Chem., Int. Ed. 2012, 51, 5915-5919. (b) Deb, A.; Bag, S.; Kancherla, R.; Maiti, D. Palladium-Catalyzed Aryl C-H Olefination with Unactivated, Aliphatic Alkenes. J. Am. Chem. Soc. 2014, 136, 13602-13605. (c) Zheng, C.; Stahl, S. S. Regioselective Aerobic Oxidative Heck Reactions with Electronically Unbiased Alkenes: Efficient Access to Α-Alkyl Vinylarenes. Chem. Commun. 2015, 51, 12771-12774. (d) Morimoto, M.; Miura, T.; Murakami, M. Rhodium-Catalyzed Dehydrogenative Borylation of Aliphatic Terminal Alkenes with Pinacolborane. Angew. Chem., Int. Ed. 2015, 54, 12659-12663. (e) Takahama, Y.; Shibata, Y.; Tanaka, K. Heteroarene-Directed Oxidative sp2 C-H Bond Allylation with Aliphatic Alkenes Catalyzed by an (Electron-Deficient η5Cyclopentadienyl)rhodium(III) Complex. Org. Lett. 2016, 18, 29342937. (f) Maity, S.; Dolui, P.; Kancherla, R.; Maiti, D. Introducing Unactivated Acyclic Internal Aliphatic Olefins into a Cobalt Catalyzed Allylic Selective Dehydrogenative Heck Reaction. Chem. Sci. 2017, 8, 5181-5185. (g) Deb, A.; Hazra, A.; Peng, Q.; Paton, R. S.; Maiti, D. Detailed Mechanistic Studies on Palladium-Catalyzed Selective C-H Olefination with Aliphatic Alkenes: A Significant Influence of Proton Shuttling. J. Am. Chem. Soc. 2017, 139, 763-775. (h) Dhungana, R. K.; KC, S.; Basnet, P.; Giri, R. Transition Metal-Catalyzed Dicarbofunctionalization of Unactivated Olefins. Chem. Rec. 2018, 18, 1314-1340. (i) Schmidt, V. A.; Kennedy, C. R.; Bezdek, M. J.; Chirik, P. J. Selective [1,4]-Hydrovinylation of 1,3-Dienes with Unactivated Olefins Enabled by Iron Diimine Catalysts. J. Am. Chem. Soc. 2018, 140, 3443-3453. (6) (a) Ilies, L.; Matsubara, T.; Ichikawa, S.; Asako, S.; Nakamura, E. Iron-Catalyzed Directed Alkylation of Aromatic and Olefinic Carboxamides with Primary and Secondary Alkyl Tosylates, Mesylates, and Halides. J. Am. Chem. Soc. 2014, 136, 13126-13129. (b) Monks, B. M.; Fruchey, E. R.; Cook, S. P. Iron-Catalyzed C(sp2)-H Alkylation of Carboxamides with PrimaryElectrophiles. Angew. Chem., Int. Ed. 2014, 53, 11065-11069. (c) Ilies, L.; Ichikawa, S.; Asako, S.; Matsubara, T.; Nakamura, E. Iron-Catalyzed Directed Alkylation of Alkenes and Arenes with Alkylzinc Halides. Adv. Synth. Catal. 2015, 357, 21752179. (d) Cera, G.; Haven, T.; Ackermann, L. Expedient Iron-
Catalyzed C-H Allylation/Alkylation by Triazole Assistance with Ample Scope. Angew. Chem., Int. Ed. 2016, 55, 1484-1488. (7) (a) Gensch, T.; Vasquez-Cespedes, S.; Yu, D.-G.; Glorius, F. Cobalt(III)-Catalyzed Directed C-H Allylation. Org. Lett. 2015, 17, 3714-3717. (b) Wang, H.; Zhang, S.; Wang, Z.; He, M.; Xu, K. CobaltCatalyzed Monoselective Ortho-C-H Functionalization of Carboxamides with Organoaluminum Reagent. Org. Lett. 2016, 18, 5628-5631. (c) Yu, W.; Zhang, W.; Liu, Y.; Liu, Z.; Zhang, Y. Cobalt(III)-Catalyzed Cross-Coupling of Enamides with Allyl Acetates/Maleimides. Org. Chem. Front. 2017, 4, 77-80. (d) Kawai, K.; Bunno, Y.; Yoshino, T.; Matsunaga, S. Weinreb Amide Directed Versatile C-H Bond Functionalization under (η5Pentamethylcyclopentadienyl)cobalt(III) Catalysis. Chem. Eur. J. 2018, 24, 10231-10237. (8) Aihara, Y.; Chatani, N. Nickel-Catalyzed Direct Alkylation of C−H Bonds in Benzamides and Acrylamides with Functionalized Alkyl Halides via Bidentate-Chelation Assistance. J. Am. Chem. Soc. 2013, 135, 5308-5311. (9) (a) Zhu, R.-Y.; He, J.; Wang, X.-C.; Yu, J.-Q. Ligand-promoted alkylation of C(sp3)-H and C(sp2)-H bonds. J. Am. Chem. Soc. 2014, 136, 13194-13197. (b) Koy, M.; Sandfort, F.; Tlahuext-Aca, A.; Quach, L.; Daniluc, C. G.; Glorious, F. Palladium-Catalyzed Decarboxylative Heck-Type Coupling of Activated Aliphatic Carboxylic Acids Enabled by Visible Light. Chem. Eur. J. 2018, 24, 4552-4555. (10) Kuninobu, Y.; Ohta, K.; Takai, K. Rhenium-Catalyzed Allylation of C-H Bonds of Benzoic and Acrylic Acids. Chem. Commun. 2011, 47, 10791-10793. (11) Kim, M.; Sharma, S.; Mishra, N. K.; Han, S.; Park, J.; Kim, M.; Shin, Y.; Kwak, J. H.; Han, S. H.; Kim, I. S. Direct Allylation of Aromatic and α,β-Unsaturated Carboxamides under Ruthenium Catalysis.Chem. Commun. 2014, 50, 11303-11306. (12) (a) Zhang, S.-S.; Wu, J.-Q.; Lao, Y.-X.; Liu, X.-G.; Liu, Y.; Lv, W.X.; Tan, D.-H.; Zeng, Y.-F.; Wang, H. Mild Rhodium(III)-Catalyzed C−H Allylation with 4‑Vinyl-1,3dioxolan-2-ones: Direct and Stereoselective Synthesis of (E)‑Allylic Alcohols. Org. Lett. 2014, 16, 6412-6415. (b) Zhang, S.-S.; Wu, J.-Q.; Liu, X.; Wang, H. Tandem Catalysis: Rh(III)-Catalyzed C–H Allylation/Pd(II)-Catalyzed NAllylation Toward the Synthesis of Vinyl-Substituted N-Heterocycles. ACS Catal. 2014, 5, 210-214. (c) Wu, J.-Q.; Qiu, Z.-P.; Zhang, S.-S.; Liu, J.-G.; Lao, Y.-X.; Gu, L.-Q.; Huang, Z.-S.; Li, J.; Wang, H. Rhodium(III)-Catalyzed C-H/C-C Activation Sequence: Vinylcyclopropanes as Versatile Synthons in Direct C-H Allylation Reactions. Chem. Commun. 2015, 51, 77-80. (d) Feng, C.; Feng, D.; Loh, T.-P. Rhodium(III)-Catalyzed C-H Allylation of ElectronDeficient Alkenes with Allyl Acetates. Chem. Commun. 2015, 51, 342345. (e) Sharma, S.; Han, S. H.; Oh, Y.; Mishra, N. K.; Han, S.; Kwak, J. H.; Lee, S.-Y.; Jung, Y. H.; Kim, I. S. Mild and Site-Selective Allylation of Enol Carbamates with Allylic Carbonates under Rhodium Catalysis. J. Org. Chem. 2016, 81, 2243-2251. (f) Song, S.; Lu, P.; Liu, H.; Cai, S.-H.; Feng, C.; Loh, T.-P. Switchable C–H Functionalization of N-Tosyl Acrylamides with Acryloylsilanes. Org. Lett. 2017, 19, 28692872. (g) Yan, R.; Wang, Z.-X. Rhodium-Catalyzed Alkenyl C−H Activation and Oxidative Coupling with Allylic Alcohols. Asian J. Org. Chem. 2018, 7, 240-247. (13) Zhang, Y. J.; Skucas, E.; Krische, M. J. Direct Prenylation of Aromatic and α,β-Unsaturated Carboxamides via Iridium-Catalyzed CH Oxidative Addition-Allene Insertion. Org. Lett. 2009, 11, 4248-4250. (14) Hu, S.; Wang, D.; Liu, J.; Li, X. Rhodium(III)-Catalyzed Oxidative Olefination of N-Allyl Sulfonamides. Org. Biomol. Chem. 2013, 11, 2761-2765. (15) (a) Wang, C.; Zhang, L.; Chen, C.; Han, J.; Yao, Y.; Zhao, Y. Oxalyl Amide Assisted Palladium-Catalyzed Synthesis of Pyrrolidones via Carbonylation of γ-C(sp3)–H Bonds of Aliphatic Amine Substrates. Chem. Sci. 2015, 6, 4610-4614. (b) Chen, C.; Guan, M.; Zhang, J.; Wen, Z.; Zhao, Y. Palladium-Catalyzed Oxalyl Amide Directed Silylation and Germanylation of Amine Derivatives. Org. Lett. 2015, 17, 3646-3649.
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Catalyzed Annulation of Secondary Alkyl Iodides. Angew. Chem., Int. Ed. 2007, 46, 1485–1488. (d) Rudolph, A.; Lautens, M. Secondary Alkyl Halides in Transition-Metal-Catalyzed Cross-Coupling Reactions. Angew. Chem., Int. Ed. 2009, 48, 2656–2670. (e) Zhang, S. Y.; Li, Q.; He, G.; Nack, W. A.; Chen, G. Pd-Catalyzed Monoselective ortho-C−H Alkylation of N‑Quinolyl Benzamides: Evidence for Stereoretentive Coupling of Secondary Alkyl Iodides. J. Am. Chem. Soc. 2015, 137, 531-539. (f) Liu, Z.-S.; Gao, Q.; Cheng, H.-G.; Zhou, Q. Alkylating Reagents Employed in Catellani-Type Reactions. Chem. Eur. J. 2018, 24, 15461–15476. (22) Zhao, Y.; Chen, G. Palladium-Catalyzed Alkylation of orthoC(sp2)-H Bonds of Benzylamide Substrates with Alkyl Halides. Org. Lett. 2011, 13, 4850-4853. (23) Hong, L.; Sun, W.; Yang, D.; Li, G.; Wang, R. Additive Effects on Asymmetric Catalysis. Chem. Rev. 2016, 116, 4006-4123. (24) (a) Seki, A.; Takahashi, Y.; Miyake, T. Synthesis of cis-3-Arylated Cycloalkylamines through Palladium-Catalyzed Methylene sp3 Carbon–Hydrogen Bond Activation. Tetrahedron Lett. 2014, 55, 28382841. (b) Van Steijvoort, B. F.; Kaval, N.; Kulago, A. A.; Maes, B. U. W. Remote Functionalization: Palladium-Catalyzed C5(sp3)-H Arylation of 1-Boc-3-aminopiperidine through the Use of a Bidentate Directing Group. ACS Catal. 2016, 6, 4486-4490. (25) (a) Kogen, H.; Tago, K.; Arai, M.; Minami, E.; Masuda, K.; Akiyama, T. A Highly Stereoselective Synthesis of Plaunotol and Its Thiourea Derivatives as Potent Antibacterial Agents against Helicobacter Pylori. Bioorg. Med. Chem. 1999, 9, 1347-1350. (b) Pitzele, B. S.; Sikorski, J. A.; JR., D. W. H.; JR., R. K. W.; Toth, M. V.; Scholten, J. A.; Snyder, Jeffrey S. 2-Amino-5, 6 Heptenoic Acid Derivatives Useful as Nitric Oxide Synthase Inhibitors. U. S. Patent 0,143,061, Oct. 3, 2002. (c) Nguyen, T. B.; Adisechan, A. K.; Kumar, E. V. K. S.; Balakrishna, R.; Kimbrell, M. R.; Miller, K. A.; Datta, A.; David, S. A. Protection from Endotoxic Shock by EVK-203, A NovelAlkylpolyamine Sequestrant of Lipopolysaccharide. Bioorg. Med. Chem. 2007, 15, 5694-5709. (26) Goto, H.; Hayakawa, T.; Furutachi, K.; Sugimoto, H.; Inoue, S. Planar-Chiral Metal Complexes Comprised of Square-Planar Metal and Achiral Tetradentate Ligands: Design, Optical Resolution, and Thermodynamics. Inorg. Chem. 2012, 51, 4134-4142. (27) (a) Anslyn, E. V.; Dougherty, D. A. Modern Physical Organic Chemistry; University Science Books: California, 2004; pp355-420. (b) Baxter, R. D.; Sale, D.; Engle, K. M.; Yu, J.-Q.; Blackmond, D. G. Mechanistic Rationalization of Unusual Kinetics in Pd-Catalyzed C−H Olefination. J. Am. Chem. Soc. 2012, 134, 4600-4606; (c) Smalley, A. P.; Gaunt, M. J. Mechanistic Insights into the Palladium-Catalyzed Aziridination of Aliphatic Amines by C-H Activation. J. Am. Chem. Soc. 2015, 137, 10632-10641.
(16) Parella, R.; Babu, S. A. Pd(II)-Catalyzed, Picolinamide-Assisted, Z-Selective γ-Arylation of Allylamines To Construct ZCinnamylamines. J. Org. Chem. 2017, 82, 6550-6567. (17) Liang, Q.-J.; Yang, C.; Meng, F.-F.; Jiang, B.; Xu, Y.-H.; Loh, T.P. Chelation versus Non-Chelation Control in the Stereoselective Alkenyl sp2C-H Bond Functionalization Reaction. Angew. Chem., Int. Ed. 2017, 56, 5091-5095. (18) (a) Zang, Z.-L.; Zhao, S.; Karnakanti, S.; Liu, C.-L.; Shao, P.-L.; He, Y. Catalytic Multisite-Selective Acetoxylation Reactions at sp2 vs sp3 C-H Bonds in Cyclic Olefins. Org. Lett. 2016, 18, 5014-5017. (b) Viart, H. M.F.; Bachmann, A.; Kayitare, W.; Sarpong, R. β-Carboline Amides as Intrinsic Directing Groups for C(sp2)-H Functionalization. J. Am. Chem. Soc. 2017, 139, 1325-1329. (c) Liu, M.; Yang, P.; Karunananda, M. K.; Wang, Y.; Liu, P.; Engle, K. M. C(alkenyl)-H Activation via Six-Membered Palladacycles: Catalytic 1,3-Diene Synthesis. J. Am. Chem. Soc. 2018, 140, 5805-5813. (19) (a) Xu, Y.-H.; Lu, J.; Loh, T.-P. Direct Cross-Coupling Reaction of Simple Alkenes with Acrylates Catalyzed by Palladium Catalyst. J. Am. Chem. Soc. 2009, 131, 1372-1373. (b) Zhou, H.; Xu, Y.-H.; Chung, W. J.; Loh, T.-P. Palladium-Catalyzed Direct Arylation of Cyclic Enamides with Aryl Silanes by sp2 C-H Activation. Angew. Chem., Int. Ed. 2009, 48, 5355-5357. (c) Hu, X.-H.; Yang, X.-F.; Loh, T.-P. SelectiveAlkenylation and Hydroalkenylation of Enol Phosphates through Direct C-HFunctionalization. Angew. Chem., Int. Ed. 2015, 54, 15535-15539. For the reviews on alkenyl C-H bond functionalization, see: (d) Yeung, C. S.; Dong, V. M. Catalytic Dehydrogenative CrossCoupling: Forming Carbon-Carbon Bonds by Oxidizing Two CarbonHydrogen Bonds. Chem. Rev. 2011, 111, 1215-1292. (e) Shang, X.; Liu, Z. Q. Transition Metal-Catalyzed Cvinyl–CvinylBond Formation via Double Cvinyl–H Bond Activation. Chem. Soc. Rev. 2013, 42, 3253-3260. (20) (a) Daugulis, O.; Roane, J.; Tran, L. D. Bidentate, Monoanionic Auxiliary-Directed Functionalization of Carbon−Hydrogen Bonds. Acc. Chem. Res. 2015, 48, 1053–1064. see examples of IQA group: (b) Pradhan, S.; De, P. B.; Punniyamurthy, T. Copper(II)-Mediated Chelation-Assisted Regioselective N‑Naphthylation of Indoles, Pyrazoles and Pyrrole through Dehydrogenative Cross-Coupling. J. Org. Chem. 2017, 82, 4883-4890. (c) Li, J.-Ming.; Wang, Y.-H.; Yu, Y.; Wu, R.-B.; Weng, J.; Lu, G. Copper-Catalyzed Remote C−H Functionalizations of Naphthylamides through a Coordinating Activation Strategy and Single-Electron-Transfer (SET) Mechanism. ACS Catal. 2017, 7, 2661-2667. (21) Selective examples see: (a) Catellani, M.; Frignani, F.; Rangoni, A. A Complex Catalytic Cycle Leading to a Regioselective Synthesis of o,o'-Disubstituted Vinylarenes. Angew. Chem., Int. Ed. 1997, 36, 119– 122. (b) Zhou, J.; Fu, G. C. Cross-Couplings of Unactivated Secondary Alkyl Halides: Room-Temperature Nickel-Catalyzed Negishi Reactions of Alkyl Bromides and Iodides. J. Am. Chem. Soc. 2003, 125, 14726-14727. (c) Rudolph, A.; Rackelmann, N.; Lautens, M. Stereochemical and Mechanistic Investigations of a Palladium-
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