Directed Cobalt-Catalyzed anti-Markovnikov Hydroalkylation of Unactivated Alkenes Enabled by "co-H" Catalysis

Article abstract of DOI:10.1021/acs.orglett.0c01365

The earth-abundant cobalt-catalyzed anti-Markovnikov hydroalkylation of unactivated alkenes with oxime esters was achieved by introducing an 8-aminoquinoline directing group on the alkenes. The catalytic system, consisting of commercially available Co(acac)3 and PhMeSiH2, enables the construction of unfunctionalized C(sp3)-C(sp3) bonds and features exclusive anti-Markovnikov selectivity, good functional group tolerance, and the avoidance of an extra ligand, oxidant, or base. Mechanistic insight into this new catalytic system indicates the involvement of both alkyl radical and cobalt hydride intermediates.

Full text of DOI:10.1021/acs.orglett.0c01365

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Letter
Directed Cobalt-Catalyzed anti-Markovnikov Hydroalkylation of
Unactivated Alkenes Enabled by “Co−H” Catalysis
Dandan Yang, Hai Huang, Meng-Hui Li, Xiao-Ju Si, He Zhang, Jun-Long Niu,* and Mao-Ping Song*
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ABSTRACT: The earth-abundant cobalt-catalyzed anti-Markov-
nikov hydroalkylation of unactivated alkenes with oxime esters was
achieved by introducing an 8-aminoquinoline directing group on
the alkenes. The catalytic system, consisting of commercially
available Co(acac)3 and PhMeSiH2, enables the construction of
unfunctionalized C(sp3)−C(sp3) bonds and features exclusive anti-
Markovnikov selectivity, good functional group tolerance, and the
avoidance of an extra ligand, oxidant, or base. Mechanistic insight into this new catalytic system indicates the involvement of both
alkyl radical and cobalt hydride intermediates.
ew methods for the construction of C−C bonds1 play an
problem can be addressed by employing bulky electron-rich
phosphine5 or N-heterocyclic carbene (NHC)6 as ligands. As
Nimportant role in the diversity-oriented synthesis of
natural products and pharmaceutical molecules.2 Among them,
an alternative, the nickel-catalyzed cross-coupling of organo-
the construction of C(sp3)−C(sp3) bonds has received
metallic nucleophiles and alkyl electrophiles has been
intensively investigated.7 However, pregenerated organo-
metallic reagents or organoborane species are commonly
required.
significant advances3 in recent years as a result of the
developments in transition-metal-catalyzed cross-coupling
chemistry (Figure 1a).4 In general, palladium-catalyzed
alkyl−alkyl cross-couplings have long been a challenge due
to the competitive β-hydride elimination, although this
Given the widespread availability and the unique reactivity
of alkenes,8 the hydrocarbofunctionalization of olefinic starting
materials has become an attractive strategy to construct carbon
skeletons.9 Thus far, such a transformation is known to
proceed with a diverse collection of carbon nucleophiles,
whereas the addition of neutral free alkyl radicals (forming
3
3
Csp −Csp bonds) is significantly less studied and remains an
unmet challenge.10 In this content, strained cyclobutanone
oximes and other derivatives are efficient substrates to obtain
γ-cyanoalkyl radicals through the β-carbon elimination path-
way, originally reported by Zard (Figure 1b).11 Later,
transition-metal-catalyzed or visible-light-induced cross-cou-
pling reactions of cyclobutanone oximes were extensively
developed by Uemura,12 Leonori,13 Shi,14 Guo,15 Xiao,16 and
other groups.17 In these coupling reactions, the alkene
substrates were commonly limited to conjugated alkene
substrates. For the unactivated alkenes, an attractive option
would be to use an auxiliary-based chelation control strategy to
facilitate CC bond activation as well as stabilize the
analogous alkyl metal intermediate by metallacycle forma-
Received: April 20, 2020
Figure 1. Background and project synopsis.
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© XXXX American Chemical Society
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Letter
tion.18 Notably, Engle,19 Chen,20 and other groups21 have
developed a suite of chelation-controlled Ni-, Pd-, and Cu-
catalyzed functionalizations of unactivated alkenes using
Daugluis’s 8-aminoquinoline (AQ)22 directing group (Figure
1c). However, the cross-coupling of unfunctionalized alkyl
reagents remains relatively rare, probably due to the undesired
β-hydride elimination.
a
Table 1. Optimization of Reaction Conditions
entry
catalyst
Co(acac)2
Co(acac)2
Co(acac)2
Co(acac)2
Co(acac)2
Co(acac)3
Co(OAc)2·4H2O
CoC2O4·4H2O
Co(acac)3
silane
PhSiH3
Ph2SiH2
yield %
Despite these significant advances, exploring the earth-
abundant cobalt-catalyzed hydrofunctionalization of unacti-
vated alkenes to enrich the diversification of the introduced
functionality is still highly desirable. Previously, Mukaiyama,23
Carreira,24 Shigehisa,25 Krische,26 Huang,27 and others28 have
developed an array of Co-catalyzed alkene hydrofunctionaliza-
tion reactions involving cobalt hydrides (Co−H)29 to
construct various C−C and C−X bonds (Figure 1d). In
particular, Zhang reported that cobalt(II) porphyrin complexes
were highly effective for a wide range of functionalizations of
alkenes.30 However, these methods were commonly limited to
conjugated alkene substrates and afforded Markovnikov-
selective nonlinear products; the cobalt catalysts were largely
installed with synthetic ligands, which undoubtedly increases
the complexity of the catalytic reactions. Therefore, our
ongoing Co-catalyzed research program31 has led us to develop
a concise and efficient method for the selective hydro-
functionalization of unactivated alkenes using an easily
available cobalt catalyst. Herein we disclose the first example
of the cobalt-catalyzed hydroalkylation reaction of unactivated
alkenes with oxime esters, which exhibited exclusive anti-
Markovnikov selectivity by using an amide-linked aminoquino-
line directing group.
1
2
3
4
5
6
7
8
44
62
68
49
21
70
21
17
78
66
87
0
PhMeSiH2
(Me2SiH)2O
Et3SiH
PhMeSiH2
PhMeSiH2
PhMeSiH2
PhMeSiH2
PhMeSiH2
PhMeSiH2
PhMeSiH2
b
9
c
10
Co(acac)3
Co(acac)3
b d
,
11
b
12
b
13
Co(acac)3
0
a
Reaction conditions: 1a (0.2 mmol), 2a′ (0.3 mmol), [Co] (20 mol
%), silane (2.0 equiv), Ar atmosphere, solvent (1 mL), 10 h, isolated
b
c
d
yields. R = C6F5CO, 2a. R = p-CF3C6H4CO, 2a″. PhMeSiH2 (1.5
equiv), 4 h. acac = acetylacetonate.
Scheme 1. Unactivated Alkene Scope for Co(III)-Catalyzed
a
Hydroalkylation
To initiate our investigation, we elected to use a 3-butenoic-
acid derivative bearing 8-aminoquinoline (AQ) directing group
1a as an alkene substrate and cyclobutanone O-benzoyl oxime
2a′ as an alkyl radical precursor. Gratifyingly, the desired
hydroalkylation product 3aa was observed and isolated in 44%
yield when Co(acac)2 (20 mol %) was used as the catalyst with
PhSiH3 as the reductant in DMF at 70 °C for 10 h (entry 1,
Table 1). It was noteworthy that the exclusive anti-
Markovnikov addition product was observed according to
1
the H NMR analysis. The initially employed solvent, DMF,
was found to be more efficient compared with other solvents.
(See the Supporting Information, Table S1.) Then, various
silanes were evaluated. It was found that silanes played an
important role in the reaction, and PhMeSiH2 proved to be the
optimal choice, producing 3aa in 68% yield (entries 2−5 and
Table S2). A subsequent investigation on cobalt catalysts
showed that Co(acac)3 was the most effective catalyst,
affording 3aa in 70% yield (entry 6). Further exploration
revealed that oxime 2a with O-perfluorobenzoyl moiety was
superior to its analogues (entries 9 and 10 and Table S4).
Additionally, upon the optimization of the temperature, ratio
of reactants, silane equivalents, cobalt loading, and reaction
time, the final optimized conditions gave an 87% yield of the
desired product with 1.5 equiv of PhMeSiH2 in only 4 h (entry
11 and Tables S5−S7). A control experiment confirmed that
the model reaction did not occur in the absence of the cobalt
catalysts or silanes (entries 12 and 13).
a
Reaction conditions: 1 (0.2 mmol), 2a (0.3 mmol), Co(acac)3 (20
mol %), PhMeSiH2 (1.5 equiv), Ar atmosphere, DMF (1 mL), 4 h,
isolated yields. Yield of 1.0 mmol scale, 5 h. 1 was treated with
Co(acac)3, PhMeSiH2 under standard conditions for 40 min, then 2a
b
c
d
was added and stirred for 4 h. Determined by HRMS.
With the optimized reaction conditions in hand, we next
investigated the scope of unactivated alkenes in this Co(III)-
catalyzed hydroalkylation reaction. As shown in Scheme 1, the
α-substituted terminal olefins (1a−i) were initially examined
under standard conditions. To our delight, these terminal
alkenes were found to be suitable substrates and underwent
anti-Markovnikov hydroalkylation in good to excellent yields
(68−92%). Specifically, for the sterically hindered α,α-
dimethyl-substituted alkene 1c, the reaction furnished desired
product 3ca in 92% yield. In addition, the hydroalkylation
B
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reaction proved to be chemoselective. The β−γ double bond
could be preferentially functionalized in the presence of distal
γ−δ or δ−ε alkenes as well as acetylenes (3ga−ha). An entity
with a −SiMe3 group was also compatible in this process,
affording 3la in a high yield of 84%. A terminal alkene bearing
a single substituent at the β position could be successfully
transformed into the desired product 3ja under modified
reaction conditions. It should be noted that this protocol was
also effective with nonconjugated internal alkenes, affording
3ka−ma in acceptable yields, with some of the alkene
substrates recovered. As expected, internal alkenes were
completely regioselective for addition at the γ position,
which is consistent with the result for terminal alkenes.
Encouragingly, a styrene substrate bearing an AQ directing
group at the ortho position of 1n was viable in the reaction,
furnishing a completely anti-Markovnikov hydroalkylation
product 3na. For the pentenoic-acid-derived substrate 1o,
only a trace amount of δ-functionalized product 3oa was
detected, which might arise from the less stable and larger
cobaltacyclic intermediate.
to deliver the corresponding hydroalkylation products,
respectively. With regard to the less-strained O-acyl oxime
(Table S9), it unfortunately gave no reaction under optimized
conditions.
To gain further insights into the reaction mechanism, a
series of control experiments were carried out (Scheme 3).
Scheme 3. Mechanistic Studies
We then evaluated the scope of cyclobutanone derivatives in
this transformation (Scheme 2). Along with 2a, a variety of O-
a
Scheme 2. Scope of the Cyclobutanone Oximes
First, upon the addition of stoichiometric amounts of either
TEMPO or 1,4-BQ (well-known radical scavengers), the
formation of 3aa was obviously suppressed (Scheme 3a).
Notably, the cyanoalkyl-TEMPO adduct 4 was indeed
observed and isolated in 15% yield (Scheme 3a). These results
indicated that the formation of a cyanoalkyl radical might be
involved in the progress. Furthermore, subjecting the radical
clock substrate 5 containing a vinylcyclopropane moiety and
2a to the standard conditions afforded the normal hydro-
alkylation product 6a in 35% yield as well as the ring-opened
product 6b in 44% yield, suggesting the intermediacy of the
carbon radical species in the reaction (Scheme 3b).32,13a,15b,22
Isotope-labeling experiments were performed by using
PhMeSiD2 to identify the source of hydrogen (Scheme
3c).33 The expected deuterated product 3aa-d was isolated
in 9% yield when the reaction time was extended to 30 h
(Scheme 3c). Additionally, no deuterium incorporation was
observed upon the addition of small amounts of D2O to the
model reaction (Scheme 3c). These results indicated that the
source of hydrogen might derive from the PhMeSiH2.
On the basis of the above mechanistic results and insightful
precedents, albeit being applied to other systems,34 a plausible
catalytic cycle is provided in Scheme 4. Initially, the cobalt
catalyst, Co(acac)3, undergoes ligand exchange to coordinate
with the directing group, which brings it in close proximity to
the alkene A, thus facilitating CC double-bond activation. A
SET (single-electron transfer) process between A and 2a gave
the oxidized Co(IV)31d species B and an iminyl radical, which
underwent β-carbon elimination to generate γ-cyanoalkyl
radical C. Next, the addition of radical C to alkene A leads
to radical intermediate D, which is supported by the radical
clock experiment (Scheme 3b). Then, the Co(IV)−OBz
a
Reaction conditions: 1a (0.2 mmol), 2 (0.3 mmol), Co(acac)3 (20
mol %), PhMeSiH2 (1.5 equiv), Ar atmosphere, DMF (1 mL), 4 h,
isolated yields. 1a was treated with Co(acac)3, PhMeSiH2 under
b
standard conditions for 40 min, then 2 was added and stirred for 4 h.
Cbz = −COOBn; Boc = −COOtBu.
acyl esters bearing functional groups at the 3-position were
well-tolerated to give the desired products 3ab−ah in
moderate to good yields. It is noteworthy that substrates
containing the ester (−COOtBu), carbamate (−NHCbz), and
benzyloxy (−OBn) survived well, giving the target products in
70−74% yields. Notably, the 3-cyano cyclobutanone oxime
ester 2c was also compatible in this transformation and
furnished product 3ac in 37% yield. Furthermore, the 2-
substituted oxime esters could afford the desired products
(3ai−aj), albeit in somewhat lower yields, probably due to the
large steric hindrance. In addition, both 1-Cbz- and 1-Boc-3-
azetidinone-derived oxime esters 2k and 2l reacted smoothly
C
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Authors
Scheme 4. Proposed Mechanism
Dandan Yang − Green Catalysis Center, and College of
Chemistry, Zhengzhou University, Zhengzhou 450001, P. R.
China; orcid.org/0000-0002-1880-8417
Hai Huang − Jiangsu Key Laboratory of Advanced Catalytic
Materials & Technology, School of Petrochemical Engineering,
Changzhou University, Changzhou 213164, China
Meng-Hui Li − Green Catalysis Center, and College of
Chemistry, Zhengzhou University, Zhengzhou 450001, P. R.
China
Xiao-Ju Si − Green Catalysis Center, and College of Chemistry,
Zhengzhou University, Zhengzhou 450001, P. R. China
He Zhang − Green Catalysis Center, and College of Chemistry,
Zhengzhou University, Zhengzhou 450001, P. R. China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c01365
Notes
The authors declare no competing financial interest.
species D transforms to the Co−H species E in the presence of
PhMeSiH2, followed by the intramolecular construction of a
C−H bond to afford Co(III) species F.34,35 It is worth noting
that the extended reaction time for isotope-labeling experi-
ments (Scheme 3c) suggested that the Co−H formation (D →
E) might be involved in the rate-limiting step. Furthermore,
demetallization of intermediate F delivers the desired product
3aa and affords the CoIIIX3 species for a new catalytic cycle.
This mechanism reasonably accounts for the fact that
Co(acac)2 could also give a comparable yield (entry 3, Table
1), which might undergo a catalytic Co(II)−Co(III)−Co(II)
cycle.
In conclusion, we have developed an efficient cobalt-
catalyzed hydroalkylation reaction of unactivated alkenes
with O-acyl oximes using a directing group approach. The
exclusive anti-Markovnikov selectivity, functional group
tolerance, easily available cobalt catalyst, and mild conditions
make this reaction an attractive protocol for the hydro-
functionalization of olefins and the construction of C(sp3)−
C(sp3) bonds. Mechanistic studies are consistent with a
mechanism in which a carbon radical intermediate and a cobalt
hydride (Co−H) species are involved. The development of
other related types of alkene hydrofunctionalization is under
investigation in our laboratory, and the progress will be
reported in due course.
ACKNOWLEDGMENTS
■
The work described in this Letter was supported by the
National Natural Science Foundation of China (21772179 and
21672192), the Program for Science & Technology Innovation
Talents in Universities of Henan Province (19HASTIT038),
and Jiangsu Key Laboratory of Advanced Catalytic Materials
and Technology (BM2012110).
REFERENCES
■
(1) For selected reviews and examples, see: (a) Werner, E. W.; Mei,
T.-S.; Burckle, A. J.; Sigman, M. S. Science 2012, 338, 1455. (b) Saini,
V.; Stokes, B. J.; Sigman, M. S. Angew. Chem., Int. Ed. 2013, 52, 11206.
(c) Mei, T.-S.; Patel, H. H.; Sigman, M. S. Nature 2014, 508, 340.
(d) Green, S. A.; Matos, J. L. M.; Yagi, A.; Shenvi, R. A. J. Am. Chem.
Soc. 2016, 138, 12779. (e) Yamauchi, D.; Nishimura, T.; Yorimitsu,
H. Angew. Chem., Int. Ed. 2017, 56, 7200. (f) Liu, B.; Li, J.; Hu, P.;
Zhou, X.; Bai, D.; Li, X. ACS Catal. 2018, 8, 9463. (g) Sun, F.-N.;
Yang, W.-C.; Chen, X.-B.; Sun, Y.-L.; Cao, J.; Xu, Z.; Xu, L.-W. Chem.
Sci. 2019, 10, 7579. (h) Rej, S.; Ano, Y.; Chatani, N. Chem. Rev. 2020,
120, 1788.
(2) For selected reviews and examples, see: (a) Lo, J. C.; Gui, J.;
Yabe, Y.; Pan, C.-M.; Baran, P. S. Nature 2014, 516, 343. (b) Huang,
Y.; Ma, C.; Lee, Y. X.; Huang, R.-Z.; Zhao, Y. Angew. Chem., Int. Ed.
2015, 54, 13696. (c) Johnston, C. P.; Smith, R. T.; Allmendinger, S.;
MacMillan, D. W. C. Nature 2016, 536, 322. (d) Luo, Y.-C.; Yang, C.;
Qiu, S.-Q.; Liang, Q.-J.; Xu, Y.-H; Loh, T.-P. ACS Catal. 2019, 9,
4271. (e) Zhang, K.; Lu, L.-Q.; Jia, Y.; Wang, Y.; Lu, F.-D.; Pan, F.;
Xiao, W.-J. Angew. Chem., Int. Ed. 2019, 58, 13375. (f) Chen, Z.-N.;
Rong, M.-Y.; Nie, J.; Zhu, X.-F.; Shi, B.-F.; Ma, J.-A. Chem. Soc. Rev.
2019, 48, 4921.
ASSOCIATED CONTENT
* Supporting Information
■
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c01365.
(3) (a) Geist, E.; Kirschning, A.; Schmidt, T. Nat. Prod. Rep. 2014,
31, 441. (b) Lovering, F.; Bikker, J.; Humblet, C. J. Med. Chem. 2009,
52, 6752.
Experimental procedures and spectral data for new
compounds (PDF)
(4) (a) de Meijere, A.; Diederich, F. In Metal-Catalyzed Cross-
Coupling Reactions, 2nd ed.; Wiley-VCH: Weinheim, Germany, 2004.
(b) Frisch, A. C.; Beller, M. Angew. Chem., Int. Ed. 2005, 44, 674.
(5) Netherton, M. R.; Dai, C.; Neuschutz, K.; Fu, G. C. J. Am. Chem.
Soc. 2001, 123, 10099.
(6) (a) Hadei, N. E.; Kantchev, A. B.; O’Brie, C. J.; Organ, M. G.
Org. Lett. 2005, 7, 3805. (b) McCann, L. C.; Hunter, H. N.; Clyburne,
J. A. C.; Organ, M. G. Angew. Chem., Int. Ed. 2012, 51, 7024.
(7) For selected reviews, see: (a) Choi, J.; Fu, G. C. Science 2017,
356, 7230. (b) Jana, R.; Pathak, T. P.; Sigman, M. S. Chem. Rev. 2011,
111, 1417. (c) Hu, X. Chem. Sci. 2011, 2, 1867. (d) Tasker, S. Z.;
Standley, E. A.; Jamison, T. F. Nature 2014, 509, 299. For selected
AUTHOR INFORMATION
Corresponding Authors
■
Jun-Long Niu − Green Catalysis Center, and College of
Chemistry, Zhengzhou University, Zhengzhou 450001, P. R.
China; orcid.org/0000-0001-8012-4676;
Email: niujunlong@zzu.edu.cn
Mao-Ping Song − Green Catalysis Center, and College of
Chemistry, Zhengzhou University, Zhengzhou 450001, P. R.
China; orcid.org/0000-0003-3883-2622;
Email: mpsong@zzu.edu.cn
D
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examples, see: (e) Qin, T.; Cornella, J.; Li, C.; Malins, L. R.; Edwards,
J. T.; Kawamura, S. B.; Maxwell, D.; Eastgate, M. D.; Baran, P. S.
Science 2016, 352, 801. (f) Schmidt, J.; Choi, J.; Liu, A. T.; Slusarczyk,
M.; Fu, G. C. Science 2016, 354, 1265. (g) Ye, Y.; Chen, H.; Sessler, J.
L.; Gong, H. J. Am. Chem. Soc. 2019, 141, 820.
(8) For representative alkene functionalization reactions, see:
(a) Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem.
Rev. 1994, 94, 2483. (b) Beller, M.; Seayad, J.; Tillack, A.; Jiao, H.
Angew. Chem., Int. Ed. 2004, 43, 3368. (c) McDonald, R. I.; Liu, G.;
Stahl, S. S. Chem. Rev. 2011, 111, 2981. For selected reviews on
J. S.; Liu, P.; Engle, K. M. Angew. Chem., Int. Ed. 2019, 58, 3923.
(c) Derosa, J.; Kang, T.; Tran, V. T.; Wisniewski, S. R.; Karunananda,
M. K.; Jankins, T. C.; Xu, K. L.; Engle, K. M. Angew. Chem., Int. Ed.
2020, 59, 1201.
(20) (a) Wang, H.; Bai, Z.; Jiao, T.; Deng, Z.; Tong, H.; He, G.;
Peng, Q.; Chen, G. J. Am. Chem. Soc. 2018, 140, 3542. (b) Bai, Z.; Bai,
Z.; Song, F.; Wang, H.; Chen, G.; He, G. ACS Catal. 2020, 10, 933.
(21) For selected examples, see: (a) Lv, H.; Xiao, L.-J.; Zhao, D.;
Zhou, Q.-L. Chem. Sci. 2018, 9, 6839. (b) Lv, H.; Kang, H.; Zhou, B.;
Xue, X.; Engle, K. M.; Zhao, D. Nat. Commun. 2019, 10, 5025. (c) Li,
Y.; Liang, Y.; Dong, J.; Deng, Yi; Zhao, C.; Su, Z.; Guan, W.; Bi, X.;
Liu, Q.; Fu, J. J. Am. Chem. Soc. 2019, 141, 18475. (d) Shen, H.-C.;
Zhang, L.; Chen, S.-S.; Feng, J.; Zhang, B.-W.; Zhang, Y.; Zhang, X.;
Wu, Y.-D.; Gong, L.-Z. ACS Catal. 2019, 9, 791.
hydrofunctionalization of alkenes, see: (d) Muller, T. E.; Hultzsch, K.
̈
C.; Yus, M.; Foubelo, F.; Tada, M. Chem. Rev. 2008, 108, 3795.
(e) Yadav, J. S.; Antony, A.; Rao, T. S.; Subba Reddy, B. V. J.
Organomet. Chem. 2011, 696, 16. (f) Huang, L.; Arndt, K.; Gooßen,
K.; Heydt, H.; Gooßen, L. J. Chem. Rev. 2015, 115, 2596. (g) Dong,
Z.; Ren, Z.; Thompson, S. J.; Xu, Y.; Dong, G. Chem. Rev. 2017, 117,
9333. (h) Obligacion, J. V.; Chirik, P. J. Nat. Rev. Chem. 2018, 2, 15.
(9) For selected examples of alkene hydrocarbofunctionalization,
see: (a) Villa, M.; Jacobi von Wangelin, A. Angew. Chem., Int. Ed.
2015, 54, 11906. (b) Nguyen, K. D.; Herkommer, D.; Krische, M. J. J.
Am. Chem. Soc. 2016, 138, 5238. (c) Fang, X.; Yu, P.; Morandi, B.
Science 2016, 351, 832. For selected examples of alkene hydro-
carbofunctionalization involving M−H, see: Ni−H: (d) Chen, F.;
Chen, K.; Zhang, Y.; He, Y.; Wang, Y.-M.; Zhu, S. J. Am. Chem. Soc.
2017, 139, 13929. (e) Zhou, F.; Zhang, Y.; Xu, X.; Zhu, S. Angew.
Chem., Int. Ed. 2019, 58, 1754. (f) Lu, X.; Xiao, B.; Zhang, Z.; Gong,
T.; Su, W.; Yi, J.; Fu, Y.; Liu, L. Nat. Commun. 2016, 7, 11129.
(g) Xiao, L.-J.; Cheng, L.; Feng, W.-M.; Li, M.-L.; Xie, J.-H.; Zhou,
Q.-L. Angew. Chem., Int. Ed. 2018, 57, 461. (h) Lv, L.; Zhu, D.; Qiu,
Z.; Li, J.; Li, C.-J. ACS Catal. 2019, 9, 9199. Cu−H: (i) Wang, Y.-M.;
(22) For a representative review, see: Daugulis, O.; Do, H.-Q.;
Shabashov, D. Acc. Chem. Res. 2009, 42, 1074.
(23) (a) Mukaiyama, T.; Isayama, S.; Inoki, S.; Kato, K.; Yamada, T.;
Takai, T. Chem. Lett. 1989, 18, 449. (b) Isayama, S.; Mukaiyama, T.
Chem. Lett. 1989, 18, 569.
(24) For selected examples, see: (a) Waser, J.; Carreira, E. M. J. Am.
Chem. Soc. 2004, 126, 5676. (b) Gaspar, B.; Carreira, E. M. Angew.
Chem., Int. Ed. 2007, 46, 4519. (c) Gaspar, B.; Carreira, E. M. J. Am.
Chem. Soc. 2009, 131, 13214. (d) Morandi, B.; Mariampillai, B.;
Carreira, E. M. Angew. Chem., Int. Ed. 2011, 50, 1101.
(25) Shigehisa, H.; Koseki, N.; Shimizu, N.; Fujisawa, M.; Niitsu,
M.; Hiroya, K. J. Am. Chem. Soc. 2014, 136, 13534.
(26) Wang, L.-C.; Jang, H.-Y.; Roh, Y.; Lynch, V.; Schultz, A. J.;
Wang, X.; Krische, M. J. J. Am. Chem. Soc. 2002, 124, 9448.
(27) (a) Du, X.; Zhang, Y.; Peng, D.; Huang, Z. Angew. Chem., Int.
Ed. 2016, 55, 6671. (b) Wen, H.; Liu, G.; Huang, Z. Coord. Chem.
Rev. 2019, 386, 138. (c) Wen, H.; Wang, K.; Zhang, Y.; Liu, G.;
Huang, Z. ACS Catal. 2019, 9, 1612.
(28) (a) Hayashi, C.; Hayashi, T.; Kikuchi, S.; Yamada, T. Chem.
Lett. 2014, 43, 565. (b) Pellissier, H.; Clavier, H. Chem. Rev. 2014,
114, 2775. (c) Yu, S.; Wu, C.; Ge, S. J. Am. Chem. Soc. 2017, 139,
6526. (d) Wu, C.; Liao, J.; Ge, S. Angew. Chem., Int. Ed. 2019, 58,
8882. (e) Discolo, C. A.; Touney, E. E.; Pronin, S. V. J. Am. Chem.
Soc. 2019, 141, 17527.
(29) For selected reviews on metal-hydride chemistry, see:
(a) Rendler, S.; Oestreich, M. Angew. Chem., Int. Ed. 2007, 46, 498.
(b) Deutsch, C.; Krause, N.; Lipshutz, B. H. Chem. Rev. 2008, 108,
2916. (c) Greenhalgh, M. D.; Jones, A. S.; Thomas, S. P.
ChemCatChem 2015, 7, 190. (d) Pirnot, M. T.; Wang, Y.-M.;
Buchwald, S. L. Angew. Chem., Int. Ed. 2016, 55, 48. (e) Crossley, S.
W. M.; Obradors, C.; Martinez, R. M.; Shenvi, R. A. Chem. Rev. 2016,
116, 8912. (f) Nguyen, K. D.; Park, B. Y.; Luong, T.; Sato, H.; Garza,
V. J.; Krische, M. J. Science 2016, 354, 5133. (g) Green, S. A.;
́
Bruno, N. C.; Placeres, A. L.; Zhu, S.; Buchwald, S. L. J. Am. Chem.
Soc. 2015, 137, 10524. Fe−H: (j) George, D. T.; Kuenstner, E. J.;
Pronin, S. V. J. Am. Chem. Soc. 2015, 137, 15410. (k) Shen, Y.; Qi, J.;
Mao, Z.; Cui, S. Org. Lett. 2016, 18, 2722. Ru−H: (l) Lv, L.; Yu, L.;
Qiu, Z.; Li, C.-J. Angew. Chem., Int. Ed. 2020, 59, 6466.
(10) Yan, M.; Lo, J. C.; Edwards, J. T.; Baran, P. S. J. Am. Chem. Soc.
2016, 138, 12692.
(11) Boivin, J.; Fouquet, E.; Zard, S. Z. J. Am. Chem. Soc. 1991, 113,
1055.
(12) (a) Nishimura, T.; Uemura, S. J. Am. Chem. Soc. 2000, 122,
12049. (b) Nishimura, T.; Yoshinaka, T.; Nishiguchi, Y.; Maeda, Y.;
Uemura, S. Org. Lett. 2005, 7, 2425.
(13) (a) Davies, J.; Booth, S. G.; Essafi, S.; Dryfe, R. A. W.; Leonori,
D. Angew. Chem., Int. Ed. 2015, 54, 14017. (b) Dauncey, E. M.;
Morcillo, S. P.; Douglas, J. J.; Sheikh, N. S.; Leonori, D. Angew. Chem.,
Int. Ed. 2018, 57, 744.
(14) (a) Zhao, B.; Shi, Z. Angew. Chem., Int. Ed. 2017, 56, 12727.
(b) Wang, P.; Zhao, B.; Yuan, Y.; Shi, Z. Chem. Commun. 2019, 55,
1971.
(15) (a) Gu, Y.-R.; Duan, X.-H.; Yang, L.; Guo, L.-N. Org. Lett.
2017, 19, 5908. (b) Zhang, J.-J.; Duan, X.-H.; Wu, Y.; Yang, J.-C.;
Guo, L.-N. Chem. Sci. 2019, 10, 161.
(16) (a) Yu, X.-Y.; Chen, J.-R.; Wang, P.-Z.; Yang, M.-N.; Liang, D.;
Xiao, W.-J. Angew. Chem., Int. Ed. 2018, 57, 738. (b) Yao, S.; Zhang,
K.; Zhou, Q.-Q.; Zhao, Y.; Shi, D.-Q.; Xiao, W.-J. Chem. Commun.
2018, 54, 8096. (c) Lu, B.; Cheng, Y.; Chen, L.-Y.; Chen, J.-R.; Xiao,
W.-J. ACS Catal. 2019, 9, 8159.
(17) For selected examples, see: (a) Yang, H.-B.; Pathipati, S. R.;
Selander, N. ACS Catal. 2017, 7, 8441. (b) Li, L.; Chen, H.; Mei, M.;
Zhou, L. Chem. Commun. 2017, 53, 11544. (c) Le Vaillant, F.;
Garreau, M.; Nicolai, S.; Gryn’ova, G.; Corminboeuf, C.; Waser, J.
Chem. Sci. 2018, 9, 5883. (d) Ding, D.; Wang, C. ACS Catal. 2018, 8,
11324.
(18) (a) Rouquet, G.; Chatani, N. Angew. Chem., Int. Ed. 2013, 52,
11726. (b) Daugulis, O.; Roane, J.; Tran, L. D. Acc. Chem. Res. 2015,
48, 1053. (c) Lin, C.; Shen, L. ChemCatChem 2019, 11, 961.
(19) For selected examples, see: (a) Yang, K. S.; Gurak, Jr J. A.; Liu,
Z.; Engle, K. M. J. Am. Chem. Soc. 2016, 138, 14705. (b) Nimmagadda,
S. K.; Liu, M.; Karunananda, M. K.; Gao, D.-W.; Apolinar, O.; Chen,
́
́
Crossley, S. W. M.; Matos, J. L. M.; Vasquez-Cespedes, Ce; Shevick,
S. L.; Shenvi, R. A. Acc. Chem. Res. 2018, 51, 2628.
(30) For selected examples, see: (a) Xu, X.; Zhu, S.; Cui, X.; Wojtas,
L.; Zhang, X. P. Angew. Chem., Int. Ed. 2013, 52, 11857. (b) Wang, Y.;
Wen, X.; Cui, X.; Wojtas, L.; Zhang, X. P. J. Am. Chem. Soc. 2017,
139, 1049. (c) Hu, Y.; Lang, K.; Tao, J.-R.; Marshall, M. K.; Cheng,
Q.-G.; Cui, X.; Wojtas, L.; Zhang, X. P. Angew. Chem., Int. Ed. 2019,
58, 2670.
(31) (a) Liu, M.; Niu, J.-L.; Yang, D.; Song, M.-P. J. Org. Chem.
2020, 85, 4067. (b) Li, X.-C.; Du, C.; Zhang, H.; Niu, J.-L.; Song, M.-
P. Org. Lett. 2019, 21, 2863. (c) Du, C.; Li, P.-X.; Zhu, X.; Han, J.-N.;
Niu, J.-L.; Song, M.-P. ACS Catal. 2017, 7, 2810. (d) Du, C.; Li, P.-X.;
Zhu, X.; Suo, J.-F.; Niu, J.-L.; Song, M.-P. Angew. Chem., Int. Ed. 2016,
55, 13571. (e) Zhang, L.-B.; Hao, X.-Q.; Zhang, S.-K.; Liu, Z.-J.;
Zheng, X.-X.; Gong, J.-F.; Niu, J.-L.; Song, M.-P. Angew. Chem., Int.
Ed. 2015, 54, 272. (f) Zhang, L.-B.; Hao, X.-Q.; Liu, Z.-J.; Zheng, X.-
X.; Zhang, S.-K.; Niu, J.-L.; Song, M.-P. Angew. Chem., Int. Ed. 2015,
54, 10012. (g) Guo, X. K.; Zhang, L.-B.; Wei, D.; Niu, J.-L. Chem. Sci.
2015, 6, 7059.
(32) (a) Griller, D.; Ingold, K. U. Acc. Chem. Res. 1980, 13, 317.
(b) Bullock, R. M.; Samsel, E. G. J. Am. Chem. Soc. 1990, 112, 6886.
E
https://dx.doi.org/10.1021/acs.orglett.0c01365
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
(33) (a) Obradors, C.; Martinez, R. M.; Shenvi, R. A. J. Am. Chem.
Soc. 2016, 138, 4962. (b) Zhang, J.; Park, S.; Chang, S. J. Am. Chem.
Soc. 2018, 140, 13209.
(34) (a) Shigehisa, H.; Hayashi, M.; Ohkawa, H.; Suzuki, T.;
Okayasu, H.; Mukai, M.; Yamazaki, A.; Kawai, R.; Kikuchi, H.; Satoh,
Y.; Fukuyama, A.; Hiroya, K. J. Am. Chem. Soc. 2016, 138, 10597.
(b) Shigehisa, H.; Nishi, E.; Fujisawa, M.; Hiroya, K. Org. Lett. 2013,
15, 5158. (c) Shigehisa, H.; Aoki, T.; Yamaguchi, S.; Shimizu, N.;
Hiroya, K. J. Am. Chem. Soc. 2013, 135, 10306. (d) Deng, Y.; Zhao,
C.; Zhou, Y.; Wang, H.; Li, X.; Cheng, G.-J.; Fu, J. Org. Lett. 2020, 22,
3524.
(35) (a) See ref 29e, Section 7: Mechanistic Overview. (b) Ungvary,
F.; Marko, L. Organometallics 1982, 1, 1120. (c) Santhoshkumar, R.;
Mannathan, S.; Cheng, C.-H. J. Am. Chem. Soc. 2015, 137, 16116.
(d) Hapke, M.; Hilt, G. Section 3. In Cobalt Catalysis in Organic
Synthesis: Methods and Reactions; Wiley: 2020; pp 67−84.
F
https://dx.doi.org/10.1021/acs.orglett.0c01365
Org. Lett. XXXX, XXX, XXX−XXX