Arylation of

Subscriber access provided by UNIV OF LOUISIANA

Article

Oxone-Mediated Radical C-C Bond Acetmethylation/Arylation of Methylenecyclopropanes and Vinylcyclopropanes with Alpha Alkyl Ketones: Facile Access to Oxoalkyl-Substituted 3,4-Dihydronaphthalenes Yu Liu, Qiao-Lin Wang, Zan Chen, Quan Zhou, Hua Li, Wen-Yuan Xu, Biquan Xiong, and Ke-Wen Tang J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 25 Mar 2019 Downloaded from http://pubs.acs.org on March 25, 2019

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 46 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

The Journal of Organic Chemistry

Oxone-Mediated Radical C−C Bond Acetmethylation/Arylation of Methylenecyclopropanes and Vinylcyclopropanes with Alpha Alkyl Ketones: Facile Access to OxoalkylSubstituted 3,4-Dihydronaphthalenes Yu Liu,* Qiao-Lin Wang, Zan Chen, Quan Zhou, Hua Li, Wen-Yuan Xu, Bi-Quan Xiong, Ke-Wen Tang*

†

Department of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang 414006, China

[email protected] and [email protected]

RECEIVED DATE (to be automatically inserted after your manuscript is accepted if required according to the journal that you are submitting your paper to)

Abstract

ACS Paragon Plus Environment

1

The Journal of Organic Chemistry 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

R1 R2

O +

R4

R3 H

Page 2 of 46

Ag2 SO4 (10 mol %) Oxone (2 equiv) Ar, 90 o C, 24 h

O R2

R3 R1

R4

Ox idati ve r ad ical ri ng-opening/ cycli zat ion str ategy Acet met hyl at ion and ar yl ati on of C -C σ -bond i n MCPs Gener al : 43 ex ampl es, up to 85% yi el d

An efficient oxone-mediated radical carbon-carbon σ–bond acetmethylation/arylation of methylenecyclopropanes with a-C(sp3)–H bonds of ketones is described for the preparation of 2-(2-oxopropyl)-3,4-dihydronaphthalenes. This acetmethylation/arylation undergoes a series of

a-C(sp3)–H bond activation, carbon-carbon double bond acetmethylation, carbon-carbon σ– bond cleavage and cyclization with intramolecular aromatic ring. The experimental result indicates that the carbon-carbon σ–bond acetmethylation/arylation transformation contains a radical process. The difunctionalization method can also be applied to carbon-carbon σ–bond acetmethylation/arylation of vinylcyclopropanes with ketones. This strategy offers an efficient and convenient method for acetmethylation/arylation of carbon-carbon σ–bond with a αcarbonyl radical and an aromatic carbon by one-pot building two new carbon-carbon bonds.

Introduction The direct C–H functionalization is an efficient method for constructing carbon-heteroatom bonds or carbon-carbon bonds.1-3 The C–H functionalization, especially C(sp3)–H functionalization, has attracted much attention from organic synthetic chemists as it is usually used in the preparation of complex


2

Page 3 of 46 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


structures.4-6 Recently, significant advances have been made in functionalization of a-C(sp3)–H bonds in ketones, nitrile, ethers, alcohols, amines, alkanes, and other activated compounds.7 Acetone, a widely used solvent, is a common starting material in organic synthesis for the building of new chemical bonds via activation and functionalization of a-C(sp3)–H bonds.8 Products from these processes are really important skeletons and useful intermediates in medicinal chemistry and pharmaceutical synthesis.9 Thus, as shown in Scheme 1, much attention have been paid to develop efficient strategies for the activation and functionalization of a-C(sp3)–H bonds of acetone.10 In 2016, Ji et al. developed the copper-mediated functionalization of a-C(sp3)–H bonds of acetone with unactivated alkenes for constructing highly functionalized fluorine derivatives (path I).10a In 2018, Yu’s group also developed the acetmethylation/arylation of unactivated alkenes with a-C(sp3)–H bonds of acetone for building 3-(3-oxobutyl)indolines under metal- and acid-free conditions (path II).10b In the same year, Yu et al. presented the functionalization of a-C(sp3)–H bonds of acetone with o-acyloximes and quinines for accessing 6H-benzo[c]chromenes in the presence of Rh(III) catalyst (path III).10c In 2017, Kwong et al. reported the palladium/norbornene cooperative mediated monoarylation of aC(sp3)–H bonds in acetone with aryl iodides for constructing a-(aminoaryl)-substituted acetones (path IV).10d In 2018, Chen’s group reported the TBAI-mediated cross-dehydroenative-coupling (CDC) of acetone with β-carbonyl compounds for constructing 2-carbonyl-1,4-diketones under mild conditions (path V).10e In 2016, Xu et al. developed the KI-mediated acyloxylation of a-C(sp3)–H bonds in acetone with carboxylic acids to construct α-acyloxycarbonyl compounds (path VI).10f


3


O

R1 R2

O R N Ac

R R1

O

N Ac

R

O

LPO, 100 path II AcO N O

R

R1

O

H R2

OH

H

oC

O

Ar 1

R3

O

KI, K2 S2O8 , K2 HPO4 H2 O, 80 o C, 12 h path VI

or

R2

R 4 R3 N O

N 3 R4 R (when R 1 = H) O Ar 2

O

COOH

O

O

Ar 1

O

R

[Cp*RhCl2 ]2 /AgSbF6 Zn(NTf2 )2 EtOH/Acetone, 70 oC path III

R1

O Ar2

TBHP (70% in water) TBAI, 50 o C, 2 h path V

R2

+

BzO

N + R2 R4 I Pd(OAc) 2, P(2-furyl)3, Cs 2 CO 3 N 3 norbornene, 100 o C, 18 h R4 R path IV

R Cu(OTf)2 , Phen, K2 CO3 DTBP, 140 oC, 19 h path I

R

Page 4 of 46

R

O O

Scheme 1. Selected Reactions for the Direct Functionalization of a-C(sp3)–H Bonds of Acetone Carbon-carbon σ–bonds are stable covalent bonds and exist universally in most of organic molecules and drug molecules. As the carbon-carbon σ–bonds are more stable than carbon–carbon π–bonds, thus, the carbon-carbon σ–bond activation is a challenging task and attracts continuing interest.11 In recent years, the activation and functionalization of carbon-carbon σ–bond have become a hot topic because they provide simple and convenient ways for accessing complex biological scaffolds and important natural products.12 Organic chemists have developed numerous carbon-carbon σ–bonds activation protocols by using transition-metal catalysts.13 In view of the high cost and environmental pollution, a number of oxidative carbon-carbon σ–bond functionalization strategies have also been recently presented and also been applied to a lot of different substrates.14-15 The activation and difunctionalization of C–C σ–bonds in three-16 and four-membered17 carbocyclic compounds would be highly interesting. Methylenecyclopropanes (MCPs) are a class of important starting materials in organic synthesis.18 In recent years, a lot of novel methods for radical carbon-carbon σ–bonds difunctionalization of MCPs were reported.19-20 Several kinds of radicals, including CF3,19a SCF3,19b alkyl,19c acyl19d and sulfonyl19eACS Paragon Plus Environment

4

Page 5 of 46 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


containing radicals, were used into the radical carbon-carbon σ–bonds difunctionalization for accessing various 2-substituted 3,4-dihydronaphthalenes (above in Scheme 2). However, strategies for radical carbon-carbon σ–bonds difunctionalization of MCPs with a-C(sp3)–H bond of acetone are lacking. Herein,

we

develop

a

oxone-mediated

novel

radical

carbon-carbon

σ–bond

acetmethylation/arylation of methylenecyclopropanes protocol for constructing 2-(2-oxopropyl)3,4-dihydronaphthalene, achieving by silver promoting21 acetmethylation/arylation of carbon-carbon σ–bonds in MCPs with a α-carbonyl radical and an aromatic carbon (below in Scheme 2). Previous work: R1 +

R2

R

R2

R R1

R = CF 3, SCF3 , alkyl, acryl, sulfonyl-containing radicals This work: R1 R2

O +

R4

R3 H

O

Ag2SO 4 (10 mol %), Oxone (2 equiv) Ar, 90 oC, 24 h

R2

R3 R1

R4

Scheme 2. Oxidative Radical C–C σ–Bonds Difunctionalization in MCPs

Results and discussion Initially, we investigated the C–C σ–bonds acetmethylation/arylation reaction between o’benzyloxyphenyl-substituted MCP 1a and acetone 2a to determine the best reaction conditions (Table 1). The difunctional product 3aa was obtained in 61% yield when the difunctionalization reaction between substrate 1a and acetone 2a was performed in the presence of oxone (KHSO5, 2 equiv) at 90 oC for 24 h (entry 1). Based on the previous literature, silver salts could improve the reaction.21 Thus, a series of ACS Paragon Plus Environment

5


Page 6 of 46

silver salts, including AgOTf, AgOAc, AgNO3, Ag2CO3, AgSCN and Ag2SO4, could accelerate this transformation and Ag2SO4 showed the highest catalytic activity (entries 2–7). Decrease the amount of Ag2SO4 from 10 mol % to 5 mol % led to a lower yield of the desired product 3aa (entry 8). The product yield did not increase when 20 mol % of Ag2SO4 was utilized (entry 9). A number of other oxidants, such as K2S2O8, PhI(OAc)2, BPO, TBHP, DTBP, TBPB, and CHP were subsequently tested (entries 10–16).3f, 4i, 5c, 6b The results suggested that K2S2O8 showed lower reactivity than oxone, the reaction still furnished product 3aa in 73% yield (entry 10). However, other oxidants, such as PhI(OAc)2, BPO, TBHP, DTBP, TBPB and CHP, were not suitable for this transformation (entries 11– 16). Using BPO in this reaction resulted in complete decomposition of the starting material (entry 12). Different amount of oxone was also examined and the results indicated that 2 equiv of oxone gave the best result (entry 9 vs. entries 17–18). The investigation of different reaction temperatures suggested that lower temperature (70 oC) and higher temperature (110 oC) were inappropriate temperatures (entries 19–20). Conducting the reaction for 36 h afforded the similar yield as the reaction for 24 h (Entry 21). Other solvents (toluene, THF, DMF) were also tested in the presence of acetone (50 equiv) as the reactant, and using THF as solvent generated the product 3aa in 35% yield (entries 22–24). Additionally, the amplified experiment (1 g scale of substrate 1a) could also afford the difunctional product 3aa in moderate yield (entry 25).


6

Page 7 of 46 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


Table 1. Screening Optimal Conditionsa

O +

H

OBn 1a

O

Ag2 SO4 , Oxone OBn

2a

AgOTf (10)

Oxidant (eqiuv) Oxone (2) Oxone (2)

T (oC) 90 90

t (h) 24 24

Yield (%)b 61 68

3

AgOAc (10)

Oxone (2)

90

24

63

4

Oxone (2)

90

24

75

5 6 7 8 9 10

AgNO3 (10) Ag2CO3 (10) AgSCN (10) Ag2SO4 (10) Ag2SO4 (5) Ag2SO4 (20) Ag2SO4 (10)

K2S2O8 (2)

90 90 90 90 90 90

24 24 24 24 24 24

66 62 81 73 82 73

11

Ag2SO4 (10)

PhI(OAc)2 (2)

90

24

23

12c

Ag2SO4 (10)

BPO (2)

90

24

0

13

Ag2SO4 (10)

TBHP (2)

90

24

24

14

Ag2SO4 (10)

DTBP (2)

90

24

13

15

Ag2SO4 (10)

TBPB (2)

90

24

24

16

Ag2SO4 (10)

Entry 1 2

[Cat.] (mol %) —

Oxone (2) Oxone (2) Oxone (2) Oxone (2) Oxone (2)

90 24 28 CHP (2) 17 Ag2SO4 (10) Oxone(3) 90 24 80 18 Ag2SO4 (10) Oxone(1) 90 24 51 19 Ag2SO4 (10) Oxone (2) 70 24 45 20 Ag2SO4 (10) Oxone (2) 110 24 74 21 Ag2SO4 (10) Oxone (2) 90 36 82 d 22 Ag2SO4 (10) Oxone (2) 90 24 26 e 23 Ag2SO4 (10) Oxone (2) 90 24 35 24f Ag2SO4 (10) Oxone (2) 90 24 18 g 25 Ag2SO4 (10) Oxone (2) 90 24 74 a Reaction conditions: 1a (0.2 mmol), 2a (2 mL), [Cat.] (10 mol %), and oxidant (0.4 mmol, 2 equiv) at 90 oC in an argon atmosphere for 24 h. b Isolated yield. c Over 85% of raw material 1a was recovered, and the rest was decomposed. d acetone (50 equiv) and toluene (1 mL). e acetone (50 equiv) and THF (1 mL). f acetone (50 equiv) and DMF (1 mL). g 1a (1g, 4.23 mmol) and solvent (20 mL) for 60 h.


7


Page 8 of 46

Based on the established standard reaction conditions, the scope of MCPs 1 and ketones 2 was screened (Table 2). Firstly, various substituted substrates 1 were used to react with acetone (2a). A series of aryl-substituted MCPs (1b−w, R1 = H) were able to undergo the acetmethylation/arylation to give 2-(2-oxopropyl)-3,4-dihydronaphthalenes 3 in satisfactory yields (products 3ba−wa). The steric effect of the monosubstituted phenyl rings affected the transformation and the reactivtity order of substrates is para > meta > ortho (products 3ba–3pa). To our delight, MCP 1e with an ortho-phenylethynyl substituted phenyl ring also underwent acetmethylation/arylation smoothly to provide the target product 3ea in 60% yield. To our surprise, MCP 1f with a meta-benzyloxy substituted phenyl group reacted with acetone 2a smoothly and generated the single product 3fa in 78% yield. The product 3fa’ could not be obtained due to its low yield. However, other two meta-substituted MCPs 1g−h could undergo this transformation to afford two isomers 3ga/3ga’ (3 : 1) and 3ha/3ha’ (7 : 3) in moderate yields. The yield of this acetmethylation/arylation process was also affected by the electronic effect and the substrates 1 with electron-withdrawing substituted aryl groups gave lower yields than that with electron-donating aryl groups (products 3ia–pa). The electron-withdrawing groups on the aromatic rings decreased the electron density of C=C bonds and aromatic rings, which resulted in the addition of radicals to the C=C bonds and the intramolecular cyclization more difficult. MCP 1q with a disubstituted aryl group was compatible for this transformation in the presence of acetone 2a, Ag2SO4, and oxone at 90 oC under


8

Page 9 of 46 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


argon atmosphere for 24 h, and two isomers 3qa (1-(6,7-dimethoxy-3,4-dihydronaphthalen-2yl)propan-2-one)

and

3qa’

(1-(5,6-dimethoxy-3,4-dihydronaphthalen-2-yl)propan-2-one)

were

obtained in 68% yield (1 : 1). Most importantly, this transformation also tolerated halogen groups, including Br, Cl and F groups, which could provide possibility for further transformation at the halogen substituted position (products 3ra–va). Table 2. The carbon-carbon σ–Bond Acetmethylation/Arylation of MCPs (1) and Ketones (2) a

R1

O +

R2 1

H

O R3

R4 2a

Ag2 SO4 (10 mol %), Oxone (2 equiv) Ar, 90 o C, 24 h

R2

R3 R1 3

R4


9


R= R= R= R=

O

R

Page 10 of 46

OBn

OMe, 3ba, 73% CN, 3ca, 52% NO 2, 3da, 47% phenylethynyl, 3ea, 60%

O

OMe

NO2 O

O

O

O

MeO

O2 N

3ga

3ga'

3ha

77%, 3ga /3ga' = 3 : 1 R

R = OBn, 3fa, 78%

R= R= R= R= R = OBn, 3ia, 85% R = R = OMe, 3ja, 81% R = O

3ha' 3ha 3ha' 56%, / =7:3 OMe

Me, 3ka , 75% MeO Ph, 3la, 79% Cl, 3ma, 70% CN, 3na, 63% MeO CF3 , 3oa, 60% NO 2, 3pa, 54%

MeO

O

O

3qa

3qa' 68%, 3qa/3qa' = 1 : 1 F

F

O

Br

O

Br

3ra, 66%

Cl

O

Br

3sa, 70%

O

Br

3ta, 72%

3ua, 68%

O O

Br R1

O

O

O

O 3wa, 74%

3va, 52% O

3xa, 0%

R 1 = R 2 = H, 3za, 84% R 1 = R 2 = Me, 3aaa, 82% R 1 = R 2 = F, 3aba, 78% R 1 = R 2 = Cl, 3aca, 81% R 1 = R 2 = Br, 3ada , 74%

3ya, 61% O

O Et

Ph 3zb

Ph 3zb' 63%, 3zb/3zb' = 1 : 1

R2 O

O

O

O Ph

Ph 3zc, 57%

Ph 3zd, 0%

Ph 3ze, 50%

Ph 3zf, 46%

a

Reaction conditions: 1 (0.2 mmol), 2 (2 mL), Ag2SO4 (10 mol %), and oxone (0.4 mmol, 2 equiv) at 90 oC in an argon atmosphere for 24 h. Interestingly, using MCP 1w (a phenyl-substituted MCP) in the reaction led to the difunctional product in 74% yield (product 3wa). Methylenecyclobutane 1x (MCB) failed to furnish the product 3xa. However, MCP 1y (R1 = Me) was compatible with this reaction system (product 3ya). Next, diaryl substituted MCPs 1z–ad (R1 = Ar) were used in this carbon-carbon σ–bond acetmethylation/arylation and the difunctional products 3za–ada could be obtained in good yields. Subsequently, we examined the scope of ketones 2 for the radical carbon-carbon σ–bonds acetmethylation/arylation reaction. A series of common ketones such as butan-2-one (2b), ACS Paragon Plus Environment

10

Page 11 of 46 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


cyclopropyl methyl ketone (2c), acetophenone (2d), cyclobutanone (2e) and cyclopentanone (2f) were used to react with MCP 1z in the presence of Ag2SO4 and oxone. To our delight, butan-2-one (2b) reacted smoothly with MCP 1z to generate 1-(1-phenyl-3,4-dihydronaphthalen-2-yl)butan-2-one (3zb) and 3-(1-phenyl-3,4-dihydronaphthalen-2-yl)butan-2-one (3zb’) in 1 : 1, and the total yield was 63%. The ratio of these two isomers depended on the stabilities and steric hindrance properties of the two different radical intermediates, which generated from the cleavage of two different a-C(sp3)–H bonds in butan-2-one (2b). To our surprise, cyclopropyl methyl ketone (2c) could undergo this carbon-carbon σ–bonds acetmethylation/arylation process and only the single product 3zc was obtained in 57% yield (product 3zc). Another tertiary carbon radical addition product could not be obtained, the reason maybe that the large steric hindrance of the tertiary carbon radical, albeit it could form easily and had high stability. However, acetophenone (2d) was not suitable substrate for this reaction (product 3zd). The reason maybe that the a-C(sp3)–H bond of acetophenone was inert and the

α-carbonyl radical could not generate easily. Subsequently, the cyclic ketones 2e (cyclobutanone) and 2f (cyclopentanone) were tested and produced the corresponding product 3ze and 3zf in 50% and 46% yields, respectively. Additionally, the N, N-dimethylacetamide, and cyclohexanone were examined under the optimal conditions instead of acetone. However, none of them furnished the desired product 3 and most of MCP 1z was recovered. Table 3. The C−C σ–Bond Acetmethylation/Arylation of cyclopropyl olefins (4) and Ketones (2) a


11


Page 12 of 46 R4 R3

O + H

R

R3

Ag 2SO 4 (10 mol %), Oxone (2 equiv) Ar, 90 oC, 24 h

R4 2

4

5

O

O F

O Cl

5ba, 80%

5aa, 77%

O R

O Br

5ca, 74%

5da, 68%

Ph

5ab, 71%

O

O

O

5ad, 0%

5ae, 0%

O

5ag, 52%

a

Reaction conditions: 4 (0.2 mmol), 2 (2 mL), Ag2SO4 (10 mol %), and oxone (0.4 mmol, 2 equiv) at 90 oC in an argon atmosphere for 24 h. This radical carbon-carbon σ–bonds acetmethylation/arylation method was also applied to difunctionalization of cyclopropyl olefins (4) with ketones (2). A series of substituted cyclopropyl olefins (4a–d) were first used to react with acetone 2a and successfully provided the products 5aa–da, respectively. Several ketones, such as butan-2-one (2b), acetophenone (2d), cyclobutanone (2e) and 3methylbutan-2-one (2g) were examined under the standard conditions in the presence of (1cyclopropylvinyl)benzene 4a, Ag2SO4 and oxone. Only butan-2-one (2b) and 3-methylbutan-2-one (2g) could afford the corresponding product 5ab and 5ag in moderate yields. To our surprise, only the presented products, which generated from the addition of secondary carbon radical or tertiary carbon radical to the double bond, were obtained. In these transformations, the effect of radical stability was more important than that of the radical steric hindrance property. The steric hindrance of radical addition to the double bond in cyclopropyl olefins (4) was much less than that of radical


12

Page 13 of 46 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


addition to the double bond in MCPs (1). Thus, in this reaction, the reactive position mainly depended on the stability of the radical intermediate.

To investigate the mechanism of this carbon-carbon bond acetmethylation/arylation process, several control experiments were conducted (Scheme 3). Based on the previously reported literature, it is supposed that this acetmethylation/arylation reaction contained a radical process.10,19−21 Hence, the radical carbon-carbon σ–bonds acetmethylation/arylation of MCP 1a with acetone 2a was carried out in the presence of several radical inhibitors, including TEMPO, BHT or 1,1-diphenylethylene (eq 1). The results indicated that the reaction was obviously suppressed (eq 1). These experimental results suggested that a radical process was definitely contained in the transformation.12 A KIE (kinetic isotope effect, kH/kD = 2) implied that the activation and cleavage of a-C(sp3)–H bond in acetone was a ratelimiting step (eq 2, Scheme 3)3d−g,6b,19d. Scheme 3. Control Experiments.

Ag 2SO4 (10 mol %) Oxone (2 equiv) Ar, 90 o C, 24 h

O + OBn 1a

1a

acetone 2a + acetone-D6 2a-D6

3aa Ag2 SO 4 (10 mol %) Oxone (2 equiv) Ar, 90 o C, 24 h kH/ D = 2.0

quencher TEMPO BHT 1,1-diphenylethylene

OBn

2a

+ OBn

O

O

H(D)

H(D) OBn (D)H H(D) H(D)

3aa 88% (1) 36% 41% 28%

(2)

3aa + 3aa-D5 = 78%

Based on the presented results and reported literature,10, 19−23 a possible mechanism was presented for the carbon-carbon bond acetmethylation/arylation process (Scheme 4). Under


13


Page 14 of 46

heating conditions, oxone (KHSO5) decomposes into hydroxyl ion and sulfate radical, which facilitates by Ag(I) catalyst via single electron transfer (SET).22a,23a In this process, Ag(I) transforms into Ag(II). Next, the addition of the α-carbonyl radical A, which forms from acetone 2a under the action of sulfate radical,23 to the double bond of MCP 1a leads to the stable intermediate B. Subsequently, the intermediate B undergoes carbon-carbon bond cleavage to afford the intermediate C, which occurs cyclization with intramolecular aromatic ring to afford the intermediate D. Next, the intermediate D undergoes deprotonation to generate the product 3aa by the oxidation of Ag(II), which can generate from Ag(I) by the action of sulfate radical (path I).21 The last hydrogen abstraction step can also be conducted directly by SO4•−, which comes from the decomposition of HSO5- (path II).19e This path is definitely contained in the aromatization step, as Ag2SO4 is not used in the reaction, the acetmethylation/arylation product 3aa can also be obtained. Scheme 4. Possible Mechanisms.


14

Page 15 of 46 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

The Journal of Organic Chemistry Ag(I)

HOOSO3

OH + SO4

+ Ag(II) O H

OBn 1a

OBn

B

O

O OBn C

O

HSO4

H 2a

A SO 4

Ag(I)

SO4 2-

Ag(II)

H

O

pat h I

O

path I I

OBn 3aa

HSO4

OBn D

SO 4

Conclusions

In conclusion, we have presented a novel oxone-mediated radical carbon-carbon σ–bond acetmethylation/arylation of methylenecyclopropanes with a-C(sp3)–H bonds of ketones for constructing diverse 2-(2-oxopropyl)-3,4-dihydronaphthalenes under mild conditions. This radical carbon-carbon σ–bond acetmethylation/arylation proceeds via a sequence of a-C(sp3)– H bond activation, carbon-carbon double bond acetmethylation, carbon-carbon σ–bond cleavage and cyclization with intramolecular aromatic ring, and the experiment result suggests that the

carbon-carbon

difunctionalization

σ–bond method

acetmethylation/arylation can

also

be

contains

applied

to

a

radical

process.

carbon-carbon

The

σ–bond


15


Page 16 of 46

acetmethylation/arylation of cyclopropyl olefins with ketones. This strategy offers an efficient and convenient method for acetmethylation/arylation of carbon-carbon σ–bond with a αcarbonyl radical and an aromatic carbon by one-pot building two new carbon-carbon bonds. Further

application

of

a-C(sp3)–H

bond

activation

and

carbon-carbon

σ–bond

difunctionalization is currently underway in our laboratory.

Experimental Section General Considerations: The 1H and 13C NMR spectra were recorded in CDCl3 solvent on a NMR spectrometer using TMS as internal standard. LRMS was performed on a GC-MS instrument and HRMS was measured on an electrospray ionization (ESI) apparatus using time-of-flight (TOF) mass spectrometry. Melting points are uncorrected. Preparation of MCPs 1 and cyclopropyl olefins 4: MCPs 119-20 and cyclopropyl olefins 419f were synthesized according to the literatures. MCPs 1a, 1b, 1d, 1h, 1i, 1j, 1k, 1l, 1m, 1z;19b 1c, 1f, 1n, 1x;19a 1p, 1q, 1s, 1t, 1u, 1v;19c 1o, 1w, 1aa, 1ab, 1ac;20a 1y;20b 1g, 1r;20c and 1e20d were reported in previous literatures, MCP 1ad was reported for the first time and its physical data and spectroscopic were presented as follow:


16

Page 17 of 46 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


4,4'-(cyclopropylidenemethylene)bis(bromobenzene) (1ad): Yield: 2244.4 mg, 62%; yellow solid, mp 99.2 oC (uncorrected); 1H NMR (400 MHz, CDCl3) : 7.45 (d, J = 8.4 Hz, 4H), 7.27 (d, J = 8.4 Hz, 4H), 1.40 (s, 4H); 13C {1H}NMR (100 MHz, CDCl3) δ: 139.2, 131.3, 129.8, 128.2, 125.8, 121.0, 3.67; HRMS (ESI-TOF) m/z: C16H1379Br2 (M + H)+ calcd for 362.9379, found 362.9383. Typical

Experimental

Procedure

for

the

Synthesis

of

2-(2-oxopropyl)-3,4-

dihydronaphthalene and amplified experiment: To a Schlenk tube were added MCPs 1 (0.2 mmol), ketones 2 (2 mL), Ag2SO4 (0.02 mmol, 10 mol %) and oxone (0.4 mmol, 2 equiv). Then the tube was stirred at 90 oC (oil bath temperature) in argon atmosphere for 24 hour until complete consumption of starting material as monitored by TLC and/or GC-MS analysis. After the reaction was finished, the reaction mixture was filtered, organic layer was dried over Na2SO4. Then removal of the solvent, the crude product was purified by column chromatography (petroleum ether/ethyl acetate, 10 : 1 to 5 : 1) to provide the desired products 3. An amplified experiment conducted in the presence of MCP 1a (2 g, 8.47 mmol), acetone 2a (50 mL), Ag2SO4 (10 mol %) and oxone (2 equiv) at 90 oC

under argon atmosphere for 96 h could successfully afford the desired product 3aa in 68%

yield (1681.8 mg). ACS Paragon Plus Environment

17


Page 18 of 46

1-(8-(benzyloxy)-3,4-dihydronaphthalen-2-yl)propan-2-one (3aa): Yield: 47.3 mg, 81%; yellow oil; 1H NMR (400 MHz, CDCl3) δ: 7.45-7.37 (m, 4H), 7.35-7.31 (m, 1H), 7.06 (t, J = 8.0 Hz, 1H), 6.81 (s, 1H), 6.76 (t, J = 7.6 Hz, 2H), 5.07 (s, 2H), 3.30 (s, 2H), 2.81 (t, J = 8.0 Hz, 2H), 2.24 (t, J = 8.0 Hz, 2H), 2.19 (s, 3H);

13C

{1H}NMR (100 MHz, CDCl3) δ: 207.0, 153.7,

137.3, 136.1, 133.5, 128.5, 127.8, 127.3, 127.3, 123.2, 120.6, 120.2, 110.2, 70.2, 53.0, 29.2, 28.2, 26.7; HRMS (ESI-TOF) m/z: C20H21O2 (M + H)+ calcd for 293.1536, found 293.1542.

1-(8-methoxy-3,4-dihydronaphthalen-2-yl)propan-2-one (3ba): Yield: 31.6 mg, 73%; yellow oil; 1H NMR (400 MHz, CDCl3) δ: 7.09 (t, J = 8.0 Hz, 1H), 6.73 (t, J = 8.0 Hz, 3H), 3.83 (s, 3H), 3.31 (s, 2H), 2.80 (t, J = 8.0 Hz, 2H), 2.25-2.18 (m, 5H);

13C

{1H}NMR (100 MHz, CDCl3) δ:

207.0, 154.5, 135.9, 133.4, 127.3, 122.8, 120.5, 119.9, 108.7, 55.4, 53.0, 29.2, 28.2, 26.7; HRMS (ESI-TOF) m/z: C14H17O2 (M + H)+ calcd for 217.1223, found 217.1229.

7-(2-oxopropyl)-5,6-dihydronaphthalene-1-carbonitrile (3ca): Yield: 22.0 mg, 52%; yellow oil; 1H

NMR (400 MHz, CDCl3) δ: 7.37 (d, J = 7.6 Hz, 1H), 7.24 (d, J = 7.6 Hz, 1H), 7.10 (t, J = 7.6

Hz, 1H), 6.64 (s, 1H), 3.34 (s, 2H), 2.80 (t, J = 8.0 Hz, 2H), 2.25 (t, J = 8.0 Hz, 2H), 2.17 (s, 3H); 13C {1H}NMR (100 MHz, CDCl3) δ: 205.5, 139.9, 136.9, 135.6, 131.5, 130.4, 126.9, 123.0,


18

Page 19 of 46 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


117.9, 108.2, 52.4, 29.7, 27.6, 26.8; HRMS (ESI-TOF) m/z: C14H14NO (M + H)+ calcd for 212.1070, found 212.1077.

1-(8-nitro-3,4-dihydronaphthalen-2-yl)propan-2-one (3da): Yield: 21.7 mg, 47%; yellow oil; 1H

NMR (400 MHz, CDCl3) δ: 7.72 (d, J = 8.4 Hz, 1H), 7.35 (s, 1H), 7.22 (d, J = 8.0 Hz, 1H),

6.92 (s, 1H), 3.41 (s, 2H), 2.90 (t, J = 8.0 Hz, 2H), 2.30 (t, J = 8.0 Hz, 2H), 2.24 (s, 3H);

13C

{1H}NMR (100 MHz, CDCl3) δ: 205.7, 146.2, 140.5, 137.5, 131.9, 128.0, 126.6, 122.7, 120.9, 52.8, 29.6, 28.2, 26.3; HRMS (ESI-TOF) m/z: C13H14NO3 (M + H)+ calcd for 232.0968, found 232.0976.

1-(8-(phenylethynyl)-3,4-dihydronaphthalen-2-yl)propan-2-one (3ea): Yield: 34.3 mg, 60%; yellow oil; 1H NMR (400 MHz, CDCl3) δ: 7.5- 7.53 (m, 2H), 7.38-7.35 (m, 4H), 7.10-7.08 (m, 2H), 6.93 (s, 1H), 3.37 (s, 2H), 2.81 (t, J = 8.0 Hz, 2H), 2.29 (t, J = 8.0 Hz, 2H), 2.24 (s, 3H); 13C

{1H}NMR (100 MHz, CDCl3) δ: 206.5, 136.3, 135.2, 134.8, 131.5, 130.2, 128.4, 128.2,

127.5, 126.4, 124.7, 123.4, 119.2, 93.4, 87.6, 52.9, 29.4, 28.2, 27.0; HRMS (ESI-TOF) m/z: C21H19O (M + H)+ calcd for 287.1430, found 287.1435.

1-(5-(benzyloxy)-3,4-dihydronaphthalen-2-yl)propan-2-one (3fa): Yield: 45.6 mg, 78%; yellow oil; 1H NMR (400 MHz, CDCl3) δ: 7.44 (d, J = 7.2 Hz, 2H), 7.39 (t, J = 7.6 Hz, 2H), 7.33 (d, J =7.2 Hz, 1H), 7.10 (t, J = 8.0 Hz, 1H), 6.81 (d, J = 8.0 Hz, 1H), 6.69 (t, J = 7.6 Hz, 1H), ACS Paragon Plus Environment

19


Page 20 of 46

6.33 (s, 1H), 5.08 (s, 2H), 3.28 (s, 2H), 2.91 (t, J = 7.6 Hz, 2H), 2.26 (t, J = 8.4 Hz, 2H), 2.20 (s, 3H);

13C

{1H}NMR (100 MHz, CDCl3) δ: 206.7, 155.3, 137.4, 135.3, 134.6, 128.5, 127.8,

127.2, 126.7, 126.4, 122.6, 119.1, 111.1, 70.1, 52.7, 29.3, 26.7, 20.4; HRMS (ESI-TOF) m/z: C20H21O2 (M + H)+ calcd for 293.1536, found 293.1542.

1-(7-methoxy-3,4-dihydronaphthalen-2-yl)propan-2-one (3ga): Yield: 33.3 mg, 77%; yellow oil; 1H NMR (400 MHz, CDCl3) δ: 7.12 (t, J = 8.0 Hz, 1H), 6.75 (d, J = 8.0 Hz, 1H), 6.67 (d, J = 7.6 Hz, 1H), 6.32 (s, 1H), 3.83 (s, 3H), 3.27 (s, 2H), 2.83 (t, J = 8.4 Hz, 2H), 2.25 (t, J = 8.4 Hz, 2H), 2.20 (s, 3H);

13C {1H}NMR

(100 MHz, CDCl3) δ: 206.8, 156.1, 135.1, 134.5, 126.7, 126.4,

122.0, 118.8, 109.6, 55.5, 52.7, 29.3, 26.7, 20.2; HRMS (ESI-TOF) m/z: C14H17O2 (M + H)+ calcd for 217.1223, found 217.1229.

1-(5-methoxy-3,4-dihydronaphthalen-2-yl)propan-2-one (3ga’): Yield: 33.3 mg, 77%; yellow oil; 1H NMR (400 MHz, CDCl3) δ: 7.02 (d, J = 8.4 Hz, 1H), 6.68 (s, 1H), 6.60-6.59 (m, 1H), 6.31 (s, 1H), 3.79 (s, 3H), 3.28 (s, 2H), 2.77 (t, J = 8.0 Hz, 2H), 2.26 (t, J = 8.0 Hz, 2H), 2.21 (s, 3H);

13C

{1H}NMR (100 MHz, CDCl3) δ: 206.7, 158.3, 135.2, 135.1, 128.0, 126.7, 126.6,

111.8, 111.6, 55.3, 52.7, 29.3, 27.7, 27.0; HRMS (ESI-TOF) m/z: C14H17O2 (M + H)+ calcd for 217.1223, found 217.1229.


20

Page 21 of 46 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


1-(7-nitro-3,4-dihydronaphthalen-2-yl)propan-2-one

(3ha)

and

1-(5-nitro-3,4-

dihydronaphthalen-2-yl)propan-2-one (3ha’): Yield: 25.9 mg, 56%; yellow oil; 1H NMR (400 MHz, CDCl3) δ: 7.98 (d, J = 8.0 Hz, 0.3H), 7.96-7.85 (m, 0.3H), 7.68-7.66 (m, 0.7H), 7.29-7.22 (m, 2H), 6.38 (s, 1H), 3.36-3.35 (m, 2H), 3.10 (t, J = 8.0 Hz, 1.4H), 2.94 (d, J = 8.0 Hz, 0.6H), 2.36-2.28 (m, 2H), 2.23 (s, 3H); 13C {1H}NMR (100 MHz, CDCl3) δ: 205.7, 205.7, 149.0, 142.0, 137.5, 136.8, 135.5, 136.2, 135.2, 130.0, 129.1, 127.9, 126.8, 125.3, 125.1, 122.5, 121.8, 120.1, 52.1, 51.9, 29.7, 27.9, 26.7, 26.5, 23.7; HRMS (ESI-TOF) m/z: C13H14NO3 (M + H)+ calcd for 232.0968, found 232.0976.

1-(6-(benzyloxy)-3,4-dihydronaphthalen-2-yl)propan-2-one (3ia): Yield: 49.7 mg, 85%; yellow oil; 1H NMR (400 MHz, CDCl3) δ: 7.44-7.36 (m, 4H), 7.32 (t, J = 7.2 Hz, 1H), 6.94 (d, J = 8.0 Hz, 1H), 6.77-6.74 (m, 2H), 6.30 (s, 1H), 5.05 (s, 2H), 3.26 (s, 2H), 2.81 (t, J = 8.0 Hz, 2H), 2.24 (t, J = 8.0 Hz, 2H), 2.20 (s, 3H);

13C

{1H}NMR (100 MHz, CDCl3) δ: 207.0, 157.8,

137.0, 136.2, 131.7, 128.6, 127.9, 127.5, 127.4, 126.8, 126.0, 114.5, 112.1, 69.9, 52.6, 29.2, 28.4, 27.0; HRMS (ESI-TOF) m/z: C20H21O2 (M + H)+ calcd for 293.1536, found 293.1542.

1-(6-methoxy-3,4-dihydronaphthalen-2-yl)propan-2-one (3ja): Yield: 35.0 mg, 81%; yellow oil; 1H NMR (400 MHz, CDCl3) δ: 6.95 (t, J = 8.4 Hz, 1H), 6.69-6.68 (m, 2H), 6.30 (s, 1H), 3.79 (s, 3H), 3.26 (s, 2H), 2.81 (t, J = 8.0 Hz, 2H), 2.24 (t, J = 8.0 Hz, 2H), 2.20 (s, 3H);

13C


21


Page 22 of 46

{1H}NMR (100 MHz, CDCl3) δ: 207.1, 158.6, 136.1, 131.6, 127.3, 126.8, 126.0, 113.5, 111.1, 55.2, 52.6, 29.2, 28.4, 27.0; HRMS (ESI-TOF) m/z: C14H17O2 (M + H)+ calcd for 217.1223, found 217.1229.

1-(6-methyl-3,4-dihydronaphthalen-2-yl)propan-2-one (3ka): Yield: 30.0 mg, 75%; yellow oil; 1H

NMR (400 MHz, CDCl3) δ: 7.04-6.95 (m, 3H), 6.54 (s, 1H), 3.33 (s, 2H), 2.81 (t, J = 8.0 Hz,

2H), 2.32 (s, 3H), 2.56-2.20 (m, 5H);

13C

{1H}NMR (100 MHz, CDCl3) δ: 206.9, 134.6, 132.8,

132.2, 128.3 (2C) , 126.5, 125.1, 123.5, 53.1, 29.2, 28.6, 27.0, 19.0; HRMS (ESI-TOF) m/z: C14H17O (M + H)+ calcd for 201.1274, found 201.1282.

1-(6-phenyl-3,4-dihydronaphthalen-2-yl)propan-2-one (3la): Yield: 41.4 mg, 79%; yellow oil; 1H

NMR (400 MHz, CDCl3) δ: 7.59 (d, J = 8.4 Hz, 2H), 7.44-7.38 (m, 3H), 7.36-7.30 (m, 2H),

7.09 (d, J = 8.0 Hz, 1H), 6.39 (s, 1H), 3.31 (s, 2H), 2.91 (t, J = 8.0 Hz, 2H), 2.32 (t, J = 8.0 Hz, 2H), 2.22 (s, 3H);

13C {1H}NMR

(100 MHz, CDCl3) δ: 206.7, 141.0, 139.7, 134.9, 134.6, 133.2,

128.7, 127.1, 126.9, 126.3, 126.2, 126.1, 125.2, 52.7, 29.3, 28.1, 27.3; HRMS (ESI-TOF) m/z: C19H19O (M + H)+ calcd for 263.1430, found 263.1441.

1-(6-chloro-3,4-dihydronaphthalen-2-yl)propan-2-one (3ma): Yield: 30.8 mg, 70%; yellow oil; 1H

NMR (400 MHz, CDCl3) δ: 7.11-7.09 (m, 2H), 6.92 (d, J = 8.0 Hz, 1H), 6.29 (s, 1H), 3.29 (s,

2H), 2.81 (t, J = 8.0 Hz, 2H), 2.56 (t, J = 8.0 Hz, 2H), 2.21 (s, 3H);

13C

{1H}NMR (100 MHz,


22

Page 23 of 46 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


CDCl3) δ: 206.4, 136.2, 134.8, 132.5, 1320, 127.4, 126.8, 126.4, 125.6, 52.4, 29.5, 27.8, 26.9; HRMS (ESI-TOF) m/z: C13H1435ClO (M + H)+ calcd for 221.0728, found 221.0734.

6-(2-oxopropyl)-7,8-dihydronaphthalene-2-carbonitrile (3na): Yield: 26.6 mg, 63%; yellow oil; 1H

NMR (400 MHz, CDCl3) δ: 7.44-7.42 (m, 1H), 7.37 (s, 1H), 7.06 (d, J = 8.0 Hz, 1H), 6.35 (s,

1H), 3.35 (s, 2H), 2.87 (t, J = 8.0 Hz, 2H), 2.32 (t, J = 8.0 Hz, 2H), 2.23 (s, 3H);

13C {1H}NMR

(100 MHz, CDCl3) δ: 205.6, 139.0, 138.4, 135.3, 130.7, 130.5, 126.0, 125.5, 119.3, 109.7, 52.2, 29.7, 27.3, 27.0; HRMS (ESI-TOF) m/z: C14H14NO (M + H)+ calcd for 212.1070, found 212.1077.

1-(6-(trifluoromethyl)-3,4-dihydronaphthalen-2-yl)propan-2-one (3oa): Yield: 30.5 mg, 60%; yellow oil; 1H NMR (400 MHz, CDCl3) δ: 7.39 (d, J = 8.0 Hz, 1H), 7.35 (s, 1H), 7.08 (d, J = 8.0 Hz, 1H), 6.37 (s, 1H), 3.33 (s, 2H), 2.89 (t, J = 8.0 Hz, 2H), 2.31 (t, J = 8.0 Hz, 2H), 2.22 (s, 3H); 13C {1H}NMR (100 MHz, CDCl3) δ: 206.0, 137.4, 137.3, 134.9, 128.5 (d, J = 31.9 Hz, 1C), 125.7, 125.7, 124.0 (q, J = 11.1 Hz, 1C), 123.5 (q, J = 11.9 Hz, 1C), 122.9, 52.3, 29.6, 27.7, 27.1;

19F

NMR (282 MHz, CDCl3): -62.3 (s, 1F); HRMS (ESI-TOF) m/z: C14H1419F3O (M + H)+

calcd for 255.0991, found 255.0996.

1-(6-nitro-3,4-dihydronaphthalen-2-yl)propan-2-one (3pa): Yield: 25.0 mg, 54%; yellow oil; 1H

NMR (400 MHz, CDCl3) δ: 8.00 (t, J = 8.4 Hz, 2H), 7.11 (d, J = 8.4 Hz, 1H), 6.40 (s, 1H), ACS Paragon Plus Environment

23


Page 24 of 46

3.38 (s, 2H), 2.94 (t, J = 8.0 Hz, 2H), 2.36 (t, J = 8.0 Hz, 2H), 2.24 (s, 3H);

13C {1H}NMR

(100

MHz, CDCl3) δ: 205.4, 146.2, 140.3, 140.2, 135.6, 125.9, 125.3, 122.3, 122.2, 52.2, 29.8, 27.5, 27.0; HRMS (ESI-TOF) m/z: C13H14NO3 (M + H)+ calcd for 232.0968, found 232.0976.

1-(6,7-dimethoxy-3,4-dihydronaphthalen-2-yl)propan-2-one (3qa): Yield: 43.8 mg, 68%; yellow oil; 1H NMR (400 MHz, CDCl3) δ: 6.77-3.69 (m, 2H), 6.28 (s, 1H), 3.85 (s, 3H), 3.79 (s, 3H), 3.26 (s, 2H), 2.88 (t, J = 8.0 Hz, 2H), 2.25-2.20 (m, 5H);

13C {1H}NMR

(100 MHz, CDCl3)

δ: 207.0, 152.0, 145.9, 132.0, 128.2, 128.1, 126.0, 121.6, 109.5, 60.4, 55.7, 52.5, 29.2, 26.6, 21.1; HRMS (ESI-TOF) m/z: C15H19O3 (M + H)+ calcd for 247.1329, found 247.1337.

1-(8-bromo-3,4-dihydronaphthalen-2-yl)propan-2-one (3ra): Yield: 34.8 mg, 66%; yellow oil; 1H

NMR (400 MHz, CDCl3) δ: 7.37 (d, J = 8.0 Hz, 1H), 7.04 (d, J = 7.2 Hz, 1H), 6.95 (t, J = 8.0

Hz, 1H), 6.72 (s, 1H), 3.36 (s, 2H), 2.82 (t, J = 8.0 Hz, 2H), 2.27-2.23 (m, 5H);

13C

{1H}NMR

(100 MHz, CDCl3) δ: 206.2, 137.1, 137.1, 133.0, 130.7, 127.8, 126.4, 125.1, 121.6, 52.6, 29.4, 28.7, 26.8; HRMS (ESI-TOF) m/z: C13H1479BrO (M + H)+ calcd for 265.0223, found 265.0228.

1-(8-bromo-6-fluoro-3,4-dihydronaphthalen-2-yl)propan-2-one (3sa): Yield: 39.5 mg, 70%; yellow oil; 1H NMR (400 MHz, CDCl3) δ: 7.14- 7.11 (m, 1H), 6.82-6.80 (m, 1H), 6.64 (s, 1H), 3.36 (s, 2H), 2.82 (t, J = 8.0 Hz, 2H), 2.26-2.19 (m, 5H);

13C


206.2, 160.7 (d, J = 248.6 Hz, 1C), 138.7, 138.7, 136.1 (d, J = 2.5 Hz, 1C), 129.4 (d, J = 3.0 ACS Paragon Plus Environment

24

Page 25 of 46 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


Hz, 1C), 124.2, 124.2, 121.3, 121.2, 117.5 (d, J = 24.3 Hz, 1C), 114.0 (d, J = 21.3 Hz, 1C), 52.4, 29.5, 29.0, 29.0, 26.5; 19F NMR (282 MHz, CDCl3): -113.7 (s, 1F); HRMS (ESI-TOF) m/z: C13H1379Br19F1O (M + H)+ calcd for 283.0128, found 283.0136.

1-(8-bromo-6-chloro-3,4-dihydronaphthalen-2-yl)propan-2-one (3ta): Yield: 42.9 mg, 72%; yellow oil; 1H NMR (400 MHz, CDCl3) δ: 7.38 (s, 1H), 7.05 (s, 1H), 6.64 (s, 1H), 3.37 (s, 2H), 2.81 (t, J = 8.0 Hz, 2H), 2.26-2.18 (m, 5H);

13C

{1H}NMR (100 MHz, CDCl3) δ: 206.0, 138.2,

137.5, 132.2, 131.6, 130.1, 126.7, 124.3, 121.5, 52.5, 29.6, 28.7, 26.6; HRMS (ESI-TOF) m/z: C13H1379Br35ClO (M + H)+ calcd for 298.9833, found 298.9842.

1-(8-bromo-5-fluoro-3,4-dihydronaphthalen-2-yl)propan-2-one (3ua): Yield: 38.4 mg, 68%; yellow oil; 1H NMR (400 MHz, CDCl3) δ: 7.34-7.30 (m, 1H), 6.77 (t, J = 8.8 Hz, 1H), 6.67-6.66 (m, 1H), 3.38 (s, 2H), 2.86 (t, J = 8.0 Hz, 2H), 2.28-2.23 (m, 5H);

13C

{1H}NMR (100 MHz,

CDCl3) δ: 205.8, 158.8 (d, J = 242.0 Hz, 1C), 138.0, 134.7 (d, J = 5.3 Hz, 1C), 131.0, 131.0, 124.8 (d, J = 3.1 Hz, 1C), 115.7 (d, J = 2.8 Hz, 1C), 115.2 (d, J = 24.1 Hz, 1C), 52.5, 29.6, 25.9, 20.3, 20.3;

19F

NMR (282 MHz, CDCl3): -121.1 (s, 1F); HRMS (ESI-TOF) m/z:

C13H1379Br19FO (M + H)+ calcd for 283.0128, found 283.0136.

1-(5-bromo-8,9-dihydronaphtho[1,2-d][1,3]dioxol-7-yl)propan-2-one (3va): Yield: 32.0 mg, 52%; yellow oil; 1H NMR (400 MHz, CDCl3) δ: 6.86 (s, 1H), 6.62 (s, 1H), 5.95 (s, 2H), 3.33 (s, ACS Paragon Plus Environment

25


2H), 2.76 (t, J = 8.0 Hz, 2H), 2.24-2.20 (m, 5H);

13C

Page 26 of 46

{1H}NMR (100 MHz, CDCl3) δ: 206.4,

146.8, 144.0, 134.3, 127.1, 125.0, 117.2, 112.5, 110.2, 101.5, 52.8, 29.4, 25.8, 21.4; HRMS (ESI-TOF) m/z: C14H1479BrO3 (M + H)+ calcd for 309.0121, found 309.0128.

1-(3,4-dihydronaphthalen-2-yl)propan-2-one (3wa): Yield: 27.5 mg, 74%; yellow oil; 1H NMR (400 MHz, CDCl3) δ: 7.17-7.09 (m, 3H), 7.02- 7.00 (m, 1H), 6.35 (s, 1H), 3.29 (s, 2H), 2.84 (t,

J = 8.0 Hz, 2H), 2.27 (t, J = 8.0 Hz, 2H), 2.21 (s, 3H);

13C


206.7, 134.4, 134.1, 127.3 (2C), 126.9, 126.6, 126.5, 125.8, 52.6, 29.3, 27.9, 27.2; HRMS (ESI-TOF) m/z: C13H15O (M + H)+ calcd for 187.1117, found 187.1126.

1-(1-methyl-3,4-dihydronaphthalen-2-yl)propan-2-one (3ya): Yield: 24.4 mg, 61%; yellow oil; 1H

NMR (400 MHz, CDCl3) δ: 7.30-7.26 (m, 1H), 7.23-7.19 (m, 1H), 7.16-7.11 (m, 2H), 3.38 (s,

2H), 2.77 (t, J = 8.0 Hz, 2H), 2.25 (t, J = 7.6 Hz, 2H), 2.19 (s, 3H), 2.07 (s, 3H);

13C {1H}NMR

(100 MHz, CDCl3) δ: 206.7, 136.4, 135.6, 129.0, 128.8, 127.1, 126.4, 126.4, 123.1, 49.9, 29.3, 29.2, 28.3, 14.7; HRMS (ESI-TOF) m/z: C14H17O (M + H)+ calcd for 201.1274, found 201.1282.

1-(1-phenyl-3,4-dihydronaphthalen-2-yl)propan-2-one (3za): Yield: 44.0 mg, 84%; yellow oil; 1H

NMR (400 MHz, CDCl3) δ: 7.41 (t, J = 7.2 Hz, 2H), 7.38-7.33 (m, 1H), 7.16 (d, J = 8.0 Hz,

3H), 7.10 (t, J = 6.8 Hz, 1H), 7.02 (t, J = 7.6 Hz, 1H), 6.60 (d, J = 7.6 Hz, 1H), 3.18 (s, 2H), 2.91 (t, J = 8.0 Hz, 2H), 2.39 (t, J = 8.0 Hz, 2H), 2.04 (s, 3H);

13C {1H}NMR

(100 MHz, CDCl3)


26

Page 27 of 46 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


δ: 206.8, 139.1, 137.1, 136.2, 135.2, 130.8, 129.8, 128.5, 127.1, 127.1, 126.6, 126.2, 125.8, 50.1, 29.7, 28.3, 28.1; HRMS (ESI-TOF) m/z: C19H19O (M + H)+ calcd for 263.1430, found 263.1441.

1-(6-methyl-1-(p-tolyl)-3,4-dihydronaphthalen-2-yl)propan-2-one (3aaa): Yield: 47.6 mg, 82%; yellow oil; 1H NMR (400 MHz, CDCl3) δ: 7.21 (d, J = 8.0 Hz, 2H), 7.04 (d, J = 8.0 Hz, 2H), 6.99-6.97 (m, 1H), 6.83 (d, J = 7.6 Hz, 1H), 6.52 (d, J = 8.0 Hz, 1H), 3.17 (s, 2H), 2.86 (t,

J = 8.0 Hz, 2H), 2.40 (s, 3H), 2.36 (t, J = 8.0 Hz, 2H), 2.29 (s, 3H), 2.04 (s, 3H); 13C {1H}NMR (100 MHz, CDCl3) δ: 207.1, 136.9, 136.6, 136.3, 136.1, 135.2, 133.7, 129.7, 129.5, 129.2, 128.0, 126.7, 125.9, 50.1, 29.6, 28.3, 28.2, 21.2, 21.0; HRMS (ESI-TOF) m/z: C21H23O (M + H)+ calcd for 291.1743, found 291.1754.

1-(6-fluoro-1-(4-fluorophenyl)-3,4-dihydronaphthalen-2-yl)propan-2-one (3aba): Yield: 46.5 mg, 78%; yellow oil; 1H NMR (400 MHz, CDCl3) δ: 7.11-7.10 (m, 4H), 6.88-6.85 (m, 1H), 6.736.68 (m, 1H), 6.54-6.50 (m, 1H), 3.17 (s, 2H), 2.89 (t, J = 8.0 Hz, 2H), 2.37 (t, J = 8.0 Hz, 2H), 2.06 (s, 3H);

13C {1H}NMR

(100 MHz, CDCl3) δ: 206.3, 163.0 (d, J = 49.6 Hz, 1C), 160.5 (d, J

= 50.4 Hz, 1C), 137.8, 137.7, 135.3, 134.7, 132.3, 131.4, 131.3, 130.4, 127.2, 127.2, 115.7, 115.5, 114.4, 114.2, 112.6, 112.4, 49.8, 29.8, 28.1; 19F NMR (282 MHz, CDCl3): -114.9 (s, 1F),


27


Page 28 of 46

-115.7 (s, 1F); HRMS (ESI-TOF) m/z: C19H1719F2O (M + H)+ calcd for 299.1242, found 299.1249.

1-(6-chloro-1-(4-chlorophenyl)-3,4-dihydronaphthalen-2-yl)propan-2-one (3aca): Yield: 53.5 mg, 81%; yellow oil; 1H NMR (400 MHz, CDCl3) δ: 7.39 (d, J = 8.4 Hz, 2H), 7.14 (s, 1H), 7.07 (d, J = 8.4 Hz, 2H), 6.99 (d, J = 8.4 Hz, 1H), 6.48 (d, J = 8.4 Hz, 1H), 3.18 (s, 2H), 2.87 (t, J = 8.0 Hz, 2H), 2.70 (t, J = 8.0 Hz, 2H), 2.06 (s, 3H);

13C

{1H}NMR (100 MHz, CDCl3) δ: 206.0,

137.1, 135.2, 134.3, 133.3, 132.2, 131.7, 131.2 (2C), 128.9, 127.2, 126.9, 126.2, 49.9, 29.9, 28.2, 27.8; HRMS (ESI-TOF) m/z: C19H1735Cl2O (M + H)+ calcd for 331.0651, found 331.0657.

1-(6-bromo-1-(4-bromophenyl)-3,4-dihydronaphthalen-2-yl)propan-2-one (3ada): Yield: 61.9 mg, 74%; yellow oil; 1H NMR (400 MHz, CDCl3) δ: 7.54 (d, J = 8.4 Hz, 2H), 7.29 (s, 1H), 7.157.12 (m, 1H), 7.01 (d, J = 7.6 Hz, 2H), 6.42 (d, J = 8.4 Hz, 1H), 3.17 (s, 2H), 2.87 (t, J = 8.0 Hz, 2H), 2.36 (t, J = 8.0 Hz, 2H), 2.06 (s, 3H); 13C {1H}NMR (100 MHz, CDCl3) δ: 205.9, 137.5, 137.4, 135.3, 134.7, 131.9, 131.9, 131.5, 130.1, 129.2, 127.2, 121.5, 120.4, 49.9, 29.9, 28.3, 27.7; HRMS (ESI-TOF) m/z: C19H1779Br2O (M + H)+ calcd for 418.9641, found 418.9647.

1-(1-phenyl-3,4-dihydronaphthalen-2-yl)butan-2-one

(3zb)

and

3-(1-phenyl-3,4-

dihydronaphthalen-2-yl)butan-2-one (3zb’): Yield: 34.8 mg, 63%; yellow oil; 1H NMR (400 MHz, CDCl3) δ: 7.46 (t, J = 7.2 Hz, 2H), 7.43-7.31 (m, 4H), 7.35 (d, J = 8.0 Hz, 1H), 7.33-7.29 ACS Paragon Plus Environment

28

Page 29 of 46 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


(m, 1H),7.26-7.20 (m, 2H), 7.17-7.14 (m, 3H), 7.11 (d, J = 7.2 Hz, 1H),7.08-7.02 (m, 2H), 6.60 (d, J = 7.6 Hz, 2H), 3.47-3.45 (m, 1H), 3.17 (s, 2H), 2.93-2.83 (m, 4H), 2.41-2.29 (m, 5H), 2.14 (s, 1H), 2.08 (s, 3H), 1.11 (d, J = 6.8 Hz, 3H), 0.96 (t, J = 7.6 Hz, 3H); 13C {1H}NMR (100 MHz, CDCl3) δ: 209.6, 209.5, 142.0, 139.3, 139.2, 136.9, 136.8, 136.3, 136.2, 136.1, 135.2, 131.0, 129.9, 129.6, 128.7, 128.5, 127.2, 127.1, 127.0, 126.9, 126.8, 126.5, 126.3, 126.2, 126.1, 125.8, 51.4, 48.8, 35.5, 28.7, 28.5, 28.3, 28.1, 23.4, 13.4,7.8; HRMS (ESI-TOF) m/z: C20H21O (M + H)+ calcd for 277.1587, found 277.1596.

1-cyclopropyl-2-(1-phenyl-3,4-dihydronaphthalen-2-yl)ethanone (3zc): Yield: 32.8 mg, 57%; yellow oil; 1H NMR (400 MHz, CDCl3) δ: 7.43-7.35 (m, 3H), 7.26-7.15 (m, 3H), 7.12-.08 (m, 1H), 7.03 (t, J = 7.6 Hz, 1H), 6.61 (d, J = 7.6 Hz, 1H), 3.30 (s, 2H), 2.91 (t, J = 8.0 Hz, 2H), 2.40 (t, J = 8.0 Hz, 2H), 1.89-1.85 (m, 1H), 0.98-0.96 (m, 2H), 0.83-0.79 (m, 2H); 13C {1H}NMR (100 MHz, CDCl3) δ: 208.9, 139.1, 137.0, 136.3, 135.3, 131.0, 129.9, 128.5, 127.1, 127.0, 126.6, 126.2, 125.8, 49.9, 28.2, 28.1, 20.1, 11.1; HRMS (ESI-TOF) m/z: C21H21O (M + H)+ calcd for 289.1587, found 289.1594.

2-(1-phenyl-3,4-dihydronaphthalen-2-yl)cyclobutanone (3ze): Yield: 27.4 mg, 50%; yellow oil; 1H NMR (400 MHz, CDCl3) δ: 7.43-7.35 (m, 3H), 7.16-7.08 (m, 4H), 7.02 (t, J = 7.6 Hz, 1H), 6.59 (d, J = 7.6 Hz, 1H), 4.19-4.14 (m, 1H), 3.03-2.82 (m, 4H), 2.40-2.33 (m, 2H), 2.13ACS Paragon Plus Environment

29


2.03 (m, 2H);

13C

Page 30 of 46

{1H}NMR (100 MHz, CDCl3) δ: 209.1, 138.8, 136.9, 136.1, 135.2, 131.5,

128.5, 128.4, 127.1, 127.1, 127.7, 126.2, 64.6, 45.3, 28.1 (2C), 24.4, 16.0; HRMS (ESI-TOF)

m/z: C20H19O (M + H)+ calcd for 275.1430, found 275.1433. 1-cyclopentyl-2-(1-phenyl-3,4-dihydronaphthalen-2-yl)ethanone (3zf): Yield: 29.1 mg, 46%; yellow oil; 7.42-7.38 (m, 2H), 7.36-7.34 (m, 1H), 7.29-7.26 (m, 1H), 7.14 (d, J = 7.2 Hz, 2H), 7.11-7.07 (m, 1H), 7.03-7.01 (m, 1H), 6.57 (d, J = 7.6 Hz, 1H), 3.05-2.99 (m, 1H), 2.97-2.91 (m, 1H), 2.86-2.78 (m, 1H), 2.40.-2.18 (m, 3H), 2.16-1.95 (m, 4H), 1.72-1.65 (m, 1H);

13C

{1H}NMR (100 MHz, CDCl3) δ: 219.3, 139.2, 138.0, 136.2, 135.3, 133.9, 130.5, 128.6, 127.0, 127.0, 126.5, 126.1, 125.8, 55.1, 38.7, 29.1, 28.3, 24.9, 20.9; HRMS (ESI-TOF) m/z: C21H21O (M + H)+ calcd for 289.1587, found 289.1594.

4-(3,4-dihydronaphthalen-1-yl)butan-2-one (5aa): Yield: 28.7 mg, 77%; yellow oil; 1H NMR (400 MHz, CDCl3) δ: 7.21-7.20 (m, 2H), 7.15- 7.14 (m, 2H), 5.86 (t, J = 4.4 Hz, 1H), 2.75-2.71 (m, 4H), 2.69-2.65 (m, 2H), 2.26-2.21 (m, 2H), 2.16 (s, 3H); 13C {1H}NMR (100 MHz, CDCl3) δ: 208.6, 136.8, 135.1, 134.3, 127.7, 126.8, 126.4, 125.4, 122.3, 42.6, 30.1, 28.3, 26.6, 23.0; HRMS (ESI-TOF) m/z: C14H17O (M + H)+ calcd for 201.1274, found 201.1281.

4-(6-fluoro-3,4-dihydronaphthalen-1-yl)butan-2-one (5ba): Yield: 34.9 mg, 80%; yellow oil; 1H

NMR (400 MHz, CDCl3) δ: 7.17-7.14 (m, 1H), 6.90-6.85 (m, 2H), 5.82-5.80 (m, 1H), 2.73ACS Paragon Plus Environment

30

Page 31 of 46 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


2.64 (m, 6H), 2.25-2.20 (m, 2H), 2.16 (s, 3H); 13C {1H}NMR (100 MHz, CDCl3) δ: 208.4, 162.7, 160.3, 139.3, 139.3, 134.5, 130.5, 130.5, 126.2, 124.3, 124.3, 123.8, 123.7, 114.9, 114.7, 112.7, 112.5, 42.4, 30.1, 28.4, 26.6, 22.7;

19F

NMR (282 MHz, CDCl3): -115.7 (s, 1F); HRMS

(ESI-TOF) m/z: C14H1619FO (M + H)+ calcd for 219.1180, found 219.1186.

4-(6-chloro-3,4-dihydronaphthalen-1-yl)butan-2-one (5ca). Yield: 32.6 mg, 74%; yellow oil; 1H

NMR (400 MHz, CDCl3) δ: 7.33-7.30 (m, 1H), 7.28 (s, 1H), 7.06 (d, J = 8.0 Hz, 1H), 5.87 (t,

J =4.4 Hz, 1H), 2.72-2.62 (m, 6H), 2.23 (t, J = 8.0 Hz, 2H), 2.16 (s, 3H);

13C

{1H}NMR (100

MHz, CDCl3) δ: 208.3, 138.9, 134.5, 133.3, 130.6, 129.3, 125.7, 123.9, 120.3, 42.3, 30.1, 28.0, 26.3, 22.8; HRMS (ESI-TOF) m/z: C14H1635ClO (M + H)+ calcd for 235.0884, found 235.0889.

4-(6-bromo-3,4-dihydronaphthalen-1-yl)butan-2-one (5da): Yield: 37.8 mg, 68%; yellow oil; 1H

NMR (400 MHz, CDCl3) δ: 7.17-7.11 (m, 3H), 5.87-5.85 (m, 1H), 2.71-2.62 (m, 6H), 2.25-

2.20 (m, 2H), 2.16 (s, 3H);

13C

{1H}NMR (100 MHz, CDCl3) δ: 208.3, 138.6, 134.5, 132.8,

132.0, 127.7, 126.3, 125.5, 123.6, 42.3, 30.1, 28.1, 26.4, 22.8; HRMS (ESI-TOF) m/z: C14H1679BrO (M + H)+ calcd for 279.0379, found 279.0386.

4-(3,4-dihydronaphthalen-1-yl)-3-methylbutan-2-one (5ab): Yield: 30.4 mg, 71%; yellow oil; 1H

NMR (400 MHz, CDCl3) δ: 7.32-7.21 (m, 2H), 7.17-7.15 (m, 2H), 5.87-5.84 (m, 1H), 2.92-

2.87 (m, 1H), 2.84-2.79 (m, 1H), 2.75-2.70 (m, 2H), 2.37-2.32 (m, 1H), 2.27-2.22 (m, 2H), 2.14 ACS Paragon Plus Environment

31


Page 32 of 46

(s, 3H), 1.10 (d, J = 6.8 Hz, 3H); 13C {1H}NMR (100 MHz, CDCl3) δ: 212.8, 136.9, 134.1, 133.8, 127.7, 127.4, 126.8, 126.4, 122.4, 45.1, 36.0, 29.0, 28.3, 23.0, 16.3; HRMS (ESI-TOF) m/z: C15H19O (M + H)+ calcd for 215.1430, found 215.1437.

4-(3,4-dihydronaphthalen-1-yl)-3,3-dimethylbutan-2-one (5ag): Yield: 23.7 mg, 52%; yellow oil; 1H NMR (400 MHz, CDCl3) δ: 7.27-7.26 (m, 1H), 7.20-7.17 (m, 1H), 7.16-7.13 (m, 2H), 2.82-5.80 (m, 1H), 2.73-2.39 (m, 4H), 2.24-2.19 (m, 2H), 2.11 (s, 3H), 1.11 (s, 6H);

13C

{1H}NMR (100 MHz, CDCl3) δ: 214.5, 136.5, 135.4, 133.1, 128.8, 127.6, 126.6, 126.1, 123.0, 48.3, 40.5, 28.6, 26.1, 24.9 (2C), 23.2; HRMS (ESI-TOF) m/z: C16H21O (M + H)+ calcd for 229.1587, found 229.1592.

3aa and 3aa-D5: Yield: 45.6 mg, 78%; 1H NMR (400 MHz, CDCl3) δ: 7.45-7.38 (m, 4H), 7.35-7.26 (m, 1H), 7.06 (t, J = 8.0 Hz, 1H), 6.81-6.74 (m, 3H), 5.08 (s, 2H), 3.31 (s, 1.33H), 2.81 (t, J = 8.0 Hz, 2H), 2.24 (t, J = 8.0 Hz, 2H), 2.20 (s, 2H).

Acknowledgments. We thank the Scientific Research Fund of Hunan Provincial Education Department (No. 16A087), Natural Science Foundation of Hunan Province (No. 2018JJ3208, 2017JJ2103) and National Natural Science Foundation of China (No. 21602056) for financial support.


32

Page 33 of 46 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


Supporting Information Available: The copies of spectra. This material is available free of charge via the Internet at http://pubs.acs.org.

References and notes (1) (a) Labinger, J.-A.; Platinum-Catalyzed C–H Functionalization. Chem. Rev. 2017, 117, 8483–8496. (b) Wei, Y.; Hu, P.; Zhang, M.; Su, W.-P. Metal-Catalyzed Decarboxylative C–H Functionalization. Chem. Rev. 2017, 117, 8864–8907. (c) Lyons, T.W., Sanford, M. S.; PalladiumCatalyzed Ligand-Directed C−H Functionalization Reactions. Chem. Rev. 2010, 110, 1147–1169. (d) Guo, X.-X.; Gu, D.-W.; Wu, Z.-X.; Zhang, W.-B. Copper-Catalyzed C–H Functionalization Reactions: Efficient Synthesis of Heterocycles. Chem. Rev. 2015, 115, 1622–1651. (e) Qin, Y.; Zhu, L.-H.; Luo, S.-Z. Organocatalysis in Inert C–H Bond Functionalization. Chem. Rev. 2017, 117, 9433–9520. (f) Crabtree, R. H. Introduction to Selective Functionalization of C−H Bonds. Chem. Rev. 2010, 110, 575–575. (g) Xue, X.-S.; Ji, P.-J.; Zhou, B.-Y.; Cheng, J.-P. The Essential Role of Bond Energetics in C–H Activation/Functionalization. Chem. Rev. 2017, 117, 8622–8648. (h) Song, G.-Y.; Wang, F.; Li, X.-W.; C–C, C–O and C–N bond formation via rhodium(III)catalyzed oxidative C–H activation. Chem. Soc. Rev. 2012, 41, 3651–3678. (i) Ramirez, T.-A.; Zhao, B.-G.; Shi, Y. Recent Advances in Transition Metal-Catalyzed sp3 C–H Amination Adjacent to Double Bonds and Carbonyl Groups. Chem. Soc. Rev. 2012, 41, 931–942. (2) (a) Li, L.; Wang, H.; Yu, S.-J.; Yang, X.-F.; Li, X.-W. Cooperative Co(III)/Cu(II)-Catalyzed C– N/N–N Coupling of Imidates with Anthranils: Access to 1H-Indazoles via C–H Activation. Org. Lett. 2016, 18, 3662–3665. (b) Ouyang, X.-H.; Song, R.-J.; Hu, M.; Yang, Y.; Li, J.-H. SilverMediated Intermolecular 1,2-Alkylarylation of Styrenes with α-Carbonyl Alkyl Bromides and Indoles. Angew. Chem. Int. Ed. 2016, 55, 3187–3191. (c) Yu, S.-J.; Liu, S.; Lan, Y.; Wan, B.-S.; Li, X.-W. Rhodium-Catalyzed C–H Activation of Phenacyl Ammonium Salts Assisted by an


33


Page 34 of 46

Oxidizing C–N Bond: A Combination of Experimental and Theoretical Studies. J. Am. Chem. Soc. 2015, 137, 1623–1631. (d) Li, Y.; Pan, G.-H.; Hu, M.; Liu, B.; Song R.-J.; Li, J.-H. Intermolecular oxidative decarbonylative [2+2+2] carbocyclization of N-(2-ethynylaryl)acrylamides with tertiary and secondary alkyl aldehydes involving C(sp3)–H functionalization. Chem. Sci. 2016, 7, 7050– 7054. (e) Yang, Y.; Zhou, M.-B.; Ouyang, X.-H.; Pi, R.; Song, R.-J.; Li, J.-H. Rhodium(III)Catalyzed [3+2]/[5+2] Annulation of 4-Aryl 1,2,3-Triazoles with Internal Alkynes through Dual C(sp2)–H Functionalization. Angew. Chem. Int. Ed. 2015, 54, 6595–6599. (f) Zhou, X.-K.; Luo, Y.-X.; Kong, L.-H.; Xu, Y.-W.; Zheng, G.-F.; Lan, Y.; Li, X.-W. Cp*CoIII-Catalyzed BranchSelective Hydroarylation of Alkynes via C–H Activation: Efficient Access to α-gem-Vinylindoles. ACS Catal. 2017, 7, 7296–7304. (g) Bai, D.-C.; Xu, T.; Ma, C.-R.; Zheng, X.; Liu, B.-X.; Xie, F.; Li, X.-W. Rh(III)-Catalyzed Mild Coupling of Nitrones and Azomethine Imines with Alkylidenecyclopropanes via C–H Activation: Facile Access to Bridged Cycles. ACS Catal. 2018, 8, 4194–4200. (h) Li, Z.-P.; Li, C.-J. CuBr-Catalyzed Efficient Alkynylation of sp3 C–H Bonds Adjacent to a Nitrogen Atom. J. Am. Chem. Soc. 2004, 126, 11810–11811. (3) (a) Qi, Z.-S.; Yu, S.-J.; Li, X.-W. Rh(III)-Catalyzed Synthesis of N-Unprotected Indoles from Imidamides and Diazo Ketoesters via C–H Activation and C–C/C–N Bond Cleavage. Org. Lett. 2016, 18, 700–703. (b)Liu, X.-D.; Tong, K.; Zhang, A.-H.; R.-X.; Tan, Yu, S.-Y. Metal-Free Chloroamidation of Indoles with Sulfonamides and NaClO. Org. Chem. Front. 2017, 4, 1354– 1357. (c) Chen, H.; Guo, L.-L.; Yu, S.-Y. Primary, Secondary, and Tertiary γ-C(sp3)–H Vinylation of Amides via Organic Photoredox-Catalyzed Hydrogen Atom Transfer. Org. Lett. 2018, 20, 6255–6259. (d) Fan, J.-H.; Wei, W.-T.; Zhou, M.-B.; Song, R.-J.; Li, J.-H. Palladium-Catalyzed Oxidative Difunctionalization of Alkenes with α-Carbonyl Alkyl Bromides Initiated through a Heck-Type Insertion: A Route to Indolin-2-ones. Angew. Chem. Int. Ed. 2014, 53, 6650–6654. (e) Shen, X.; Zhao, J.-J.; Yu, S.-Y. Photoredox-Catalyzed Intermolecular Remote C–H and C–C Vinylation via Iminyl Radicals. Org. Lett. 2018, 20, 5523–5527. (f) Zhou, M.-B.; Song, R.-J.; Ouyang, X.-H.; Liu, Y.; Wei, W.-T.; Deng, G.-B.; Li, J.-H. Metal-Free Oxidative Tandem ACS Paragon Plus Environment

34

Page 35 of 46 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


Coupling of Activated Alkenes with Carbonyl C(sp2)–H bonds and Aryl C(sp2)–H bonds Using TBHP. Chem. Sci. 2013, 4, 2690–2694. (g) Zhou, M.-B.; Huang, X.-C.; Liu, Y.-Y.; Song, R.-J.; Li, J.-H. Alkylation of Terminal Alkynes with Transient σ-Alkylpalladium(II) Complexes: A Carboalkynylation Route to Alkyl-Substituted Alkynes. Chem. Eur. J. 2014, 20, 1843–1846. (4) (a) Heiba, E. I.; Dessau, R. M.; Koehl Jr, W. J. Oxidation by Metal Salts. IV. A New Method for the Preparation of .Gamma.-Lactones by the Reaction of Manganic Acetate with Olefins. J. Am. Chem. Soc. 1968, 90, 5905–5906. (b) Li, B.; Fang, S.-L.; Huang, D.-Y.; Shi, B.-F.; Ru-Catalyzed Meta-C–H Benzylation of Arenes with Toluene Derivatives. Org. Lett. 2017, 19, 3950–3953. (c) Jiang, H.; He, J.; Liu, T.; Yu, J.-Q. Ligand-Enabled γ-C(sp3)–H Olefination of Amines: En Route to Pyrrolidines. J. Am. Chem. Soc. 2016, 138, 2055–2059. (d) Jiang, H.; Studer, A.; α-AminoxyAcid-Auxiliary-Enabled Intermolecular Radical γ-C(sp3)−H Functionalization of Ketones. Angew. Chem. Int. Ed. 2018, 57, 1692–1696. (e) Wang, Z.-Q.; Hu, M.; Huang, X.-C.; Gong, L.-B.; Xie, Y.-X.; Li, J.-H. Direct α-Arylation of α-Amino Carbonyl Compounds with Indoles Using Visible Light Photoredox Catalysis. J. Org. Chem. 2012, 77, 8705−8711. (f) Zhang, Q.; Yin, X.-S.; Chen, K.; Zhang, S.-Q.; Shi, B.-F. Stereoselective Synthesis of Chiral β-Fluoro α-Amino Acids via Pd(II)-Catalyzed Fluorination of Unactivated Methylene C(sp3)–H Bonds: Scope and Mechanistic Studies. J. Am. Chem. Soc. 2015, 137, 8219–8226. (g) He, J.; Takise, R.; Fu, H.; Yu, J.-Q. LigandEnabled Cross-Coupling of C(sp3)–H Bonds with Arylsilanes. J. Am. Chem. Soc. 2015, 137, 4618– 4621. (h) Li, Z.-D.; Wang Q.; Zhu, J.-P. Copper-Catalyzed Arylation of Remote C(sp3)−H Bonds in Carboxamides and Sulfonamides. Angew. Chem. Int. Ed. 2018, 57, 13288–13292. (i) Hu, M.; Guo, L.-Y.; Han, Y.; Tan, F.-L.; Song, R.-J.; Li, J.-H. Intermolecular Cascade Annulations of N(Arylsulfonyl)acrylamides with Dual C(sp3)–H Bonds: Divergent Access to Indanes and Pyrrolidin-2-ones. Chem. Commun. 2017, 53, 6081–6084. (j) Zhang, Z.-Z.; Han, Y.-Q.; Zhan, B.B.; Wang, S.; Shi, B.-F. Synthesis of Bicyclo[n.1.0]alkanes by a Cobalt-Catalyzed Multiple C(sp3)−H Activation Strategy. Angew. Chem. Int. Ed. 2017, 56, 13145–13149.


35


Page 36 of 46

(5) (a) Wu, J.-W.; Zhou, Y.; Zhou, Y.-C.; Chiang, C.-W; Lei, A.-W. Electro-oxidative C(sp3)–H Amination of Azoles via Intermolecular Oxidative C(sp3)–H/N–H Cross-Coupling. ACS Catal. 2017, 7, 8320–8323. (b) Heiba, E. I.; Dessau, R. M.; Koehl Jr, W. J. Oxidation by metal salts. II. The Formation of Gamma.-Lactones by the Reaction of Lead Tetraacetate with Olefins in Acetic acid. J. Am. Chem. Soc. 1968, 90, 2706–2707. (c) Rout, S.-K.; Guin, S.; Ali, W.; Gogoi, A.; Patel, B.-K. Copper-Catalyzed Esterification of Alkylbenzenes with Cyclic Ethers and Cycloalkanes via C(sp3)–H Activation Following Cross-Dehydrogenative Coupling. Org. Lett. 2014, 16, 3086–3089. (d) Xu, G.-Q.; Xu, J.-T.; Feng, Z.-T.; Liang, H.; Wang, Z.-Y.; Qin, Y.; Xu, P.-F. Dual C(sp3)−H Bond Functionalization of N‐Heterocycles through Sequential Visible‐Light Photocatalyzed Dehydrogenation/[2+2] Cycloaddition Reactions Angew. Chem. Int. Ed. 2018, 57, 5110–5114. (e) Ling, P.-X.; Fang, S.-L.; Yin, X.-S; Zhang, Q.; Chen, K.; Shi, B.-F. Palladium-Catalyzed Sequential Monoarylation/Amidation of C(sp3)–H Bonds: Sstereoselective Synthesis of α-Aminoβ-Lactams and Anti-α, β-Diamino Acid. Chem. Commun. 2017, 53, 6351–6354. (f) Liu, Y.-J.; Liu, Y.-H.; Zhang, Z.-Z.; Yan, S.-Y.; Chen, K.; Shi, B.-F. Divergent and Stereoselective Synthesis of βSilyl-α-Amino Acids through Palladium-Catalyzed Intermolecular Silylation of Unactivated Primary and Secondary C−H Bonds. Angew. Chem. Int. Ed. 2016, 55, 13859–13562. (g) Zhu, C.L.; Zeng, H.; Chen, F.-L.; Yang, Z.-Y.; Cai, Y.-Y.; Jiang, H.-F. Intermolecular C(sp3)−H Amination Promoted by Internal Oxidants: Synthesis of Trifluoroacetylated Hydrazones. Angew. Chem. Int. Ed. 2018, 57, 17215–17219. (h) Ouyang, X.-H.; Cheng, J.; Li, J.-H. 1,2-Diarylation of Alkenes with Aryldiazonium Salts and Arenes Enabled by Visible Light Photoredox Catalysis. Chem. Commun. 2018, 54, 8745–8748. (i) Zhang, Y.-H.; Li, C.-J. DDQ-Mediated Direct CrossDehydrogenative-Coupling (CDC) between Benzyl Ethers and Simple Ketones. J. Am. Chem. Soc. 1968, 128, 4242–4243. (6) (a) Su, R.-K.; Li, Y.; Min, M.-Y.; Ouyang, X.-H.; Song, R.-J; Li, J.-H. Copper-Catalyzed Oxidative Intermolecular 1,2-Alkylarylation of Styrenes with Ethers and Indoles. Chem. Commun. 2018, 54, 13511–13514. (b) Wei, W.-T.; Zhou, M.-B.; Fan, J.-H.; Liu, W.; Song, R.-J.; Liu, Y.; ACS Paragon Plus Environment

36

Page 37 of 46 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


Hu, M.; Xie, P.; Li, J.-H. Synthesis of Oxindoles by Iron-Catalyzed Oxidative 1,2-Alkylarylation of Activated Alkenes with an Aryl C(sp2)–H Bond and a C(sp3)–H Bond Adjacent to a Heteroatom. Angew. Chem. Int. Ed. 2013, 52, 3638–3641. (c) Xu, J.-W.; Zhang, Z.-Z.; Rao, W.H.; Shi, B.-F. Site-Selective Alkenylation of δ-C(sp3)–H Bonds with Alkynes via a Six-Membered Palladacycle. J. Am. Chem. Soc. 2016, 138, 10750–10753. (d) Wang, Q.-N.; Lou, J.; Wu, P.; Wu, K.-K.; Yu, Z.-K. Iron-Mediated Oxidative C–H Alkylation of S,S‐Functionalized Internal Olefins via C(sp2)–H/C(sp3)–H Cross-Coupling. Angew. Chem. Int. Ed. 2017, 359, 2981–2988. (e) Chen, K.; Li, X.; Zhang, S.-Q.; Shi, B.-F. Palladium-Catalyzed C(sp3)–H Arylation of Lactic Acid: Efficient Synthesis of Chiral β-aryl-α-Hydroxy Acids. Org. Chem. Front. 2016, 3, 204–208. (f) Liu, Y.-F.; Hu, Y.-Q.; Cao, Z.-Z.; Zhan, X.; Luo, W.-P.; Q. L.; Guo, C.-C. Direct Assembly of Polysubstituted Furans via C(sp3)–H Bonds Functionalization Reaction Using Dimethyl Sulfoxide as a Dual Synthon. Adv. Synth. Catal. 2019, 361, 1084–1091. (g) Wei, W.-T.; Song, R.-J.; Li, J.-H. Copper-Catalyzed Oxidative α-Alkylation of a-Amino Carbonyl Compounds with Ethers via Dual C(sp3)-H Oxidative Cross Coupling. Adv. Synth. Catal. 2014, 356, 1703–1707. (h) Tobisu, M.; Chatani, N. A Catalytic Approach for the Functionalization of C(sp3)–H Bonds. Angew. Chem. Int. Ed. 2006, 45, 1683–1684. (7) (a) Campos, K-R. Direct sp3 C–H bond Activation Adjacent to Nitrogen in Heterocycles. Chem. Soc. Rev. 2007, 36, 1069–1084. (b) Zhang, S.-Y.; Zhan, F.-M.; Tu, Y.-Q. Direct sp3 α-C–H Activation and Functionalization of Alcohol and Ether. Chem. Soc. Rev. 2011, 40, 1937–1949. (c) Wu, X.-F.; Gong, J.-L.; Qi, X. A Powerful Combination: Recent Achievements on Using TBAI and TBHP as Oxidation System. Org. Biomol. Chem. 2014, 12, 5807–5817. (d) Liu, D.; Liu, C.; Li, H.; Lei, A-W. Direct Functionalization of Tetrahydrofuran and 1,4-Dioxane: Nickel-Catalyzed Oxidative C(sp3)–H Arylation. Angew. Chem. Int. Ed. 2013, 52, 4453–4456. (e) Wang, H.; Guo, L.-N.; Duan, X.-H. Silver-catalyzed Oxidative Coupling/Cyclization of Acrylamides with 1,3Dicarbonyl Compounds. Chem. Commun. 2013, 49, 10370–10372. (f) Zhao, J.-C.; Fang, H.; Han, J.-L.; Pan, Y. Cu-Catalyzed C(sp3)–H Bond Activation Reaction for Direct Preparation of ACS Paragon Plus Environment

37


Page 38 of 46

Cycloallyl Esters from Cycloalkanes and Aromatic Aldehydes. Org Lett. 2014, 16, 2530–2533. (g) Zhu, Y.-F.; Wei, Y.-Y. Copper catalyzed direct alkenylation of simple alkanes with styrenes. Chem. Sci. 2014, 5, 2379–2382.(h) Barve, B.-D.; Wu, Y.-C.; El-Shazly, M.; Korinek, M.; Cheng, Y.-B.; Wang. J.-J.; Chang, F.-R. Iron-Catalyzed Oxidative Direct α-C–H Bond Functionalization of Cyclic Ethers: Selective C–O Bond Formation in the Presence of a Labile Aldehyde Group. Org. Lett. 2014, 16, 1912–1915. (i) Cao, J.-J.; Zhu, T.-H.; Wang, S.-Y.; Gu, Z.-Y.; Wang, X.; Ji, S.-J. tert-Butyl peroxybenzoate (TBPB)-Mediated 2-Isocyanobiaryl Insertion with 1,4-Dioxane: Efficient Synthesis of 6-Alkyl Phenanthridines via C(sp3)–H/C(sp2)–H Bond Functionalization. Chem. Commun. 2014, 50, 6439–6442. (j) Ouyang, X.-H.; Hu, M.; Song, R.-J.; Li, J.-H. Oxidative Three-Component 1,2-Alkylarylation of Alkenes with Alkyl Nitriles and N-Heteroarenes. Chem. Commun. 2018, 54, 12345–12348. (8) (a) Zhang, H.; Wang, Y.-M.; Zhou, Z.-H.; Bifunctional Thiophosphinamide Catalyzed Highly Enantioselective Michael Addition of Acetone to (E)-2-azido β-nitrostyrenes and the Subsequent Reductive Cyclization. Tetrahedron. 2018, 74, 6071–6077. (b) Assem, N.; Ferreira, David. J.; Wolan, D. W.; Dawson, P. E. Acetone-Linked Peptides: A Convergent Approach for Peptide Macrocyclization and Labeling. Angew. Chem. Int. Ed. 2015, 54, 8665–8667. (c) Zhang, R.-X.; Jin, S.-Z.; Liu, Q.; Lin, S.; Yan, Z.-H. Transition Metal-Free Cross-Dehydrogenative Coupling Reaction of Coumarins with Acetonitrile or Acetone. J. Org. Chem. 2018, 83, 13030–13035. (d) MacQueen, P. M.; Chisholm, A. J.; Hargreaves, B. K. V.; Stradiotto, M. Palladium-Catalyzed Mono-α-arylation of Acetone at Room Temperature. Chem. Eur. J. 2015, 21, 11006–11009. (e) Kabeshov, M. A.; Kysilka, O.; Rulíšek, L.; Suleimanov, Y. V.; Bella, M.; Malkov, A. V.; Kočovský, P. Cross-Aldol Reaction of Isatin with Acetone Catalyzed by Leucinol: A Mechanistic Investigation. Chem. Eur. J. 2015, 21, 12026–12033. (f) Xu, Y.-G.; Zhang, S.; Li, L.-J.; Wang, Y.K.; Zha, Z.-G.; Wang, Z.-Y. L-Phenylalanine Potassium Catalyzed Asymmetric Formal [3+3] Annulation of 2-Enoyl-pyridine N-oxides with Acetone. Org. Chem. Front. 2018, 5, 376–379. (g) Fu, W.-C.; So, C.-M.; Chow, W.-K.; Yuen, O.-Y.; Kwong, F.-Y. Design of an Indolylphosphine ACS Paragon Plus Environment

38

Page 39 of 46 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


Ligand for Reductive Elimination-Demanding Monoarylation of Acetone Using Aryl Chlorides. Org. Lett. 2015, 17, 4612–4615. (h) Fu, W.-C.; Zhou, Z.-y.; Kwong, F.-Y. Preparation of a Highly Congested Carbazoyl-Derived P,N-Type Phosphine Ligand for Acetone Monoarylations. Organometallics. 2016, 35, 1553–1558. (9) (a) Wang, C.-C.; Lei, S.; Cao, H.; Qiu, S.-X.; Liu, J.-Y.; Deng, H.; Yan, C.-J. Regioselective Copper-Catalyzed Dicarbonylation of Imidazo[1,2-a]pyridines with N,N-Disubstituted Acetamide or Acetone: An Approach to 1,2-Diketones Using Molecular Oxygen. J. Org. Chem. 2015, 80, 12725–12732. (b) Lim, H. N.; Dong, G.-B. Catalytic Intramolecular Ketone Alkylation with Olefins by Dual Activation. Angew. Chem. Int. Ed. 2015, 54, 15294–15298. (c) Tu, J.; Lee, D.; Zhao, Yu. Direct Enantioselective α-Allylation of Unfunctionalized Cyclic Ketones with Alkynes through Pd-Amine Cooperative Catalysis. Chem. Eur. J. 2018, 24, 9520–9524. (d) Tang, S.-Z.; Zhao, W.-S.; Chen, T.; Liu, Y.; Zhang, X.-M.; Zhang, F.-M. A Simple and Efficient Method for the Preparation of α-Halogenated Ketones Using Iron(III) Chloride and Iron(III) Bromide as Halogen Sources with Phenyliodonium Diacetate as Oxidant. Adv. Synth. Catal. 2017, 359, 4177– 4183. (e) Gurka, A. A.; lSzőri, K.; Szőllősi, G.; Bartók, M.; London, G. Tuning the Sense of Product Stereochemistry in Aldol Reactions of Acetone and Aromatic Aldehydes in the Presence of Water with a Single Chiral Catalyst. Tetrahedron Lett. 2015, 56, 7201–7205. (f) Xu, L.; Wang, F.; Huang, J.-J.; Yang, C.-G.; Yu, L.; Fan, Y.-N. L-Proline and Thiourea Co-Catalyzed Condensation of Acetone. Tetrahedron Lett. 2016, 72, 4076–4080. (10) (a) Chu, X.-Q.; Xing, Z.-H.; Meng, H.; Xu, X.-P.; Ji, S.-J. Copper-Mediated Radical Alkylarylation of Unactivated Alkenes with Acetonitrile Leading to Fluorenes and Pyrroloindoles. Org. Chem. Front. 2016, 3, 165–169. (b) Pan, C.-D.; Yang, Z.-K.; Gao, D.; Yu, J.-T. Metal-Free Oxidative Radical Cascade Addition/ Oxobutylation of Unactivated Alkenes with Acetone Towards 3-(3-Oxobutyl)indolines. Org. Biomol. Chem. 2018, 16, 6035–6038. (c) Yang, W.; Wang, J.-Y.; Wang, H.; Li, L.; Guan, Y.-K.; Xu, X.-X.; Yu, D.-Y. Rhodium(III)-Catalyzed ThreeComponent Cascade Synthesis of 6H-Benzo[c]chromenes Through C–H Activation. Org. Biomol. ACS Paragon Plus Environment

39


Page 40 of 46

Chem. 2018, 16, 6865–6869. (d) Fu, W.-C.; Zheng, B.; Zhao, Q.-Y.; Chan, W.-T.-K.; Kwong, F.Y. Cascade Amination and Acetone Monoarylation with Aryl Iodides by Palladium/Norbornene Cooperative Catalysis. Org. Lett. 2017, 19, 4335–4338. (e) Lv, Y.; Pu, W.; Niu, J.-J.; Wang, Q.Q.; Chen, Q. nBu4NI-Catalyzed C–C Bond Formation to Construct 2-Carbonyl-1,4-diketones Under Mild Conditions. Tetrahedron Lett. 2018, 59, 1497–1500. (f) González-Martínez, D.; Gotor, V.; Gotor-Fernández, V. Application of Deep Eutectic Solvents in Promiscuous LipaseCatalysed Aldol Reactions. Eur. J. Org. Chem. 2016, 1513–1519. (g) Mao, Z.-Y.; Liu, Y.-W.; Han, P.; Dong, H.-Q.; Si, C.-M.; Wei, B.-G.; Lin, G.-Q. Regio- and Stereoselective Cascades via Aldol Condensation and 1,3-Dipolar Cycloaddition for Construction of Functional Pyrrolizidine Derivatives. Org. Lett. 2018, 20, 1090−1093. (h) Wu, Y.-D.; Huang, B.; Zhang, Y.-X.; Wang, X.X.; Dai, J.-J.; Xu, J.; Xu, H.-J. KI-Catalyzed α-Acyloxylation of Acetone with Carboxylic Acids. Org. Biomol. Chem. 2016, 14, 5936–5939. (i) Heiba, E. I.; Dessau, R. M. Oxidation by Metal Salts. IX. Formation of Cyclic Ketones. J. Am. Chem. Soc. 1972, 94, 2888–2889. (11) (a) Rybtchinski, B.; Milstein, D. Metal Insertion into C−C Bonds in Solution Angew. Chem. Int. Ed. 1999, 38, 870–883. (b) van der Boom, M.-E.; Milstein, D. Cyclometalated Phosphine-Based Pincer Complexes: Mechanistic Insight in Catalysis, Coordination, and Bond Activation. Chem. Rev. 2003, 103, 1759–1792. (c) Jun, C.-H. Transition Metal-Catalyzed Carbon–Carbon Bond Activation. Chem. Soc. Rev. 2004, 33, 610–618. (d) Satoh, T.; Miura, M. Catalytic Processes Involving β-Carbon Elimination. Top. Organomet. Chem. 2005, 14, 1–20. (e) Jun, C.-H.; Park, J.W. Directed C–C Bond Activation by Transition Metal Complexes. Top. Organomet. Chem. 2007, 24, 117–143. (f) Liang, Y.-F.; Müller, V.; Liu, W.-P.; Münch, A.; Stalke, D.; Ackermann, L. Methylenecyclopropane Annulation by Manganese(I)-Catalyzed Stereoselective C−H/C−C Activation. Angew. Chem. Int. Ed. 2017, 56, 9415–9419. (g) Liang, Y.-F.; Jiao, N. Oxygenation via C–H/C–C Bond Activation with Molecular Oxygen. ACS Catal. 2017, 50, 1640–1653. (12) (a) Jones, W.-D. The Fall of the C-C Bond. Nature 1993, 364, 676–677. (b) Seiser, T.; Saget, T.; Tran, D.-N.; Cramer, N. Cyclobutanes in Catalysis. Angew. Chem. Int. Ed. 2011, 50, 7740–7752. ACS Paragon Plus Environment

40

Page 41 of 46 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


(c) Seiser, T.; Cramer, N. Enantioselective Metal-Catalyzed Activation of Strained Rings. Org. Biomol. Chem. 2009, 7, 2835–2840. (d) Aïssa, C. Transition-Metal-Catalyzed Rearrangements of Small Cycloalkanes: Regioselectivity Trends in β-Carbon Elimination Reactions. Synthesis 2011, 3389–3407. (e) Zeng, R.; Dong G.-B. Rh-Catalyzed Decarbonylative Coupling with Alkynes via C–C Activation of Isatins. J. Am. Chem. Soc. 2015, 137, 1408–1411. (f) Zhou, X.; Dong, G.-B. (4+1) vs (4+2): Catalytic Intramolecular Coupling between Cyclobutanones and Trisubstituted Allenes via C–C Activation. J. Am. Chem. Soc. 2015, 137, 13715–13721. (13) (a) Chen, P.-H.; Billett, B.-A.; Tsukamoto T.; Dong, G. “Cut and Sew” Transformations via Transition-Metal-Catalyzed Carbon–Carbon Bond Activation. ACS Catal. 2017, 7, 1340–1360. (b) Dermenci, A.; Coe, J.-W.; Dong, G. Direct Activation of Relatively Unstrained Carbon–Carbon Bonds in Homogeneous Systems. Org. Chem. Front. 2014, 1, 567–581. (c) Souillart, L.; Cramer, N. Catalytic C–C Bond Activations via Oxidative Addition to Transition Metals. Chem. Rev. 2015, 115, 9410–9464. (d) Avullala, T.; Asgari, P.; Hua, Y.; Bokka, A.; Ridlen, S. G.; Yum, K.; Dias, H. V. R.; Jeon, J. Umpolung α-Silylation of Cyclopropyl Acetates via Low-Temperature Catalytic C– C Activation. ACS Catal. 2019, 9, 402–408. (14) (a) Shuai, L.; Sitison, J.; Sadula, S.; Junhuan; D., Thies, M. C.; Saha, B. Selective C–C Bond Cleavage of Methylene-Linked Lignin Models and Kraft Lignin. ACS Catal. 2018, 8, 6507–6512. (b) Liu, J.-Z.; Wen, X.-J.; Qin, C.; Li, X.-Y.; Luo ,X.; Sun A.; Zhu, B.-C.; Song, S.; Jiao, N. Oxygenation of Simple Olefins through Selective Allylic C−C Bond Cleavage: A Direct Approach to Cinnamyl Aldehydes. Angew. Chem. Int. Ed. 2017, 56, 11940–11944. (c) Sen, C.; Ghosh, S. C. Transition-Metal-Free Regioselective Alkylation of Quinoline N-Oxides via Oxidative Alkyl Migration and C−C Bond Cleavage of tert-/sec-Alcohols. Adv. Synth. Catal. 2018, 360, 905–910. (d) Huang, G.-H.; Lu, L.; Jiang, H.-F.; Yin, B.-L. Aerobic Oxidative α-Arylation of Furans with Boronic Acids via Pd(II)-Catalyzed C–C Bond Cleavage of Primary Furfuryl Alcohols: Sustainable Access to Arylfurans. Chem. Commun. 2017, 53, 12217–12220. (e) Zhang, C.-Y.; Jiang, H.-F.; Zhu, S.-F. Gold-Catalyzed Ring-Expansion through Acyl Migration to Afford FuranACS Paragon Plus Environment

41


Page 42 of 46

Fused Polycyclic Compounds. Chem. Commun. 2017, 53, 2677–2680. (f) Jiang, M.; Liu, L.-P.; Shi, M.; Li, Y.-X. Gold(I)-Catalyzed Tandem C−H and C−C Activation (Cleavage). Org. Lett. 2010, 12, 116–119. (g) Murakami, M.; Ito, Y. Cleavage of Carbon—Carbon Single Bonds by Transition Metals. Top. Organomet. Chem. 1999, 3, 97–129. (15) (a) Necas, D.; Kotora, M. Rhodium-Catalyzed C–C Bond Cleavage Reactions. Curr. Org. Chem. 2007, 11, 1566–1591. (b) Korotvicka, A.; Necas, D.; Kotora, M. Rhodium-catalyzed C–C Bond Cleavage Reactions-An Update. Curr. Org. Chem. 2012, 16, 1170–1214. (c) Murakami, M.; Matsuda, T. Metal-Catalysed Cleavage of Carbon–Carbon Bonds. Chem. Commun. 2011, 47, 1100–1105. (d) Murakami, M.; Ishida, N. Potential of Metal-Catalyzed C–C Single Bond Cleavage for Organic Synthesis. J. Am. Chem. Soc. 2016, 138, 13759–13769. (e) Fumagalli, G.; Stanton, S.; Bower, J.-F. Recent Methodologies That Exploit C–C Single-Bond Cleavage of Strained Ring Systems by Transition Metal Complexes. Chem. Rev. 2017, 117, 9404–9432. (16) (a) Tsuritani, T.; Shinokubo, H.; Oshima, K. Coupling of Vinylcyclopropanes with Aldehydes Induced by a TiCl4/n-Bu4NI Combination: Synthesis of Conjugated Dienols. Synlett. 2002, 6, 978– 980. (b) Wang, S.-C.; Troast, D.-M.; Conda-Sheridan, M.; Zuo, G.; LaGarde, D.; Louie, J.; Tantillo, D.-J. Mechanism of the Ni(0)-Catalyzed Vinylcyclopropane−Cyclopentene Rearrangement. J. Org. Chem. 2009, 74, 7822–7833. (c) Zuo, G.; Louie, J. Highly Active Nickel Catalysts for the Isomerization of Unactivated Vinyl Cyclopropanes to Cyclopentenes. Angew. Chem. Int. Ed. 2004, 43, 2277–2279. (d) Amador, A.-G.; Sherbrook, E.-M.; Yoon, T.-P. Enantioselective Photocatalytic [3+2] Cycloadditions of Aryl Cyclopropyl Ketones. J. Am. Chem. Soc. 2016, 138, 4722–4725. (e) Hao, W.; Harenberg, J.-H.; Wu, X.-Y.; MacMillan, S,-N.; Lin, S. Diastereo- and Enantioselective Formal [3+2] Cycloaddition of Cyclopropyl Ketones and Alkenes via Ti-Catalyzed Radical Redox Relay. J. Am. Chem. Soc. 2018, 140, 3514–3517. (f) Ke, Z.-H.; Wong, Y.-C.; See, J.-Y.; Yeung, Y.-Y. Electrophilic Bromolactonization of Cyclopropyl Carboxylic Acids Using Lewis Basic Sulfide Catalyst. Adv. Synth. Catal. 2016, 358, 1719–1724.


42

Page 43 of 46 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


(17) (a) Yu, X.-Y.; Chen, J.-R.; Wang, P.-Z.; Yang, M.-N.; Liang, D.; Xiao, W.-J. A Visible-LightDriven Iminyl Radical-Mediated C−C Single Bond Cleavage/Radical Addition Cascade of Oxime Esters. Angew. Chem. Int. Ed. 2018, 57, 738–743. (b) Nishimura, T.; Yoshinaka, T.; Nishiguchi, Y. Iridium-Catalyzed Ring Cleavage Reaction of Cyclobutanone O-Benzoyloximes Providing Nitriles. Org. Lett. 2005, 7, 2425–2427. (c) Li, L-Y.; Chen, H-G.; Mei, M.-J.; Zhou, L. VisibleLight Promoted γ-Cyanoalkyl Radical Generation: Three-Component Cyanopropylation/Etherification of Unactivated Alkenes. Chem. Commun. 2017, 53, 11544–11547. (d) Gu, Y.-R.; Duan, X.-H.; Yang, L.; Guo, L.-N. Direct C–H Cyanoalkylation of Heteroaromatic N-Oxides and Quinones via C–C Bond Cleavage of Cyclobutanone Oximes. Org. Lett. 2017, 19, 5908–5911. (e) Yao, S.; Zhang, K.; Zhou, Q.-Q.; Zhao, Y.; Shi, D.-Q.; Xiao, W-J. PhotoredoxPromoted Alkyl Radical Addition/Semipinacol Rearrangement Sequences of Alkenylcyclobutanols: Rapid Access to Cyclic Ketones. Chem. Commun. 2018, 54, 8096–8099. (f) Wang, P.-Z.; Yu, X.-Y.; Li, C.-Y.; Chen, B.-Q.; Chen, J.-R.; Xiao, W.-J. A Photocatalytic Iminyl Radical-Mediated C–C Bond Cleavage/Addition/Cyclization Cascade for the Synthesis of 1,2,3,4Tetrahydrophenanthrenes. Chem. Commun. 2018, 54, 9925–9928. (18) (a) Rubin, M.; Rubina, M.; Gevorgyan, V. Transition Metal Chemistry of Cyclopropenes and Cyclopropanes. Chem. Rev. 2007, 107, 3117−3179. (b) Shao, L.-X.; Shi, M. Lewis and Bronsted Acid Mediated Ring-Opening Reactions of Methylenecyclopropanes and Further Transformation of the Ring-Opened Products. Curr. Org. Chem. 2007, 11, 1135−1153. (c) Purser, S.; Moore, P.R.; Swallow, S.; Gouverneur, V. Fluorine in Medicinal Chemistry. Chem. Soc. Rev. 2008, 37, 320−330. (d) Shi, M.; Shao, L.-X.; Lu, J.-M.; Wei, Y.; Mizuno, K.; Maeda, H. Chemistry of Vinylidenecyclopropanes. Chem. Rev. 2010, 110, 5883−5913. (e) Shi, M.; Lu, J.-M.; Wei, Y.; Shao, L.-X. Rapid Generation of Molecular Complexity in the Lewis or Brønsted Acid-Mediated Reactions of Methylenecyclopropanes. Acc. Chem. Res. 2012, 45, 641−652. (f) Brandi, A.; Cicchi, S.; Cordero, F.M.; Goti, A. Progress in the Synthesis and Transformations of Alkylidenecyclopropanes and Alkylidenecyclobutanes. Chem. Rev. 2014, 114, 7317−7420. (g) ACS Paragon Plus Environment

43


Page 44 of 46

Zhang, D.-H.; Tang, X.-Y.; Shi, M. Gold-Catalyzed Tandem Reactions of Methylenecyclopropanes and Vinylidenecyclopropanes. Acc. Chem. Res. 2014, 47, 913−924. (19) (a) Zhu, Z.-Z.; Chen, K.; Yu, L.-Z.; Tang, X. -Y.; Shi, M. Copper(I)-Catalyzed Intramolecular Trifluoromethylation of Methylenecyclopropanes Org. Lett. 2015, 17, 5994–5997. (b) Chen, M.T.; Tang, X.-Y.; Shi, M. A Facile Approach for the Trifluoromethylthiolation of Methylenecyclopropanes. Org. Chem. Front. 2017, 4, 86–90. (c) Liu, Y.; Wang, Q.-L.; Zhou, C.S.; Xiong, B.-Q.; Zhang, P.-L.; Yang, C.-A.; Tang, K.-W. Metal-Free Oxidative C–C Bond Functionalization of Methylenecyclopropanes with Ethers Leading to 2-Substituted 3,4Dihydronaphthalenes. J. Org. Chem. 2017, 82, 7394−7401. (d) Liu, Y.; Wang, Q.-L.; Zhou, C.-S.; Xiong, B.-Q.; Zhang, P.-L.; Yang, C.-A.; Tang, K.-W. Oxidative C–C Bond Functionalization of Methylenecyclopropanes with Aldehydes for the Formation of 2-Acyl-3,4-dihydronaphthalenes. J. Org. Chem. 2018, 83, 4657−4664. (e) Liu, Y.; Wang, Q.-L.; Chen, Z.; Zhou, Q.; Zhou, C.-S.; Xiong, B.-Q.; Zhang, P.-L.; Yang, C.-A.; Tang, K.-W. Silver-Mediated Oxidative C–C Bond Sulfonylation/Arylation of Methylenecyclopropanes with Sodium Sulfinates: Facile Access to 3Sulfonyl-1,2-Dihydronaphthalenes. Org. Biomol. Chem. 2019, 17, 1365−1369. (f) Li, J.; Chen, J.Z.; Jiao, W.; Wang, G.-Q.; Li, Y.; Cheng, X.; Li, G.-G. Difluoroalkylation/C–H Annulation Cascade Reaction Induced by Visible-Light Photoredox Catalysis. J. Org. Chem. 2016, 81, 9992−10001. (g) Zhu, Z.-Z.; Chen, K.; Yu, L.-Z.; Tang, X.-Y.; Shi, M. Copper(I)-Catalyzed Intramolecular Trifluoromethylation of Methylenecyclopropanes. Org. Lett. 2015, 17, 5994−5997. (h) Huang, J.-W.; Shi, M. Manganese(III)-Mediated Oxidative Annulation of Methylenecyclopropanes with 1,3-Dicarbonyl Compounds. J. Org. Chem. 2005, 70, 3859−3863. (20) (a) Yu, L.; Wu, Y.-L.; Chen, T.; Pan, Y.; Xu, Q. Direct Synthesis of Methylene-1, 2dichalcogenolanes via Radical [3+2] Cycloaddition of Methylenecyclopropanes with Elemental Chalcogens. Org. Lett. 2013, 15, 144–147. (b) Xu, B.; Chen, Y.; Shi, M. The Reactions of Thiols and Diphenyldisulﬁde with Terminally Substituted Methylenecyclopropanes. Tetrahedron Lett. 2002, 43, 2781–2784. (c) Chen, M.-T.; Wei, Y.; Shi, M. A Facile Method for the Synthesis of ACS Paragon Plus Environment

44

Page 45 of 46 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


Trifluoromethylthio-/chloro-homoallylic alcohols from Methylenecyclopropanes. Org. Chem. Front. 2018,5, 2030–2034. (d) Fang, W.; Wei Y.; Shi, M. A Gold(I)-Catalyzed Intramolecular Tandem Cyclization Reaction of Alkylidenecyclopropanecontaining Alkynes. Chem. Commun.2017, 53, 11666–11669. (21) (a) Wu, W.-Q.; Yi, S.-J.; Yu, Y.; Huang, W.; Jiang, H.-F. Synthesis of Sulfonylated Lactones via Ag-Catalyzed Cascade Sulfonylation/Cyclization of 1,6-Enynes with Sodium Sulfinates. J. Org. Chem. 2017, 82, 1224−1230. (b) Wu, W.-Q.; Yi, S.-J.; Huang, W.; Luo, D.; Jiang, H.-F. AgCatalyzed Oxidative Cyclization Reaction of 1,6-Enynes and Sodium Sulfinate: Access to Sulfonylated Benzofurans. Org. Lett. 2017, 19, 2825−2828. (c) Zhao, Q.-C.; Lu, L.; Shen, Q.-L. Direct Monofluoromethylthiolation with S‐(Fluoromethyl) Benzenesulfonothioate. Angew. Chem. Int. Ed. 2017, 56, 11575−11578. (d) Singh, A.-K.; Chawla, R.; Keshari, T.; Yadav, V.-K.; Yadav, L.-D.-S. Aerobic Oxysulfonylation of Alkenes Using Thiophenols: An Efficient One-pot Route to β-Ketosulfones. Org. Biomol. Chem. 2014, 12, 8550−8554. (e) Ilangovan, A.; Saravanakumar, S.; Malayappasamy, S. γ-Carbonyl Quinones: Radical Strategy for the Synthesis of Evelynin and Its Analogues by C–H Activation of Quinones Using Cyclopropanols. Org. Lett. 2013, 15, 4968−4971. (f) Hossian, A.; Jana, R. Org. Biomol. Chem. 2016, 14, 9768−9779.(g) Wang, C.-Y.; Song, R.-J.; Xie, Y.-X.; Li, J.-H. Silver-Promoted Oxidative Ring Opening/Alkynylation of Cyclopropanols: Facile Synthesis of 4-Yn-1-ones. Synthesis 2016, 48, 223−230. (22) (a) Zhang, M.-Z.; Ji, P.-Y.; Liu, Y.-F.; Guo, C.-C. Transition-Metal-Free Synthesis of CarbonylContaining Oxindoles from N-Arylacrylamides and α-Diketones via TBHP- or Oxone-Mediated Oxidative Cleavage of C(sp2)–C(sp2) Bonds. J. Org. Chem. 2015, 80, 10777–10786. (b) Parida, K. N.; Moorthy, J. N. Synthesis of o-Carboxyarylacrylic Acids by Room Temperature Oxidative Cleavage of Hydroxynaphthalenes and Higher Aromatics with Oxone. J. Org. Chem. 2015, 80, 8354–8360. (c) Zhao, M.; Lu, W. Visible Light-Induced Oxidative Chlorination of Alkyl sp3 C–H Bonds with NaCl/Oxone at Room Temperature. Org. Lett. 2017, 19, 4560–4563. (d) Hou, F.; ACS Paragon Plus Environment

45


Page 46 of 46

Wang, X.-C.; Quan, Z.-J. Efficient Synthesis of Esters Through Oxone-catalyzed Dehydrogenation of Carboxylic Acids and Alcohols. Org. Biomol. Chem. 2018, 16, 9472–9476. (e) Saha, R.; Perveen, N.; Nihesh, N.; Sekar, G. Reusable Palladium Nanoparticles Catalyzed Oxime Ether Directed Mono Ortho-Hydroxylation under Phosphine Free Neutral Condition. Adv. Synth. Catal. 2019, 361, 510–519. (23) (a) Antoniou, M. G.; de la Cruz, A. A.; Dionysiou, D. D. Degradation of Microcystin-LR Using Sulfate Radicals Generated Through Photolysis, Thermolysis and e− Transfer Mechanisms. Applied Catalysis B: Environmental. 2010, 96, 290−298. (b) Coffman, D. D.; Jenner, E. L.; Lipscomb, R. D. Syntheses by Free-radical Reactions. I. Oxidative Coupling Effected by Hydroxyl Radicals. J. Am. Chem. Soc. 1958, 80, 2864–2872.


46

Arylation of

Recommend Documents