Gold-Catalyzed [5+2]- and [5+1]-Annulations between Ynamides and

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Gold-catalyzed [5+2]- and [5+1]-Annulations between Ynamides and 1,2-Benzisoxazoles with Ligand-Controlled Chemoselectivity Prakash Daulat Jadhav, Xin Lu, and Rai-Shung Liu ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.8b03011 • Publication Date (Web): 20 Sep 2018 Downloaded from http://pubs.acs.org on September 20, 2018

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ACS Catalysis

Gold-catalyzed [5+2]- and [5+1]-Annulations between Ynamides and 1,2Benzisoxazoles with Ligand-Controlled Chemoselectivity Prakash D. Jadhav, Xin Lu,b Rai-Shung Liua* a

Frontier Research Center for Matter Science and Technology, Department of Chemistry, National Tsing-Hua University, Hsinchu, Taiwan, ROC b

State Key Laboratory of Physical Chemistry of Solid Surface & Fujian Provincial Key Laboratory for Theoretical and Computational Chemistry, Departmental of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, PRC ABSTRACT: This work describes two distinct annulations between ynamides and 1,2-benzisoxazoles with chemoselectivity controlled by ligands. With IPrAuCl/AgNTf2, arylsubstituted ynamides undergo [5+2]-annulation reactions whereas P(t-Bu)2(o-biphenyl)AuCl/AgNTf2 alters the chemoselectivity of the same ynamides to implement [5+1]-annulation reactions. 13C-labeling experiments confirm that a 1,2-sulfonamide shift is involved in the [5+1]-annulation process. A plausible mechanism is postulated to rationalize the mechanisms of the two annulations. KEYWORDS: ynamides, 1,2-benzisoxazole, [5+2]-annulations, [5+1]-annulations, ligand-controlled chemoselectivity.

INTRODUCTION Benzo[f][1,4]oxazepine cores are seven-membered N,Ocontaining heterocycles that exist as the core structures of bioactive molecules.1 Figure 1 provides selected representatives I-V. Among them, GDC-0326 (I)2 is a potent inhibitor of the phosphoinositide 3-kinsases (PI3Ks) whereas amoxapine (II), loxapine (III), sintamil (IV) and compounds V serve as antidepressants and antipsychotics.2-7 Despite biological significance, these compounds were generally prepared with long procedures.8-9 We envisaged that catalytic [5+2]-annulations of 1,2-benzisoxazoles with alkynes would emerge as a short route to access the benzo[f][1,4]oxazepine cores. This task is challenging as Miura reported Rh-catalyzed [4+2]-annulations of alkynes with 1,2-benzisoxazoles to yield isoquinoline products (Figure 2, eq 2).10 Liang reported similar [4+2]-annulations between alkyn-3-ols and 1,2-benzisoxazoles to afford quinoline derivatives (eq 3).11 We are aware of no [5+2]-annulations between 1,2-benzisoxazoles and alkynes or alkenes using any metal catalyst.

Isoxazoles and anthranils are structurally related to 1,2-benzisoxazoles. Gold-catalyzed annulations of ynamides or propiolates12-16 with anthranils17-20 or isoxazoles21-25 have been intensively studied by Ye, Hashmi and our group;17-25 attempts to realize their [5+2]annulations are still unsuccessful. Reported reactions yielded pyrrole and indole derivatives.17-25 In very few instances, [5+2]-annulation intermediates were postulated but not isolable because of their facile rearrangement to other six-membered heterocyclic products.20,25 Here, we report new [5+2]-annulations between 1,2benzisoxazoles and ynamides with IPrAuCl/AgNTf2, selectively affording

Figure 2. Reaction protocols between alkynes and 1,2benzisoxazoles ACS Paragon Plus Environment

Figure 1. A [5+2]-route to access bioactive molecules

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benzo[f][1,4]oxazepine derivatives 3 (eq 4). We employed ynamides because their gold -alkyne species (VI) are also characterized by keteniminium structures (VI”), thus increasing their electrophilicity toward weak nucleophiles.2628 In this work, the chemoselectivity is alterable with P(tBu)2(o-biphenyl)AuCl/AgNTf2 to deliver [5+1]-annulation products 4 preferably (eq 5). Herein, the two N,Ocontaining heterocycles 3 and 4 are not convertible to each other with any gold catalyst. RESULTS and DISCUSSION Table 1 depicts the effects of gold catalysts on the annulation chemoselectivity. Our initial tests on the reacTable 1. Catalysts and Chemoselectivity

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(vide infra).29 The molecular structure of compound 3a was inferred from x-ray diffraction of its relative 3p.29 Notably, heterocycles 3a and 4a are chemically irrelevant because they are very stable in DCE in the presence of P(t-Bu)2(obiphenyl)Cl/AgNTf2 and IPrAuCl/AgNTf2. Our first task is to examine the substrate scope of the two annulations using IPrAuCl/AgNTf2 and P(t-Bu)2(obiphenyl)PAuCl/AgNTf2 respectively. Table 2 shows catalytic [5+2]-annulations of aryl-substituted ynamides 1b-1h and 1,2-benzisoxazoles 2a-2g; herein, we found no tractable amount of the other [5+1]-annulation products 4. For various 4-phenyl-substituted ynamides 1b-1e, their resulting benzo[f][1,4]oxazepines 3b-3e were obtained in excellent yields (87-92%). We varied the sulfonamides of ynaTable 2. The Scope of [5+2]-Annulations

Yield [%]b

entry

Catalyst [mol%]

t[h] 3a

4a (Z:E)

1a’

1a

1

IPrAuCl/AgSbF6 (5)

10

88

--

--

--

2

IPrAuCl/AgNTf2 (5)

10

90

--

--

--

3

(PhO)3PAuCl/AgNTf2(5)

12

22

74 (1:1.2)

--

--

4

Ph3PAuCl/AgNTf2(5)

12

21

76 (1.3:1)

--

---

5

LAuCl/AgNTf2 (5)

12

16

80 (1.3:1)

--

6

LAuCl/AgSbF6 (5)

12

25

60(1.2:1)

--

--

7

AgNTf2 (5)

12

--

--

--

95

8

Zn(OTf)2 (10)

12

--

--

70

--

9

Sc(OTf)3 (10)

12

--

--

68

--

10

AuCl3 (10)

3

52

12 (10:1)

--

--

11

PtCl2/CO (10)c

12

30

45 (1.3:1)

--

--

a[1a]

= 0.17 M, bProduct yields are reported after purification from a silica column, L = P(t-Bu)2(o-biphenyl), creaction heated to 60 °C, IPr = 1,3-bis(diisopropylphenyl)imidazole2ylidene), DCE = 1,2-dichloroethane.

tions of ynamide 1a with 1,2-benzisoxazole 2a in dichloroethane (DCE, 25 0C) with IPrAuCl/AgSbF6 and IPrAuCl/AgNTf2, each at 5 mol %, led to a complete consumption of initial 1a, affording a [5+2]-annulation product 3a in 88-90% yields (entries 1-2). The use of LAuCl/AgNTf2 (L’= PPh3 and P(OPh)3) gave a [5+1]annulation product 4a as the major species (74-76%) with species 3a at only 21-22% (entries 3-4). The selectivity of compound 4a was slightly improved with LAuCl/AgNTf2, giving 80% yield and a Z/E ratio of 1.2:1 (entry 5); altering silver salt to AgSbF6 gave species 4a in a decreased yield (60%, entry 6). AgNTf2 alone was catalytically inactive whereas Zn(OTf)2 and Sc(OTf)3, each at 10 mol %, were active in the alkyne hydration (entries 7-9). AuCl3 and PtCl2/CO gave two annulation products 3a and 4a with poor chemoselectivity (entries 10-11). 1H NMR assignment of the E- and Z- isomers of compound 4a was made possible after the isomeric separation of their relatives 4b and 4q were successfully achieved for x-ray diffraction study

a[1]

= 0.17 M. bProduct yields are reported after purification from a silica gel column, IPr = 1,3-bis(diisopropyl phenyl) imidazol-2-ylidene

mides [N(PG)R’=NMsMe, NMs(n-Bu), NTs(n-Bu) and N(SO2Bu)Me] that were also amenable to these [5+2]annulations; their resulting products 3f-3i were generated efficiently (entries 5-8). We prepared 5-substituted 1,2benzisoxazoles 2b-2d (X = Cl, Br and Me), further affording the desired products 3j-3l in 86-90% yields (entries 911). 6-Substituted 1,2-benzisoxazoles 2e-2g were also cata lytically active to deliver compounds 3m-3o in high yields (entries 12-14). Our next task is to test the compatibility of these ynamides and 1,2-benzisoxazoles with catalytic [5+1]annulations using P(t-Bu)2(o-biphenyl)P-AuCl/AgNTf2; these reactants afforded six-membered heterocyles 4 as the major products (75-87%, Table 3), with sevenmembered heterocycles 3 in small proportions (6-18%). To assign the NMR spectra of Z- and E-isomers 4, the Zisomer of compound 4b was separated from its E-isomer by a silica column, and subjected to x-ray diffraction.29 The phenyl C(9)-H proton of the Z-4b isomer appears at δ 6.13 ppm because of a shielding effect of the cis-tosyl group whereas the E-isomer has this proton resonance at δ 6.96 ppm. This assignment is also supported by compound 4q, of which the Z- and E-isomers were also separated for x-

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ACS Catalysis ray diffraction study.29 For various ynamides 1b-1i bearing alterable 4-phenyl substituents (X = Cl, Br, Me and OMe) and sufonamides [N(PG)R’=NMsMe, NMs(n-Bu), NTs(nTable 3. The Scope of [5+1]-Annulations

P(t-Bu)2(o-biphenyl)AuCl/AgNTf2 yielded only a [5+2]annulation product 3p in high yields (entry 1). For ynamide 1k bearing an ester at the 4-phenyl position, the two catalysts gave a [5+1]-annulation product 4q exclusively (entry 2). We tested the reactions on additional ynamides 1l-1n (R = 2-thienyl, E-styryl and cyclopropyl), with two catalysts, further affording six-membered heterocycles 4r4t in satisfactory yields (78-88%, entries 3-5); these experimental data suggest that small R substituents prefer [5+1]annulation reactions. Among these products, the molecular structures of compounds 3p, E-4q, Z-4s and Z-4t were characterized by x-ray diffraction.29 We also tested the reactions of ynamide 1a with benzisoxazole 2h (R’ = Me) with these two gold catalysts in hot DEC (80 0C, 24 h), yielding a complicated mixture of products. Although gold-catalyzed [5+1]-annulation afforded sixmembered heterocycle 4b in a mixture of Z- and E- isomers, a NaBH4 reduction delivered compound 4b-H as a

a[1] = 0.17 M. bProduct yields are reported after purification from a silica gel column, L = P(t-Bu)2(o-biphenyl)

Bu) and N(SO2Bu)Me], their resulting [5+1]-annulation products 4b-4i were produced in 75-87% yields (entries 18). These [5+1]-annulations were extendible to 1,2benzisoxazoles 2b-2g bearing various 5- and 6-substituents (X or Y = Cl. Br and Me), forming the desired products 4j4o in satisfactory yields (77-82%, entries 9-14). Several ynamides 1j-1n with their chemoselectivity unaffected by gold catalysts (see Table 4); this behavior assist the understanding of two reaction mechanisms. In the case of 1-naphthylynamide 1j, IPrAuCl/AgNTf2 and Table 4. Chemoselectivity Unaffted by Gold Catalysts

single product; the yield was up to 95% (eq 6). This 1,4hydrogen addition was also effective for seven-membered azacycle 3b via Pd/C hydrogenation (1 bar) to afford compound 3a-H in 75% yield (eq 7). A skeletal rearrangement is involved in the goldcatalyzed [5+1]-annulation reactions; 13C-labeling experiment was performed to clarify a 1,2-aryl30-33 or 1,2sulfonamide34 shift. We prepared 13C- labeling ynamide 13C1a from Ph*CHO, bearing a 12% 13C-content at the alkynyl C(2)-carbon; its [5+1]-annulation gave six-membered azacycle 13C-4a bearing a large 13C signal at δ 116.5 and 116.3 ppm for Z- and E-isomers respectively. Correct assignment of these NMR peaks relied a subsequent NaBH4 reduction of species 13C-4a to yield 13C-4a-H bearing a large 13CHN signal at δ 62.3 ppm (eq 8). Accordingly, this 13C-labeling experiment is indicative of a 1,2-sulfonamide shift in the [5+1]-annulation.

a[1]

= 0.15 M. bProduct yields are reported after purification from a silica gel column, c10 mol% catalyst, IPr = 1,3bis(diisopropylphenyl) imidazol-2-ylidene

Scheme 1 shows a plausible model to rationalize the two annulations using appropriate gold catalysts; both annulations have the same intermediate A via a N-attack of 1,2-benzisoxazole at gold-π-alkyne.25-27 In path a, inter-

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mediate A bears a highly electron-rich IPrAu moiety to cleave a N-O bond, forming species B that is characterized by gold-carbene character B. This carbene species undergoes a 6-π-electrocyclization to yield azacyclic species C and the observed product 3a. When phosphine gold catalysts such as P(t-Bu)2(o-biohenyl), PPh3 and P(OPh)3 are used , the resulting species B’ are visualized with goldstabilized carbocations B’ that is more energetic than goldcarbenes B because of the lack of a π-bond. Accordingly, path a would be slow for these phosphine gold catalysts. Apart from this gold carbene route, an alternative path b is likely to occur, involving an alkene shift from the nitrogen to the oxygen atom of the two conformers of intermediate A or A’. This 1,2-alkene shift in conformer A is expected to be very slow because a front and bulky sulfonamide group impedes the migration. In contrast, the shift in conformer A’ is slightly hindered by a relatively small phenyl group, rendering this 1,2-alkene shift operable for PR3Au+ catalyst. This 1,2-alkene shift in conformer A’ cleaves a N-O bond, further forming a six-membered heterocycle D. A 1,2-sulfonamide shift of intermediate D generates species E and ultimate product 4a.

path b becomes rapid, for L = IPr or PR3, because of a small hindrance in the 1,2-alkenyl shift of state A’. In contrast, this process A’ →D becomes inhibited by a large R = 1naphthyl group, rendering the alternative path a operable. In the path a, when Ar = 4-EtO2CC6H4, is present for intermediate A, the next intermediate B is unlikely to form because this electron-deficient aryl group tends to destabilize the gold carbene functionality. These assessments also rationalize the outcome of our substituent effects in Table 4. CONCLUSION In this work, we report [5+2]- and [5+1]-annulations between ynamides and 1,2-benzisoxazoles using varied ligands on gold.35-37 For most ynamides, IPrAuCl/AgNTf2 led to [5+2]-annulation38-40 products whereas P(t-Bu)2(obiphenyl)AuCl/AgNTf2 preferably afforded [5+1]annulation products;41 the latter was confirmed with a 13Clabeling experiment to involve a 1,2-sulfonamide shift. We observed also several ynamides of which the chemoselectivity was unaffected by gold catalysts. These experimental data support a postulated mechanism involving an initial common intermediate, which undergos two distinct N-O cleavages to yield gold carbenes before preceding to products.

ASSOCIATED CONTENT AUTHOR INFORMATION Corresponding Author *Email: [email protected] Notes The authors declare no competing financial interest. Supporting Information The Supporting Information is available free of charge on the ACS Publications website. Experimental procedure, characterization data, and copies of 1H and 13C NMR spectra (PDF).

ACKNOWLEDGMENT We thank the Ministry of Education (MOE 106N506CE1) and Ministry of Science and Technology (MOST 107-3017-F-007002), Taiwan, and the National Natural Science Foundation of China (No. 91545105) for financial support of this work.

Scheme 1. Two Postulated routes for two annulation reactions Paths a and b are competitive reactions for all ynamides; The rates in path a are affected by the stability of gold carbenes B whereas the rates of path b are affected by the steric hindrance of the alkyne R substituent. In several instances, the chemoselectivity is affected only by the alkyne substituents (see Table 4). For small R groups such as thienyl, cyclopropyl and styryl, the A’ →D conversion in

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REFERENCES (1) Zaware, N.; Ohlmeyer, M. Recent Advances in Dibenzo [b, f][1, 4]oxazepine Synthesis. Heterocycle. Commun. 2014, 20, 251256. (2) Heffron, T. P.; Heald, R. A.; Ndubaku, C.; Wei, B.; Augistin, M.; Do, S.; Edgar, K.; Eigenbrot, C.; Friedman, L.; Gancia, E.; Jackson, P. S.; Jones, G.; Kolesnikov, A.; Lee, L. B.; Lesnick, J. D.; Lewis, C.; McLean, N.; Mörtl, M.; Nonomiya, J.; Pang, J.; Price, S.; Prior, W. W.; Salphati, L.; Steve Sideris, S.; Staben, S. T.; Steinbacher, S.; Tsui, V.; Wallin J.; Sampath, D.; Olivero, A. G. The Rational Design of Selective Benzoxazepin Inhibitors of the Isoform of Phosphoinositide 3-Kinase Culminating in the Identifica-

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Page 5 of 7 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 Catalysis tion of (S)-2-((2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)oxy)propan-amide (GDC-0326). J. Med. Chem. 2016, 59, 985-1002. (3) Bruce Lydiard, R.; Gelenberg, A. J. Amoxapine - An Antidepressant With Some Neuroleptic Properties?. Pharmacotherapy. 1981, 1, 163-178. (4) Liao, Y.; Venhuis, B. J.; Rodenhuis, N.; Timmerman, W.; Wikstrom, H. New (Sulfonyloxy)piperazinyldibenzazepines as Potential Atypical Antipsychotics: Chemistry and Pharmacological Evaluation. J. Med. Chem., 1999, 42, 2235-2244. (5) Nagarajan, K.; David, J.; Kulkarni, Y. S.; Hendi, S. B.; Shenoy, S. J.; Upadhyaya, P. Piperazinyl Benzonaphthoxazepines with CNS Depressant Properties. Eur. J. Med. Chem., 1986, 21, 2126. (6) Singh, H.; Chawla A. S.; Kapoor, V. K. Medicinal Chemistry Research in India. Prog. Med. Chem., 1985, 22, 243-266. (7) Dols, P. P. M. A.; Folmer, B. J. B.; Hamersma, H.; Kuil, C. W.; Lucas, H.; Ollero, L.; Rewinkel, J. B. M.; Hermkens, P. H. SAR Study of 2,3,4,14b-tetrahydro-1H-dibenzo[b,f]pyrido[1,2d][1,4]oxazepines as Progesterone Receptor Agonists. Bioorg. Med. Chem. Lett., 2008, 18, 1461-1467. (8) Chernysheva, N. B.; Samet, A. V.; Marshalkin, V. N.; Polukeev, V. A.; Semenov, V. V. Synthesis of Nitro-substituted Benzoannelated Seven-membered Heterocycles from Trinitrotoluene. Mendeleev Communications, 2001, 11,109-110. (9) Hadou, A.; Hamid, A.; Mathouet, H.; Deïda, M.-F.; Daïch, A. An Easy Access to the Exocyclic Lactams Analogous of the Central Nervous System Active Tricyclic Nitroxapine, Mianserine and Chlothiapine Agents Using N-Acyliminium Chemistry. Heterocyces, 2008, 76, 1017-1022. (10) Noguchi, T.; Nishii, Y.; Miyura, M. Chem. Lett. Rhodiumcatalyzed Synthesis of 1-Arylisoquinoline Derivatives through Annulative Coupling of 3-Aryl-1,2-benzisoxazoles and Alkynes. 2017, 46, 1512-1514. (11) Han, Y.-P.; Li, X.-S.; Sun, Z.; Zhu X.-Y.; Li, M.; Song X.-R.; Liang Y.-M. Lewis Acid-Catalyzed [4+ +2] Annulation between Propargylic Alcohols with Benzo[d]isoxazoles. Adv. Synth. Catal. 2017, 359, 2735-2740. (12) Hashmi, A. S. K. Gold-Catalyzed Organic Reactions. Chem. Rev. 2007, 107, 3180-3211. (13) Patil, N. T.; Yamamoto, Y. Coinage Metal-Assisted Synthesis of Heterocycles. Chem. Rev. 2008, 108, 3395-3442. (14) Abu Sohel, S. M.; Liu, R.-S. Carbocyclisation of Alkynes with External Nucleophiles Catalysed by Gold, Platinum and other Electrophilic Metals. Chem. Soc. Rev. 2009, 38, 2269-2281. (15) Muratore, M. E.; Homs, A.; Obradors, C.; Echavarren, A. M. Meeting the Challenge of Intermolecular Gold(I)-Catalyzed Cycloadditions of Alkynes and Allenes. Chem. Asian J. 2014, 9, 3066-3082. (16) Huple, D. B.; Ghorpade, S.; Liu, R.-S. Recent Advances in Gold-Catalyzed N- and O-Functionalizations of Alkynes with Nitrones, Nitroso, Nitro and Nitroxy Species. Adv. Syn. Catal. 2016, 358, 1348-1367. (17) Zhou, A.-H.; He, Q.; Shu, C.; Yu, Y.-F.; Liu, S.; Zhao, T.; Zhang, W.; Lu X.; Ye. L.-W. Atom-economic Generation of Gold Carbenes: Gold-Catalyzed Formal [3+2] Cycloaddition Between Ynamides and Isoxazoles. Chem. Sci., 2015, 6, 1265-1271. (18) Xiao, X.-Y.; Zhou, A.-H.; Shu, C.; Pan F.; Li, T.; Ye, L.-W. Atom-Economic Synthesis of Fully Substituted 2-Aminopyrroles via Gold-Catalyzed Formal [3+ +2] Cycloaddition between Ynamides and Isoxazoles. Chem. Asian J., 2015, 10, 1854-1858. (19) Sahani, R. L.; Liu, R.-S. Development of Gold-catalyzed [4+1] and [2+2+1]/[4+2] Annulations between Propiolate Derivatives and Isoxazoles. Angew. Chem. Int. Ed. 2017, 56, 1026-1030. (20) Shen, W.-B.; Xiao, X.-Y.; Sun, Q.; Zhou, B.; Zhu, X.-Q.; Yan, J.-Z.; Lu X.; Ye, L.-W. Highly Site Selective Formal [5+2] and [4+2] Annulations of Isoxazoles with Heterosubstituted Alkynes

by Platinum Catalysis: Rapid Access to Functionalized 1,3Oxazepines and 2,5-Dihydropyridines. Angew. Chem. Int. Ed. 2017, 56, 605-609. (21) Giri, S. S.; Liu, R.-S. Gold-Catalyzed [4+3]- and [4+2]Annulations of 3-En-1-ynamides with Isoxazoles via Novel 6πElectrocyclizations of 3-azahepta Trienyl Cations. Chem. Sci., 2018, 9, 2991-2995. (22) Mokar, B. D.; Jadhav, P. D.; Pandit Y. B.; Liu R.-S. GoldCatalyzed (4 + 2)-Annulations between α-Alkyl Alkenyl Gold Carbenes and Benzisoxazoles with Reactive Alkyl Groups. Chem. Sci. 2018, 9, 4488-4492. (23) Jin, H.; Huang, L.; Xie, J.; Rudolph, M.; Rominger, F.; Hashmi, A. S. K. Gold-Catalyzed C-H Annulation of Anthranils with Alkynes: A Facile, Flexible, and Atom-Economical Synthesis of Unprotected 7-Acylindoles. Angew. Chem. Int. Ed., 2016, 55, 794-797. (24) Jin, H.; Tian, B.; Song, X.; Xie, J.; Rudolph, M.; Rominger F.; Hashmi, A. S. K. Gold-Catalyzed Synthesis of Quinolines from Propargyl Silyl Ethers and Anthranils through the Umpolung of a Gold Carbene Carbon. Angew. Chem. Int. Ed., 2016, 55, 1268812692. (25) Sahani, R. L.; Liu, R.-S. Gold-Catalyzed [4+ +2] Annulation/Cyclization Cascades of Benzisoxazoles with Propiolate Derivatives to Access Highly Oxygenated Tetrahydroquinolines. Angew. Chem. Int. Ed. 2017, 56, 12736-12740. (26) Wang, X.-N.; Yeom, H.-S.; Fang, L.-C.; He, S.; Ma, Z.-X.; Kedrowski, B. L.; Hsung, R. P. Ynamides in Ring Forming Transformations. Acc. Chem. Res., 2014, 47, 560–578. (27) DeKorver, K. A.; Li, H.; Lohse, A. G.; Hayashi, R.; Lu, Z.; Zhang, Y.; Hsung, R. P. Ynamides: A Modern Functional Group for the New Millennium. Chem. Rev., 2010, 110, 5064–5106. (28) Evano, G.; Coste, A.; Jouvin, K. Ynamides: Versatile Tools in Organic Synthesis. Angew. Chem., Int. Ed., 2010, 49, 2840– 2859. (29) Crystallographic data of compounds 3p, 4b, 4q, 4s and 4t were deposited at Cambridge Crystallographic Data Center: 3p (CCDC 1856341), 4b (CCDC 1856351), 4q (CCDC 1856346), 4s (CCDC 1856344), and 4t (CCDC 1856352). (30) Chen, M.; Chen, Y.; Sun, N.; Zhao, J.; Liu, Y.; Li Y. GoldCatalyzed Oxidative Ring Expansion of 2-Alkynyl-1,2Dihydropyridines or Quinolines: Highly Efficient Synthesis of Functionalized Azepine or Benzazepine Scaffolds. Angew. Chem. Int. Ed. 2015, 54, 1200-1204. (31) Dudnik A. S.; Gevorgyan, V. Metal-Catalyzed [1,2]-Alkyl Shift in Allenyl Ketones: Synthesis of Multisubstituted Furans. Angew. Chem. Int. Ed. 2007, 46, 5195-5197. (32) Benedetti, E.; Lemière, G.; Chapellet, L.-L.; Penoni, A.; Palmisano, G.; Malacria, M.; Goddard, J.-P.; Fensterbank, L. Gold(I)-Catalyzed Cyclization of β-Allenylhydrazones: An Efficient Synthesis of Multisubstituted N-Aminopyrroles. Org. Lett., 2010, 12, 4396-4399. (33) Qiu, Y.; Fu, C.; Zhang, X.; Ma S. Studies on [PtCl2]- or [AuCl]-Catalyzed Cyclization of 1-(Indol-2-yl)2,3-Allenols: The Effects of Water/Steric Hindrance and 1,2-Migration Selectivity. Chem. Eur. J. 2014, 20, 10314-10322. (34) For gold-catalyzed a 1,2-nitrogen shift, see ref 27 and Adcock, H. V.; Langer, T.; Davies, P. W. 1,2-N-Migration in a GoldCatalysed Synthesis of Functionalised Indenes by the 1,1Carboalkoxylation of Ynamides. Chem. Eur. J. 2014, 20, 72627266. (35) Christian, A. H.; Niemeyer, Z. L.; Sigman, M. S.; Toste, F. D. Uncovering Subtle Ligand Effects of Phosphines Using Gold(I) Catalysis. ACS Catal. 2017, 7, 3973-3978. (36) Alonso, I.; Faustino, H.; López, F.; Mascareñas, J. L. Enantioselective Gold(I)-Catalyzed Intramolecular (4+3) Cycloadditions of Allenedienes. Angew. Chem. Int. Ed. 2011, 50, 11496-11500.

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(37) Mauleón, P.; Zeldin, R.M.; González, A. Z.; Toste, F.D. Enantioselective Gold(I)-Catalyzed Intramolecular (4+3) Cycloadditions of Allenedienes. J. Am. Chem. Soc. 2009, 131, 6348-6349. (38) De, N.; Song, C. E.; Ryu D. H.; Yoo, E. J. Gold-Catalyzed [5+2] Cycloaddition of Quinolinium Zwitterions and Allenamides as an Efficient Route to Fused 1,4-Diazepines. Chem. Commun., 2018, 54, 6911-6914. (39) Iqbal, N.; Fiksdahl, A. Gold(I)-Catalyzed Benz[c]azepin-4ol Synthesis by Intermolecular [5 + 2] Cycloaddition. J. Org. Chem., 2013, 78, 7885-7895. (40) Cui, L.; Ye, L.-W.; Zhang, L. Gold-Catalyzed Efficient Synthesis of Azepan-4-ones via a Two-step [5+2] Annulation. Chem. Commun., 2010, 46, 3351-3353. (41) Li, C.-W.; Pati, K.; Lin, G.-Y. Lin, Abu Sohel, S. M.; Hung, H.-H.; Liu, R.-S. Gold-Catalyzed Oxidative Ring Expansions and Ring Cleavages of Alkynylcyclopropanes by Intermolecular Reactions Oxidized by Diphenylsulfoxide. Angew. Chem. Int. Ed. 2010, 49, 9891-9894.

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