Regioselective Nitrative Cyclization of 1,6-Enynes with t-BuONO under

Subscriber access provided by Kaohsiung Medical University

Article

Regioselective Nitrative Cyclization of 1,6Enynes with t-BuONO under Metal-Free Conditions Wen-Ting Wei, Wei-Wei Ying, Wen-Hui Bao, Le-Han Gao, Xu-Dong Xu, Yi-Ning Wang, Xiao-Xiao Meng, Gan-Ping Chen, and Qiang Li ACS Sustainable Chem. Eng., Just Accepted Manuscript • DOI: 10.1021/ acssuschemeng.8b03752 • Publication Date (Web): 04 Oct 2018 Downloaded from http://pubs.acs.org on October 5, 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 13 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Sustainable Chemistry & Engineering

Regioselective Nitrative Cyclization of 1,6-Enynes with t-BuONO under Metal-Free Conditions Wen-Ting Wei,*† Wei-Wei Ying,† Wen-Hui Bao,† Le-Han Gao,† Xu-Dong Xu,† Yi-Ning Wang,† Xiao-Xiao Meng,† Gan-Ping Chen,† and Qiang Li‡ †

School of Materials Science and Chemical Engineering, Ningbo University, No. 818, Fenghua Street, Ningbo, China, 315211. ‡

Institution of Functional Organic Molecules and Materials, School of Chemistry and Chemical Engineering, Liaocheng University, No. 1, Hunan Street, Liaocheng, China, 252059. E-mail: [email protected].

ABSTRACT A new pattern for nitrative cyclization of 1,6-enynes with t-BuONO has been reported for the synthesis of various 2-pyrrolidinone derivatives in 45% to 88% yields. This novel method operationally simple and proceeds under very mild conditions without using any additives. The reaction pathway involves nitro radical addition toward alkenyl group/5-exo-cyclization/H-abstraction sequence, allowing a highly regioselective and practical protocol toward the formation of a new C−N and C−C bonds. KEYWORDS metal-free; radical reaction; nitrative cyclization; t-BuONO INTRODUCTION The development of highly regioselective transformations in organic synthesis has been a long-term goal and attracted signiﬁcant attention.1-5 In generally, the regioselective of a transformation is mainly influenced by the reaction conditions, electronic and steric factors.6-8 Although highly regioselective reactions are still challenging today, great achievement has been obtained during the past decades.10-16 ACS Paragon Plus Environment 1

ACS Sustainable Chemistry & Engineering 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 13

In particular, the metal-free strategy is an appealing method that provides economy and green access to realize regioselective in modern synthetic chemistry.17-22 Cyclization of 1,n-enynes has emerged as a versatile and unique strategy for the synthesis of cyclic ring structures because of its high atom and step economy.23-30 Among these, particular attention focused on radical cyclization is driven by the relatively mild reaction conditions and conveniently incorporation of new radicals.31-36 Recently, efficient protocols for introduction two different functional groups into radical initiated cyclization of 1,n-enynes have been developed and extensively applied in modern organic chemistry, biochemistry and material synthesis.37-46 In contrast, selectivity introduce a sole functional group into radical cyclization, especially in a regioselective manner is challenging.47-52 Hence, it is highly desirable to expand the regioselective functionalization of 1,n-enynes via radical cyclization tactics, especially using t-BuONO as the nitrating reagent. In 2015, Liang group successfully reported a 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) promoted nitrative cyclization initiated by the nitro radical addition toward alkynyl group of 1,6-enynes (Scheme 1a).53 In 2018, we developed a radical

chloroazidation

of

1,6-enynes,

which

underwent

radical

addition

toward

alkenyl

group/5-exo-cyclization/radical coupling sequence to give access to a series of 2-pyrrolidinone derivatives.54 We envisioned that, with the right set of reaction system and substrate structure, the nitro radical could be preferentially occupied in alkenyl group of 1,6-enynes to control the reaction selectivity. Herein, we report the nitrative cyclization of 1,6-enynes with t-BuONO under metal-free raction conditions in a highly controlled manner (Scheme 1b).

Scheme 1. Regioselective nitrative cyclization of 1,6-enynes. ACS Paragon Plus Environment 2

Page 3 of 13 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


RESULTS AND DISCUSSION At the initial investigation, 1,6-enyne 1a and t-BuONO 2a were employed as model substrates for condition optimization (Table 1). It was found that the regioselective nitrative cyclization compound 3-methyl-4-methylene-3-(nitromethyl)-1-phenylpyrrolidin-2-one 3aa can be obtained with a yield of 60% Table 1. Screening of optimal conditionsa

Entry

Solvent

Temperature

Yield (%)

1

THF

90 oC

60

2

1,4-Dioxane

90 oC

83

3

MeCN

90 oC

28

4b

EtOAc

90 oC

11

5c

Toluene

90 oC

10

6d

DMSO

90 oC

8

7

H2O

90 oC

5

8

1,4-Dioxane

110 oC

71

9

1,4-Dioxane

70 oC

83

10e

1,4-Dioxane

50 oC

24

11f

1,4-Dioxane

25 oC

45

12g

1,4-Dioxane

70 oC

65

13h

1,4-Dioxane

70 oC

84

14i

1,4-Dioxane

70 oC

85

15j

1,4-Dioxane

70 oC

83

ACS Paragon Plus Environment 3


16k a

1,4-Dioxane

70 oC

Page 4 of 13

39

Unless otherwise annotated, the reactions were performed using 1a (0.2 mmol), 2a (0.6 mmol) and solvent (2 mL) in

open air for 12 h. All of the solvents contained approximately 0.2 to 0.3% w/w water. Yields are of pure isolated products.

b

75% of 1a was recovered.

c

77% of 1a was recovered. d 80% of 1a was recovered.

e

For 24 h. f Using

ultrasound or microwave. g 2a (0.4 mmol, 2.0 equiv). h 2a (0.8 mmol, 4.0 equiv).i 1.0 equiv of K2S2O8 was added. j 1.0 equiv of DBU was added. k Under nitrogen atmosphere.

in tetrahydrofuran (THF) under air at 90 °C (entry 1). Encouraged by this result, we started to optimize the reaction conditions by screening a string of solvents, including 1,4-dioxane, MeCN, EtOAc, toluene, dimethyl sulfoxide (DMSO) and H2O (entries 2–7). Our investigation showed that 1,4-dioxane gave the best results, providing 3aa in 83 % yield (entry 2 vs entries 3–7). The increase in temperature is not advantageous to the nitrative cyclization, probably due to the decomposition of the 2a under high temperature (entry 8). Reducing the reaction temperature to 70 oC gave an identical yield to that of 90 o

C (entry 9), and further reducing the temperature to 50 °C only obtained a 24% yield of 3aa (entry 10).

The product 3aa was achieved in 45% yield when using ultrasound or microwave in place of heating condition (Table 1, entry 11). Decreasing the amount of 2a from 3.0 equiv to 2.0 equiv cause slightly lower yield of the desired product 3aa (entry 12). No promotion in this nitrative cyclization was detected when 4.0 equiv of 2a was employed (entry 13). When 1.0 equiv of K2S2O8 or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) was added, a similar yield of 3aa was achieved (entries 14-15). The presence of nitrogen atmosphere enabled a lower yield relative to aerobic reaction conditions implies the oxygen may be benefit for the nitrative cyclization (entry 16). Under the optimal conditions (Table 1, entry 8), we evaluated the generality of this nitrative cyclization by subjecting various 1,6-enynes to the optimal reaction conditions and employing 2a as the reaction partner (Table 2). We firstly examined the substitution effect on the aromatic ring of the N-aryl substituent 1,6-enynes. It showed that a variety of different substitution including electron-donating groups (−OMe, −Me and −t-Bu) and electron-withdrawing groups (−F, −Cl, −Br and −CF3) at the para-position were well tolerated in the reaction with 2a and provided the desired nitrative cyclization products 3ba-3ha in 71−86% yields. In generally, the reactivity continuous decline from ACS Paragon Plus Environment 4

Page 5 of 13 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


electron-donating to electron-withdrawing substitution. For example, MeO-substituted 1,6-enyne 1b when treated with 2a afforded product 3ba in 86% yield, whereas CF3-substituted 1,6-enyne 1h gave the corresponding product 3ha in 71% yield. However, no product observed when a pyridine substituted 1,6-enyne 1i was used as the substrate. Next, we studied the impact of N-alkyl substituent 1,6-enynes on the reaction. Substrates 1j, 1k and 1l, bearing a benzyl, phenylethyl and 3,4-dimethoxyphenethyl groups at the N-substituent position, also yielded Table 2. Scope of 1,6-enynes.a R2

R2 R1 N O

R3

+ t-BuONO 2a

1,4-Dioxane o

70 C, Air

R3 R1 N O NO2 3

1

MeO

t-Bu

Me

Me Ph

N

N O NO2 3aa, 83%

Me

O O2N 3ba, 86%

F

O O2N 3ea, 78%

N

Ph Me

Me N O Bn O2N O NO2 3ia, traceb 3ja, 88% O Ph S N O Me N Me O Ts O2N O NO2 3na, 70% 3ma, 67% Ph Ph

N

O O2N 3ha, 71%

Me O O2N 3ka, 85% Me

Me

N

MeO

O O2N 3la, 87%

Me

Me N Ph

NO2

O 3oa, 45%, Z:E > 20:1 O O

N

NO2 O 3pa, no reactionc

Ph

Me

Me

N O NO2 3qa, 72%

Me

N

Me O O2N 3ga, 79% MeO

Me

O O2N 3fa, 76%

N N

O O2N 3da, 83% F3C

N Me

Me

O O2N 3ca, 84% Br

Cl N

N

N

Ph

NO2 3ra, no reactiond

N

O NO2 Ph 3sa, trace


ACS Sustainable Chemistry & Engineering a

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 6 of 13

Reaction conditions: 1 (0.2 mmol), 2a (0.6 mmol), and 1,4-dioxane (2 mL) in open air at 70 oC for 12 h. Yields are of

pure isolated products. b 72% of 1i was recovered. c 86% of 1p was recovered. d 79% of 1r was recovered.

nitrative cyclization products in 88%, 85% and 87% yields, respectively (3ja-3la). Notably, N-sulfonyl substituent 1,6-enynes showed a slightly lower reactivity than that of N-alkyl substituent 1,6-enynes and produced the products 3ma and 3na in 67% and 70% yields, respectively. To our delight, on expanding the substrate tolerance, N-(but-2-yn-1-yl)-N-phenylmethacrylamideallenylpyridine (1o) was smoothly converted

to

the

expected

product

3oa

in

45%

yield.

Unfortunately,

N-phenyl-N-(prop-2-yn-1-yl)acrylamide (1p) was not transformed to the corresponding product 3pa and 86% of 1p was recovered. When N,2-diphenyl-N-(prop-2-yn-1-yl)acrylamidea (1q) was applied to the optimal conditions, product 3qa was isolated in 72% yield. However, O-centered 1,6-enyne (1r) and 1,7-enyne (1s) failed to afforded the nitrative cyclization products under the current conditions (3ra-3sa). To prove the synthetic utility of this reaction, product 3aa was further elaborated as shown in Scheme 2a. The nitro group of 3aa could be readily converted into amino group through reduction reaction.55 Moreover, the nitrative cyclization is practical since we gained 65% yield of desired product when the transformation was performed on 1 gram scale (Scheme 2b).

Scheme 2. Synthesis applications. Finally, five control experiments were performed to obtained mechanistic insight into this reaction. We were surprised to find that substrate 1q with 1,1-disubstituted group on the alkenyl afforded the nitrative cyclization product 5aa through the nitro radical addition toward alkynyl group of 1q in 31% ACS Paragon Plus Environment 6

Page 7 of 13 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


yield (Scheme 3a). Substrate 1a was subjected to treatment with 2a in the presence of butylhydroxytoluene (BHT), hydroquinone, or 1,1-diphenylethylene, but not

expected product 3aa was

examined and >90% of 1a was recovered, whichindicating a radical mechanism involve in this

reaction (Scheme 3b). Furthermore, in the presence of anhydrous 1,4-dioxane, the desired product 3aa was only abserved in 12% yield, which suggested that H2O plays a significant role in this nitrative cyclization (Scheme 3c). When 1.0 equiv of H2O was added to the anhydrous 1,4-dioxane, the yield of 3aa increased to 79% (Scheme 3d). The deuterium-labeled result suggest that one of hydrogen atom in the end of olefin comes from water (Scheme 3e).

Ph N

1,4-Dioxane Me

+ t-BuONO 70 oC, Air 2a

Me 1q

N

Me Me NO2

Ph 5aa, 31%, E:Z > 20:1

Additive (3.2 equiv) 1,4-Dioxane

Me + t-BuONO N o 70 C, Air 2a Ph O >90% of 1a was recovered O NO2 1a 3aa, trace Additive = BHT, hydroquinone, 1,1-diphenylethylene

Ph N

Me

Ph N

Me

O 1a

Ph N O 1a

Ph N O 1a

+ t-BuONO 2a

1,4-Dioxane (Anhydrous) o

70 C, Air

(a)

Me Ph

N

(b)

(c)

O NO2 3aa, 12%

1,4-Dioxane (Anhydrous)

Me (d) + t-BuONO H2O (1.0 equiv) Ph N 2a 70 oC, Air O NO2 3aa, 79% D only D 1,4-Dioxane Me (Anhydrous) Me (e) + t-BuONO D2O (1.5 equiv) Ph N 2a 70 oC, Air O NO2 3aa-D, 82%

Me

Scheme 3. Control experiments Based on the experimental evidence of the above studies and those reported in literature,52, 56-61 a plausible mechanism is proposed as shown in Scheme 4. Initially, the present system led to the generate of NO2 radical.56-61 Subsequently, addition of NO2 radical to the double bond of 1a gives alkyl radical ACS Paragon Plus Environment 7


Page 8 of 13

intermediate A, which cyclizes to form vinyl radical intermediate B.58-59 Finally, H-abstraction convert intermediate B into the final product 3aa.52

Scheme 4. Possible mechanism. CONCLUSIONS In conclusion, a simple and green approach has been developed for rapid construction of 2-pyrrolidinone derivatives through a highly regioselective nitrative cyclization of 1,6-enynes with t-BuONO without using any additives in moderate to excellent yields. The scope of various 1,6-enynes was investigated, and substrates containing N-aryl and alkyl substituents were participants in this cascade process. This efficient and economical protocol represents a new platform for the regioselective nitration of 1, n-enynes, and it will be extensively applied in the chemical industry. ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acssuschemeng.xxxxxxx. 1

H and 13C NMR spectra of compounds 3aa-3qa, 4a, 5aa, 3aa-D. (PDF)

ACKNOWLEDGMENT


Page 9 of 13 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


We thank the National Natural Science Foundation of China (Grants 21801142), the Natural Science Foundation of Zhejiang Province (No. LQ18B020002), Education Foundation of Zhejiang Province (No. Y201737123), State Key Laboratory of Analytical Chemistry for Life Science (No. SKLACLS1804), Open Subject of State Key Laboratory of Chemo/Biosensing and Chemometrics (2017016), and the K. C. Wong Magna Fund in Ningbo University for financial support.

REFERENCES (1) Peng, J.-B.; Wu, X.-F. Ligand- and solvent-controlled regio- and chemodivergent carbonylative reactions. Angew. Chem. Int. Ed. 2018, 57, 2-11. (2) Hartwig, J. F. Regioselectivity of the borylation of alkanes and arenes. Chem. Soc. Rev. 2011, 40, 1992-2002. (3) Ping, L.; Chung, D. S.; Bouffard, J.; Lee, S.-G. Transition metal-catalyzed site- and regio-divergent C–H bond functionalization. Chem. Soc. Rev. 2017, 46, 4299-4328. (4) Wu, C.; Lu, L.-H.; Peng, A.-Z.; Jia, G.-K.; Peng, C.; Cao, Z.; Tang, Z. L.; He, W.-M.; Xu, X. H. Ultrasound-promoted Brønsted acid ionic liquid-catalyzed hydrothiocyanation of activated alkynes under minimal solvent conditions. Green Chem. 2018, 20, 3683-3688. (5) Wu, C.; Xin, X.; Fu, Z.-M.; Xie, L.-Y.; Liu, K.-J.; Wang, Z.; Li, W. Y.; Yuan, Z.-H.; He, W.-M. Water-controlled selective preparation of α-mono or α,α’-dihalo ketones via catalytic cascade reaction of unactivated alkynes with 1,3-dihalo-5,5-dimethylhydantoin. Green Chem. 2017, 19, 1983-1989. (6) Ojha, D. P.; Prabhu, K. R. Pd-catalyzed hydroborylation of alkynes: A ligand controlled regioselectivity Switch for the synthesis of α- or β-vinylboronates. Org. Lett. 2016, 18, 432-435. (7) Jin, S. F.; Jiang, C. G.; Peng, X. S.; Shan, C. H.; Cui, S. S.; Niu, Y. Y.; Liu, Y.; Lan, Y.; Liu, Y. X.; Cheng, M. S. Gold(I)-catalyzed angle strain controlled strategy to furopyran derivatives from propargyl vinyl ethers: insight into the regioselectivity of cycloisomerization. Org. Lett. 2016, 18, 680-683. (8) Weber, S. M.; Hilt, G. Control of the regioselectivity in cobalt-versus ruthenium-catalyzed alder-ene reaction of unsymmetrical 1,3-diynes. Org. Lett. 2017, 19, 564-567. (9) Garcia-Borràs, M.; Osuna, S.; Swart, M.; Luisa, J. M.; Solà, M. Electrochemical control of the regioselectivity in the exohedral functionalization of C60. The role of aromaticity. Chem. Commun. 2013, 49, 1220-1222. (10) Fang, R.; Zhou, L.; Tu, P.-C.; Kirillov, A. M.; Yang, L. Z. Computational study on gold-catalyzed cascade reactions of 1,4-diynes and pyrroles: mechanism, regioselectivity, role of catalyst, and effects of substituent and solvent. Organometallics 2018, 37, 1927-1936. (11) Jiang, P. P.; Li, F.; Xu, Y. B.; Liu, Q. W.; Wang, J.; Ding, H.; Yu, R. F.; Wang, Q. F. Aromaticity-dependent regioselectivity in Pd(II)-catalyzed C–H direct arylation of aryl ureas. Org. Lett. 2015, 17, 5918-5921. (12) Griffin, J. D.; Cavanaugh, C. L.; Nicewicz, D. A. Reversing the regioselectivity of halofunctionalization reactions through cooperative photoredox and copper catalysis. Angew. Chem. Int. Ed. 2017, 56, 2097-2100. (13) Trost, B. M.; Rudd, M. T.; Costa, M. G.; Lee, P. I.; Pomerantz, A. E. Regioselectivity control in a ruthenium-catalyzed cycloisomerization of diyne-ols. Org. Lett. 2004, 6, 4235-4238. (14) Garr, A. N.; Luo, D. H.; Brown, N.; Cramer, C. J.; Buszek, K. R.; VanderVelde, D. Experimental and theoretical investigations into the unusual regioselectivity of 4,5-, 5,6-, and 6,7-indole aryne cycloadditions. Org. Lett. 2010, 12, 96-99. (15) Zhang, H. W.; Song, Y. C.; Zhao, J. B.; Zhang, J. P.; Zhang, Q. Regioselective radical aminofluorination of styrenes. Angew. Chem. Int. Ed. 2014, 53, 11079-11083. ACS Paragon Plus Environment 9


Page 10 of 13

(16) Xie, L.-Y.; Peng, S.; Liu, F.; Chen, G.-R.; Xia, W.; Yu, X. Y.; Li, W.-F.; Cao, Z.; He, W.-M. Metal-free deoxygenative sulfonylation of quinoline N-oxides with sodium sulﬁnates via a dual radical coupling process. Org. Chem. Front. 2018, 5, 2604-2609. (17) Gao, X. F.; Yang, H. L.; Cheng, C.; Jia, Q.; Gao, F.; Chen, H. X.; Cai, Q. C.; Wang, J. Iodide reagents controlled the reaction pathway of iodoperoxidation of alkenes: A high regioselectivity synthesis of α- and β- iodoperoxidates under solvent-free conditions. Green Chem. 2018, 20, 2225-2230. (18) Campbell, C. D.; Joannesse, C.; Morrill, L. C.; Philp, D.; Smith, A. D. Regiodivergent Lewis base-promoted O– to C–carboxyl transfer of furanyl carbonates. Org. Biomol. Chem. 2015, 13, 2895-2900. (19) Chen, T.; Yeung, Y.-Y. Trifluoroacetic acid catalyzed highly regioselective bromocyclization of styrene-type carboxylic acid. Org. Biomol. Chem. 2016, 14, 4571-4575. (20) Ni, H. Z.; Yu, Z. Y.; Yao, W. J.; Lan, Y.; Ullah, N.; Lu, Y. X. Catalyst-controlled regioselectivity in phosphine catalysis: synthesis of spirocyclic benzofuranones via regiodivergent [3+2] annulations of aurones and an allenoate. Chem. Sci. 2017, 8, 5699-5704. (21) Karmakar, R.; Yun, S. Y.; Wang, K.-P.; Lee, D. Regioselectivity in the nucleophile trapping of arynes: The electronic and steric effects of nucleophiles and substituents. Org. Lett. 2014, 16, 6-9. (22) Akai, S.; Kawashita, N.; Satoh, H.; Wada, Y.; Kakiguchi, K.; Kuriwaki, I.; Kita, Y. Highly regioselective nucleophilic carbon−carbon bond formation on furans and thiophenes initiated by pummerer-type reaction. Org. Lett. 2004, 6, 3793-3796. (23) Aubert, C.; Buisine, O.; Malacri, M. The Behavior of 1,n-Enynes in the Presence of Transition Metals. Chem. Rev. 2002, 102, 813-834. (24) Marinetti, A.; Jullien, H.; Voituri, A. Enantioselective, transition metal catalyzed cycloisomerizations. Chem. Soc. Rev. 2012, 41, 4884-4908. (25) Xuan, J.; Studer, A. Radical cascade cyclization of 1,n-enynes and diynes for the synthesis of carbocycles and heterocycles. Chem. Soc. Rev. 2017, 46, 4329-4346. (26) Xi, T.; Lu, Z. Cobalt-catalyzed hydrosilylation/cyclization of 1,6-enynes. J. Org. Chem. 2016, 81, 8858-8866. (27) Zhou, Y. Y.; Yu, L.; Chen, J. C.; Xu, J. B.; He, Z. X.; Shen, G. L.; Fan, B. M. Rhodium-catalyzed asymmetric cyclization/addition reactions of 1,6-enynes and oxa/azabenzonorbornadienes. Org. Lett. 2018, 20, 1291-1294. (28) Xi, T.; Lu, Z. Cobalt-catalyzed ligand-controlled regioselective hydroboration/cyclization of 1,6-enynes. ACS Catal. 2017, 7, 1181-1185. (29) Lin, A. J.; Zhang, Z.-W.; Yang, J. Iron-Catalyzed Reductive Cyclization of 1,6-Enynes. Org. Lett. 2014, 16, 386-389. (30) He, Y.-T.; Li, L.-H.; Zhou, Z.-Z.; Hua, H.-L.; Qiu, Y.-F.; Liu, X.-Y.; Liang, Y.-M. Copper-catalyzed three-component cyanotrifluoromethylation/azidotrifluoromethylation and carbocyclization of 1,6-enynes. Org. Lett. 2014, 16, 3896-3899. (31) Huang, H. G.; Li, Y. Sustainable difluoroalkylation cyclization cascades of 1,8-enynes. J. Org. Chem. 2017, 82, 4449-4457. (32) Qiu, Y.-F.; Zhu, X.-Y.; Li, Y.-X.; He, Y.-T.; Yang, F.; Wang, J.; Hua, H.-L.; Zheng, L.; Wang, L.-C.; Liu, X.-Y.; Liang, Y.-M. AgSCF3 mediated trifluoromethylthiolation/radical cascade cyclization of 1,6-enynes. Org. Lett. 2015, 17, 3694-3697. (33) Peng, X.-X.; Wei, D.; Han, W.-J.; Chen, F.; Yu, W.; Han, B. Dioxygen activation via Cu-catalyzed cascade radical reaction: An approach to isoxazoline/cyclic nitrone-featured α-ketols. ACS Catal. 2017, 7, 7830-7834. (34) He, Y.-T.; Wang, Q.; Zhao, J. H.; Wang, X.-Z.; Qiu, Y.-F.; Yang, Y.-C.; Hu, J.-Y.; Liu, X.-Y.; Liang, Y.-M. Copper-catalyzed cascade cyclization for the synthesis of trifluoromethyl-substituted spiro-2H-azirines from 1,6-enynes. Adv. Synth. Catal. 2015, 357, 3069-3075. (35) Qiu, J.-K.; Shan, C.; Wang, D.-C.; Wei, P.; Jiang, B.; Tu, S.-J.; Li, G. G.; Guo, K. Metal-free radical-triggered selenosulfonation of 1,7-enynes for the rapid synthesis of 3,4-dihydroquinolin-2(1H)-ones in batch and flow. Adv. Synth. Catal. 2017, 359, 4332-4339. ACS Paragon Plus Environment 10

Page 11 of 13 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


(36) Wang, A.-F.; Zhu, Y.-L.; Wang, S.-L.; Hao, W.-J.; Li, G. G.; Tu, S.-J.; Jiang, B. Metal-free radical haloazidation of benzene-tethered 1,7-enynes leading to polyfunctionalized 3,4-dihydroquinolin-2(1H)-ones. J. Org. Chem. 2016, 81, 1099-1105. (37) Li, M.; Wang, C.-T.; Qiu, Y.-F.; Zhu, X.-Y.; Han, Y.-P.; Xia, Y.; Li, X.-S.; Liang, Y.-M. Base promoted direct difunctionalization/cascade cyclization of 1,6-enynes. Chem. Commun. 2018, 54, 5334-5337. (38) Wang, Y.-Q.; He, Y.-T.; Zhang, L.-L.; Wu, X.-X.; Liu, X.-Y.; Liang, Y.-M. Palladium-catalyzed radical cascade iododifluoromethylation/cyclization of 1,6-enynes with ethyl difluoroiodoacetate. Org. Lett. 2015, 17, 4280-4283. (39) Hu, M.; Zou, H.-X.; Song, R.-J.; Xiang, J.-N.; Li, J.-H. Copper-catalyzed C-H oxidative radical functionalization and annulation of aniline-linked 1,7-enynes: evidence for a 1,5-hydride shift mechanism. Org. Lett. 2016, 18, 6460-6463. (40) Meng, Q.; Chen, F.; Yu, W.; Han, B. Copper-catalyzed cascade cyclization of 1,7-enynes toward trifluoromethyl-substituted 1′H spiro[azirine-2,4′-quinolin]-2′(3′H) ones. Org. Lett. 2017, 19, 5186-5189. (41) Cao, X.; Cheng, X.; Xuan, J. Arylsulfonyl radical triggered 1,6-enyne cyclization: Synthesis of γ-lactams containing alkenyl C–X bonds. Org. Lett. 2018, 20, 449-452. (42) Pan, R.; Hu, L. Y.; Han, C. H.; Lin, A. J.; Yao, H. Q. Cascade radical 1,6-addition/cyclization of para-quinone methides: Leading to spiro[4.5]deca-6,9-dien-8-ones. Org. Lett. 2018, 20, 1974-1977. (43) An, Y. Y.; Kuang, Y. Y.; Wu, J. Synthesis of trifluoromethylated 3,4-dihydroquinolin-2(1H)-ones via a photo-induced radical cyclization of benzene -tethered 1,7-enynes with Togni reagent. Org. Chem. Front. 2016, 3, 994-998. (44) Hu, M.; Song, R.-J.; Li, J.-H. Metal-free radical 5-exo-dig cyclizations of phenol-linked 1,6-enynes for the synthesis of carbonylated benzofurans. Angew. Chem. Int. Ed. 2015, 54, 608-612. (45) Liu, Y.; Song, R.-J.; Luo, S. L.; Li, J.-H. Visible-light-promoted tandem annulation of N-(o-ethynylaryl)acrylamides with CH2Cl2. Org. Lett. 2018, 20, 212-215. (46) Zhu, Y.-L.; Jiang, B.; Hao, W.-J.; Wang, A.-F.; Qiu, J.-K.; Wei, P.; Wang, D.-C.; Li, G. G.; Tu, S.-J. A new cascade halosulfonylation of 1,7-enynes toward 3,4-dihydroquinolin-2(1H)-ones via sulfonyl radical-triggered addition/6-exo-dig cyclization. Chem. Commun. 2016, 52, 1907-1910. (47) Fu, R.; Hao, W.-J.; Wu, Y.-N.; Wang, N.-N.; Tu, S.-J.; Li, G. G.; Jiang, B. Sulfonyl radical-enabled 6-endo-trig cyclization for regiospecific synthesis of unsymmetrical diaryl sulfones. Org. Chem. Front. 2016, 3, 1452-1456. (48) 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. (49) Ren, S.-C.; Zhang, F.-L.; Qi, J.; Huang, Y.-S.; Xu, A.-Q.; Yan, H.-Y.; Wang, Y.-F. Radical borylation/cyclization cascade of 1,6-enynes for the synthesis of boron-handled hetero- and carbocycles. J. Am. Chem. Soc. 2017, 139, 6050-6053. (50) Liu, B.; Wang, C.-Y.; Hu, M.; Song, R.-J.; Chen, F.; Li, J.-H. Copper-promoted [2+2+2] annulation of 1,n-enynes through decomposition of azobis(alkyl nitrile)s. Chem. Commun. 2017, 53, 1265-1268. (51) Xia, X.-F.; Yu, J. P.; Wang, D. W. Copper/iron-cocatalyzed cascade perfluoroalkylation/cyclization of 1,6-enynes with iodoperfluoroalkanes. Adv. Synth. Catal. 2018, 360, 562-567. (52) Zhu, Y.-L.; Wang, D.-C.; Jiang, B.; Hao, W.-J.; Wei, P.; Wang, A.-F.; Qiu, J.-K.; Tu, S.-J. Metal-free oxidative hydrophosphinylation of 1,7-enynes. Org. Chem. Front. 2016, 3, 385-393. (53) Hao, X.-H.; Gao, P.; Song, X.-R.; Qiu, Y.-F.; Jin, D.-P.; Liu, X.-Y.; Liang, Y.-M. Metal-free nitro-carbocyclization of 1,6-enynes with tBuONO and TEMPO. Chem. Commun. 2015, 51, 6839-6842. (54) Ying, W.-W.; Chen, W.-T.; Bao, W.-H.; Gao, L.-H.; Wang, X.-Y.; Chen, G.-P.; Ge, G.-P.; Wei. W.-T. Room Temperature, Metal-free, radical chloroazidation of 1,6-enynes. Synlett 2018, 29, 1664-1668. (55) Yang, X.; Toste, F. D. Direct asymmetric amination of α-branched cyclic ketones catalyzed by a chiral phosphoric acid. J. Am. Chem. Soc. 2015, 137, 3205-3208. ACS Paragon Plus Environment 11


Page 12 of 13

(56) Doyle, M. P.; Terpstra, J. W.; Pickering, R. A.; LePoire, D. M. Hydrolysis, nitrosyl exchange, and synthesis of alkyl nitrites. J. Org. Chem. 1983, 48, 3379-3382. (57) Ranganathan, S.; Kar, S. K. Novel cis-hydroxylation with nitrous acid. J. Org. Chem. 1970, 35, 3962-3964. (58) Liu, Y.; Zhang, J.-L.; Song, R.-J.; Qian, P.-C.; Li, J.-H. Cascade nitration/cyclization of 1,7-enynes with tBuONO and H2O: One-Pot self-assembly of pyrrolo [4,3,2-de] quinolinones. Angew. Chem. Int. Ed. 2014, 53, 9017-9020. (59) Hu, M.; Liu, B.; Ouyang, X.-H.; Song, R.-J.; Li, J.-H. Nitrative cyclization of 1-ethynyl-2-(vinyloxy)benzenes to access 1-[2-(nitromethyl)benzofuran-3-yl] ketones through dioxygen activation. Adv. Synth. Catal. 2015, 357, 3332-3340. (60) Maity, S.; Naveen, T.; Sharma, U.; Maiti, D. Stereoselective nitration of olefins with tBuONO and TEMPO: Direct access to nitroolefins under metal-free conditions. Org. Lett. 2013, 15, 3384-3387. (61) Yang, X.-H.; Ouyang, X.-H.; Wei, W.-T.; Song, R.-J.; Li, J.-H. Nitrative spirocyclization mediated by TEMPO: Synthesis of nitrated spirocycles from N-arylpropiolamides, tert-butyl nitrite and water. Adv. Synth. Catal. 2015, 357, 1161-1166.


Page 13 of 13 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


For Table of Contents Use Only

Regioselective nitrative cyclization External catalyst and initiator-free Operationl simplicity and gram scale


Regioselective Nitrative Cyclization of 1,6-Enynes with t-BuONO under

Recommend Documents