N-Heterocyclic Carbene-Catalyzed Formal Conjugate Hydroacylation

Subscriber access provided by EKU Libraries

Article

N-Heterocyclic Carbene-Catalyzed Formal Conjugate Hydroacylation: An Atom Economic Synthesis of 1H-Indol-3-yl Esters Jindong Zhu, Shuaishuai Fang, Kewen Sun, Chao Fang, Tao Lu, and Ding Du J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01488 • Publication Date (Web): 16 Aug 2018 Downloaded from http://pubs.acs.org on August 16, 2018

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 18 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

electrophiles (Scheme 1).

N O R

O

X N

OH R

H

NHC

E N

N X

R'

R

O

or OH Benzoin O

R acyl anions

R EWG Stetter reaction

a1-d1 umpolung

Scheme 1. NHC-catalyzed hydroacylations via the a1-d1 umpolung process. In

2006,

Scheidt and

coworkers24

reported

an

NHC-catalyzed

unique

hydroacylation reduction of activated ketones with aldehydes via a Cannizzaro-type hydride transfer process (Scheme 2a). In this process, the collapse of NHC-bound intermediate I afforded an acylazolium intermediate accompanied with the generation of a hydride adding to the carbon of ketones. However, after this finding, there are very limited examples of NHC-catalyzed hydroacylations that involve a hydride transfer process.25-29 Chen’s group28 reported a carbene-catalyzed conjugate reduction of alkenes through an intramolecular 1,5-hydride transfer from the aldehyde group. Recently, Wang’s group29 disclosed a novel intramolecular NHC-catalyzed dehydrogenative coupling reaction of enals via a hydride transfer process. Among these NHC-catalyzed hydroacylations, the hydride was either transferred to the carbon of unsaturated double bonds or transferred to combine with the proton. To the best of our knowledge, there is no documented literature related to NHC-catalyzed hydroacylation with the hydride transferred to a heteroatom. Herein, we report a novel NHC-catalyzed formal conjugate hydroacylation of 2-aryl-3H-indol-3-ones 2 with aldehydes 1. In this reaction, the hydride was formally transferred to the nitrogen of substrates 2, affording a series of 2-aryl 1H-indol-3-yl esters. It is noteworthy that indol-3-yl esters are important materials in organic synthesis as well as in bioorganic chemistry, and also distribute in many bioactive compounds.30-35

ACS Paragon Plus Environment

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

Page 2 of 18

a) Hydride transferred to the carbon of carbonyls (Scheidt's work)

O R

N N

N

O

O H

R

H

N

NHC

O R

R1

OEt 1,2-addition O hydroacylation

O

H

O OEt

R1

N X I b) Hydride transferred to the carbon of alkenes (Chen's work) COOMe

CHO Ph

NHC

CN Ph MeOH H CN 1,5-hydride transfer

CN CN

c) Hydride transferred to combine with the proton (W ang's work) O NH

H

R1 2

3

R

R3

O

O

R

NHC dehydrogenative coupling

O

N

R2

+ H-H

R1 d) Hydride formally transferred to the nitrogen (this work)

R1

H 1

R2

O

R2

O

R1 O

NHC

+

R3 N 2

formal conjugate hydroacylation

O R3

N 3 H

Scheme 2. NHC-catalyzed hydroacylations via a hydride transfer process. RESULTS AND DISCUSSION We initiated our study by examining the reaction of benzaldehyde 1a with 2-phenyl-indol-3-one 2a in the presence of an NHC (Table 1). In a preliminary investigation of the efficiency of carbene precursors A-E, the reaction catalyzed by catalyst A, C or D afforded the desired product 3a in moderate yields (entries 1-5). Further screening of the bases and solvents (entries 6-12) convinced us that Cs2CO3 and THF are the optimal base and solvent, respectively, affording product 3a in 64% yield (entry 7). It was found that the reaction yield could be enhanced to 80% when the catalyst-loading was increased to 15 mol% (entry 13), and further increase of the catalyst-loading to 20 mol% did not lead to significant enhancement of the yield (entry 14). Therefore, the optimal reaction conditions were established as shown in entry 13.


Page 3 of 18 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. Optimization of the reaction conditions a

entry 1 2 3 4 5 6 7 8 9 10 11 12 13c 14d

cat A B C D E A A A A A A A A A

base DBU DBU DBU DBU DBU DIPEA Cs2CO3 K2CO3 Cs2CO3 Cs2CO3 Cs2CO3 Cs2CO3 Cs2CO3 Cs2CO3

solvent THF THF THF THF THF THF THF THF 1,2-DCE Toluene 1,4-dioxane CH3CN THF THF

yield (%)b 50 trace 47 40 trace trace 64 60 52 58 trace 40 80 83

a

Unless otherwise stated, all reactions were performed with 0.26 mmol of 1a, 0.2 mmol of 2a, 0.02 mmol of a catalyst, 0.06 mmol of a base, and 100 mg of 4Å MS in a dry solvent at 60 oC for 2.5 h under N2. b Isolated yields based on 2a. c 15 mol% of A was used. d 20 mol% of A was used.

After optimizing the reaction conditions, we examined the scope and limitations of this reaction. Initially, a variety of aldehydes 1 were used to react with 2-phenyl-3H-indol-3-one 2a in the presence of catalyst A (Table 2). Substituted benzaldehydes 1b-m with diverse substituents at different positions were well tolerated to this protocol, furnishing the desired products 3b-m in moderate to high yields (entries 1-12). Notably, the reaction time of 2-methylbenzaldehyde 1m was shorter than other substrates since prolonged reaction time led to a lower yield due to the decomposition of product 3m under this condition. Gratifyingly, 1- and 2-naphthaldehyde as well as 2-furaldehyde and 2-thenaldehyde were also suitable to



Page 4 of 18

this reaction, affording products 3n-q in high yields (entries 13-16). The reaction of cinnamaldehyde 1r equally worked smoothly to give product 3r in 75% yield (entry 17). Unfortunately, 3-phenylpropiolaldehyde 1s, ethyl 2-oxoacetate 1t and aliphatic aldehyde 1u were not tolerated to this protocol (entry 18-20). Table 2. Scope of the reaction between aldehydes 1 and 2-phenyl-3H-indol-3-one 2a a

entry

R1, 1

3, yield (%) b

1 2 3 4 5 6 7 8 9 10 11 12c 13 14 15 16 17 18 19 20

4-FC6H4, b 4-ClC6H4, c 4-BrC6H4, d 4-MeC6H4, e 4-OMeC6H4, f 3-FC6H4, g 3-ClC6H4, h 3-OMeC6H4, i 3-MeC6H4, j 2-ClC6H4, k 2-OMeC6H4, l 2-MeC6H4, m 1-naphthyl, n 2-naphthyl, o 2-thienyl, p 2-furyl, q

3b, 87 3c, 85 3d, 87 3e, 98 3f, 98 3g, 88 3h, 83 3i, 92 3j, 97 3k, 97 3l, 62 3m, 97 3n, 96 3o, 96 3p, 93 3q, 96 3r, 75 0 0 0

,r ,s CO2Et, t n-Bu, u

a

Unless otherwise stated, all reactions were performed with 0.26 mmol of 1, 0.2 mmol of 2a, 0.03 mmol of catalyst A, 0.06 mmol of Cs2CO3, and 100 mg of 4Å MS in dry THF at 60 oC for 2.5 h under N2. b Isolated yields based on 2a. c The reaction time was 1 h.

We then moved to investigate the scope of the reaction between benzaldehyde 1a and diverse 2-aryl-3H-indol-3-ones 2 (Table 3). It was found that the reaction of 2-substituted-phenyl-3H-indol-3-ones 2b-f worked equally well to afford products


Page 5 of 18 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


3s-w in good to high yields (entries 1-5). However, due to the instability of the products under the reaction conditions, the reaction of substrates 2b, 2e and 2f should be monitored carefully and quenched timely as long as substrates 2 were completely consumed (entries 1, 3 and 5). We were happy to find that the reaction of substrate 2g with a steric hindered 1-naphthyl group also gave rise to product 3x in 91% yield (entry 6). Finally, two typical 5-substituted 2- phenyl-3H-indol-3-ones 2h and 2i were tested (entries 7 and 8). The reaction of substrate 2h with 5-OMe group afforded product 3y in a good yield, while the reaction of substrate 2i with 5-Cl group gave product 3z in a lower yield. However, the reaction of 6-OMe-substituted 2-phenyl indol-3-one 2j resulted in low conversion of the substrates without any desired product (entry 9). Table 3. Scope of the reaction between 1a and 2-aryl-3H-indol-3-ones 2 a

entry

R2, R3, 2

time (h)

3, yield (%) b

1 2 3 4 5 6 7 8 9c

H, 4-ClC6H4, b H, 4-MeC6H4, c H, 4-OMeC6H4, d H, 3-ClC6H4, e H, 3-MeC6H4, f H, 1-naphthyl, g 5-OMe, C6H5, h 5-Cl, C6H5, i 6-OMe, C6H5, j

0.8 2.5 2.5 1 1.2 2.5 2.5 2.5 5

3s, 87 3t, 96 3u, 96 3v, 89 3w, 85 3x, 91 3y, 87 3z, 53 0

a

Unless otherwise stated, all reactions were performed with 0.26 mmol of 1a, 0.2 mmol of 2, 0.03 mmol of catalyst A, 0.06 mmol of Cs2CO3, and 100 mg of 4Å MS in dry THF at 60 oC under N2. b Isolated yields based on 2. c Low conversion of both 1a and 2j was observed via TLC.

In order to further explore the utility of this protocol, a scale-up synthesis and derivatization of product 3a were carried out as shown in Scheme 3. With a 1.5 mmol scale under the standard conditions, the reaction yield of 3a was maintained. The acylation of N-H free product 3a with acetyl chloride afforded compound 4a in 82% yield.



Scheme 3. A scale-up synthesis and acylation of 3a. A plausible mechanism for this transformation is proposed as shown in Scheme 4 using 1a and 2a as the model substrates. Deprotonation of carbene precursor A with a base gives rise to carbene A that attacks the carbonyl group of benzaldehyde 1a to form the tetrahedral intermediate. A rapid hydride transfer from II to the carbonyl of 2a via a 1,2-addition (similar to the Cannizzaro-type reaction) affords acylazolium III and intermediate IV, which undergoes 1,3-H shift to give intermediate V (path a). There is another possible pathway for the generation of V; hydride transfer from II to 2a via a direct conjugate addition could also furnish intermediate V and acylazolium III (path b). Since the hydride includes a proton and two electrons, the hydride transfer process may be also considered as that the proton transfers to the nitrogen of 2a coupled with the transfer of two electrons.36 Finally, O-acylation of V with III affords product 3a accompanied with the release of NHC A’ for the next catalytic cycle. In terms of the structure of the products, hydrogen and acyl group of the aldehydes were transferred to the nitrogen and oxygen of 2-aryl-3H-indol-3-ones, respectively, in an atom-economic manner.


Page 6 of 18

Page 7 of 18 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


Scheme 4. Proposed mechanism for this hydroacylation reaction. CONCLUSION In conclusion, we have explored a transition-metal-free NHC-catalyzed formal conjugate hydroacylation of 2-aryl-3H-indol-3-ones with diverse aldehydes. This is the first example related to NHC-catalyzed hydroacylation with hydride formally transferred to a heteroatom. This protocol also offers a rapid and efficient pathway for the atom-economic synthesis of useful 2-aryl 1H-indol-3-yl esters starting from simple materials. EXPERIMENTAL SECTION General Information. All reactions were carried out in dry glassware, and were monitored by analytical thin-layer chromatography (TLC), which was visualized by ultraviolet light (254 nm). All solvents were obtained from commercial sources and were purified according to standard procedures. All aldehydes 1 are commercially available and 2-aryl-3H-indol-3-ones 2 are prepared according to known procedures.37 Purification of the products was accomplished by flash chromatography using silica gel (200-300 mesh). All NMR spectra were recorded on Bruker spectrometers,



running at 300 MHz or 500 MHz for 1H and 75 MHz or 125 MHz for 13C respectively. Chemical shifts (δ) and coupling constants (J) are reported in ppm and Hz respectively. The solvent signals were used as references (residual CHCl3 in CDCl3: δH = 7.26 ppm, δc = 77.0 ppm). The following abbreviations are used to indicate the multiplicity in NMR spectra: s (singlet); d (doublet); t (triplet); q (quartet); m (multiplet). High resolution mass spectrometry (HRMS) was recorded on TOF perimer for ESI+. General procedure for the synthesis of 1H-indol-3-yl esters 3. To an oven-dried 10 mL flask was charged with an aldehyde 1 (0.26 mmol), an 2-aryl-3H-indol-3-one 2 (0.2 mmol), 19.5 mg of Cs2CO3 (0.06 mmol), 10 mg of catalyst A (0.03 mmol), and 100 mg of 4 Å molecular sieves. Then, 2 mL of dry THF was added and the resulting mixture was stirred at 60 oC under N2. Upon completion of the reaction as monitored by TLC, the mixture was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by flash chromatography on silica gel using hexane/ethyl acetate (15:1) as the eluent to afford products 3. Procedure for the scale-up synthesis of product 3a. To an oven-dried 25 mL flask was charged with benzaldehyde 1a (207 mg, 1.95 mmol), 2-phenyl-3H-indol-3-one 2a (311 mg, 1.5 mmol), Cs2CO3 (159 mg, 0.45 mmol), catalyst A (77 mg, 0.225 mmol), and 200 mg of 4 Å molecular sieves. Then, 10 mL of dry THF was added and the resulting mixture was stirred at 60 oC under N2. Upon completion of the reaction as monitored by TLC, the mixture was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by flash chromatography on silica gel using hexane/ethyl acetate (15:1) as the eluent to afford 394 mg (84%) of products 3a as a yellowish solid. Procedure for the acylation of compound 3a. To an oven-dried 25 mL flask was charged with compound 3a (63 mg, 0.2 mmol) and 2 mL of dry DMF followed by addition of NaH (80 mg, 2 mmol, 60%) at 0 oC. Then, DMF (1 mL) solution of acetyl chloride (78 mg, 1 mmol) was added dropwise at 0 oC. The resulting mixture was stirred at 0 oC until the completion of the reaction as monitored by TLC. Then, the reaction mixture was quenched with 10 mL of water and was further extracted with


Page 8 of 18

Page 9 of 18 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


EtOAc (10 mL×3). The combined organic phase was washed with brine (20 mL) and was dried over anhydrous Na2SO4. The mixture was then filtered and the resulting filtrate was concentrated under reduced pressure. The obtained residue was purified by flash chromatography on silica gel using hexane/ethyl acetate (20:1) as the eluent to afford 58 mg (82%) of product 4. 2-Phenyl-1H-indol-3-yl benzoate (3a). 50 mg (80%), yellowish solid, mp: 142-144oC. 1

H NMR (300 MHz, CDCl3) δ 8.39-8.25 (m, 2H), 8.11 (brs, 1H), 7.69-7.66 (m, 3H),

7.56 (t, J = 7.5 Hz, 2H), 7.48-7.34 (m, 4H), 7.31 (d, J = 7.4 Hz, 1H), 7.25-7.18 (m, 1H), 7.13 (t, J = 7.4 Hz, 1H).

13

C NMR (75 MHz, CDCl3) δ 165.0, 133.7, 133.6,

130.6, 130.4, 129.3, 129.0, 128.7, 127.7, 127.0, 126.2, 126.1, 123.1, 122.3, 120.4, 117.9, 111.5. HRMS (ESI) calcd for C21H16NO2 (M+H)+: 314.1181, found 313.1171. 2-Phenyl-1H-indol-3-yl 4-fluorobenzoate (3b). 58 mg (87%), yellowish solid, mp: 153-155oC. 1H NMR (300 MHz, CDCl3) δ 8.36-8.30 (m, 2H), 8.20 (brs, 1H), 7.62 (d, J = 7.3 Hz, 2H), 7.44 (d, J = 7.8 Hz, 1H), 7.37 (t, J = 7.4 Hz, 2H), 7.32-7.10 (m, 6H). 13

C NMR (75 MHz, CDCl3) δ 166.3 (d, J = 253.5 Hz), 164.0, 133.6, 133.0 (d, J = 9.4

Hz), 130.5, 129.0, 127.8, 126.9, 126.2, 126.1, 125.4 (d, J = 2.9 Hz), 123.1, 122.2, 120.5, 117.8, 115.9 (d, J = 21.9 Hz), 111.5. HRMS (ESI) calcd for C21H15FNO2 (M+H)+: 332.1087, found 332.1086. 2-Phenyl-1H-indol-3-yl 4-chlorobenzoate (3c). 59 mg (85%), yellowish solid, mp: 165-167oC. 1H NMR (300 MHz, CDCl3) δ 8.24 (d, J = 8.5 Hz, 2H), 8.16 (brs, 1H), 7.62 (d, J = 7.4 Hz, 2H), 7.53 (d, J = 8.5 Hz, 2H), 7.46-7.34 (m, 3H), 7.31 (d, J = 8.1 Hz, 2H), 7.21 (t, J = 7.2 Hz, 1H), 7.14 (t, J = 7.3 Hz, 1H). 13C NMR (75 MHz, CDCl3) δ 164.1, 140.3, 133.6, 131.7, 130.5, 129.1, 129.0, 127.8, 127.7, 126.8, 126.2, 126.1, 123.2, 122.1, 120.5, 117.8, 111.5. HRMS (ESI) calcd for C21H15ClNO2 (M+H)+: 348.0791, found 348.0790. 2-Phenyl-1H-indol-3-yl 4-bromobenzoate (3d). 68 mg (87%), yellowish solid, mp: 160-162oC. 1H NMR (300 MHz, CDCl3) δ 8.20-8.17 (m, 3H), 7.72 (d, J = 7.5 Hz, 2H), 7.65 (d, J = 7.0 Hz, 2H), 7.47-7.14 (m, 7H). 13C NMR (75 MHz, CDCl3) δ 164.3, 133.7, 132.1, 131.9, 130.5, 129.1, 128.2, 127.9, 127.3, 126.9, 126.3, 126.2, 123.2, 122.2, 120.6, 117.9, 111.5. HRMS (ESI) calcd for C21H15BrNO2 (M+H)+: 392.0286, ACS Paragon Plus Environment


found 392.0283. 2-Phenyl-1H-indol-3-yl 4-methylbenzoate (3e). 64 mg (98%), yellowish solid, mp: 92-94oC. 1H NMR (300 MHz, CDCl3) δ 8.20-8.18 (m, 3H), 7.60 (d, J = 6.8 Hz, 2H), 7.42 (d, J = 7.3 Hz, 1H), 7.34-7.28 (m, 4H), 7.26-7.20 (m, 2H), 7.18-7.07 (m, 2H), 2.46 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 165.1, 144.6, 133.6, 130.6, 130.4, 129.4, 128.9, 127.6, 127.0, 126.5, 126.1, 126.0, 123.0, 122.3, 120.3, 117.9, 111.5. HRMS (ESI) calcd for C22H18NO2 (M+H)+: 328.1338, found 328.1332. 2-Phenyl-1H-indol-3-yl 4-methoxybenzoate (3f). 67 mg (98%), yellowish solid, mp: 198-200oC. 1H NMR (300 MHz, CDCl3) δ 8.32 (d, J = 7.3 Hz, 2H), 8.11 (brs, 1H), 7.68 (t, J = 6.9 Hz, 1H), 7.59-7.52 (m, 4H), 7.43 (d, J = 7.2 Hz, 1H), 7.25 (d, J = 7.0 Hz, 1H), 7.21-7.06 (m, 2H), 6.87 (d, J = 7.6 Hz, 2H), 3.79 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 165.0, 159.3, 133.6, 133.5, 130.4, 129.4, 128.7, 127.5, 126.4, 126.2, 123.3, 122.7, 122.5, 120.3, 117.6, 114.5, 111.3, 55.3. HRMS (ESI) calcd for C22H18NO3 (M+H)+: 344.1287, found 344.1286. 2-Phenyl-1H-indol-3-yl 3-fluorobenzoate (3g). 58 mg (88%), yellowish solid, mp: 130-132oC. 1H NMR (300 MHz, CDCl3) δ 8.20 (brs, 1H), 8.13 (d, J = 7.5 Hz, 1H), 8.02 (d, J = 9.1 Hz, 1H), 7.65 (d, J = 7.0 Hz, 2H), 7.61 -7.51 (m, 1H), 7.51-7.36 (m, 4H), 7.36-7.28 (m, 2H), 7.26-7.14 (m, 2H). 13C NMR (75 MHz, CDCl3) δ 162.7 (J = 246 Hz), 163.8 (J = 3.0 Hz), 133.6, 131.4 (J = 7.5 Hz), 130.5, 130.4 (J = 8.0 Hz), 129.0, 127.8, 126.8, 126.3, 126.2, 126.1, 123.2, 122.1, 120.8 (J = 21.2 Hz), 120.5, 117.8, 117.2 (J = 22.8 Hz), 111.5. HRMS (ESI) calcd for C21H15FNO2 (M+H)+: 332.1087, found 332.1089. 2-Phenyl-1H-indol-3-yl 3-chlorobenzoate (3h). 58 mg (83%), yellowish solid, mp: 139-141oC. 1H NMR (300 MHz, CDCl3) δ 8.30 (t, J = 1.8 Hz, 1H), 8.23-8.12 (m, 2H), 7.69-7.59 (m, 3H), 7.50 (t, J = 7.9 Hz, 1H), 7.45-7.36 (m 3H), 7.34 – 7.27 (m, 2H), 7.25-7.18 (m, 1H), 7.17-7.11 (m, 1H).

13

C NMR (75 MHz, CDCl3) δ 163.8, 134.9,

133.7, 133.6, 130.9, 130.4, 130.3, 130.0, 129.0, 128.5, 127.8, 126.7, 126.3, 126.1, 123.2, 122.0, 120.5, 117.8, 111.5. HRMS (ESI) calcd for C21H15ClNO2 (M+H)+: 348.0791, found 348.0785. 2-Phenyl-1H-indol-3-yl 3-methoxybenzoate (3i). 63 mg (92%), yellowish solid, mp: ACS Paragon Plus Environment

Page 10 of 18

Page 11 of 18 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


154-156oC. 1H NMR (300 MHz, CDCl3) δ 8.17 (brs, 1H), 7.96 (d, J = 7.2 Hz, 1H), 7.85 (s, 1H), 7.68 (d, J = 7.0 Hz, 2H), 7.54-7.10 (m, 9H), 3.92 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 164.8, 159.9, 133.8, 130.7, 129.7, 129.0, 127.7, 127.2, 126.3, 126.2, 123.1, 122.8, 122.4, 120.5, 120.3, 118.0, 114.8, 111.4, 55.5. HRMS (ESI) calcd for C22H18NO3 (M+H)+: 344.1287, found 344.1290. 2-Phenyl-1H-indol-3-yl 3-methylbenzoate (3j). 63 mg (97%), yellowish solid, mp: 144-146oC. 1H NMR (300 MHz, CDCl3) δ 8.20 (brs, 1H), 8.11 (s, 2H), 7.59 (d, J = 7.1 Hz, 2H), 7.48-7.41 (m, 3H), 7.31 (t, J = 7.0 Hz, 2H), 7.27-7.18 (m, 2H), 7.15-7.07 (m, 2H), 2.44 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 165.2, 138.6, 134.5, 133.6, 130.9, 130.6, 129.1, 128.9, 128.6, 127.6, 127.5, 127.0, 126.2, 126.1, 123.0, 122.2, 120.3, 117.8, 111.5. HRMS (ESI) calcd for C22H18NO2 (M+H)+: 328.1338, found 328.1335. 2-Phenyl-1H-indol-3-yl 2-chlorobenzoate (3k). 67 mg (97%), yellow oil. 1H NMR (300 MHz, CDCl3) δ 8.15-8.08 (m, 2H), 7.66 (d, J = 7.2 Hz, 2H), 7.60-7.48 (m, 3H), 7.45-7.36 (m, 3H), 7.32 (d, J = 7.5 Hz, 2H), 7.25-7.14 (m, 2H). 13C NMR (75 MHz, CDCl3) δ 163.9, 134.4, 133.7, 133.1, 131.8, 131.3, 130.6, 129.6, 128.9, 127.9, 126.9, 126.8, 126.5, 126.4, 123.2, 122.2, 120.6, 118.0, 111.5. HRMS (ESI) calcd for C21H15ClNO2 (M+H)+: 348.0791, found 348.0790. 2-Phenyl-1H-indol-3-yl 2-methoxybenzoate (3l). 43 mg (62%), yellowish solid, mp: 157-159oC. 1H NMR (300 MHz, CDCl3) δ 8.24 (brs, 1H), 8.13 (d, J = 7.3 Hz, 1H), 7.73 (d, J = 6.9 Hz, 2H), 7.64-7.56 (m, 1H), 7.52 (d, J = 7.5 Hz, 1H), 7.38 (t, J = 6.9 Hz, 2H), 7.30 (d, J = 7.8 Hz, 2H), 7.22-7.07 (m, 4H), 3.95 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 164.5, 159.8, 134.3, 133.7, 132.3, 130.8, 128.8, 127.6, 127.2, 126.2, 123.0, 122.5, 120.34, 120.30, 119.3, 118.2, 112.3, 111.4, 56.0. HRMS (ESI) calcd for C22H18NO3 (M+H)+: 344.1287, found 344.1280. 2-Phenyl-1H-indol-3-yl 2-methylbenzoate (3m). 63 mg (97%), yellowish solid, mp: 108-110oC. 1H NMR (300 MHz, CDCl3) δ 8.32 (d, J = 7.9 Hz, 1H), 8.18 (brs, 1H), 7.70-7.60 (m, 2H), 7.53 (td, J = 7.5, 1.3 Hz, 1H), 7.48 (d, J = 7.6 Hz, 1H), 7.43-7.33 (m, 4H), 7.33-7.26 (m, 2H), 7.24-7.11 (m, 2H), 2.71 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 165.5, 141.5, 133.7, 132.8, 132.0, 131.3, 130.6, 128.9, 128.4, 127.7, 127.0, 126.3, 126.1, 126.0, 123.0, 122.3, 120.4, 117.8, 111.5. HRMS (ESI) calcd for ACS Paragon Plus Environment


C22H18NO2 (M+H)+: 328.1338, found 328.1333. 2-Phenyl-1H-indol-3-yl 1-naphthoate (3n). 70 mg (96%), yellowish solid, mp: 82-84oC. 1H NMR (300 MHz, CDCl3) δ 9.08 (d, J = 8.2 Hz, 1H), 8.61 (d, J = 6.5 Hz, 1H), 8.23-8.07 (m, 2H), 7.93 (d, J = 7.6 Hz, 1H), 7.72-7.47 (m, 6H), 7.39-7.10 (m, 6H).

13

C NMR (75 MHz, CDCl3) δ 165.5, 134.4, 134.0, 133.8, 131.8, 131.4, 130.7,

129.0, 128.7, 128.3, 127.8, 127.1, 126.5, 126.2, 125.9, 125.7, 124.6, 123.1, 122.4, 120.5, 117.9, 111.5. HRMS (ESI) calcd for C25H18NO2 (M+H)+: 364.1338, found 364.1331. 2-Phenyl-1H-indol-3-yl 2-naphthoate (3o). 70 mg (96%), yellowish solid, mp: 170-171oC. 1H NMR (300 MHz, CDCl3) δ 8.88 (s, 1H), 8.28 (d, J = 8.0 Hz, 1H), 8.13 (brs, 1H), 8.05-7.85 (m, 3H), 7.73-7.52 (m, 4H), 7.47 (d, J = 7.1 Hz, 1H), 7.42-7.04 (m, 6H).

13

C NMR (75 MHz, CDCl3) δ 165.2, 136.0, 133.8, 132.7, 132.2, 130.7,

129.6, 129.0, 128.7, 128.5, 127.9, 127.7, 127.3, 126.9, 126.6, 126.3, 126.2, 125.7, 123.2, 122.5, 120.5, 118.0, 111.5. HRMS (ESI) calcd for C25H18NO2 (M+H)+: 364.1338, found 364.1337. 2-Phenyl-1H-indol-3-yl thiophene-2-carboxylate (3p). 59 mg (93%), yellowish solid, mp: 159-161oC. 1H NMR (300 MHz, CDCl3) δ 8.16-8.09 (m, 2H), 7.75-7.67 (m, 3H), 7.52 (d, J = 7.5 Hz, 1H), 7.41 (t, J = 7.2 Hz, 2H), 7.35-7.11 (m, 5H). 13C NMR (75 MHz, CDCl3) δ 160.4, 134.9, 133.7, 133.6, 132.6, 130.6, 129.0, 128.1, 127.7, 127.0, 126.3, 126.2, 123.1, 122.4, 120.5, 118.1, 111.4. HRMS (ESI) calcd for C19H14NO2S (M+H)+: 320.0745, found 320.0746. 2-Phenyl-1H-indol-3-yl furan-2-carboxylate (3q). 58 mg (96%), yellowish solid, mp: 135-137oC. 1H NMR (300 MHz, CDCl3) δ 8.12 (brs, 1H), 7.71-7.56 (m, 3H), 7.47-7.41 (m, 2H), 7.36 (t, J = 6.8 Hz, 2H), 7.26 (t, J = 7.0 Hz, 2H), 7.21-7.04 (m, 2H), 6.59 (s, 1H).

13

C NMR (75 MHz, CDCl3) δ 156.8, 147.3, 144.0, 133.7, 130.5,

128.9, 127.8, 126.5, 126.4, 126.2, 123.2, 122.3, 120.5, 119.6, 118.0, 112.2, 111.4. HRMS (ESI) calcd for C19H14NO3 (M+H)+: 304.0974, found 304.0972. 2-Phenyl-1H-indol-3-yl cinnamate (3r). 51 mg (75%), yellowish solid, mp: 175-177oC. 1H NMR (300 MHz, CDCl3) δ 8.16 (brs, 1H), 7.98 (d, J = 16.0 Hz, 1H), 7.69-7.58 (m, 4H), 7.50-7.36 (m, 6H), 7.35-7.27 (m, 2H), 7.24-7.11 (m, 2H), 6.79 (d, ACS Paragon Plus Environment

Page 12 of 18

Page 13 of 18 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


J = 16.0 Hz, 1H).

13

C NMR (75 MHz, CDCl3) δ 165.3, 147.0, 134.1, 133.6, 130.8,

130.6, 129.00, 128.97, 128.4, 127.7, 127.0, 126.12, 126.09, 123.1, 122.3, 120.4, 117.9, 116.7, 111.5. HRMS (ESI) calcd for C23H18NO2 (M+H)+: 340.1338, found 340.1341. 2-(4-Chlorophenyl)-1H-indol-3-yl benzoate (3s). 60 mg (87%), yellowish solid, mp: 147-149oC. 1H NMR (300 MHz, CDCl3) δ 8.36-8.26 (m, 2H), 8.18 (brs, 1H), 7.69 (t, J = 7.4 Hz, 1H), 7.56 (t, J = 7.6 Hz, 2H), 7.48 (d, J = 8.6 Hz, 2H), 7.42 (d, J = 7.5 Hz, 1H), 7.28-7.23 (m, 2H), 7.22-7.14 (m, 2H), 7.14-7.07 (m, 1H).

13

C NMR (75 MHz,

CDCl3) δ 165.0, 133.9, 133.7, 133.5, 130.4, 129.2, 129.0, 128.9, 128.8, 127.2, 127.1, 125.1, 123.4, 122.1, 120.6, 117.8, 111.5. HRMS (ESI) calcd for C21H15ClNO2 (M+H)+: 348.0791, found 348.0788. 2-(4-Methylphenyl)-1H-indol-3-yl benzoate (3t). 63 mg (96%), yellowish solid, mp: 152-154oC. 1H NMR (300 MHz, CDCl3) δ 8.33-8.30 (m, 2H), 8.11 (brs, 1H), 7.72-7.64 (m, 1H), 7.61-7.52 (m, 4H), 7.45 (d, J = 7.7 Hz, 1H), 7.31 (d, J = 8.0 Hz, 1H), 7.23-7.08 (m, 4H), 2.35 (s, 3H).

13

C NMR (75 MHz, CDCl3) δ 164.9, 137.7,

133.6, 130.4, 129.7, 129.5, 128.7, 128.5, 127.8, 126.8, 126.5, 126.1, 122.9, 122.5, 120.4, 117.9, 111.4, 21.2. HRMS (ESI) calcd for C22H18NO2 (M+H)+: 328.1338, found 328.1331. 2-(4-Methoxyphenyl)-1H-indol-3-yl benzoate (3u). 66 mg (96%), yellowish solid, mp: 141-143oC. 1H NMR (300 MHz, CDCl3) δ 8.27 (d, J = 8.8 Hz, 2H), 8.18 (brs, 1H), 7.64 (d, J = 7.4 Hz, 2H), 7.45 (d, J = 7.7 Hz, 1H), 7.35 (t, J = 7.5 Hz, 2H), 7.26 (t, J = 7.3 Hz, 2H), 7.18 (t, J = 7.2 Hz, 1H), 7.12 (t, J = 7.4 Hz, 1H), 7.03 (d, J = 8.8 Hz, 2H), 3.91 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 164.7, 164.0, 133.7, 132.5, 130.6, 128.9, 127.6, 127.2, 126.14, 126.06, 123.0, 122.4, 121.6, 120.4, 118.0, 114.0, 111.4, 55.5. HRMS (ESI) calcd for C22H18NO3 (M+H)+: 344.1287, found 344.1280. 2-(3-Chlorophenyl)-1H-indol-3-yl benzoate (3v). 62 mg (89%), yellowish solid, mp: 112-114oC. 1H NMR (300 MHz, CDCl3) δ 8.41-8.30 (m, 2H), 8.20 (brs, 1H), 7.75-7.69 (m, 1H), 7.68-7.56 (m, 3H), 7.53-7.46 (m, 2H), 7.33-7.18 (m, 4H), 7.17-7.10 (m, 1H).

13

C NMR (75 MHz, CDCl3) δ 164.9, 134.9, 133.9, 133.8, 132.3,

130.4, 130.2, 129.1, 128.8, 127.8, 127.6, 126.0, 124.7, 124.1, 123.6, 122.2, 120.6, 118.1, 111.6. HRMS (ESI) calcd for C21H15ClNO2 (M+H)+: 348.0791, found ACS Paragon Plus Environment


Page 14 of 18

348.0790. 2-(3-Methylphenyl)-1H-indol-3-yl benzoate (3w). 56 mg (85%), yellow oil. 1H NMR (300 MHz, CDCl3) δ 8.37-8.24 (m, 2H), 8.11 (brs, 1H), 7.73-7.63 (m, 1H), 7.56 (t, J = 7.5 Hz, 2H), 7.51-7.43 (m, 3H), 7.37 (d, J = 8.1 Hz, 1H), 7.30 (d, J = 7.7 Hz, 1H), 7.25-7.18 (m, 1H), 7.16-7.10 (m, 2H), 2.34 (s, 3H).

13

C NMR (75 MHz, CDCl3) δ

164.9, 138.6, 133.62, 133.57, 130.5, 130.4, 129.6, 129.3, 128.9, 128.7, 128.6, 126.8, 126.3, 123.4, 123.1, 122.3, 120.4, 118.0, 111.4, 21.5. HRMS (ESI) calcd for C22H18NO2 (M+H)+: 328.1338, found 328.1333. 2-(Naphthalen-1-yl)-1H-indol-3-yl benzoate (3x). 66 mg (91%), yellowish solid, mp: 61-63oC. 1H NMR (300 MHz, CDCl3) δ 8.26-8.03 (m, 4H), 7.91 (d, J = 6.8 Hz, 2H), 7.70 (d, J = 6.6 Hz, 1H), 7.62-7.48 (m, 5H), 7.46-7.37 (m, 3H), 7.35-7.28 (m, 1H), 7.23 (t, J = 7.1 Hz, 1H).

13

C NMR (75 MHz, CDCl3) δ 164.9, 133.8, 133.3, 131.7,

130.2, 129.3, 129.1, 128.4, 128.2, 128.0, 126.7, 126.2, 125.96, 125.93, 125.3, 123.0, 121.8, 120.5, 118.2, 111.4. HRMS (ESI) calcd for C25H18NO2 (M+H)+: 364.1338, found 364.1336. 5-Methoxy-2-phenyl-1H-indol-3-yl benzoate (3y). 60 mg (87%), yellowish solid, mp: 139-141oC. 1H NMR (300 MHz, CDCl3) δ 8.39-8.28 (m, 2H), 8.14 (brs, 1H), 7.70 (t, J = 7.4 Hz, 1H), 7.65-7.52 (m, 4H), 7.35 (t, J = 7.4 Hz, 2H), 7.30-7.22 (m, 1H), 7.21-7.13 (m, 1H), 6.85 (dd, J = 7.4, 2.2 Hz, 2H), 3.81 (s, 3H).

13

C NMR (75 MHz,

CDCl3) δ 164.9, 154.5, 133.7, 130.6, 130.4, 129.2, 128.9, 128.8, 128.7, 127.6, 126.9, 126.8, 125.9, 122.5, 113.8, 112.5, 98.9, 55.7. HRMS (ESI) calcd for C22H18NO3 (M+H)+: 344.1287, found 344.1285. 5-Chloro-2-phenyl-1H-indol-3-yl benzoate (3z). 37 mg (53%), yellowish solid, mp: 140-142oC. 1H NMR (300 MHz, CDCl3) δ 8.38-8.24 (m, 3H), 7.70 (t, J = 7.4 Hz, 1H), 7.63-7.51 (m, 4H), 7.41-7.25 (m, 4H), 7.12-7.05 (m, 2H). 13C NMR (75 MHz, CDCl3) δ 165.1, 133.9, 131.9, 130.4, 130.0, 129.0, 128.9, 128.8, 128.0, 127.7, 126.2, 126.1, 126.0, 123.4, 123.1, 117.2, 112.6. HRMS (ESI) calcd for C21H15ClNO2 (M+H)+: 348.0791, found 348.0793. 1-Acetyl-2-phenyl-1H-indol-3-yl benzoate (4). yellowish solid, mp: 111-113oC. 1H NMR (300 MHz, CDCl3) δ 8.50 (d, J = 8.0 Hz, 1H), 8.19-8.09 (m, 2H), 7.65 (t, J = ACS Paragon Plus Environment

Page 15 of 18 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


7.4 Hz, 1H), 7.56-7.40 (m, 9H), 7.34 (d, J = 7.8 Hz, 1H), 2.08 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 171.0, 164.8, 135.1, 133.8, 133.7, 130.5, 130.3, 129.7, 129.0, 128.8, 128.6, 128.5, 128.4, 126.2, 123.9, 123.1, 117.6, 116.5, 27.7. HRMS (ESI) calcd for C23H18NO3 (M+H)+: 356.1287, found 356.1290. ASSOCIATED CONTENT Supporting Information 1

H NMR and 13C NMR spectra of the compounds.

AUTHOR INFORMATION Corresponding Author *E-mail: [email protected] ORCID Ding Du: 0000-0002-4615-5433 Notes The authors declare no competing financial interest. ACKNOWLEDGMENT This work is funded by the National Natural Science Foundation of China (No. 21572270), the Qing Lan Project of Jiangsu Province, and the Priority Academic Program Development of Jiangsu Higher Education Institutions. REFERENCES (1) Willis, M. C. Transition Metal Catalyzed Alkene and Alkyne Hydroacylation. Chem. Rev. 2010, 110, 725-748. (2) Ghosh, A.; Johnson, K. F.; Vickerman, K. L.; Walker, J. A.; Stanley, L. M. Recent Advances in Transition Metal-Catalysed Hydroacylation of Alkenes and Alkynes. Org. Chem. Front. 2016, 3, 639-644. (3) Oonishi, Y. Development of Novel Cyclizations via Rhodacycle Intermediate and Its Application to Synthetic Organic Chemistry. Chem. Pharm. Bull. 2015, 63, 397-407. (4) Zhang, T.; Zhang, X.; Chung, L. W. Computational Insights into the Reaction Mechanisms of Nickel-Catalyzed Hydrofunctionalizations and Nickel-Dependent Enzymes. Asian J. Org. Chem. 2018, 7, 522-536. (5) Murphy, S. K.; Dong, V. M. Enantioselective Hydroacylation of Olefins with Rhodium Catalysts. Chem. Commun. 2014, 50, 13645-13649. (6) Leung, J. C.; Krische, M. J. Catalytic Intermolecular Hydroacylation of C-C π-Bonds in the



Absence of Chelation Assistance. Chem. Sci. 2012, 3, 2202-2209. (7) Biju, A. T.; Kuhl, N.; Glorius, F. Extending NHC-Catalysis: Coupling Aldehydes with Unconventional Reaction Partners. Acc. Chem. Res. 2011, 44, 1182-1195. (8) Enders, D.; Balensiefer, T. Nucleophilic Carbenes in Asymmetric Organocatalysis. Acc. Chem. Res. 2004, 37, 534-541. (9) Flanigan, D. M.; Romanov-Michailidis, F.; White, N. A.; Rovis, T. Organocatalytic Reactions Enabled by N-Heterocyclic Carbenes. Chem. Rev. 2015, 115, 9307-9387. (10) Bugaut, X.; Glorius, F. Organocatalytic Umpolung: N-Heterocyclic Carbenes and Beyond. Chem. Soc. Rev. 2012, 41, 3511-3522. (11) Dominguez de Maria, P.; Shanmuganathan, S. Umpolung Catalysis in Benzoin-type and Stetter-type Reactions: From Enzymatic Performances to Bio-mimetic Organocatalytic Concepts. Curr. Org. Chem. 2011, 15, 2083-2097. (12) Enders, D.; Niemeier, O.; Henseler, A. Organocatalysis by N-Heterocyclic Carbenes. Chem. Rev. 2007, 107, 5606-5655. (13) Haghshenas, P.; Langdon, S. M.; Gravel, M. Thieme Chemistry Journals Awardees-Where Are They Now? Carbene Organocatalysis for Stetter, Benzoin, Domino, and Ring-Expansion Reactions. Synlett 2017, 28, 542-559. (14) Gaggero, N.; Pandini, S. Advances in Chemoselective Intermolecular Cross-benzoin-type Condensation Reactions. Org. Biomol. Chem. 2017, 15, 6867-6887. (15) Peng, Q.; Guo, D.; Bie, J.; Wang, J. Catalytic Enantioselective Aza-Benzoin Reactions of Aldehydes with 2H-Azirines. Angew. Chem. Int. Ed. 2018, 57, 3767-3771. (16) Delany, E. G.; Connon, S. J. Highly Chemoselective Intermolecular Cross-benzoin Reactions Using an Ad Hoc Designed Novel N-Heterocyclic Carbene Catalyst. Org. Biomol. Chem. 2018, 16, 780-786. (17) Soeta, T.; Mizuno, S.; Hatanaka, Y.; Ukaji, Y. Asymmetric Cross-benzoin Condensation Promoted by A Chiral Triazolium Precatalyst Bearing A Pyridine Moiety. Tetrahedron 2017, 73, 3430-3437. (18) Wen, G.; Su, Y.; Zhang, G.; Lin, Q.; Zhu, Y.; Zhang, Q.; Fang, X. Stereodivergent Synthesis of Chromanones and Flavanones via Intramolecular Benzoin Reaction. Org. Lett. 2016, 18, 3980-3983. (19) Zhao, M.; Liu, J.-L.; Liu, H.-F.; Chen, J.; Zhou, L. Construction of Bisbenzopyrone via N-Heterocyclic Carbene Catalyzed Intramolecular Hydroacylation–Stetter Reaction Cascade. Org. Lett. 2018, 20, 2676-2679. (20) Ahire, M. M.; Mhaske, S. B. Isa-NHC-catalyzed Intermolecular Stetter Reaction of Aromatic Aldehydes with Maleimides: An Efficient Access to 3-Aroylsuccinimides. Tetrahedron 2018, 74, 2079-2084. (21) Ahire, M. M.; Mhaske, S. B. Synthesis of Succinimide Derivatives by NHC-Catalyzed Stetter Reaction of Aromatic Aldehydes with N-Substituted Itaconimides. ACS Omega 2017, 2, 6598-6604. (22) Walden, D. M.; Jaworski, A. A.; Johnston, R. C.; Hovey, M. T.; Baker, H. V.; Meyer, M. P.; Scheidt, K. A.; Cheong, P. H.-Y. Formation of Aza-ortho-quinone Methides Under Room Temperature Conditions: Cs2CO3 Effect. J. Org. Chem. 2017, 82, 7183-7189. (23) Mirco, F.; Frank, G. α-Unsubstituted Pyrroles by NHC-Catalyzed Three-Component Coupling: Direct Synthesis of a Versatile Atorvastatin Derivative. Chem.-Eur. J. 2017, 23,


Page 16 of 18

Page 17 of 18 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


10773-10776. (24) Chan, A.; Scheidt, K. A. Hydroacylation of Activated Ketones Catalyzed by N-Heterocyclic Carbenes. J. Am. Chem. Soc. 2006, 128, 4558-4559. (25) Molina, M. T.; Navarro, C.; Moreno, A.; Csaky, A. G. N-Heterocyclic Carbene-Catalyzed Monoacylation of 1,4-Naphthoquinones with Aldehydes. J. Org. Chem. 2009, 74, 9573-9575. (26) Du, D.; Lu, Y.; Jin, J.; Tang, W.; Lu, T. N-Heterocyclic Carbene-Catalyzed Hydroacylation of Isatins with Aldehydes: Access to 3-Acyloxy-1,3-dihydro-2H-indol-2-ones. Tetrahedron 2011, 67, 7557-7562. (27) Sreenivasulu, M.; Kumar, K. A.; Reddy, K. S.; Kumar, K. S.; Kumar, P. R.; Chandrasekhar, K. B.; Pal, M. 1,3-Bis(2,4,6-trimethylphenyl)imidazolium Chloride in Combination with Triethylamine: An Improved Catalytic System for Hydroacylation/Reduction of Activated Ketones. Tetrahedron Lett. 2011, 52, 727-732. (28) Ma, C.; Jia, Z.-J.; Liu, J.-X.; Zhou, Q.-Q.; Dong, L.; Chen, Y.-C. A Concise Assembly of Electron-Deficient 2,4-Dienes and 2,4-Dienals: Regio- and Stereoselective exo-Diels–Alder and Redox Reactions through Sequential Amine and Carbene Catalysis. Angew. Chem. Int. Ed. 2013, 52, 948-951. (29) Li, F.; Zhao, C.; Wang, J. N-Heterocyclic Carbene Catalyzed Dehydrogenative Coupling of Enals: Synthesis of Monobactams. Org. Chem. Front. 2016, 3, 335-338. (30) Pohanka, M.; Drtinova, L. Spectrophotometric Methods Based on 2,6-Dichloroindophenol acetate and Indoxylacetate for Butyrylcholinesterase Activity Assay in Plasma. Talanta 2013, 106, 281-285. (31) Nirogia, R. V. S.; Kambhampati, R.; Daulatabad, A. V.; Gudla, P.; Shaikh, M.; Achanta, P. K.; Shinde, A. K.; Dubey, P. K. Design, Synthesis and Pharmacological Evaluation of Conformationally Restricted N-Arylsulfonyl-3-Aminoalkoxy Indoles as A Potential 5-HT6 Receptor Ligands. J. Enzym. Inhib. Med. Chem. 2011, 26, 341-349. (32) Armistead, D. M.; Bemis, J. E.; Buchanan, J. L.; Dipietro, L. V.; Elbaum, D.; Geuns-Meyer, S. D.; Habgood, G. J.; Kim, J. L.; Marshall, T. L.; Novak, P. M.; Nunes, J. J.; Patel, V. F.; Toledo-Sherman, L. M.; Zhu, X. Preparation of 1,3,5-Triazines as Kinase Inhibitors for Treatment of Angiogenesis or Vasculogenesis. US 20040116388, 2004. (33) Corey, P. F.; Felman, S. W.; Rehm, G. E.; Pugia, M. J. Preparation of Arginine Derivatives for Assay of Trypsin Urinary Inhibitor. EP 1157984, 2001. (34) Ohlendorf, H. W.; Kaupmann, W.; Kuehl, U. G.; Buschmann, G.; Magda, S. J. 3-Acyloxy-1phenyl-2-aminocarbonylindole Compounds with Antiarrhythmic Properties. DE 3304019, 1984. (35) Pevarello, P.; Orsini, P.; Traquandi, G.; Varasi, M.; Fritzen, E. L.; Warpehoski, M. A.; Pierce, B. S.; Brasca, M. G. Preparation of 3(5)-Acylaminopyrazole Derivatives for Use as Therapeutic Agents, Particularly Antitumor Agents. US 7034049, 2006. (36) Li, X.; Wang, Y,; Wang, Y.; Tang, M.; Qu, L.-B.; Li, Z.; Wei D. Insights into the N-Heterocyclic Carbene (NHC)-Catalyzed Oxidative γ-C (sp3)-H Deprotonation of Alkylenals and Cascade [4+2] Cycloaddition with Alkenylisoxazoles. J. Org. Chem. 2018, DOI: 10.1021/acs.joc.8b01112. (37) Li, J.-S.; Liu, Y.-J.; Zhang, G.-W.; Ma, J.-A. Catalytic Asymmetric Mukaiyama-Mannich Reaction of Cyclic C-Acylimines with Difluoroenoxysilanes: Access to Difluoroalkylated Indolin-3-ones. Org. Lett. 2017, 19, 6364-6367.


N-Heterocyclic Carbene-Catalyzed Formal Conjugate Hydroacylation

Recommend Documents