Copper-Catalyzed Unstrained CC Single Bond Cleavage of Acyclic

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Copper-Catalyzed Unstrained C-C Single Bond Cleavage of Acyclic Oxime Acetates Using Air: An Internal Oxidants Triggered Strategy toward Nitriles and Ketones Chuanle Zhu, Fulin Chen, Chi Liu, Hao Zeng, Zhiyi Yang, Wanqing Wu, and Huanfeng Jiang J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02103 • Publication Date (Web): 10 Oct 2018 Downloaded from http://pubs.acs.org on October 10, 2018

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The Journal of Organic Chemistry

Copper-Catalyzed Unstrained C-C Single Bond Cleavage of Acyclic Oxime Acetates Using Air: An Internal Oxidants Triggered Strategy toward Nitriles and Ketones Chuanle Zhu, Fulin Chen, Chi Liu, Hao Zeng, Zhiyi Yang, Wanqing Wu, and Huanfeng Jiang* Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, P. R. China Fax: (+86) 20-8711-2906; E-mail: [email protected]

NOAc R2

Ar

N

[Cu]

R2

Ar

R1

[Cu]/air Ar CN

R1

O

+ R1

R2

Unstrained C-C bond cleavage of acyclic oxime acetates Internal oxidants triggered strategy toward aryl nitirles and ketones Catalytic copper/air system

Abstract: A copper-catalyzed aerobic oxidative C-C single bond cleavage of acyclic unstrained oxime acetates is reported, providing various aryl nitriles and ketones in good yields. Mechanistic studies indicate a radical procedure is involved in this transformation, and the oxygen atom in the ketone products is originated from O2 in the air. Oxime acetates as an internal oxidant have been proved to be an initiator, which may promote the discovery of novel protocol for C-C bond cleavage and dioxygen activation.

Carbon-carbon bond cleavage is an attractive research area in organic chemistry and petroleum industry.1 Due to their thermodynamic stability, the selective cleavage of relative inertness C-C single bonds is one of the most challenging and on the cutting edge research topics.2 The most common strategies to promote C-C single bond cleavage focused on strain relief of strained skeletons (three and four membered rings),3 the use of chelation assistance,4 and C-CN bond cleavage.5 However, to cleave unstrained inert C-C bonds, harsh conditions with stoichiometric oxidants such as toxic metal salts and peroxides have been required traditionally. Thus, the ACS Paragon Plus Environment

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development of environmentally sustainable and efficient methods to cleave unstrained inert C-C bonds is highly desired but still underdeveloped.6 In recent years, aerobic oxidative cleavage of C-C multiple bonds with dioxygen has attracted significant research interest,7 because molecular oxygen has been recognized as an ideal oxidant in organic synthesis due to its environmentally benign character.8 The elegant early works for the challenging aerobic oxidative cleavage of unstrained C-C single bond with dioxygen were focused on the cleavage of C(CO)-C(alkyl) single bonds, and these reactions were usually performed under dioxygen atmosphere (Scheme 1, a).9 Given the issues of relative safety, sustainable abundance, extremely low cost, and ease of manipulation, the development of novel aerobic oxidative unstrained C-C single bond cleavage reactions employing air is highly preferred. However, owing to the high activation energy and reduced reactivity at lower concentration of dioxygen,10 it is often challenging to use air instead of dioxygen in aerobic oxidative C-C single bond cleavage.9 Oxime esters as an internal oxidant, which serves as both a substrate and an oxidant in reactions, have attracted considerable attention.11-14 Recently, the groups of Uemura,12a Selander12b, Shi12c and Guo12d-f independently reported Pd, Fe, Cu, and Ni-catalyzed C-C single bond cleavage of strained or less strained cyclic oxime esters to give aliphatic nitriles, driving by internal oxidant triggered strain relief of strained or less strained four or five membered rings (Scheme 1, b). In sharp contrast, transition-metal catalyzed C-C single bond cleavage of unstrained acyclic oxime esters remains an unsolved challenge, because this internal oxidant triggered strategy for acyclic oxime esters prefers to the α-Csp3-H bond activation process, especially under copper catalysis.11,

13-14

As our continuous effort toward aerobic C-C bond

cleavage reactions under air,7a, 11b as well as our interest in exploiting the potential abilities of oxime acetates,11, 14 we herein report a copper-catalyzed unstrained C-C bond cleavage of oxime acetates that gives rise to valuable aryl nitriles and ketones avoiding the use of toxic cyanide sources (Scheme 1, c). Remarkably, this process is a novel aerobic oxidative cleavage of unstrained C-C bond under air triggered by an internal oxidant. ACS Paragon Plus Environment

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Scheme 1. C-C Single Bond Cleavage by Aerobic or/and Internal Oxidation a) Aerobic oxidation: under O2 atmosphere O C FG

[TM]/O2/[FG]

O C

C

-H2O

b) Internal oxidation: strained or less strained C-C single bond N

OR R3

n 1

N R1 R2

TM

R3

NC n

-ROH

2

R3

n 1

2

R R n = 1, 2

R R n = 1, 2

c) This work: unstrained C-C single bond using air

Ar

NOAc R2 1

R

N

[Cu]

R2

Ar R1

[Cu]/air Ar CN

O

+ R1

R2

After tremendous attempts, acyclic oxime acetate 1aa was selected as the model substrate to establish the optimized reaction conditions (Table 1). First, different types of copper catalysts, such as CuCl, CuBr, CuI, CuCl2, Cu(OAc)2, Cu(OTf)2, Cu(MeCN)4BF4, and Cu(MeCN)4PF6 were investigated, a catalyst of CuI gave the aryl nitrile product 2a in 88% isolated yield, and the corresponding ketone product 3a was not determined (entries 1-8). Next, other well documented metal catalysts such as Pd2(dba)3, FeCl2, and NiCl2 for C-C single bond cleavage of strained or less strained cyclic oxime esters were examined, they were almost uneffective in this transformation (entries 9-11). No product was detected without copper catalyst (entry 12). Furthermore, we evaluated other reaction solvents, DMF, 1,4-dioxane, MeCN, DCE (1,2-dichloroethane), toluene, and EtOH, but we found DMSO was optimum for this unstrained C-C single bond cleavage reaction (entries 13-18). Additionally, either reducing or increasing the reaction temperature eroded the yield of 3a slightly (entries 19-20).

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Table 1. Optimization of the Reaction Conditionsa

catalyst

solvent

temperature (oC)

1

CuCl

DMSO

90

32

2

CuBr

DMSO

90

50

91 (88)

entry

a

yield (%)b

3

CuI

DMSO

90

4

CuCl2

DMSO

90

53

5

Cu(OAc)2

DMSO

90

23

6

Cu(OTf)2

DMSO

90

51

7

Cu(MeCN)4BF4

DMSO

90

20

8

Cu(MeCN)4PF6

DMSO

90

15

9

Pd2(dba)3

DMSO

90

3

10

FeCl2

DMSO

90

5

11

NiCl2

DMSO

90

3

12

-

DMSO

90

0

13

CuI

DMF

90

80

14

CuI

1.4-dioxane

90

79

15

CuI

MeCN

90

33 11

16

CuI

DCE

90

17

CuI

toluene

90

6

18

CuI

EtOH

90

21

19

CuI

DMSO

80

84

20

CuI

DMSO

100

89

Unless otherwise noted, all reactions were carried out with 1aa (0.2 mmol), catalyst (10 mol%), and solvent (2

mL) in a 25 mL test tube at 90 oC for 12 h under air. bThe yields were determined by 1H NMR spectroscopy of the crude product with CH2Br2 as an internal standard. The number in the parentheses was isolated yield. n.d. = not determined.

Under the optimized reaction conditions, we turned our attention to the generality of acyclic oxime acetates in this internal oxidants-triggered unstrained C-C single bond cleavage reaction under air. The results were outlined in Scheme 2. In general, substituted oxime acetates with electron-donating groups such as alkoxyl and alkyl groups, electron-neutral group, and electron-withdrawing groups such as fluoro, chloro, bromo, iodo, and trifluoromethyl groups on the para-, meta-, and ortho-position of the phenyl ring all could give the desired aryl nitriles in high yields (2a-2p). Oxime acetates derived from 1-(naphthalen-2-yl)ethan-1-one was applicable to this internal oxidants-triggered system, providing the desired product 2q in 74% yield. Furthermore, different hetereo aromatic groups such as thienyl, and indolyl-bearing oxime acetates were also found to be good substrates, delivering the corresponding products with high yields (2r-2s). Acyclic aliphatic nitrile 2t was also obtained in 13% GC yield. Additionally, although five-membered cyclic oxime acetate


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1ua did not give the desired ketonitrile 2u in isolatable yield (< 10%) under the standard reaction conditions, six-membered cyclic oxime acetate 1va afforded ketonitrile 2v in 23% yield. Scheme 2. Substrate Scope of Oxime Acetatesa NOAc R

CuI, DMSO

3a: n.d.

2 CN

MeO

Me

MeO

CN

MeO

CN

MeO 2a: 88%b

2b: 77%

2c: 71% CN

F

c

CN

2p: 73%

a

2j: 71% CN

I

2n: 63% CN

2o: 61%

S CN

2q: 74%

8

N Bn 2s: 64%

2r: 64%

2t: 13%[b]

O 2u: < 10%

CN

CN

NOAc

CN F

1ua

CN

2m: 75%

CN

NOAc

F

CN

Cl

2i: 65% CN

Br

2l: 61%

CN

F3C

2e: 71%

Br

CN 2k: 73%

CN

2h: 64%

Cl

Cl

CN

2d: 73% F

CN

2g: 63%

2f: 56% (71% )

Cl

CN

Me

F CN

O

+

R CN

Air, 90 oC, 12 h 1

O 1va

2v: 23%

Unless otherwise noted, the reaction was run at 0.2 mmol scale under the standard reaction conditions. bThe

average isolated yield of two parallel runs. cGC-MS yield. n.d. = not determined.

To further define the limitation of our protocol, as well as figuring out the other products from this C-C bond cleavage reaction, diverse α-substituted oxime acetates were investigated under the standard reaction conditions (Scheme 3). Interestingly, oxime acetates with only one α-H were more suitable in this internal oxidants-triggered unstrained C-C single bond cleavage transformation (1fa-1ff). We assumed that the α-tertiary carbon might be very important for the stability of the reaction intermediates. Besides the benzonitrile product, it is worth to mentioning that ketone products such as aryl ketone 3e and 4-alphatic ketone 3f were isolated in 53% and 35% yields from the corresponding oxime acetates (3fe-3ff), respectively. Additionally, different types of oxime acetates with α-tertiary carbon were investigated (1fg-1fj), no better results were obtained compared to that of 1fa.



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Scheme 3. α-Substituted Oxime Acetatesa Ph

NOAc R2 R1

CuI, DMSO CN 2f

2f

2f

NOAc

NOAc

3c: n.d.

1fd

H

O

1fi NOAc

O 67% Ph

3i: n.d. 50%

Ph

3e: 50%c

1fe

3h: n.d. 20%

Ph

3d: 6%

NOAc Ph

O

1fh NOAc

O 34% Ph

3g: n.d. 7%

Ph

H 1fc

O 27%

1fg NOAc

O

NOAc Ph

3f: 35% c

NOAc Ph

11%

Ph

Ph

O H H 3b: n.d.

Ph

O 45%

1ff

6% 1fb

Ph

Ph

Ph 3a: n.d.

Ph

3

NOAc

O

71% b 1fa

3

3

NOAc

R2

R1

1

Ph

O

+

90 oC, 12 h, air

1fj

O 3j: 20%

a

Unless otherwise noted, the reaction was run at 0.2 mmol scale under the standard reaction conditions.

b

GC-MS yield. cIsolated yield. n.d. = not determined.

To

cast

some

light

on

the

mechanism

details

of

this

internal

oxidants-triggered unstrained C-C single bond cleavage reaction, a series of control experiments were performed. First, different types of oxime esters (1fa-1fc) and unprotected oxime 1fd were examined under the standard reaction conditions. The product benzonitrile 2f was obtained in 0% to 71% GC yields, indicating that the oxidative property of oxime esters is very important to this transformation (Scheme 4, eq 1). Next, the C-C single bond cleavage reaction of oxime acetate 1fa was independently performed under N2, O2, and air. Owing to only 5% of benzonitrile 2f was detected under N2, which is a dramatically lower yield compared to that under O2 (71%), or air (71%). We believed that O2 is necessary to promote this unstrained C-C single bond cleavage reaction (Scheme 4, eq 2). Interestingly, oxidizing radical scavenger TEMPO enhanced the yield of product 2f to 76% GC yield, probably related to the excellent dioxygen activation property of CuI/TEMPO system (Scheme 4, eq 3).15 While non oxidizing radical scavenger tert-butylhydroxytoluene (BHT) completely inhibited this unstrained C-C single bond cleavage reaction, and the radical trapping product 4 was isolated in 38% yield, indicating that a radical process was involved in this reaction (Scheme 4, eq 4). Furthermore,


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α-hydroxyl oxime 5a and α-hydroxyl oxime acetate 5b were synthesized and independently

performed

this

unstrained

C-C

single

bond

cleavage

transformation under standard reaction conditions (Scheme 4, eq 5). No benzonitrile 2f was detected from α-hydroxyl oxime 5a, while α-hydroxyl oxime acetate 5b gave product 2f quantitatively. These results showed that this reaction was initially triggered by copper-catalyzed N-O bond cleavage of oxime acetates, and a hydroxyl group was introduced into one of the reaction intermediates, which further converted to the ketone product. Finally, to figure out the original source of the oxygen atom in the ketone products, the unstrained C-C single bond cleavage reaction of 1fe to give acetophenone product was selected as the model reaction. Treated 1fe with 2 equivalent of H218O under the standard reaction conditions, GC-MS analysis showed the ratio of 18O-labeled acetophenone 3e is less than 5%, indicating that the oxygen atom in acetophenone 3e is not originated from H2O (Scheme 4, eq 6). No 18

O-labeled acetophenone 3e was obtained under

16

O2 atmosphere (Scheme 4,

eq 7), while the ratio of 18O-labeled acetophenone 3e is 85% when the reaction was performed under

18

O2 atmosphere (Scheme 4, eq 8). Thus, we confirmed

that dioxygen is the original source of the oxygen atom in the ketone products. Additionally, CH3SO2CH3 as the byproduct was detected by GC-MS (Scheme 4, eqs 7-8), which indicates that DMSO can be a reductant in this transformation.



Scheme 4. Control Experiments

a

Unless otherwise noted, the yields were GC-MS yields. bIsolated yields.

On the basis of these experimental results as well as previous works,11-14 we tentatively proposed the reaction mechanism as illustrated in Scheme 5. Firstly, reduction of 1fa by CuI affords CuII salts and iminyl radical A, which may quickly isomerize to α-carbon radical B. And then the carbon radical B has priority over the iminyl radical A to be trapped by O2 providing peroxide radical intermediate C. A subsequent intramolecular 1,5-hydrogen atom transfer (1,5-HAT) procedure leads to the peroxide iminyl radical D,16 which could be reduced by DMSO17 to generate α-hydroxyl iminyl radical E. Finally, oxidative C-C bond cleavage by CuII salts regenerated the CuI catalyst and gave benzonitrile 2f and acetone 3a as the products.


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Scheme 5. Proposed Mechanism

In summary, we have reported the first copper-catalyzed aerobic oxidative unstrained C-C single bond cleavage reaction that is triggered by an internal oxidant. This unstrained C-C single bond cleavage reaction of oxime acetates provides various aryl nitriles and ketones in good yields using air. Mechanistic studies indicated that this reaction involved a radical procedure. Oxime acetates as an internal oxidant have been proved to be an initiator, which may promote the discovery of novel protocol for C-C bond cleavage and dioxygen activation. Application of this internal oxidants triggered strategy in other challenging C-C bond cleavage and dioxygen activation reactions is currently under investigation in our laboratory.

EXPERIMENTAL SECTION General

Information.

Toluene

were

distilled

from

sodium/benzophenone;

1,2-dichloroethane (DCE) was distilled from calcium hydride; acetonitrile (MeCN) was distilled from phosphorus pentoxide. Other commercially available reagents were purchased and used without further purification. Analytical thin-layer chromatography was performed on 0.20 mm silica gel plates (GF254) using UV light as a visualizing agent. Flash column chromatography was carried out using silica gel (200–300 mesh) with the indicated solvent system. All reactions were conducted in oven-dried test tubes. All the reaction temperatures reported are oil bath temperatures. Melting points were measured using a melting point instrument and are uncorrected. Chemical shifts were reported in ppm from the solvent resonance as the internal standard (CDCl3 δH = 7.26 ppm, δC = 77.16 ppm). Multiplicity was indicated as follows: s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet). Coupling constants were reported in Hertz (Hz). IR spectra were obtained with an infrared spectrometer on either



potassium bromide pellets or liquid films between two potassium bromide pellets. GC−MS data were obtained using electron ionization. HRMS was carried out on a high-resolution mass spectrometer (LCMS-IT-TOF). TLC was performed using commercially available 100−400 mesh silica gel plates (GF254).

General Procedure for the Synthesis of Oxime esters: To a round-bottome flask equipped with a reflux condenser and a magnetic bar was added ketones (5 mmol), NH2OH·HCl (7.5 mmol), NaOAc (7.5 mmol), H2O (5 mL), and EtOH (5 mL). The resulting mixture was stirred at 80 oC for 2 h, then cooled to room temperature, added water (15 mL), extracted with EtOAc (15 mL × 3). The combined organic phases were dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The resulted oxime was further purified by flash column chromatography on silica gel or directly treated with CH2Cl2 (10 mL), acid anhydride (10 mmol), and stirred at room temperature overnight. The resulting mixture was added water (15 mL), extracted with CH2Cl2 (15 mL × 3). The combined organic phases were wished with brine (15 mL × 3), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. Further purification by flash column chromatography on silica gel (eluting with petroleum ether/ethyl acetate = 30/1) provided the oxime esters 1. 1-(4-Methoxyphenyl)-2-Methylpropan-1-One O-Acetyl Oxime (1aa): colorless oil; 73% yield (857.7 mg); E/Z isomer mixtures (E/Z = 63/37); 1H NMR (400 MHz, CDCl3) δ 7.44 (d, J = 8.4 Hz, 0.76H), 7.17 (d, J = 8.4 Hz, 1.23H), 7.53−7.58 (m, 2.00H), 3.86 (s, 1.85H), 3.81 (s, 1.12H), 3.50 (hept, J = 7.2 Hz, 0.37H), 2.98 (hept, J = 6.8 Hz, 0.63H), 2.23 (s, 1.17H), 2.00 (s, 1.81H), 1.25 (d, J = 6.8 Hz, 2.33H), 1.18 (d, J = 6.8 Hz, 3.67H); 13C {1H} NMR (100 MHz, CDCl3) δ 171.2, 171.0, 169.0, 168.9, 160.7, 160.0, 129.5, 128.6, 126.4, 125.0, 113.7, 113.5, 55.2, 55.2, 32.0, 30.1, 20.0, 19.8, 19.6, 19.5; IR (KBr): 2962, 1764, 1609, 1508, 1205 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. for C13H18NO3, 236.1281; found, 236.1282 1-(3,4-Dimethoxyphenyl)-2-Methylpropan-1-One O-Acetyl Oxime (1ba): colorless oil; 65% yield (861.3 mg); E/Z isomer mixtures (E/Z = 56/44); 1H NMR (400 MHz, CDCl3) δ 6.72−7.06 (m, 3.00H), 3.87−3.91 (m, 6.00H), 3.49 (hept, J = 6.8 Hz, 0.44H), ACS Paragon Plus Environment

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2.98 (hept, J = 6.8 Hz, 0.56H), 2.23 (s, 1.25H), 2.00 (s, 1.60H), 1.26 (d, J = 7.5 Hz, 2.81H), 1.18 (d, J = 6.8 Hz, 3.20H);

13

C {1H} NMR (100 MHz, CDCl3) δ 171.4,

171.1, 169.0, 168.8, 150.4, 149.5, 148.7, 148.5, 126.7, 125.3, 121.0, 119.9, 111.3, 110.7, 110.6, 56.0, 55.9, 55.9, 55.8, 35.1, 30.2, 20.0, 19.8, 19.7, 19.6; IR (KBr): 2961, 1763, 1597, 1515, 1457, 1210 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. for C14H20NO4, 266.1387; found, 266.1388 1-(3-Methoxyphenyl)-2-Methylpropan-1-One O-Acetyl Oxime (1ca): colorless oil; 77% yield (904.7 mg); E/Z isomer mixtures (E/Z = 67/33); 1H NMR (400 MHz, CDCl3) δ 6.70−7.34 (m, 4.00H), 3.82 (s, 3.00H), 3.53 (hept, J = 6.8 Hz, 0.33H), 2.98 (hept, J = 6.8 Hz, 0.67H), 2.24 (s, 0.93H), 1.98 (s, 1.97H), 1.23 (d, J = 6.8 Hz, 1.98H), 1.18 (d, J = 6.8 Hz, 3.91H); 13C {1H} NMR (100 MHz, CDCl3) δ 171.8, 171.5, 168.8, 168.8, 159.4, 159.3, 135.3, 134.2, 129.3, 129.3, 120.4, 19.1, 115.1, 114.0, 113.8, 112.7, 55.3, 55.3, 35.0, 30.0, 19.9, 19.8, 19.6, 19.6; IR (KBr): 2961, 1765, 1589, 1464, 1204 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. for C13H18NO3, 236.1281; found, 236.1283 2-Methyl-1-(p-Tolyl)propan-1-One O-Acetyl Oxime (1da): colorless oil; 78% yield (854.1 mg); E/Z isomer mixtures (E/Z = 54/46); 1H NMR (400 MHz, CDCl3) δ 7.37 (d, J = 8.0 Hz, 0.83H), 7.08−7.24 (m, 3.33H), 3.53 (hept, J = 7.2 Hz, 0.46H), 3.00 (hept, J = 7.2 Hz, 0.54H), 2.39−2.40 (m, 3.00H), 2.25 (s, 1.27H), 1.99 (s, 1.64H), 1.25 (d, J = 7.2 Hz, 2.70H), 1.19 (d, J = 7.2 Hz, 3.28H); 13C {1H} NMR (100 MHz, CDCl3) δ 171.8, 171.7, 169.0, 139.6, 138.8, 131.2, 130.0, 128.9, 128.8, 128.0, 126.9, 35.0, 30.0, 26.1, 21.3, 20.0, 19.9, 19.6, 19.6; IR (KBr): 2928, 1764, 1619, 1454, 1368, 1202 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. for C13H18NO2, 220.1332; found, 220.1333 2-Methyl-1-(o-Tolyl)propan-1-One O-Acetyl Oxime (1ea): colorless oil; 75% yield (821.3 mg); E/Z isomer mixtures (E/Z = 60/40); 1H NMR (400 MHz, CDCl3) δ 7.18−7.30 (m, 2.86H), 6.95−7.07 (m, 1.29H), 3.52 (hept, J = 6.8 Hz, 0.40H), 2.97 (hept, J = 6.8 Hz, 0.60H), 2.36−2.37 (m, 3.00H), 2.23 (d, J = 1.2 Hz, 1.16H), 1.96 (d, J = 1.2 Hz, 1.79H), 1.23 (d, J = 7.2 Hz, 2.41H), 1.18 (d, J = 7.2 Hz, 3.57H); 13C {1H} NMR (100 MHz, CDCl3) δ 172.1, 171.8, 168.9, 168.8, 138.0, 137.8, 134.0, 133.0, ACS Paragon Plus Environment


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130.2, 129.6, 128.7, 128.1, 128.0, 127.2, 125.1, 124.0, 35.0, 30.1, 26.0, 21.4, 19.9, 19.8, 19.6, 19.6; IR (KBr): 2966, 1767, 1602, 1459, 1368, 1206 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. for C13H18NO2, 220.1332; found, 220.1334 2-Methyl-1-Phenylpropan-1-One O-Acetyl Oxime (1fa): colorless oil; 83% yield (850.7 mg); E/Z isomer mixtures (E/Z = 63/37); 1H NMR (400 MHz, CDCl3) δ 7.16−7.45 (m, 5.00H), 3.54 (hept, J = 6.8 Hz, 0.37H), 3.00 (hept, J = 6.8 Hz, 0.63H), 2.24 (s, 1.08H), 1.95 (s, 1.88H), 1.17−1.24 (m, 6.00H);

13

C {1H} NMR (100 MHz,

CDCl3) δ 171.9, 171.7, 168.8, 134.0, 133.0, 129.5, 128.8, 128.2, 128.1, 128.1, 126.8, 35.0, 30.0, 19.9, 19.8, 19.6; IR (KBr): 2970, 1766, 1620, 1454, 1369, 1205 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. for C12H16NO2, 206.1176; found, 206.1177 1-(4-Fluorophenyl)-2-Methylpropan-1-One O-Acetyl Oxime (1ga): colorless oil; 80% yield (892.0 mg); E/Z isomer mixtures (E/Z = 62/38); 1H NMR (400 MHz, CDCl3) δ 7.43−7.45 (m, 0.73H), 7.05−7.18 (m, 3.21H), 3.47−3.55 (m, 0.38H), 2.93−3.00 (m, 0.62H), 2.22 (d, J = 4.4 Hz, 1.19H), 1.97 (d, J = 4.4 Hz, 1.85H), 1.14−1.23 (m, 6.00H);

13

C {1H} NMR (100 MHz, CDCl3) δ 171.0, 170.6, 168.8,

168.6, 163.5 (d, 1JC-F = 248.5 Hz), 162.8 (d, 1JC-F = 247.2 Hz), 130.1, 130.0, 129.0, 128.9, 115.4, 115.2, 35.0, 29.9, 19.8, 19.7, 19.5, 19.5; IR (KBr): 2970, 1768, 1606, 1507, 1370, 1210 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. for C12H15FNO2, 224.1081; found, 224.1083 1-(3-Fluorophenyl)-2-Methylpropan-1-One O-Acetyl Oxime (1ha): colorless oil; 76% yield (847.4 mg); E/Z isomer mixtures (E/Z = 57/43); 1H NMR (400 MHz, CDCl3) δ 6.90−7.43 (m, 4.00H), 3.50−3.57 (m, 0.43H), 2.95−3.02 (m, 0.57H), 2.25 (s, 1.30H), 1.99 (s, 1.68H), 1.18−1.25 (m, 6.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 170.7, 170.2, 168.6, 168.5, 162.4 (d, 1JC-F = 245.5 Hz), 162.3 (d, 1JC-F = 245.8 Hz), 136.1 (d, 3JC-F = 7.8 Hz), 134.9 (d, 3JC-F = 7.5 Hz), 130.0 (d, 4JC-F = 2.1 Hz), 129.9 (d, 4

JC-F = 2.1 Hz), 123.8 (d, 3JC-F = 3.1 Hz), 122.6 (d, 3JC-F = 3.2 Hz), 116.5 (d, 2JC-F =

20.9 Hz), 115.8 (d, 2JC-F = 20.9 Hz), 115.3 (d, 2JC-F = 22.6 Hz), 114.1 (d, 2JC-F = 22.6 Hz), 34.9, 29.9, 19.8, 19.7, 19.5, 19.5; IR (KBr): 2973, 1768, 1584, 1443, 1368, 1204 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. for C12H15FNO2, 224.1081; found, 224.1082 ACS Paragon Plus Environment

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1-(2-Fluorophenyl)-2-Methylpropan-1-One O-Acetyl Oxime (1ia): colorless oil; 53% yield (591.0 mg); E/Z isomer mixtures (E/Z = 68/32); 1H NMR (400 MHz, CDCl3) δ 7.38−7.41 (m, 1.01H), 7.11−7.21 (m, 3.01H), 3.51−3.56 (m, 0.32H), 2.97−3.03 (m, 0.68H), 2.23−2.25 (m, 0.91H), 1.97−1.98 (m, 2.09H), 1.15−1.22 (m, 6.00H); 1

13

C {1H} NMR (100 MHz, CDCl3) δ 169.6, 168.5, 168.4, 166.7, 160.0 (d,

JC-F = 256.1 Hz), 158.1 (d, 1JC-F = 246.8 Hz), 131.1 (d, 3JC-F = 8.1 Hz), 130.8 (d, 3JC-F

= 7.9 Hz), 128.0 (d, 4JC-F = 3.7 Hz), 124.0 (d, 4JC-F = 4.0 Hz), 123.9 (d, 3JC-F = 3.4 Hz), 121.8 (d, 3JC-F = 16.7 Hz), 120.9 (d, 2JC-F = 18.0 Hz), 115.8 (d, 2JC-F = 21.6 Hz), 115.6 (d, 2JC-F = 21.4 Hz), 34.8, 30.2, 19.6, 19.5, 19.4, 18.9; IR (KBr): 2926, 1769, 1628, 1463, 1203 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. for C12H15FNO2, 224.1081; found, 224.1084 1-(4-Chlorophenyl)-2-Methylpropan-1-One O-Acetyl Oxime (1ja): colorless oil; 74% yield (884.3 mg); E/Z isomer mixtures (E/Z = 55/45); 1H NMR (400 MHz, CDCl3) δ 7.34−7.43 (m, 3.00H), 7.12−7.14 (m, 1.07H), 3.53 (hept, J = 6.8 Hz, 0.45H), 2.98 (hept, J = 6.8 Hz, 0.55H), 2.24 (s, 1.26H), 1.98 (s, 1.64H), 1.16−1.24 (m, 6.00H); 13

C {1H} NMR (100 MHz, CDCl3) δ 170.8, 170.4, 168.6, 168.5, 135.7, 134.9, 132.5,

131.3, 129.5, 128.5, 128.3, 34.9, 30.0, 19.8, 19.7, 19.5, 19.5; IR (KBr): 2971, 1766, 1603, 1480, 1369, 1201 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. for C12H15ClNO2, 240.0786; found, 240.0788 1-(3,4-Dichlorophenyl)-2-Methylpropan-1-One O-Acetyl Oxime (1ka): colorless oil; 77% yield (1051.5 mg); E/Z isomer mixtures (E/Z = 57/43); 1H NMR (400 MHz, CDCl3) δ 7.28−7.57 (m, 2.52H), 7.02−7.04 (m, 0.56H), 3.48−3.55 (m, 0.43H), 2.93−2.98 (m, 0.57H), 2.23−2.25 (m, 1.16H), 1.99−2.01 (m, 1.73H), 1.15−1.25 (m, 6.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 169.7, 169.0, 168.5, 168.3, 134.0, 133.3, 132.7, 130.4, 130.3, 130.1, 128.8, 127.4, 126.4, 34.9, 29.9, 19.8, 19.7, 19.5, 19.5; IR (KBr): 2970, 1770, 1623, 1464, 1371, 1199 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. for C12H14Cl2NO2, 274.0396; found, 274.0399 1-(3-Chlorophenyl)-2-Methylpropan-1-One O-Acetyl Oxime (1la): colorless oil; 77% yield (932.8 mg); E/Z isomer mixtures (E/Z = 64/36); 1H NMR (400 MHz, CDCl3) δ 7.05−7.45 (m, 4.00H), 3.53 (hept, J = 6.8 Hz, 0.36H), 2.98 (hept, J = 6.8 Hz, ACS Paragon Plus Environment


0.64H), 2.25 (s, 1.07H), 2.00 (s, 1.96H), 1.18−1.25 (m, 6.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 170.7, 170.1, 168.6, 168.5, 135.8, 134.7, 134.3, 134.3, 129.6, 129.6, 129.0, 128.3, 126.8, 126.3, 125.1, 34.9, 29.9, 19.8, 19.7, 19.6, 19.5; IR (KBr): 2969, 1766, 1604, 1462, 1371, 1199 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. for C12H15ClNO2, 240.0786; found, 240.0789 1-(4-Bromophenyl)-2-Methylpropan-1-One O-Acetyl Oxime (1ma): colorless oil; 85% yield (1207.0 mg); E/Z isomer mixtures (E/Z = 67/33); 1H NMR (400 MHz, CDCl3) δ 7.51−7.57 (m, 1.94H), 7.35 (d, J = 8.0 Hz, 0.69H), 7.07 (d, J = 8.0 Hz, 1.26H), 3.53 (hept, J = 6.8 Hz, 0.33H), 2.97 (hept, J = 6.8 Hz, 0.67H), 2.24 (s, 1.00H), 1.99 (s, 2.01H), 1.18−1.24 (m, 6.00H);

13

C {1H} NMR (100 MHz, CDCl3) δ 170.8,

170.4, 168.6, 168.5, 133.0, 131.8, 131.5, 131.4, 129.7, 128.6, 124.0, 123.1, 34.9, 29.8, 19.8, 19.7, 19.5, 19.5; IR (KBr): 2969, 1767, 1597, 1474, 1370, 1201 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. for C12H15BrNO2, 284.0281; found, 284.0283 1-(3-Bromophenyl)-2-Methylpropan-1-One O-Acetyl Oxime (1na): colorless oil; 81% yield (1150.2 mg); E/Z isomer mixtures (E/Z = 64/36); 1H NMR (400 MHz, CDCl3) δ 7.11−7.61 (m, 4.00H), 3.48−3.54 (m, 0.36H), 2.93−3.00 (m, 0.64H), 2.24 (s, 1.34H), 1.99 (s, 1.67H), 1.17−1.24 (m, 6.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 170.6, 169.9, 168.6, 168.5, 136.0, 134.9, 132.6, 132.0, 131.0, 129.8, 129.6, 126.7, 125.6, 122.4, 122.3, 34.9, 29.9, 19.8, 19.7, 19.5, 19.5; IR (KBr): 2968, 1766, 1560, 1462, 1366, 1199 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. for C12H15BrNO2, 284.0281; found, 284.0284 1-(4-Iodophenyl)-2-Methylpropan-1-One O-Acetyl Oxime (1oa): colorless oil; 53% yield (877.2 mg); E/Z isomer mixtures (E/Z = 55/45); 1H NMR (400 MHz, CDCl3) δ 7.71−7.76 (m, 2.00H), 6.90−7.02 (m, 2.00H), 3.50 (hept, J = 6.8 Hz, 0.45H), 2.95 (hept, J = 6.8 Hz, 0.55H), 2.23 (s, 1.30H), 1.98 (s, 1.65H), 1.15−1.22 (m, 6.00H); 13

C {1H} NMR (100 MHz, CDCl3) δ 171.0, 170.6, 168.7, 168.6, 137.5, 137.4, 133.6,

132.4, 129.8, 128.6, 95.9, 95.0, 34.9, 29.8, 19.8, 19.8, 19.6, 19.5; IR (KBr): 2968, 1765, 1587, 1470, 1369, 1199 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. for C12H15INO2, 332.0142; found, 332.0143 2-Methyl-1-(4-(Trifluoromethyl)phenyl)propan-1-One O-Acetyl Oxime (1pa): ACS Paragon Plus Environment

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colorless oil; 61% yield (832.7 mg); E/Z isomer mixtures (E/Z = 54/46); 1H NMR (400 MHz, CDCl3) δ 7.58−7.71 (m, 2.89H), 7.30−7.32 (m, 1.11H), 3.56 (hept, J = 6.8 Hz, 0.46H), 3.02 (hept, J = 6.8 Hz, 0.54H), 2.26 (s, 1.24H), 1.98 (s, 1.66H), 1.18−1.25 (m, 6.00H);

13

C {1H} NMR (100 MHz, CDCl3) δ 170.8, 170.3, 168.6,

168.5, 137.6, 136.7, 131.5 (q, 2JC-F = 32.6 Hz), 131.0 (q, 2JC-F = 32.7 Hz), 128.6, 127.3, 125.2 (q, 3JC-F = 3.5 Hz), 125.2 (q, 3JC-F = 3.8 Hz), 123.8 (q, 1JC-F = 260.5 Hz), 123.8 (q, 1JC-F = 260.5 Hz), 34.9, 29.8, 19.7, 19.6, 19.4, 19.2; IR (KBr): 2973, 1772, 1615, 1463, 1324, 1196, 1127 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. for C13H15F3NO2, 274.1049; found, 274.1051 2-Methyl-1-(Naphthalen-2-yl)propan-1-One O-Acetyl Oxime (1qa): colorless oil; 80% yield (1020.0 mg); E/Z isomer mixtures (E/Z = 55/45); 1H NMR (400 MHz, CDCl3) δ 7.82−7.96 (m, 3.36H), 7.50−7.65 (m, 3.11H), 7.25−7.28 (m, 0.66H), 3.61 (hept, J = 6.0 Hz, 0.45H), 3.10 (hept, J = 6.8 Hz, 0.55H), 2.26 (s, 0.96H), 1.92 (s, 2.05H), 1.21−1.31 (m, 6.00H);

13

C {1H} NMR (100 MHz, CDCl3) δ 171.8, 171.7,

168.9, 168.9, 133.6, 133.2, 132.8, 132.7, 131.6, 130.6, 128.5, 128.3, 128.0, 127.8, 127.7, 127.0, 126.9, 126.6, 126.5, 126.0, 125.1, 124.8, 35.3, 30.3, 26.1, 20.0, 19.7, 19.6; IR (KBr): 2969, 1764, 1606, 1457, 1367, 1201 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. for C16H18NO2, 256.1332; found, 256.1334 2-Methyl-1-(Thiophen-2-yl)propan-1-One O-Acetyl Oxime (1ra): colorless oil; 50% yield (527.5 mg); E/Z isomer mixtures (E/Z = 80/20); 1H NMR (400 MHz, CDCl3) δ 7.37−7.62 (m, 2.00H), 7.04−7.15 (m, 1.00H), 3.49−3.56 (m, 0.20H), 3.25−3.33 (m, 0.80H), 2.24−2.30 (m, 3.00H), 1.32−1.38 (m, 6.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 168.6, 168.2, 165.5, 160.6, 136.4, 131.8, 131.2, 128.9, 128.8, 127.3, 126.3, 33.8, 30.4, 27.2, 21.3, 20.1, 19.5; IR (KBr): 2974, 1771, 1594, 1427, 1367, 1193 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. for C10H14SNO2, 212.0740; found, 212.0742 1-(1-Benzyl-1H-Indol-3-yl)-2-Methylpropan-1-One

O-Acetyl

Oxime

(1sa):

colorless oil; 53% yield (885.1 mg); E/Z isomer mixtures (E/Z = 94/6); 1H NMR (400 MHz, CDCl3) δ 7.62 (d, J = 8.0 Hz, 0.92H), 7.43 (s, 0.98H), 7.17−7.37 (m, 8.39H), 5.38 (s, 1.99H), 3.44 (hept, J = 6.8 Hz, 0.06H), 3.23 (hept, J = 6.8 Hz, 0.94H), 2.34 (s, ACS Paragon Plus Environment


0.16H), 2.03 (s, 2.81H), 1.30−1.34 (m, 6.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 169.3, 165.5, 136.5, 136.2, 129.5, 129.0, 128.0, 126.9, 126.8, 122.6, 121.6, 120.8, 110.2, 108.0, 50.4, 35.2, 20.7, 20.0; IR (KBr): 2923, 1755, 1626, 1457, 1365, 1202 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. for C21H23N2O2, 335.1754; found, 335.1757 2-Methyltetradecan-3-One O-Acetyl Oxime (1ta): colorless oil; 67% yield (948.1 mg); E/Z isomer mixtures (E/Z = 89/11); 1H NMR (400 MHz, CDCl3) δ 3.22−3.30 (m, 0.11H), 2.66−2.72 (m, 0.89H), 2.28−2.32 (m, 2.00H), 2.16−2.16 (m, 3.00H), 1.51−1.54 (m, 2.00H), 1.27−1.32 (m, 16.00H), 1.11−1.17 (m, 6.00H), 0.87−0.90 (m, 3.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 173.4, 169.1, 34.0, 31.9, 30.0, 29.6, 29.4, 29.3, 29.1, 27.7, 26.6, 22.6, 19.8, 19.8, 14.1; IR (KBr): 2930, 2862, 1767, 1457, 1366, 1205 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. for C17H34NO2, 284.2584; found, 284.2587 5-Fluoro-2-Methyl-2,3-Dihydro-1H-Inden-1-One O-Acetyl Oxime (1ua): colorless oil; 63% yield (696.2 mg); E/Z isomer mixtures (E/Z = 64/36); 1H NMR (400 MHz, CDCl3) δ 8.23−8.27 (m, 0.36H), 7.82−7.86 (m, 0.64H), 6.98−7.04 (m, 2.00H), 3.28−3.60 (m, 2.00H), 2.61−2.72 (m, 1.00H), 2.24−2.30 (m, 3.00H), 1.32−1.39 (m, 3.00H); 1

13

C {1H} NMR (100 MHz, CDCl3) δ 171.9, 168.8, 168.6, 168.5, 165.5 (d,

JC-F = 250.6 Hz), 165.2 (d, 1JC-F = 252.9 Hz), 152.1 (d, 3JC-F = 9.3 Hz), 150.7 (d, 3JC-F

= 9.1 Hz), 131.8 (d, 3JC-F = 9.6 Hz), 129.5 (d, 4JC-F = 2.3 Hz), 128.4 (d, 4JC-F = 2.5 Hz), 125.2 (d, 3JC-F = 9.7 Hz), 115.3 (d, 2JC-F = 23.5 Hz), 114.9 (d, 2JC-F = 22.7 Hz), 112.7 (d, 2JC-F = 23.3 Hz), 112.5 (d, 2JC-F = 22.4 Hz), 38.0, 37.8, 37.2, 36.0, 20.1, 19.6, 19.5, 18.7; IR (KBr): 2942, 1765, 1603, 1472, 1356, 1207 cm−1; HRMS (ESI-TOF) m/z: [M+Na]+ Calcd. for C12H12FNO2Na, 244.0744; found, 244.0747 (E)-2-Methyl-3,4-Dihydronaphthalen-1(2H)-One O-Acetyl Oxime (1va): white solid, mp: 96−97 oC; 67% yield (727.0 mg); 1H NMR (400 MHz, CDCl3) δ 8.14 (d, J = 8.0 Hz, 1.00H), 7.30 (t, J = 7.6 Hz, 1.00H), 7.18 (t, J = 7.6 Hz, 1.00H), 7.13 (d, J = 7.6 Hz, 1.00H), 3.55−3.63 (m, 1.00H), 2.91−2.99 (m, 1.00H), 2.64−2.70 (m, 1.00H), 2.24 (s, 3.00H), 1.92−2.01 (m, 1.00H), 1.71−1.77 (m, 1.00H), 1.19 (d, J = 7.2 Hz, 3.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 169.1, 164.7, 139.9, 130.7, 128.8, 128.1, ACS Paragon Plus Environment

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126.4, 126.0, 28.5, 28.2, 24.7, 19.9, 15.6; IR (KBr): 2933, 1762, 1452, 1357, 1205 cm−1; HRMS (ESI-TOF) m/z: [M+Na]+ Calcd. for C13H15NO2Na, 240.0995; found, 240.0998 (E)-1-Phenylethan-1-One O-Acetyl Oxime (1fb): white solid, mp: 54−55 oC; 96% yield (849.6 mg); 1H NMR (400 MHz, CDCl3) δ 7.72−7.73 (m, 2.00H), 7.37−7.40 (m, 3.00H), 2.35−2.37 (m, 3.00H), 2.23−2.25 (m, 3.00H);

13


CDCl3) δ 168.9, 162.4, 134.9, 130.6, 128.6, 127.0, 19.8, 14.3; IR (KBr): 2928, 1761, 1615, 1306, 1196 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. for C10H12NO2, 178.0863; found, 178.0864 1-Phenylpropan-1-One O-Acetyl Oxime (1fc): colorless oil; 88% yield (840.4 mg); E/Z isomer mixtures (E/Z = 87/13); 1H NMR (400 MHz, CDCl3) δ 7.30−7.72 (m, 5.00H), 2.85 (q, J = 7.6 Hz, 1.75H), 2.70 (q, J = 7.6 Hz, 0.25H), 1.99−2.25 (m, 3.00H), 1.08−1.19 (m, 3.00H);

13

C {1H} NMR (100 MHz, CDCl3) δ 169.1, 167.3,

133.8, 130.5, 128.6, 127.2, 21.7, 19.8, 11.3; IR (KBr): 2964, 1765, 1616, 1450, 1361, 1201 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. for C11H14NO2, 192.1019; found, 192.1021 (E)-1,2-Diphenylethan-1-One O-Acetyl Oxime (1fd): colorless oil; 88% yield (1113.2 mg); 1H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 7.6 Hz, 2.00H), 7.32−7.39 (m, 3.00H), 7.26−7.27 (m, 2.00H), 7.17−7.19 (m, 3.00H), 4.22 (s, 2.00H), 2.20 (s, 3.00H); 13

C {1H} NMR (100 MHz, CDCl3) δ 168.7, 163.8, 135.4, 134.1, 130.7, 128.9, 128.7,

128.4, 127.6, 126.8, 34.3, 19.8; IR (KBr): 2938, 1766, 1595, 1444, 1364, 1199 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. for C16H16NO2, 254.1176; found, 254.1177 1,2-Diphenylpropan-1-One O-Acetyl Oxime (1fe): colorless oil; 94% yield (1254.9 mg); E/Z isomer mixtures (E/Z = 60/40); 1H NMR (400 MHz, CDCl3) δ 7.22−7.34 (m, 9.00H), 6.84 (d, J = 7.6 Hz, 1.00H), 4.93 (q, J = 7.2 Hz, 0.40H), 4.18 (q, J = 7.2 Hz, 0.60H), 2.14 (s, 1.27H), 1.96 (s, 1.81H), 1.53−1.57 (m, 3.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 169.4, 169.3, 168.8, 168.5, 140.3, 140.0, 133.7, 132.8, 129.8, 128.8, 128.7, 128.6, 128.5, 128.2, 128.0, 127.9, 127.2, 127.2, 127.0, 126.9, 45.9, 38.8, 19.7, 19.6, 18.2, 16.3; IR (KBr): 2926, 1762, 1609, 1444, 1364, 1194 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. for C17H18NO2, 268.1332; found, 268.1334 ACS Paragon Plus Environment


2-Methyl-1,4-Diphenylbutan-1-One O-Acetyl Oxime (1ff): colorless oil; 75% yield (1106.3 mg); E/Z isomer mixtures (E/Z = 53/47); 1H NMR (400 MHz, CDCl3) δ 7.35−7.49 (m, 4.00H), 7.08−7.26 (m, 6.00H), 3.42 (sextet, J = 7.2 Hz, 0.47H), 2.91 (sextet, J = 6.8 Hz, 0.53H), 2.55−2.76 (m, 2.00H), 1.95−2.16 (m, 4.00H), 1.65−1.91 (m, 1.00H), 1.21−1.29 (m, 3.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 170.7, 170.7, 141.8, 141.4, 134.4, 133.0, 129.7, 129.0, 128.5, 128.4, 128.4, 128.2, 128.1, 126.9, 126.1, 126.0, 39.8, 35.8, 35.5, 35.1, 34.0, 33.4, 19.8, 19.6, 18.0, 17.7; IR (KBr): 2933, 1766, 1609, 1449, 1368, 1203 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. for C19H22NO2, 296.1645; found, 296.1648 Cyclopropyl(phenyl)methanone O-Acetyl Oxime (1fg): colorless oil; 71% yield (720.6 mg); E/Z isomer mixtures (E/Z = 72/28); 1H NMR (400 MHz, CDCl3) δ 7.24−7.40 (m, 5.00H), 2.34−2.39 (m, 0.72H), 2.34 (s, 1.95H), 1.91−1.94 (m, 1.30H), 0.67−1.02 (m, 4.00H);

13

C {1H} NMR (100 MHz, CDCl3) δ 169.2, 169.0, 169.0,

168.6, 132.4, 132.0, 129.5, 129.2, 128.8, 128.1, 128.1, 127.2, 19.8, 19.5, 15.7, 10.8, 6.6, 6.3; IR (KBr): 3020, 1765, 1602, 1366, 1207 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. for C12H14NO2, 204.1019; found, 204.1021 Cyclobutyl(phenyl)methanone O-Acetyl Oxime (1fh): white solid, mp: 92−93 oC; 77% yield (835.5 mg); E/Z isomer mixtures (E/Z = 58/42); 1H NMR (400 MHz, CDCl3) δ 7.23−7.39 (m, 5.00H), 3.87 (quint, J = 9.2 Hz, 0.42H), 3.54 (quint, J = 8.4 Hz, 0.58H), 1.72−2.38 (m, 9.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 170.1, 168.8, 168.6, 168.6, 133.7, 132.9, 129.6, 129.1, 128.3, 128.2, 128.0, 126.9, 40.1, 36.6, 28.6, 26.3, 19.8, 19.6, 19.3, 18.3; IR (KBr): 2961, 1757, 1436, 1364, 1203 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. for C13H16NO2, 218.1176; found, 218.1177 Cyclopentyl(phenyl)methanone O-Acetyl Oxime (1fi): colorless oil; 76% yield (877.8 mg); E/Z isomer mixtures (E/Z = 57/43); 1H NMR (400 MHz, CDCl3) δ 7.18−7.43 (m, 5.00H), 3.51 (quint, J = 8.4 Hz, 0.43H), 3.09 (quint, J = 8.0 Hz, 0.57H), 2.21−2.24 (m, 2.00H), 1.96−2.06 (m, 3.00H), 1.87−1.91 (m, 1.00H), 1.60−1.74 (m, 5.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 171.1, 170.1, 169.0, 168.9, 134.5, 133.7, 129.4, 128.8, 128.2, 128.1, 128.1, 126.8, 45.9, 40.5, 30.4, 30.1, 25.8, 24.9, 19.9, 19.6; IR (KBr): 2955, 1766, 1615, 1367, 1204 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. ACS Paragon Plus Environment

Page 18 of 31

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for C14H18NO2, 232.1332; found, 232.1333 Cyclohexyl(phenyl)methanone O-Acetyl Oxime (1fj): colorless oil; 75% yield (918.8 mg); E/Z isomer mixtures (E/Z = 56/44); 1H NMR (400 MHz, CDCl3) δ 7.14−7.39 (m, 5.00H), 3.21−3.27 (m, 0.44H), 2.63−2.69 (m, 0.56H), 2.02−2.25 (m, 2.00H), 1.62−2.03 (m, 6.00H), 1.15−1.53 (m, 5.00H);

13


CDCl3) δ 171.2, 171.0, 169.0, 168.8, 134.4, 133.3, 129.3, 128.7, 128.1, 128.1, 126.7, 44.7, 40.5, 30.2, 29.4, 26.1, 25.9, 25.8, 19.8, 19.5; IR (KBr): 2929, 2855, 1765, 1444, 1365, 1202 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. for C15H20NO2, 246.1489; found, 246.1491 2-Methyl-1-Phenylpropan-1-One O-Pivaloyl Oxime (1fk): colorless oil; 70% yield (864.5 mg); E/Z isomer mixtures (E/Z = 66/34); 1H NMR (400 MHz, CDCl3) δ 7.13−7.47 (m, 5.00H), 3.50 (hept, J = 7.2 Hz, 0.34H), 3.01 (hept, J = 7.2 Hz, 0.66H), 1.34 (s, 3.00H), 1.19−1.26 (m, 6.00H), 0.99 (s, 6.00H);

13


CDCl3) δ 175.2, 175.0, 173.1, 172.3, 134.2, 133.2, 129.4, 128.6, 128.2, 128.1, 128.0, 126.6, 38.7, 38.3, 34.9, 30.1, 27.3, 27.1, 26.8, 19.8, 19.5; IR (KBr): 2970, 1754, 1619, 1468, 1271, 1113 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. for C15H22NO2, 248.1645; found, 248.1647 2-Methyl-1-Phenylpropan-1-One O-Benzoyl Oxime (1fl): white solid, mp: 51−52 o

C; 47% yield (627.5 mg); E/Z isomer mixtures (E/Z = 70/30); 1H NMR (400 MHz,

CDCl3) δ 8.13 (d, J = 7.2 Hz, 1.00H), 7.60−7.69 (m, 2.00H), 7.41−7.52 (m, 5.00H), 7.24−7.32 (m, 2.00H), 3.67 (hept, J = 6.8 Hz, 0.30H), 3.10 (hept, J = 6.8 Hz, 0.70H), 1.24−1.33 (m, 6.00H);

13

C {1H} NMR (100 MHz, CDCl3) δ 173.1, 172.7, 171.4,

163.9, 134.0, 133.7, 133.3, 133.2, 133.0, 130.2, 129.7, 129.6, 129.5, 129.0, 128.9, 128.6, 128.5, 128.3, 128.2, 126.9, 35.0, 30.4, 19.9, 19.7; IR (KBr): 2970, 1742, 1605, 1454, 1249 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. for C17H18NO2, 268.1332; found, 268.1334 2-Methyl-1-Phenylpropan-1-One Oxime (1fm): white solid, mp: 59−60 oC; 95% yield (774.3 mg); E/Z isomer mixtures (E/Z = 63/37); 1H NMR (400 MHz, CDCl3) δ 8.78 (brs, 1.00H), 7.24−7.43 (m, 5.00H), 3.60 (hept, J = 6.8 Hz, 0.37H), 2.83 (hept, J = 6.8 Hz, 0.63H), 1.12−1.23 (m, 6.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 163.4, ACS Paragon Plus Environment


Page 20 of 31

135.7, 133.7, 128.6, 128.5, 128.2, 128.2, 127.7, 127.6, 34.5, 27.7, 20.1, 19.4; IR (KBr): 3283, 2964, 1761, 1451, 1202 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. for C10H14NO, 164.1070; found, 164.1072

General Procedure for the Internal Oxidants-Triggered Copper-Catalyzed Unstrained C-C Bond Cleavage of Oxime acetates 1: A 25 mL oven-dried test tube equipped with a magnetic stirring bar, CuI (10 mol %), oxime acetate 1 (0.2 mmol), and DMSO (2 mL) was vigorously stirred at 90 oC for 12 h under air. Then the mixture was cooled to room temperature, added water (15 mL), extracted with EtOAc (15 mL × 3). The combined organic phases were dried over anhydrous Na2SO4, filtered and concentrated in vacuo. Further purification by flash column chromatography on silica gel or silica gel preparative plate (eluting with petroleum ether/ethyl acetate = 100/1) provided the product 2 and 3. 4-Methoxybenzonitrile (2a)18a: white solid, mp: 58−59 oC; 88% yield (23.4 mg); 1H NMR (400 MHz, CDCl3) δ 7.57 (d, J = 8.8 Hz, 2.00H), 6.95 (d, J = 8.8 Hz, 2.00H), 3.86 (s, 3.00H);

13

C {1H} NMR (100 MHz, CDCl3) δ 162.9, 133.9, 119.3, 114.8,

103.8, 55.6 3,4-Dimethoxybenzonitrile (2b)18b: white solid, mp: 65−66 oC; 77% yield (25.1 mg); 1

H NMR (400 MHz, CDCl3) δ 7.29 (dd, J = 2.0 Hz, 2.0 Hz, 1.00H), 7.08 (d, J = 2.0

Hz, 1.00H), 6.91 (d, J = 8.4 Hz, 1.00H), 3.94 (s, 3.00H), 3.91 (s, 3.00H);

13

C {1H}

NMR (100 MHz, CDCl3) δ 152.9, 149.2, 126.5, 119.2, 113.9, 111.2, 103.9, 56.1, 56.1 3-Methoxybenzonitrile (2c)18c: colorless oil; 71% yield (18.9 mg); 1H NMR (400 MHz, CDCl3) δ 7.36 (t, J = 8.4 Hz, 1.00H), 7.21 (d, J = 7.6 Hz, 1.00H), 7.11 (d, J = 6.8 Hz, 2.00H), 3.81 (s, 3.00H);

13

C {1H} NMR (100 MHz, CDCl3) δ 159.6, 130.4,

124.4, 119.3, 118.8, 116.9, 113.1, 55.5 4-Methylbenzonitrile (2d)18a: colorless oil; 73% yield (17.1 mg); 1H NMR (400 MHz, CDCl3) δ 7.53 (d, J = 8.0 Hz, 2.00H), 7.27 (d, J = 8.0 Hz, 2.00H), 2.42 (s, 3.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 143.7, 132.1, 129.9, 119.2, 109.3, 21.9 3-Methylbenzonitrile (2e)18c: colorless oil; 71% yield (16.6 mg); 1H NMR (400 MHz, CDCl3) δ 7.39−7.44 (m, 3.00H), 7.35 (q, J = 7.6 Hz, 1.00H), 2.38 (s, 3.00H); 13C {1H} ACS Paragon Plus Environment

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NMR (100 MHz, CDCl3) δ 139.3, 133.7, 132.4, 129.2, 129.0, 119.0, 112.2, 21.1 Benzonitrile (2f)18a: colorless oil; 56% yield (11.5 mg); 1H NMR (400 MHz, CDCl3) δ 7.64 (d, J = 8.0 Hz, 2.00H), 7.61 (t, J = 7.2 Hz, 1.00H), 7.47 (t, J = 7.6 Hz, 2.00H); 13

C {1H} NMR (100 MHz, CDCl3) δ 132.8, 132.1, 129.2, 118.9, 112.4

4-Fluorobenzonitrile (2g)18c: colorless oil; 63% yield (15.2 mg);1H NMR (400 MHz, CDCl3) δ 7.68−7.72 (m, 2.00H), 7.20 (t, J = 8.4 Hz, 2.00H);

13

C {1H} NMR (100

MHz, CDCl3) δ 165.0 (d, 1JF-C = 254.8 Hz), 134.7 (d, 3JF-C = 9.3 Hz), 118.1, 116.8 (d, 2

JF-C = 22.6 Hz), 108.5 (d, 4JF-C = 3.6 Hz)

3-Fluorobenzonitrile (2h)18d: colorless oil; 64% yield (15.5 mg); 1H NMR (400 MHz, CDCl3) δ 7.47−7.52 (m, 2.00H), 7.30 (t, J = 7.6 Hz, 1.00H), 7.24 (t, J = 8.8 Hz, 1.00H); 3

13

C {1H} NMR (100 MHz, CDCl3) δ 163.1 (d, 1JF-C = 257.2 Hz), 135.2 (d,

JF-C = 8.2 Hz), 133.6, 124.9 (d, 4JF-C = 3.7 Hz), 116.5 (d, 2JF-C = 19.2 Hz), 114.0,

101.5 (d, 2JF-C = 15.2 Hz) 2-Fluorobenzonitrile (2i)18e: colorless oil; 65% yield (15.8 mg); 1H NMR (400 MHz, CDCl3) δ 7.63−7.67 (m, 2.00H), 7.32−7.37 (m, 2.00H);

13


CDCl3) δ 162.2 (d, 1JF-C = 248.7 Hz), 131.2 (d, 3JF-C = 8.2 Hz), 128.2 (d, 4JF-C = 3.6 Hz), 120.5 (d, 2JF-C = 20.9 Hz), 119.1 (d, 2JF-C = 24.4 Hz), 117.5 (d, 4JF-C = 3.1 Hz), 113.9 (d, 3JF-C = 9.3 Hz) 4-Chlorobenzonitrile (2j)18a: white solid, mp: 91−92 oC; 71% yield (19.5 mg); 1H NMR (400 MHz, CDCl3) δ 7.60 (d, J = 8.4 Hz, 2.00H), 7.46 (d, J = 8.4 Hz, 2.00H); 13

C {1H} NMR (100 MHz, CDCl3) δ 139.5, 133.4, 129.7, 118.0, 110.8

3,4-Dichlorobenzonitrile (2k)18f: white solid, mp: 72−73 oC; 73% yield (25.1 mg); 1

H NMR (400 MHz, CDCl3) δ 7.75 (s, 1.00H), 7.59 (d, J = 8.4 Hz, 1.00H), 7.52−7.54

(m, 1.00H);

13

C {1H} NMR (100 MHz, CDCl3) δ 138.1, 133.9, 133.7, 131.5, 131.2,

116.8, 112.0 3-Chlorobenzonitrile (2l)18g: white solid, mp: 39−40 oC; 61% yield (16.7 mg); 1H NMR (400 MHz, CDCl3) δ 7.53−7.58 (m, 3.00H), 7.42 (t, J = 8.0 Hz, 1.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 135.1, 133.3, 131.8, 130.6, 130.3, 117.4, 113.9 4-Bromobenzonitrile (2m)18a: white solid, mp: 111−112 oC; 75% yield (27.2 mg); 1H NMR (400 MHz, CDCl3) δ 7.63 (d, J = 8.4 Hz, 2.00H), 7.53 (d, J = 8.4 Hz, 2.00H); ACS Paragon Plus Environment


Page 22 of 31

13

C {1H} NMR (100 MHz, CDCl3) δ 133.5, 132.6, 128.0, 118.1, 111.2

3-Bromobenzonitrile (2n)19a: white solid, mp: 38−39 oC; 63% yield (22.8 mg); 1H NMR (400 MHz, CDCl3) δ 7.77 (s, 1.00H), 7.74 (d, J = 8.4 Hz, 1.00H), 7.61 (d, J = 7.6 Hz, 1.00H), 7.38 (t, J = 8.0 Hz, 1.00H);

13

C {1H} NMR (100 MHz, CDCl3) δ

136.2, 134.7, 130.8, 130.7, 122.9, 117.3, 114.2 4-Iodobenzonitrile (2o)19b: white solid, mp: 120−121 oC; 61% yield (27.9 mg); 1H NMR (400 MHz, CDCl3) δ 7.84 (d, J = 8.4 Hz, 2.00H), 7.37 (d, J = 8.4 Hz, 2.00H); 13

C {1H} NMR (100 MHz, CDCl3) δ 138.5, 133.2, 118.3, 111.7, 100.4

4-(Trifluoromethyl)benzonitrile (2p)18c: colorless oil; 73% yield (25.0 mg); 1H NMR (400 MHz, CDCl3) δ 7.84 (d, J = 8.4 Hz, 2.00H), 7.78 (d, J = 8.0 Hz, 2.00H); 13

C {1H} NMR (100 MHz, CDCl3) δ 134.4 (q, 2JF-C = 33.0 Hz), 132.7, 126.1 (q, 3JF-C

= 3.7 Hz), 123.0 (1, 1JF-C = 271.2 Hz), 117.4, 116.0 2-Naphthonitrile (2q)19c: white solid, mp: 64−65 oC; 74% yield (22.6 mg); 1H NMR (400 MHz, CDCl3) 8.17 (s, 1.00H), 7.84−7.88 (m, 3.00H), 7.55−7.64 (m, 3.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 134.6, 134.2, 132.2, 129.2, 129.1, 128.4, 128.1, 127.7, 126.3, 119.3, 109.3 Thiophene-2-Carbonitrile (2r)18d: colorless oil; 64% yield (14.0 mg); 1H NMR (400 MHz, CDCl3) δ 7.63 (d, J = 4.4 Hz, 2.00H), 7.14 (t, J = 4.4 Hz, 1.00H);

13

C {1H}

NMR (100 MHz, CDCl3) δ 137.5, 132.8, 127.8, 114.3, 109.7 1-Benzyl-1H-Indole-3-Carbonitrile (2s)19d: light yellow solid, mp: 74−75 oC; 64% yield (29.7 mg); 1H NMR (400 MHz, CDCl3) 7.81 (t, J = 4.1 Hz, 1.00H), 7.62 (s, 1.00H), 7.32−7.41 (m, 6.00H), 7.17−7.19 (m, 2.00H), 5.36 (s, 2.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 135.7, 135.3, 135.1, 129.2, 128.0, 127.2, 124.1, 122.3, 120.0, 115.9, 110.9, 86.2, 50.9 2-(3-Oxobutyl)benzonitrile (2v): oil; 23% yield (8.0 mg); 1H NMR (400 MHz, CDCl3) 7.62 (d, J = 7.6 Hz, 1.00H), 7.51 (t, J = 7.6 Hz, 1.00H), 7.36 (d, J = 7.6 Hz, 1.00H), 7.31 (t, J = 7.6 Hz, 1.00H), 3.12 (t, J = 7.6 Hz, 2.00H), 2.85 (t, J = 7.6 Hz, 2.00H), 2.17 (s, 3.00H);

13

C {1H} NMR (100 MHz, CDCl3) δ 206.7, 145.1, 133.0,

130.0, 126.9, 117.9, 112.3, 43.9, 30.0, 28.4; IR (KBr): 3036, 2928, 1711, 1356, 1161 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. for C11H12NO, 174.0913; found, ACS Paragon Plus Environment

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174.0915 Acetophenone (3e)19e: colorless oil; 50% yield (12.0 mg); 1H NMR (400 MHz, CDCl3) 7.95 (d, J = 8.8 Hz, 2.00H), 7.55 (t, J = 7.2 Hz, 1.00H), 7.45 (t, J = 8.0 Hz, 2.00H), 2.59 (s, 3.00H);

13

C {1H} NMR (100 MHz, CDCl3) δ 198.1, 137.1, 133.1,

128.6, 128.3, 26.6 4-Phenylbutan-2-one (3f)19f: colorless oil; 35% yield (10.4 mg); 13C {1H} NMR (400 MHz, CDCl3) 7.27 (t, J = 8.0 Hz, 2.00H), 7.18 (t, J = 7.2 Hz, 3.00H), 2.89 (t, J = 7.6 Hz, 2.00H), 2.74 (t, J = 7.6 Hz, 2.00H), 2.12 (s, 3.00H); 13C NMR (100 MHz, CDCl3) δ 207.9, 141.0, 128.5, 128.3, 126.1, 45.2, 30.1, 29.8

Procedure for the Radical Trapping Experiment: A 25 mL oven-dried test tube equipped with a magnetic stirring bar, CuI (10 mol %), oxime acetate 1fa (0.2 mmol), BHT (0.4 mmol) and DMSO (2 mL) was vigorously stirred at 90 oC for 12 h under air. Then the mixture was cooled to room temperature, added water (15 mL), extracted with EtOAc (15 mL × 3). The combined organic phases were dried over anhydrous Na2SO4, filtered and concentrated in vacuo. Further purification by flash column chromatography on silica gel (eluting with petroleum ether/ethyl acetate = 100/1) provided the product 4. 3-(3,5-Di-tert-Butyl-4-Hydroxyphenyl)-2,2-Dimethyl-1-Phenylpropan-1-one

(4):

white solid, mp: 107−108 oC; 38% yield (27.8 mg); 1H NMR (400 MHz, CDCl3) 7.43 (d, J = 8.0 Hz, 2.00H), 7.39 (d, J = 6.8 Hz, 1.00H), 7.33 (t, J = 7.6 Hz, 2.00H), 6.84 (s, 2.00H), 5.05 (s, 1.00H), 3.00 (s, 2.00H), 1.36 (s, 18.00H), 1.30 (s, 6.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 209.8, 152.4, 139.6, 135.4, 130.6, 128.5, 128.0, 127.6, 126.9, 49.1, 46.8, 34.2, 30.3, 26.4; IR (KBr): 3584, 2961, 1664, 1442, 1223, 1123 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. for C25H35O2, 367.2632; found, 367.2635

Procedure for the synthesis of 5a: A 25 mL round-bottom flask equipped with a magnetic

stirring

bar,

2-hydroxy-2-methyl-1-phenylpropan-1-one

(5

mmol),

NH2OH·HCl (7.5 mmol), NaOAc (10 mmol), EtOH (5 mL), and H2O (5 mL) was ACS Paragon Plus Environment


Page 24 of 31

vigorously stirred at room temperature for 12 h. Then the mixture was added water (15 mL), extracted with EtOAc (30 mL × 3). The combined organic phases were dried over anhydrous Na2SO4, filtered and concentrated in vacuo. Further purification by flash column chromatography on silica gel (eluting with petroleum ether/ethyl acetate = 4/1) provided the product 5a. (E)-2-Hydroxy-2-Methyl-1-Phenylpropan-1-One Oxime (5a): white solid, mp: 109−110 oC; 97% yield (868.2 mg); 1H NMR (400 MHz, CDCl3) 7.40−7.49 (m, 3.00H), 7.25 (d, J = 6.8 Hz, 2.00H), 1.44 (s, 6.00H);

13


CDCl3) δ 163.7, 132.2, 128.6, 128.3, 127.9, 73.2, 28.3; IR (KBr): 3269, 3126, 2928, 1476, 1366, 1177, 990 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. for C10H14NO2, 180.1019; found, 180.1022

Procedure for the synthesis of 5b: A 25 mL round-bottom flask equipped with a magnetic stirring bar, 5a (3 mmol), Ac2O (6 mmol), and CH2Cl2 (5 mL) was vigorously stirred at room temperature for 12 h under N2. Then the mixture was added water (15 mL), extracted with CH2Cl2 (20 mL × 3). The combined organic phases were dried over anhydrous Na2SO4, filtered and concentrated in vacuo. Further purification by flash column chromatography on silica gel (eluting with petroleum ether/ethyl acetate = 10/1) provided the product 5b. (E)-2-Hydroxy-2-Methyl-1-Phenylpropan-1-One O-Acetyl Oxime (5b): white solid, mp: 113−114 oC; 95% yield (629.9 mg); 1H NMR (400 MHz, CDCl3) 7.36−7.38 (m, 3.00H), 7.13−7.15 (m, 2.00H), 4.45 (brs, 1.00H), 1.88 (s, 3.00H), 1.43 (s, 6.00H);

13

C {1H} NMR (100 MHz, CDCl3) δ 172.0, 169.0, 131.8, 128.8, 128.1,

127.0, 73.4, 28.1, 19.4; IR (KBr): 3275, 2980, 1752, 1450, 1370, 1188 cm−1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. for C12H16NO3, 222.1125; found, 222.1127

Supporting Information GC-MS analysis data for control experiments, Copies of 1H and

13

C NMR spectra

data for all the reactants 1 and products. This material is available free of charge via the Internet at http://pubs.acs.org. ACS Paragon Plus Environment

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Acknowledgments The

authors

thank

(2016YFA0602900),

the the

National National

Program Natural

on

Science

Key

Research

Foundation

of

Project China

(21420102003, 21702064), the Pearl River S&T Nova Program of Guangzhou (201806010138), the Guangdong Natural Science Foundation (2016A030310460), and National Undergraduate Innovative and Entrepreneurial Training Program (201810561085) for financial support.

References (1) (a) Murakami, M.; Ito, Y. Cleavage of Carbon-Carbon Single Bonds by Transition Metals. Top. Organomet. Chem. 1999, 3, 97. (b) Jun, C.-H. Transition Metal-Catalyzed Carbon-Carbon Bond Activation. Chem. Soc. Rev. 2004, 33, 610. (c) Park, Y. J.; Park, J.-W.; Jun, C.-H. Metal-Organic Cooperative Catalysis in C-H and C-C Bond Activation and Its Concurrent Recovery. Acc. Chem. Res. 2008, 41, 222. (d) Souillart, L.; Cramer, N. Catalytic C-C Bond Activations via Oxidative Addition to Transition Metals. Chem. Rev. 2015, 115, 9410. (e) Kim, D.-S.; Park, W.-J.; Jun, C.-H. Metal-Organic Cooperative Catalysis in C-H and C-C Bond Activation. Chem. Rev. 2017, 117, 8977. (2) (a) Cleavage of Carbon-Carbon Single Bonds by Transition Metal; Murakami, M., Chatani, N., Ed.; Wiley-VCH: Weinheim, 2015. (b) Murakami, M.; Ishida, N. Potential of Metal-Catalyzed C-C Single Bond Cleavage for Organic Synthesis. J. Am. Chem. Soc. 2016, 138, 13759. (3) (a) Kulinkovich, O. G. The Chemistry of Cyclopropanols. Chem. Rev. 2003, 103, 2597. (b) Rubin, M.; Rubina, M.; Gevorgyan, V. Transition Metal Chemistry of Cyclopropenes and Cyclopropanes. Chem. Rev. 2007, 107, 3117. (c) Seiser, T.; Cramer, N. Enantioselective Metal-Catalyzed Activation of Strained Rings. Org. Biomol. Chem. 2009, 7, 2835. (d) Carson, C. A.; Kerr, M. A. Heterocycles From Cyclopropanes: Applications in Natural Product Synthesis. Chem. Soc. Rev. 2009, 38,



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3051. (e) Seiser, T.; Saget, T.; Tran, D. N.; Cramer, N. Cyclobutanes in Catalysis. Angew. Chem. Int. Ed. 2011, 50, 7740. (f) Gao, Y.; Fu, X.-F.; Yu, Z.-X. In C-C Bond Activation; Dong, G., ed.; Springer: Berlin, 2014, Vol. 346, PP. 195-232. (g) Xu, T.; Dermenci, A.; Dong, G. In C-C Bond Activation; Dong, G., ed.; Springer: Berlin, 2014, Vol.

346,

PP.

133-258.

(h)

Chen,

P.;

Dong,

G.

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