Catalyst-Controlled Structural Divergence: Selective Intramolecular 7

Article Cite This: J. Org. Chem. 2018, 83, 57−68

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Catalyst-Controlled Structural Divergence: Selective Intramolecular 7-endo-dig and 6-exo-dig Post-Ugi Cyclization for the Synthesis of Benzoxazepinones and Benzoxazinones Karandeep Singh,†,‡ Bhanwar Kumar Malviya,† Tapta Kanchan Roy,§ Venus Singh Mithu,‡ Vimal K. Bhardwaj,∥ Ved Prakash Verma,⊥ Swapandeep Singh Chimni,‡ and Siddharth Sharma*,† †

Department of Chemistry, Mohanlal Sukhadia University, Udaipur 313001, India Department of Chemistry, U.G.C. Centre of Advance Studies in Chemistry, Guru Nanak Dev University, Amritsar 143005, India § Department of Chemistry and Chemical Sciences, Central University of Jammu, Jammu 180011, India ∥ Department of Chemistry, Indian Institute of Technology Ropar (IIT Ropar), Rupnagar 140001, India ⊥ Department of Chemistry, Banasthali University, Newai-Jodhpuriya Road, Vanasthali 304022, India ‡

S Supporting Information *

ABSTRACT: Metal catalyzed post-Ugi cyclization of bis-amides is reported in this study. Exposure of bis-amides to Pd(II) catalyst triggered the formation of seven-membered benzoxazepinones. This investigation established that changing the catalyst to a Echavarren’s gold(I) turned off cyclization to seven member ring and turned on 6-exo-dig annulations to afford family of sixmembered benzoxazinones. To support the proposed mechanisms, quantum chemical based density functional theory calculations have been performed and validated. This novel method obtained molecular complexity up to four modular inputs and divergence of two different skeletons. 2D NMR spectroscopic techniques and single crystal X-ray diffraction established the proposed structures.

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INTRODUCTION Diversity oriented synthesis (DOS) is defined as one of the most concise approaches for the synthesis of highly skeletal diverse small molecules, which are ubiquitous in pharmaceuticals, agrochemical, and complex natural products. Generation of skeletal diversity in a small number of steps is commonly known as reagent-based differentiation, where two or more compounds are obtained and subjected to a common starting molecule in diverse reaction conditions.1 Although the benefits of skeletal diverse process are evident, their development posed the major challenge in this realm. In this context, isocyanide-based multicomponent reactions (IMCRs) are a well recognized approach toward the synthesis of diverse heterocycles.2 In particular, Ugi four-component reaction and Passerini three-component reaction have a long history in organic chemistry and are still of enormous interest for three reasons: efficiency, diversity, and their unexplored chemical space.3 However, linear peptide backbone of the Ugi and Passerini MCR products clearly requires novel methods to synthesize more promising candidates for biological screening in a way that was neither possible nor required before. Though, chemo-selective intramolecular cyclization of Ugi reaction product comprising multiple nucleophilic/electrophilic sites, remains a challenging task. Therefore, a method that involves © 2017 American Chemical Society

the conditions-based divergence in IMCRs and generates multiple molecular scaffolds from the same starting materials by merely applying different metal catalysts should drive the diversity oriented synthesis into unexplored dimensions. Given that, DOS involving IMCR can furnish highly skeletal diverse scaffolds, we anticipated that tuning of metal catalyst, such as palladium and gold, will induce different modes of cyclization in Ugi reaction product (Figure 1).4 In this regard, pioneering work was carried out by Schreiber and co-workers in skeletal DOS to establish a diverse collection of small molecules using isocyanides.5 Extending this concept, progress has been made with several examples from Erik group relying on the distinct dichotomy in product distribution for the synthesis of divergent heterocycles utilizing IMCRs.6 Furthermore, the group of Dai developed Ullmann diaryl etherification as an efficient protocol for the post-Ugi annulation for the synthesis of dibenz[b,f][1,4]oxazepine scaffold.7 In addition, Zhu group developed a regiocontrolled Pd-catalyzed domino sequence for the synthesis of functionalized benzodiazepinediones.8 In contrast, reaction pathways that can be changed by tuning the metal catalysts thus giving rise to completely different types of products from the Received: August 22, 2017 Published: November 28, 2017 57

DOI: 10.1021/acs.joc.7b02123 J. Org. Chem. 2018, 83, 57−68

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The Journal of Organic Chemistry

Figure 1. (I) Concept of reagent-based differentiation. (II) Synthesis of benzoxazepinones and benzoxazinones by different mode of cyclization.

Table 1. Optimization of the Reaction Conditions for the Synthesis of Products 6a and 7aa

s.no. 1 2 3 4 5 6 7 8 9e 10 11 12 13 14 15 16 17 18 19 20f

catalyst (mol%) d,e

no catalyst no catalystd,e PdCl2 (20) Pd(PPh3)4 (20) PdCl2(CH3CN)2 (20) Pd(OCOCF3)2 (20) Pd(OAc)2 (20) Pd(CH3CN)4(BF4)2 (20) Pd(CH3CN)4(BF4)2 (20) Pd(CH3CN)4(BF4)2 (10) Pd(CH3CN)4(BF4)2(10) Pd(CH3CN)4(BF4)2 (10) Pd(CH3CN)4(BF4)2 (10) AuCl3 (10) (JohnPhos)Au(CH3CN)SbF6 (10) (JohnPhos)Au(CH3CN)SbF6 (5) Ph3PAuCl (10) Ph3PAuCl (5) and AgNTf2 (10) Ph3PAuCl (5) and AgSbF6 (10) (JohnPhos)Au(CH3CN)SbF6 (5)

base

solvent

6a yieldb (%)

7a yieldc (%)

K2CO3 Cs2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3

toluene toluene toluene toluene toluene toluene toluene toluene toluene toluene toluene DCE DMF CH3CN DCE DCE DCE DCE DCE DCE

27 23 38 18 58 76 32 82 36 84

8 9

K2CO3 K2CO3

76 53

16 55 67 74 28 63 57 66

All yields are isolated. bReaction carried out in Pd catalyst at 80 °C for 24 h. cReaction carried out in Au catalyst at 50 °C for 24 h. dReaction carried out at 80 °C for 48 h. eReaction have been carried out at 5 mmol scale. fReaction carried out at room temperature for 3 days. a

same reactants still remain much less explored.9 Benzoxazepinones and benzoxazinones10 are ubiquitous heterocycles found in many biologically important molecules. In particular, benzoxazepinones could serve as a multidrug-resistance modulating agent, and central nervous system agents.11 As a part of our continuing interest over exploring the reactivity of isocyanide,12 we attempted to develop a highly desirable 7endo-dig mode cyclization of 5 using palladium catalyst. We have realized gold catalyzed 6-exo-dig cyclization for the

synthesis of benzoxazinone 7 from Ugi reaction product 5. We report the results herein (Figure 1).

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RESULTS AND DISCUSSION

The cyclization precursors 5 (Figure 1) were first synthesized via an Ugi reaction using alkyne, 2-hydroxyaniline, aldehyde, and isocyanide in methanol without any catalysts or additives at ambient temperature. The Ugi products obtained as a pure solid without column chromatography were directly used for further reaction. First we choose N-(2-(tert-butylamino)-2-oxo58


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The Journal of Organic Chemistry Table 2. Palladium and Gold-Catalyzed Divergent Cyclization

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The Journal of Organic Chemistry Table 2. continued

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The Journal of Organic Chemistry Table 2. continued

a

Reactions were carried out in the presence of Pd(CH3CN)4(BF4)2 (10 mol %) catalyst, K2CO3 (1 equiv), toluene (5 mL) in a round bottomed flask at 80 °C for 24 h. bReactions were carried out in the presence of (JohnPhos)Au(CH3CN)SbF6 (5 mol %) catalyst, in DCE (5 mL) in a round bottomed flask at 50 °C for 24 h. cIsolated Yields, NS = Synthesis not attempted

1-(p-tolyl)ethyl)-N-(2-hydroxyphenyl)-3-phenylpropiolamide (5a) as model substrate to examine the regioselectivity (6-exodig vs 7-endo-dig cyclization mode) of this intramolecular cyclization using palladium and gold catalysts. The results are summarized in Table 1. From this substrate, two different products were expected (6a, 7a) (Table 1) and the mode of cyclization involved oxygen atom as the nucleophile in both of them. In order to verify our hypothesis, the regioselectivity was first examined using a base (K2CO3) mediated cyclization which afforded 27 and 8% yields of 6a and 7a, respectively, after 48 h (Table 1, entry 1). Similarly Cs2CO3 gave the desired product 6a and 7a in 23 and 9% yields, respectively (Table 1, entry 2). Well separated products on TLC were isolated by column chromatography and 2D NMR spectroscopy was used to confirm structural differences between the two products, 6a and 7a (for detail see Supporting Information, Figure S6). Furthermore, activation of the alkyne subunit (5a), by screening of a handful of palladium and gold catalysts revealed that two cyclization pathways were operative leading to the formation of benzoxazepinone (6a) and benzoxazinone (7a) selectively (Table 1). The outcome of Table 1, entries 3−5 led us to conclude that, Pd[0] and Pd[II] catalyzed reaction

proceeded with low yields even after using 20 mol % catalyst, though 7-endo-dig cyclization product (6a) was isolated exclusively. In addition, the Pd(OCOCF3)2 catalyst clearly promoted the formation of benzoxazepinones derivatives 6a in higher yield (76%) with exclusive 7-endo-dig selectivity (Table 1, entry 6). Pd(OAc)2 preferentially provided benzoxazepinones derivatives (32% yield), however low yield restricted us to use the catalyst further (Table 1, entry 7). We finally found that cationic Pd catalyst, Pd(CH3CN)4(BF4)2 (Table 1, entry 10) was not only the most efficient in controlling the regioselectivity for the formation of benzoxazepinone derivative (6a) with low catalytic loading but afforded the desired product in good yields (84%). No desired product was isolated when base was omitted from standard reaction conditions (Table 1, entry 11). Notably, toluene stood out to be the better solvent in comparison to DCE, and DMF in terms of selectivity and yield (Table 1, entries 12 and 13). Aiming to promote the switch in regioselective O-cyclization, several other Au(I) and Au(III) salts were also screened (Table 1, entries 14 and 18). Interestingly, experiments with the cationic gold catalysts, complete switch in regioselectivity was observed with gold(III) chloride (Table 1, entry 14) without using base (K2CO3). Use 61


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Figure 2. Crystal structure of compounds 6f (A) and 7d (B) (thermal ellipsoids are shown at 50% probability level).

Figure 3. Calculated transition state structures of Au-catalyzed (6-membered, 7b) and Pd-catalyzed (7-membered, 6b) systems optimized at the B3LYP/6-31G* (LANL2DZ with ECP for Pd and Au) level of theory.

delivered the products in good yields (58 and 85%). However, due to electron-donating group present on the phenyl substituent of the alkyne (Table 2, entries 13 and 14), 6m and 6n were formed in moderately lower yields of 62 and 51%, respectively. The scope of the 6-exo-dig annulation was then explored by employing Echavarren’s gold(I) catalyst [JohnPhosAu(CH3CN)]SbF6 (Table 2). A small library of 13 derivatives was prepared using the optimized synthetic protocol. Most of the tested bis-amides (5a−5n) derived from Ugi reaction underwent cyclization to afford the corresponding products (7a−7n) in good yields and with exclusive exo-dig mode of selectivity. Methyl (7a), methoxy (7c, 7e, 7h, 7i, 7m, 7n), cyano (7f), and bromo (7g) groups on aldehyde derived Ugi substrates were well tolerated under these reaction conditions. 81% yield was obtained from Ugi adducts derived from substituted 2-aminophenol (Table 2, entry 7l). The high efficiency was maintained, when different isocyanides -derived Ugi reaction product were used (Table 2, entries 7h and 7i). It is noteworthy that the 6-exo-dig annulation products were obtained exclusively in all reactions. A single crystal of 6f and 7d were obtained from the CH2Cl2/hexane solution, and X-ray structure analysis verified the proposed structure (Figure 2). To validate the experimental observations for the 7- and 6membered products using Pd- and Au-catalyzed cyclization processes, we have carried out quantum chemical based density functional theory calculations. Depending on the nucleophilic attack on Cα or Cβ by the phenolic oxygen, 6- or 7-membered products are formed, respectively. The equilibrium structures of

of 5 mol% Echavarren’s gold(I) catalyst [JohnPhosAu(CH3CN)]SbF6 (Table 1, entry 16) selectively afforded benzoxazinones derivative 7a in 74% yield. In comparison to this, only 28% yield was observed when the reaction was catalyzed using Ph3PAuCl (Table 1, entry 17). Finally, the use of in situ generated cationic gold catalyst (Table 1, entries 18 and 19) gave the desired product in satisfactory yield. To evaluate the scope of the optimized process (Table 1, entries 10 and 16) for the benzoheterocycle library construction, Ugi reactions were carried out following the usual procedure13 and subjected to intramolecular cyclization (Table 2). First, the scope of the 7-endo-dig cyclization was examined for benzoxazepinones derivatives. Various substituents on the alkynes, isonitriles, aldehydes, and amines were well tolerated with high selectivity (Table 2). As shown in Table 2, several aldehyde components (entries 1 and 9) carrying either electron-donating or electron-withdrawing substituents have been successfully engaged in this sequence and afforded the cyclized adducts in moderate to excellent yields (51−87%). Though electron-withdrawing groups, such as cyno and bromo (5f and 5g), on aldehydes of bis-amides furnished relatively lower yield (65 and 67%, respectively) for 7-endo cyclization. Further diversity in the products was introduced by using other isocyanides substrates, albeit, no specific electronic effect on the reaction yield was observed when tert-butylisonitrile (6a−6g), and cyclohexyl isonitrile (6h) were subjected to reaction, provided the products in good yields. Additionally, substituting the aryl group in the 2-aminophenol derived Ugi substrate by a tert-butyl and methyl group (Table 2, entries 11 and 12) 62


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9. Regeneration of the Pd catalyst from the σ-complex under the optimized conditions allowed the formation of benzoxazepinones 6b. When cationic gold was used, the nucleophilic attack of the phenolic oxygen on the activated alkyne occurred in an exo-dig fashion generating intermediate 11, which upon protodeauration forms substituted 1,4-benzoxazin-3-one 7b.

the reactive intermediates 8 showed that both the Pd and Au are more localized on the Cα forming stronger bonds (bond lengths, Pd−Cα: 2.042 Å and Au−Cα: 2.053 Å) than Cβ (bond lengths, Pd−Cβ: 2.860 Å and Au−Cβ: 2.816 Å). Two separate potential energy surface (PES) scans along the reaction coordinates (phenolic oxygen and Cα or Cβ) revealed interesting facts. Near the transition state (Figure 3), during the attack of phenolic oxygen to Cα, both the catalysts hopped to the Cβ making Cα more electrophilic along with change in hybridization from sp to sp2. For the case of Pd-catalyzed reaction, both the attacks on Cα and Cβ are possible leading two intervening transition states between reactants and corresponding products. For Pd-catalyzed reaction, the Gibbs free energy barrier in 6 and 7-membered transition states are found, 17.8 and 13.2 kcal/mol, respectively. Both the energy barriers show, following to the experimental observations, 7-membered cyclization is more favorable than 6-membered for Pd-catalyst. On the other hand, for Au-catalyzed reaction, 6-membered transition states is found exclusively which is followed by 6membered cyclic product. The PES scan for the search of the 7membered products showed no intervening 7-membered transition state and thus it can be concluded that 7-membered product formation is not probable for Au catalyst. The Gibbs free energy barrier for 6-membered ring is found 18.5 kcal/mol which is easily achievable in the reaction conditions mentioned earlier. Thus, it can be concluded that theoretical calculations fully support the experimental observations for the formation for Pd-catalyzed 7-membered and Au-catalyzed 6-membered cyclization processes. Although the precise mechanism for this reaction is not clear, a plausible catalytic cycle is illustrated in Scheme 1 on the basis of computational studies.14 Initially, the metal catalyst activated the alkyne π-bond of 5b to form a metal π-complex. In case of palladium the 7-endo mode cyclization was observed by the intramolecular nucleophilic attack of the phenoxide oxygen at the alkyne carbon preferentially, to form a palladium σ-complex

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CONCLUSIONS

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EXPERIMENTAL SECTION

In summary, a catalyst-controlled divergent regioselective cyclization of bis-amides was developed by integrating the modularity of the Ugi reaction. The Ugi adducts were in turn prepared via reaction of alkyne, isocyanides, aldehyde, and 2hydroxyanilines. A variety of substituted benzoxazepinones and benzoxazinones were assembled using Pd and Au catalysts, respectively. It is presumable that the rich chemistry of the post-Ugi cyclization may be exploited for the further elaboration of the heterocycles into important natural products and bioactive molecules.

Materials and Methods. All reactions were carried out in oven- or flame-dried glassware unless otherwise noted. Except as otherwise indicated, all reactions were magnetically stirred and monitored by analytical thin layer chromatography (TLC) using precoated silica gel glass plates (0.25 mm) with a F254 indicator. Visualization was accomplished by UV light (254 nm). Flash column chromatography was performed using silica gel (100−200 mesh). Yields refer to pure compounds, unless otherwise noted. Commercial grade reagents and solvents were used without further purification. 1H and 13C NMR spectra were recorded on a Bruker 500 MHz NMR spectrometer using CDCl3/DMSO-d6 as a solvent for deuterium locking, with temperature at 298 K. Chemical shifts are given in parts per million with TMS as an internal reference. J values are given in hertz. 13C NMR spectra were recorded as solutions in CDCl3 with complete proton decoupling, 13C {1H NMR}. Mass spectra were recorded on a Bruker MicroTOF Q II mass spectrometer. The solutions were made/diluted in acetonitrile/ H2O (3:7) and directly injected to the ESI source through a pump. General Procedure for Syntheses of Ugi Products (5a−5n). To a solution of aldehyde (1 mmol) in methanol (3 mL) were added successively amine (1.0 equiv), acid (1.0 equiv), and isonitrile (1.0 equiv) in a round-bottom flask equipped with a magnetic stir bar. The reaction mixture was stirred at room temperature for 24−48 h in round-bottom flask. After completion of the reaction, solid was precipitate and separated by filtration. Solid was washed with ether and used without further purification. General Procedure for the Synthesis of Benzoxazepinones (6a− 6n) Using Pd (II) Catalyst. To a dry screw capped glass vial Pd(CH3CN)4(BF4)2 (10 mol %), K2CO3 (1 equiv) were loaded along with dry toluene (2 mL). Ugi product 5a−5n (0.2 mmol) was added. The reaction vial was evacuated, backfilled with nitrogen, and was stirred at 80 °C for 24 h. After completion, the reaction mixture was cooled, directly loaded over a silica gel column, and chromatographed (1:3 EtOAc in hexane) to afford compounds. The structures of the compounds were confirmed by NMR, single crystal X-ray analysis, and HRMS data. General Procedure for the Synthesis of Benzoxazinones (7a−7n) Using Au (I) Catalyst. To a screw capped vial equipped with a magnetic stir bar was added (JohnPhos)Au(CH3CN)SbF6 (5 mol %) along with DCE (2 mL). Ugi product 5a−n (0.2 mmol) was added. The reaction vial was evacuated, backfilled with nitrogen, and was stirred at 50 °C in oil bath for 24 h. After completion, reaction mixture was partitioned between EtOAc (100 mL) and water (50 mL). Organic layer was washed with brine (50 mL), dried over sodium sulfate, and evaporated under reduced pressure. The residue obtained was purified by silica gel column chromatography (10−30% EtOAc in hexane) to afford pure compounds.

Scheme 1. Plausible Mechanism for the Intramolecular PostUgi Cylization

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3H), 7.54−7.57 (m, 1H), 7.84−7.87 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 28.7, 51.7, 105.4, 120.7, 125.6, 126.1, 126.4, 126.6, 127.8, 128.1, 128.5, 128.6, 128.9, 131.1, 132.8, 135.0, 154.3, 166.3, 167.1, 169.1; HRMS (ESI-TOF) m/z [M+H]+ calcd for C27H27N2O3 427.2016; found 427.2019. (Z)-2-(2-Benzylidene-3-oxo-2,3-dihydro-4H-benzo[b][1,4]oxazin4-yl)-N-(tert-butyl)-2-phenylacetamide (7b). Pale yellow solid (62 mg, 73% yield); mp 110−112 °C, Rf = (15% EtOAc/hexane) 0.62. 1H NMR (500 MHz, CDCl3) δ 1.33 (s, 9H), 5.96 (s, 1H), 6.21 (s, 1H), 6.64 (dt, J1 = 10 Hz, J2 = 2 Hz, 1H), 6.99−7.05 (m, 3H), 7.18 (dd, J1 = 10 Hz, J2 = 2 Hz, 1H), 7.29−7.43 (m, 8H), 7.84 (dd, J1 = 10 Hz, J2 = 1.5 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 28.6, 51.9, 62.2, 114.5, 116.3, 116.9, 123.1, 124.3, 126.4, 127.9, 128.3, 128.5, 128.6, 129.0, 130.2, 130.3, 133.5, 134.1, 141.0, 142.4, 158.8, 166.7; HRMS (ESITOF) m/z [M+H]+ calcd for C27H27N2O3 427.2016; found 427.2021. N-(2-(tert-Butylamino)-1-(4-methoxyphenyl)-2-oxoethyl)-N-(2hydroxyphenyl)-3-phenylpropiolamide (5c). White solid (72 mg, 79% yield); mp 210−213 °C, Rf = (25% EtOAc/hexane) 0.53. 1H NMR (500 MHz, CDCl3) δ 1.37 (s, 9H), 3.71 (s, 3H), 5.67 (s, 1H), 5.93 (s, 1H), 6.46−6.53 (m, 2H), 6.69 (d, J = 11 Hz, 2H), 6.90 (dd, J1 = 1.5 Hz, J2 = 10 Hz, 1H), 7.03−7.10 (m, 5H), 7.17−7.20 (m, 2H), 7.26 (tt, J1 = 9.5 Hz, J2 = 1.5 Hz, 1H), 11.17 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 28.5, 52.7, 55.2, 64.8, 82.0, 91.0, 114.2, 117.5, 118.7, 120.2, 124.8, 125.3, 128.2, 130.0, 130.3, 131.1, 132.5, 132.9, 156.0, 156.6, 160.0, 171.8; HRMS (ESI-TOF) m/z [M+H]+ calcd for C28H29N2O4 457.2122; found 457.2128. N-(tert-Butyl)-2-(4-methoxyphenyl)-2-(4-oxo-2-phenylbenzo[b][1,4]oxazepin-5(4H)-yl)acetamide (6c). Pale yellow solid (79 mg, 87% yield); mp 185−188 °C, Rf = (22% EtOAc/hexane) 0.62. 1H NMR (500 MHz, CDCl3) δ 1.41 (s, 9H), 3.74 (s, 3H), 5.76 (s, 1H), 6.13 (s, 1H), 6.62 (s, 1H), 6.78 (d, J = 11 Hz, 2H), 7.04−7.07 (m, 2H), 7.15−7.18 (m, 1H), 7.28 (d, J = 11 Hz, 2H), 7.42−7.45 (m, 3H), 7.52−7.55 (m, 1H), 7.82−7.84 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 28.7, 51.7, 55.3, 68.5, 105.4, 113.9, 120.7, 125.8, 126.0, 126.5, 127.0, 128.9, 129.6, 131.1, 132.8, 134.4, 154.3, 159.1, 166.2, 167.0, 169.3; HRMS (ESI-TOF) m/z [M+H]+ calcd for C28H29N2O4 457.2122; found 457.2117. (Z)-2-(2-Benzylidene-3-oxo-2,3-dihydro-4H-benzo[b][1,4]oxazin4-yl)-N-(tert-butyl)-2-(4-methoxyphenyl)acetamide (7c). Pale yellow solid (62 mg, 69% yield); mp 165−167 °C, Rf = (20% EtOAc/hexane) 0.65. 1H NMR (500 MHz, CDCl3) δ 1.33 (s, 9H), 3.71 (s, 3H), 6.05 (s, 1H), 6.15 (s, 1H), 6.85−6.89 (m, 3H), 6.96−6.99 (m, 2H), 7.05 (d, J = 10 Hz, 1H), 7.13 (d, J = 10 Hz, 1H), 7.28 (d, J = 9.5 Hz, 1H), 7.34−7.40 (m, 4H), 7.81 (d, J = 9.5 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 28.7, 51.9, 55.3 61.8, 114.2, 114.4, 116.2, 116.9, 123.0, 124.2, 126.1, 126.5, 128.5, 128.6, 129.4, 130.2, 133.6, 141.2, 142.4, 158.7, 159.5, 167.0; HRMS (ESI-TOF) m/z [M+H]+ calcd for C28H29N2O4 457.2122; found 457.2124. N-(2-(tert-Butylamino)-1-(2,5-dimethoxyphenyl)-2-oxoethyl)-N(2-hydroxyphenyl)-3-phenylpropiolamide (5d). White solid (82 mg, 85% yield); mp 200−203 °C, Rf = (25% EtOAc/hexane) 0.6. 1H NMR (500 MHz, CDCl3) δ 1.38 (s, 9H), 3.59 (s, 3H), 3.71 (s, 3H), 5.55 (s, 1H), 6.23 (s, 1H), 6.46 (t, J = 9.5 Hz, 1H), 6.60−6.65 (m, 2H), 6.71− 6.74 (m, 2H), 6.85 (d, J = 10 Hz, 1H), 7.04−7.08 (m, 3H), 7.16 (t, J = 9.5 Hz, 2H), 7.28−7.30 (m, 1H),11.07 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 28.5, 52.6, 55.4, 55.8, 82.1, 90.9, 111.2, 116.5, 117.2, 118.2, 120.4, 125.5, 128.2, 129.9, 130.3, 131.3, 132.9, 153.4, 156.0, 156.5, 172.0; HRMS (ESI-TOF) m/z [M+H]+ calcd for C29H31N2O5 487.2227; found 487.2243. N-(tert-Butyl)-2-(2,5-dimethoxyphenyl)-2-(4-oxo-2-phenylbenzo[b][1,4]oxazepin-5(4H)-yl)acetamide (6d). Pale yellow solid (74 mg, 76% yield); mp 165−167 °C, Rf = (25% EtOAc/hexane) 0.56. 1H NMR (500 MHz, CDCl3) δ 1.41 (s, 9H), 3.67 (s, 3H), 3.71 (s, 3H), 5.96 (s, 1H), 6.09 (s, 1H), 6.31 (s, 1H), 6.65 (d, J = 11 Hz, 1H), 6.73 (dd, J1 = 11 Hz, J2 = 3.5 Hz, 1H), 6.98−7.05 (m, 2H), 7.10 (d, J = 3.5 Hz, 1H), 7.13−7.15 (m, 1H), 7.41−7.44 (m, 3H), 7.50−7.53 (m, 1H), 7.81−7.83 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 28.7, 51.6, 55.7, 55.8, 64.2, 105.4, 111.2, 114.6, 116.0, 120.4, 124.1, 125.3, 126.1, 126.2, 126.3, 128.7, 130.8, 133.1, 151.7, 153.2, 154.7, 165.8, 166.8, 168.9;

Computational Details. Explorations of the proposed mechanism are carried out using first-principles based quantum mechanical methods. The reaction of molecule 5b is considered with two different catalysts as mentioned above. To study the Pd catalyzed reaction Pd(CH3CN)3+2 molecule is considered as catalyst, and for the Au catalyzed reaction Au(CH3CN)+ is considered as the catalyst for simplicity, keeping the framework of 5b unchanged, which mimics the actual molecule well. All stationary points including transition states, reactant intermediates and product intermediates are fully optimized using tight gradient convergence criteria with ultrafine numerical grid using density functional theory based hybrid B3LYP15 functional in conjunction with 6-31G(d) basis sets16 for all except Pd and Au atoms where LanL2DZ basis17 in conjunction with effective core potential functions are used. At each equilibrium geometry harmonic vibrational frequencies were calculated to authorize each structure as true minima. All the transition states were characterized by only one imaginary frequency representing the respective reaction coordinate. All the energy barriers given here are the Gibbs free energies to account for the temperature effects in the reactions. All the theoretical calculations have been performed using the Gaussian 16 program package.18 N-(2-(tert-Butylamino)-2-oxo-1-(p-tolyl)ethyl)-N-(2-hydroxyphenyl)-3-phenylpropiolamide (5a). White solid (73 mg, 83% yield); mp 175−178 °C, Rf = (20% EtOAc/hexane) 0.51. 1H NMR (500 MHz, CDCl3 + DMSO-d6) δ 1.36 (s, 9H), 2.22 (s, 3H), 5.74 (s, 1H), 5.95 (s, 1H), 6.46−6.52 (m, 2H), 6.89 (dd, J1 = 10.5 Hz, J2 = 1.5 Hz, 1H), 6.97 (d, J = 9.5 Hz), 7.02−7.04 (m, 3H), 7.06−7.12 (m, 2H), 6.16 (tt, J1 = 9.5 Hz, J2 = 2 Hz, 2H), 7.27−7.30 (m, 1H), 11.23 (s, 1H); 13C NMR (125 MHz, CDCl3) δ = 21.2, 28.4, 52.7, 65.1, 81.9, 91.1, 117.5, 118.7, 120.2, 125.3, 128.2, 129.5, 129.7, 129.8, 130.1, 130.3, 132.5, 132.9, 139.1, 156.1, 156.6, 171.8; HRMS (ESI-TOF) m/z [M+H]+ calcd for C28H29N2O3 441.2173; found 441.2177. N-(tert-Butyl)-2-(4-oxo-2-phenylbenzo[b][1,4]oxazepin-5(4H)-yl)2-(p-tolyl)acetamide (6a). Pale yellow solid (74 mg, 84% yield); mp 92−95 °C, Rf = (20% hexane/EtOAc) 0.56. 1H NMR (500 MHz, CDCl3) δ 1.41 (s, 9H), 2.28 (s, 3H), 5.75 (s, 1H), 6.13 (s, 1H), 6.66 (s, 1H), 7.06−7.10 (m, 4H), 7.18 (dd, J1 = 8 Hz, J2 = 1.5 Hz, 1H), 7.25−7.28 (m, 3H), 7.45−7.47 (m, 3H), 7.54 (dd, J1 = 7.5 Hz, J2 = 2 Hz, 1H), 7.84 (dd, J1 = 7.5 Hz, J2 = 2 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 21.1, 28.7, 51.7, 53.5, 105.4, 120.7, 125.6, 126.0, 126.4, 126.5, 128.1, 128.9, 129.3, 131.1, 132.0, 132.8, 134.6, 137.6, 154.2, 166.2, 167.0, 169.2; HRMS (ESI-TOF) m/z [M+H]+ calcd for C28H29N2O3 441.2173; found 441.2187. (Z)-2-(2-Benzylidene-3-oxo-2,3-dihydro-4H-benzo[b][1,4]oxazin4-yl)-N-(tert-Butyl)-2-(p-tolyl)acetamide (7a). Pale yellow solid (68 mg, 78% yield); mp 125−128 °C, Rf = (15% EtOAc/hexane) 0.56. 1H NMR (500 MHz, CDCl3) δ 1.34 (s, 9H), 2.33 (s, 3H), 5.96 (s, 1H), 6.14 (s, 1H), 6.89 (dt, J1 = 8 Hz, J2 = 1.5 Hz, 2H), 6.99−7.05 (m, 3H), 7.16−7.19 (m, 3H), 7.30−7.34 (m, 3H), 7.40 (t, J = 8 Hz, 1H), 7.85 (d, J = 7.5 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 21.1, 28.5, 51.8, 62.2, 114.3, 116.1, 116.7, 123.0, 124.1, 126.5, 127.8, 128.4, 128.5, 129.6, 130.1, 131.0, 133.5, 138.1, 141.0, 142.3, 158.6, 166.8; HRMS (ESI-TOF) m/z [M+H]+ calcd for C28H29N2O3 441.2173; found 441.2179. N-(2-(tert-Butylamino)-2-oxo-1-phenylethyl)-N-(2-hydroxyphenyl)-3-phenylpropiolamide (5b). White solid (74 mg, 87% yield), mp 190−192 °C, Rf = (25% EtOAc/hexane) 0.66. 1H NMR (500 MHz, CDCl3 + DMSO-d6) δ 1.18 (s, 9H), 5.87 (s, 1H), 6.27−6.35 (m, 2H), 6.64 (dd, J1 = 10.5 Hz, J2 = 1.5 Hz, 1H), 6.82 (dd, J1 = 10.5 Hz, J2 = 1.5 Hz, 2H), 6.86−6.91 (dt, J1 = 9.5 Hz, J2 = 2.5 Hz, 1H), 6.96−7.01 (m, 5H), 7.02−7.05 (m, 2H), 7.10−7.12 (m, 1H), 7.24 (d, J = 1 Hz, 1H), 11.32 (s, 1H); 13C NMR (125 MHz, CDCl3 + DMSO-d6) δ 28.3, 52.1, 65.1, 82.0, 90.8, 117.2, 118.4, 120.0, 125.4, 128.1, 128.2, 128.4, 128.7, 129.7, 130.0, 130.1, 132.2, 132.4, 132.7, 133.2, 155.6, 156.5, 171.7; HRMS (ESI-TOF) m/z [M+H]+ calcd for C27H27N2O3 427.2016; found 427.2028. N-(tert-Butyl)-2-(4-oxo-2-phenylbenzo[b][1,4]oxazepin-5(4H)-yl)2-phenylacetamide (6b). Pale yellow solid (69 mg, 81% yield); mp 208−210 °C, Rf = (20% EtOAc/hexane) 0.53. 1H NMR (500 MHz, CDCl3) δ 1.41 (s, 9H), 5.80 (s, 1H), 6.14 (s, 1H), 6.71 (s, 1H), 7.03− 7.10 (m, 2H), 7.18−7.31 (m, 4H), 7.37−7.40 (m, 2H), 7.45−7.48 (m, 64


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The Journal of Organic Chemistry HRMS (ESI-TOF) m/z [M+H]+ calcd for C29H31N2O5 487.2227; found 487.2230. (Z)-2-(2-Benzylidene-3-oxo-2,3-dihydro-4H-benzo[b][1,4]oxazin4-yl)-N-(tert-butyl)-2-(2,5-dimethoxyphenyl)acetamide (7d). liquid (66 mg, 68% yield); Rf = (20% EtOAc/hexane) 0.5. 1H NMR (500 MHz, CDCl3) δ 1.34 (s, 9H), 3.70 (s, 3H), 3.82 (s, 3H), 5.78 (s, 1H), 6.20 (s, 1H), 6.83−6.86 (m, 2H), 6.88−6.94 (m, 1H), 6.97 (s, 1H), 7.01 (t, J = 9 Hz, 2H), 7.07 (s, 1H), 7.15 (td, J1 = 9.5 Hz, J2 = 1.5 Hz, 1H), 7.29−7.33 (m, 1H), 7.38 (t, J = 9 Hz, 2H), 7.83 (d, J = 10 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 28.5, 51.6, 55.7, 56.2, 58.7, 65.1, 112.0, 113.7, 114.5, 114.9, 116.0, 116.1, 123.0, 123.8, 123.9, 127.3, 128.2, 128.5, 130.1, 133.6, 141.3, 142.3, 151.4, 153.8, 158.4, 166.2; HRMS (ESI-TOF) m/z [M+H]+ calcd for C29H31N2O5 487.2227; found 487.2335. N-(2-(tert-Butylamino)-1-(2-methoxyphenyl)-2-oxoethyl)-N-(2hydroxyphenyl)-3-phenylpropiolamide (5e). White solid (67 mg, 74% yield); mp 218−220 °C, Rf = (25% EtOAc/hexane) 0.5. 1H NMR (500 MHz, CDCl3 + DMSO-d6) δ 1.36 (s, 9H), 3.87 (s, 3H), 6.25 (s, 1H), 6.48 (t, J = 9.5 Hz, 1H), 6.68 (t, J = 10 Hz, 2H), 6.76 (t, J = 10.5 Hz, 2H), 7.01 (t, J = 8.5 Hz, 4H), 7.13 (t, J = 10 Hz, 1H), 7.23 (t, J = 9 Hz, 2H), 7.33 (t, J = 9.5 Hz, 1H), 8.30 (s, 1H), 11.67 (s, 1H); 13C NMR (125 MHz, CDCl3 + DMSO-d6) δ 28.5, 51.8, 55.3, 59.5, 82.6, 89.9, 110.4, 116.8, 118.1, 120.0, 120.4, 122.2, 125.7, 128.6, 130.3, 130.4, 130.5, 131.4, 132.6, 155.2, 156.2, 157.4, 172.4; HRMS (ESITOF) m/z [M+H]+ calcd for C28H29N2O4 457.2122; found 457.2143. N-(tert-Butyl)-2-(2-methoxyphenyl)-2-(4-oxo-2-phenylbenzo[b][1,4]oxazepin-5(4H)-yl)acetamide (6e). Pale yellow solid (67 mg, 73% yield); mp 175−178 °C, Rf = (20% EtOAc/hexane) 0.51. 1H NMR (500 MHz, CDCl3) δ 1.41 (s, 9H), 3.70 (s, 3H), 5.97 (s, 1H), 6.10 (s, 1H), 6.30 (s, 1H), 6.71 (d, J = 10 Hz, 1H), 6.89 (dt, J1 = 9.5 Hz, J2 = 1.5 Hz, 1H), 6.95−7.03 (m, 2H), 7.12 (dd, J1 = 10 Hz, J2 = 2 Hz, 1H), 7.19 (dt, J1 = 10 Hz, J2 = 2 Hz, 1H), 7.43 (dd, J1 = 6.5 Hz, J2 = 2.5 Hz, 3H), 7.47 (dd, J1 = 10 Hz, J2 = 1.5 Hz, 1H), 7.50 (dd, J1 = 10 Hz, J2 = 2.5 Hz, 1H),7.81−7.84 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 28.7, 51.7, 55.82, 64.4, 100.0, 105.4, 110.2, 120.2, 120.4, 123.1, 125.3, 126.1, 126.4, 126.5, 128.8, 129.7, 130.0, 130.8, 133.2, 154.8, 157.4, 165.8, 166.9, 169.2; HRMS (ESI-TOF) m/z [M+H]+ calcd for C28H29N2O4 457.2122; found 457.2114. (Z)-2-(2-Benzylidene-3-oxo-2,3-dihydro-4H-benzo[b][1,4]oxazin4-yl)-N-(tert-Butyl)-2-(2-methoxyphenyl)acetamide (7e). liquid (58 mg, 64% yield); Rf = (20% EtOAc/hexane) 0.68. 1H NMR (500 MHz, CDCl3) δ 1.33 (s, 9H), 3.87 (s, 3H), 5.74 (s, 1H), 6.21 (s, 1H), 6.90− 7.03 (m, 6H), 7.16 (dd, J1 = 10 Hz, J2 = 2 Hz, 1H), 7.29−7.36 (m, 2H), 7.39 (t, J = 9.5 Hz, 1H), 7.46 (dd, J1 = 9.5 Hz, J2 = 2 Hz, 1H), 7.83−7.86 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 28.6, 51.7, 55.8 58.8, 111.0, 113.8, 116.0, 116.1, 121.3, 123.1, 124.1, 128.3, 128.6, 128.9, 130.2, 130.3, 141.4, 142.4, 157.3, 158.5, 166.5; HRMS (ESITOF) m/z [M+H]+ calcd for C28H29N2O4 457.2122; found 457.2124. N-(2-(tert-Butylamino)-1-(4-cyanophenyl)-2-oxoethyl)-N-(2-hydroxyphenyl)-3-phenylpropiolamide (5f). White solid (71 mg, 79% yield); mp 120−123 °C, Rf = (20% EtOAc/hexane) 0.5. 1H NMR (500 MHz, CDCl3 + DMSO-d6) δ 1.33 (s, 9H), 6.12 (s, 1H), 6.50 (dt, J1 = 9 Hz, J2 = 1.5 Hz, 1H), 6.60 (t, J = 10 Hz, 1H), 6.79 (d, J = 10 Hz, 1H), 7.01 (d, J = 10.5 Hz, 2H), 7.08 (dt, J1 = 9 Hz, J2 = 1.5 Hz, 1H), 7.23 (t, J = 9 Hz, 2H), 7.34 (t, J = 9 Hz, 3H), 7.49 (t, J = 10 Hz, 2H), 8.44 (s, 1H), 11.48 (s, 1H); 13C NMR (125 MHz, CDCl3 + DMSOd6) δ 28.4, 52.0, 64.5, 82.2, 90.3, 112.2, 117.3, 118.3, 118.8, 119.8, 125.4, 128.7, 130.6, 130.9, 132.2, 132.7, 139.1, 155.1, 156.5, 171.1; HRMS (ESI-TOF) m/z [M+H]+ calcd for C28H26N3O3 452.1969; found 452.1972. N-(tert-Butyl)-2-(4-cyanophenyl)-2-(4-oxo-2-phenylbenzo[b][1,4]oxazepin-5(4H)-yl)acetamide (6f). Pale yellow solid (59 mg, 65% yield); mp 215−218 °C, Rf = (22% EtOAc/hexane) 0.58. 1H NMR (500 MHz, CDCl3) δ 1.39 (s, 9H), 5.81 (s, 1H), 6.14 (s, 1H), 7.07 (s, 1H), 7.11−7.19 (m, 2H), 7.25−7.27 (m, 1H), 7.45 (d, J = 3 Hz, 1H), 7.47−7.49 (m, 3H), 7.51 (t, J = 10 Hz, 1H), 7.53 (s, 1H), 7.58 (d, J = 10.5 Hz, 2H), 7.85 (dd, J1 = 9.5 Hz, J2 = 2 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 28.5, 51.8, 68.6, 104.9, 111.5, 118.5, 121.1, 124.6, 126.4, 126.5, 127.1, 128.4, 128.9, 131.4, 132.1, 132.3, 134.3, 140.4,

153.9, 166.9, 167.1, 168.0; HRMS (ESI-TOF) m/z [M+H]+ calcd for C28H26N3O3 452.1969; found 452.1960. (Z)-2-(2-Benzylidene-3-oxo-2,3-dihydro-4H-benzo[b][1,4]oxazin4-yl)-N-(tert-Butyl)-2-(4-cyanophenyl)acetamide (7f). Pale yellow solid (55 mg, 61% yield); mp 95−98 °C, Rf = (20% EtOAc/hexane) 0.58. 1H NMR (500 MHz, CDCl3) δ 1.33 (s, 9H), 6.18 (s, 1H), 6.50 (s, 1H), 6.90 (dt, J1 = 10 Hz, J2 = 1.5 Hz, 1H), 6.98−7.01 (m, 1H), 7.02 (s, 1H), 7.06−7.10 (m, 1H), 7.23 (dd, J1 = 10 Hz, J2 = 1.5 Hz, 1H), 7.36−7.38 (m, 1H), 7.42−7.46 (m, 2H), 7.50 (d, J = 10 Hz, 2H), 7.61 (d, J = 10.5 Hz, 2H), 7.86 (d, J = 9 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 28.5, 52.2, 60.2, 111.8, 115.6, 116.5, 116.9, 117.2, 118.4, 119.7, 123.3, 124.1, 124.9, 125.3, 127.5, 127.6, 127.8, 128.4, 128.7, 128.9, 129.0, 129.1, 130.3, 131.8, 132.2, 133.0, 133.5, 138.9, 140.4, 142.3, 153.5, 159.1, 160.7, 165.8; HRMS (ESI-TOF) m/z [M +H]+ calcd for C28H26N3O3 452.1969; found 452.1973. N-(1-(2-Bromophenyl)-2-(tert-Butylamino)-2-oxoethyl)-N-(2-hydroxyphenyl)-3-phenylpropiolamide (5g). White solid (76 mg, 75% yield); mp 149−152 °C, Rf = (20% EtOAc/hexane) 0.73. 1H NMR (500 MHz, CDCl3 + DMSO-d6) δ 1.38 (s, 9H), 6.38 (s, 1H), 6.50 (t, J = 7 Hz, 1H), 6.78 (d, J = 7.5 Hz, 1H), 6.99 (d, J = 8 Hz, 1H), 7.02− 7.05 (m, 3H), 7.07 (d, J = 8 Hz, 2H), 7.16−7.18 (m, 1H), 7.19 (t, J = 7.5 Hz, 2H), 7.30 (t, J = 7.5 Hz, 1H), 7.48−7.50 (m, 1H), 7.79 (d, J = 17.5 Hz, 1H), 11.66 (s, 1H); 13C NMR (125 MHz, CDCl3 + DMSOd6) δ 28.2, 52.1, 64.2, 81.8, 90.5, 117.0, 118.3, 119.9, 125.1, 126.4, 127.6, 128.1, 129.9, 130.0, 130.2, 130.3, 131.2, 132.5, 132.7, 133.5, 155.5, 156.0, 171.2; HRMS (ESI-TOF) m/z [M+H]+ calcd for C27H26BrN2O3 505.1121; found 505.1138. 2-(2-Bromophenyl)-N-(tert-butyl)-2-(4-oxo-2-phenylbenzo[b][1,4]oxazepin-5(4H)-yl)acetamide (6g). Pale yellow solid (67 mg, 67% yield); mp 230−233 °C, Rf = (20% EtOAc/hexane) 0.53. 1H NMR (500 MHz, CDCl3) δ 1.42 (s, 9H), 5.97 (s, 1H), 6.12 (s, 1H), 6.27 (s, 1H), 7.01−7.09 (m, 2H), 7.10 (dd, J1 = 9.5 Hz, J2 = 2 Hz, 1H), 7.16−7.18 (m, 1H), 7.24−7.28 (m, 1H), 7.41−7.46 (m, 3H), 7.48− 7.51 (m, 2H), 7.65 (dd, J1 = 10 Hz, J2 = 2 Hz, 1H), 7.82−7.85 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 28.5, 51.8, 104.8, 120.9, 125.5, 125.7, 126.3, 126.4, 127.1, 128.7, 129.8, 130.9, 131.5, 132.8, 133.1, 134.1, 154.4, 166.2, 166.9, 168.1; HRMS (ESI-TOF) m/z [M+H]+ calcd for C27H26BrN2O3 505.1121; found 505.1126. (Z)-2-(2-Benzylidene-3-oxo-2,3-dihydro-4H-benzo[b][1,4]oxazin4-yl)-2-(2-bromophenyl)-N-(tert-butyl)acetamide (7g). Pale yellow solid (62 mg, 62% yield); mp 167−170 °C, Rf = (15% EtOAc/hexane) 0.6. 1H NMR (500 MHz, CDCl3) δ 1.37 (s, 9H), 5.67 (s, 1H), 5.99 (s, 1H), 6.89−6.96 (m, 2H), 6.97 (s, 1H), 7.01 (dt, J1 = 9.5 Hz, J2 = 2.5 Hz, 1H), 7.18−7.23 (m, 2H), 7.29−7.35 (m, 2H), 7.38 (t, J = 9.5 Hz, 1H), 7.55 (dd, J1 = 9.5 Hz, J2 = 2 Hz, 1H), 7.62 (dd, J1 = 10 Hz, J2 = 1.5 Hz, 1H), 7.07 (d, J = 9 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 28.5, 52.0, 64.5, 114.5, 115.6, 116.3, 123.3, 124.4, 124.7, 127.2, 128.3, 128.5, 128.6, 129.7, 130.2, 130.4, 133.5, 133.6, 133.7, 141.1, 142.5, 158.7, 165.2; HRMS (ESI-TOF) m/z [M+H] + calcd for C27H26BrN2O3 505.1121; found 505.1143. N-(2-(Cyclohexylamino)-1-(4-methoxyphenyl)-2-oxoethyl)-N-(2hydroxyphenyl)-3-phenylpropiolamide (5h). White solid (75 mg, 78% yield); mp 195−198 °C, Rf = (25% EtOAc/hexane) 0.51. 1H NMR (500 MHz, CDCl3) δ 0.98−1.13 (m, 2H), 1.19 (dd, J1 = 13.5 Hz, J2 = 8 Hz, 1H), 1.30−1.39 (m, 2H), 1.55−1.63 (m, 2H), 1.70 (d, J = 17 Hz, 1H), 1.82 (d, J = 13 Hz, 1H), 2.01 (d, J = 15 Hz, 1H), 3.70 (s, 3H), 3.86−3.92 (m, 1H), 5.86 (d, J = 10 Hz, 1H), 6.07 (s, 1H), 6.43 (dd, J1 = 10 Hz, J2 = 2 Hz, 1H), 6.48 (dt, J1 = 9.5 Hz, J2 = 1.5 Hz, 1H), 6.88 (d, J = 11 Hz, 2H), 6.91 (dd, J1 = 10 Hz, J2 = 1.5 Hz, 1H), 7.02 (dd, J1 = 10 Hz, J2 = 1 Hz, 2H), 7.06 (d, J = 11 Hz, 2H), 7.10− 7.13 (m, 1H), 7.15 (t, J = 9.5 Hz, 2H), 7.28−7.30 (m, 1H),11.01 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 24.6, 24.7, 25.4, 32.4, 32.6, 49.5, 55.1, 64.2, 70.1, 81.9, 91.1, 114.1, 114.7, 117.6, 118.7, 120.2, 124.7, 125.2, 128.1, 128.2, 130.0, 130.3, 130.9, 131.2, 132.4, 132.8, 132.9, 156.0, 156.5, 160.0, 160.2, 171.7; HRMS (ESI-TOF) m/z [M+H]+ calcd for C30H31N2O4 483.2278; found 483.2269. N-Cyclohexyl-2-(4-methoxyphenyl)-2-(4-oxo-2-phenylbenzo[b][1,4]oxazepin-5(4H)-yl)acetamide (6h). Pale yellow solid (62 mg, 64% yield); mp 190−192 °C, Rf = (22% EtOAc/hexane) 0.51. 1H NMR (500 MHz, CDCl3) δ 1.16−1.23 (m, 3H), 1.33−1.44 (m, 2H), 65


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yield); mp 200−203 °C, Rf = (20% EtOAc/hexane) 0.55. 1H NMR (500 MHz, CDCl3) δ 1.01 (s, 9H), 1.39 (s, 9H), 5.64 (s, 1H), 6.05 (s, 1H), 6.37 (s, 1H), 6.83 (d, J = 9 Hz, 1H), 7.01 (d, J = 8 Hz, 2H), 7.10 (d, J = 8.5 Hz, 1H), 7.18−7.20 (m, 7H), 7.28−7.31 (m, 2H), 10.84 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 28.4, 31.2, 33.5, 52.7, 65.1, 82.0, 90.9, 116.8, 120.2, 124.4, 126.8, 128.1, 128.7, 128.9, 129.4, 129.9, 132.8, 133.2, 141.5, 153.8, 156.0, 171.3.; HRMS (ESI-TOF) m/z [M +H]+ calcd for C31H35N2O3 483.2642; found 483.2677. N-(tert-Butyl)-2-(7-(tert-butyl)-4-oxo-2-phenylbenzo[b][1,4]oxazepin-5(4H)-yl)-2-phenylacetamide (6k). liquid (56 mg, 58% yield); Rf = (22% EtOAc/hexane) 0.73. 1H NMR (500 MHz, CDCl3) δ 1.17 (s, 9H), 1.42 (s, 9H), 5.87 (s, 1H), 6.12 (s, 1H), 6.79 (s, 1H), 7.07 (d, J = 8 Hz, 1H), 7.11 (d, J = 8 Hz, 2H), 7.15−7.20 (m, 2H), 7.24 (s, 1H), 7.38 (d, J = 7.5 Hz, 1H), 7.44 (s, 2H), 7.54 (s, 1H), 7.83 (d, J = 6 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 28.6, 29.7, 31.7, 51.5, 68.6, 105.1, 114.1, 119.9, 122.8, 123.2, 125.6, 125.7, 126.4, 126.9, 127.6, 127.7, 128.1, 128.2, 128.3, 128.7, 130.9, 132.9, 135.1, 149.0, 151.9, 166.3, 167.2, 169.1; HRMS (ESI-TOF) m/z [M+H]+ calcd for C31H35N2O3 483.2642; found 483.2659. N-(2-(tert-Butylamino)-2-oxo-1-phenylethyl)-N-(2-hydroxy-4methylphenyl)-3-phenylpropiolamide (5l). White solid (72 mg, 82% yield); mp 210−213 °C, Rf = (20% EtOAc/hexane) 0.52. 1H NMR (500 MHz, CDCl3 + DMSO-d6) δ 1.36 (s, 9H), 2.19 (s, 3H), 6.00 (s, 1H), 6.27 (t, J = 8 Hz, 1H), 6.33 (d, J = 8 Hz, 1H), 6.48 (s, 1H), 6.69 (s, 1H), 7.03 (t, J = 7.5 Hz, 1H), 7.18−7.20 (m, 6H), 7.28−7.35 (m, 2H), 11.20 (s, 1H); 13C NMR (125 MHz, CDCl3 + DMSO-d6) δ 21.1, 28.3, 52.3, 65.1, 82.1, 90.6, 117.6, 119.4, 120.2, 122.6, 128.1, 128.6, 128.8, 129.8, 129.9, 131.9, 132.7, 133.1, 140.2, 155.9, 156.0, 171.6; HRMS (ESI-TOF) m/z [M+H]+ calcd for C28H29N2O3 441.2173; found 441.2184. N-(tert-Butyl)-2-(8-methyl-4-oxo-2-phenylbenzo[b][1,4]oxazepin5(4H)-yl)-2-phenylacetamide (6l). Pale yellow solid (75 mg, 85% yield); mp 180−182 °C, Rf = (22% EtOAc/hexane) 0.63. 1H NMR (500 MHz, CDCl3) δ 1.41 (s, 9H), 2.25 (s, 3H), 5.77 (s, 1H), 6.12 (s, 1H), 6.80 (s, 1H), 6.85 (d, J = 9.5 Hz, 1H), 6.99 (s, 1H), 7.21 (d, J = 7.5 Hz, 1H), 7.27 (t, J = 7.5 Hz, 2H), 7.38−7.41 (m, 2H), 7.46 (m, 3H), 7.84 (d, J = 5 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 20.6, 28.6, 29.7, 51.6, 105.2, 121.0, 125.0, 126.3, 126.6, 127.6, 127.9, 128.4, 128.8, 130.9, 132.8, 135.1, 136.8, 153.9, 166.2, 167.0, 169.1; HRMS (ESI-TOF) m/z [M+H]+ calcd for C28H29N2O3 441.2173; found 441.2193. (Z)-2-(2-Benzylidene-7-methyl-3-oxo-2,3-dihydro-4H-benzo[b][1,4]oxazin-4-yl)-N-(tert-butyl)-2-phenylacetamide (7l). Pale yellow solid (71 mg, 81% yield); mp 118−120 °C, Rf = (22% EtOAc/hexane) 0.73. 1H NMR (500 MHz, CDCl3) δ 1.34 (s, 9H), 2.28 (s, 3H), 6.03 (s, 1H), 6.26 (s, 1H), 6.69 (d, J = 8 Hz, 1H), 6.92 (d, J = 8.5 Hz, 1H), 6.98 (d, J = 14 Hz, 1H), 7.11 (d, J = 7.5 Hz, 1H), 7.16 (d, J = 8 Hz, 1H), 7.33 (d, J = 7.5 Hz, 2H), 7.40 (d, J = 7.5 Hz, 3H), 7.43 (s, 1H), 7.84 (d, J = 7.5 Hz, 2H; 13C NMR (125 MHz, CDCl3) δ 14.1, 20.6, 22.7, 28.5, 29.7, 51.8, 61.8, 114.2, 116.7, 116.8, 123.5, 127.8, 128.1, 128.5, 128.8, 130.1, 141.1, 142.0, 158.6, 166.7; HRMS (ESI-TOF) m/z [M+H]+ calcd for C28H29N2O3 441.2173; found 441.2181. N-(2-(tert-Butylamino)-1-(4-methoxyphenyl)-2-oxoethyl)-N-(2hydroxyphenyl)-3-(p-tolyl)propiolamide (5m). White solid (69 mg, 73% yield); mp 202−205 °C, Rf = (22% EtOAc/hexane) 0.65. 1H NMR (500 MHz, CDCl3) δ 1.36 (s, 9H), 2.27 (s, 3H), 3.70 (s, 3H), 5.78 (s, 1H), 5.94 (s, 1H), 6.46−6.51 (m, 2H), 6.69 (d, J = 8 Hz, 2H), 6.89−6.93 (m, 3H), 6.98 (d, J = 8 Hz, 2H), 7.07 (d, J = 8.5 Hz, 3H), 11.20 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 21.6, 28.4, 52.6, 55.1, 64.7, 81.6, 91.5, 114.1, 114.6, 117.0, 117.4, 118.6, 124.8, 125.3, 128.9, 130.1, 131.0, 132.4, 132.8, 140.5, 156.1, 156.5, 159.9, 171.8; HRMS (ESI-TOF) m/z [M+H]+ calcd for C29H31N2O4 471.2278; found 471.2259. N-(tert-Butyl)-2-(4-methoxyphenyl)-2-(4-oxo-2-(p-tolyl)benzo[b][1,4]oxazepin-5(4H)-yl)acetamide (6m). Pale yellow solid (58 mg, 62% yield); mp 95−98 °C, Rf = (20% EtOAc/hexane) 0.57. 1H NMR (500 MHz, CDCl3) δ 1.41 (s, 9H), 2.38 (s, 3H), 3.72 (s, 3H), 5.77 (s, 1H), 6.08 (s, 1H), 6.73 (s, 1H), 6.78 (d, J = 8.5 Hz, 1H), 7.04−7.05 (m, 2H), 7.15 (d, J = 6.5 Hz, 1H), 7.23 (d, J = 7.5 Hz, 2H), 7.29 (d, J = 8.5 Hz, 2H), 7.53−7.55 (m, 1H), 7.71 (d, J = 8 Hz, 2H); 13C NMR

1.57−1.62 (m, 1H), 1.68−1.75 (m, 2H), 1.96−1.99 (m, 2H), 3.75 (s, 3H), 3.88−3.97 (m, 1H), 5.81 (s, 1H), 6.12 (s, 1H), 6.70 (d, J = 9.5 Hz, 1H), 6.79 (d, J = 11 Hz, 2H), 7.04−7.11 (m, 2H), 7.18−7.20 (m, 1H), 7.30 (d, J = 11.5 Hz, 2H), 7.43−7.47 (m, 3H), 7.54−7.56 (m, 1H), 7.83−7.85 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 22.0, 24.7, 25.6, 32.7, 32.9, 48.7, 55.2, 105.3, 113.9, 120.8, 125.6, 126.0, 126.4, 126.5, 126.9, 128.8, 129.6, 131.1, 132.8, 134.5, 154.3, 159.1, 166.3, 167.1, 169.1; HRMS (ESI-TOF) m/z [M+H]+ calcd for C30H31N2O4 483.2278; found 483.2287. (Z)-2-(2-Benzylidene-3-oxo-2,3-dihydro-4H-benzo[b][1,4]oxazin4-yl)-N-cyclohexyl-2-(4-methoxyphenyl)acetamide (7h). Pale yellow solid (54 mg, 56% yield); mp 75−78 °C, Rf = (20% EtOAc/hexane) 0.55. 1H NMR (500 MHz, CDCl3) δ 1.01−1.18 (m, 3H), 1.28−1.40 (m, 2H), 1.54−1.67 (m, 3H), 1.81−1.99 (m, 2H), 3.80 (s, 3H), 3.81− 3.89 (m, 1H), 5.88 (d, J = 10.5 Hz, 1H), 6.06 (s, 1H), 6.89−6.94 (m, 3H), 7.00−7.01 (m, 2H), 7.03−7.05 (m, 1H), 7.17 (dd, J1 = 10.5 Hz, J2 = 2 Hz, 1H), 7.33−7.35 (m, 1H), 7.38−7.43 (m, 4H), 7.84 (d, J = 9 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 24.7, 25.5, 32.7, 32.8, 48.7, 53.5, 55.3, 61.6, 114.3, 114.5, 116.3, 116.4, 123.1, 124.3, 125.9, 128.5, 128.6, 129.5, 130.2, 141.0, 142.4, 158.6, 159.6, 166.8; HRMS (ESITOF) m/z [M+H]+ calcd for C30H31N2O4 483.2278; found 483.2290. N-(2-Hydroxyphenyl)-N-(1-(4-methoxyphenyl)-2-oxo-2(pentylamino)ethyl)-3-phenylpropiolamide (5i). White solid (60 mg, 64% yield); mp 138−140 °C, Rf = (20% EtOAc/hexane) 0.55. 1H NMR (500 MHz, CDCl3) δ 0.82 (t, J = 9 Hz, 3H), 1.20−1.28 (m, 4H), 1.46−1.53 (m, 2H), 3.26−3.39 (m, 2H), 3.70 (s, 3H), 5.96 (t, J = 7 Hz, 1H), 6.07 (s, 1H), 6.43 (dd, J1 = 10 Hz, J2 = 2 Hz, 1H), 6.49 (dt, J1 = 9 Hz, J2 = 1.5 Hz, 1H), 6.69 (d, J = 11 Hz, 2H), 6.92 (dd, J1 = 10.5 Hz, J2 = 1.5 Hz, 1H), 7.03−7.11 (m, 5H), 7.16 (dt, J1 = 9.5 Hz, J2 = 1.5 Hz, 2H), 7.26−7.30 (m, 1H), 10.98 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 13.9, 22.2, 28.8, 40.5, 55.2, 64.3, 81.9, 91.1, 114.2, 114.8, 117.6, 118.8, 120.2, 124.7, 125.3, 128.2, 130.0, 130.3, 131.0, 131.3, 132.5, 132.8, 132.9, 156.0, 156.6, 160.1, 172.6; HRMS (ESI-TOF) m/z [M+H]+ calcd for C29H31N2O4 471.2278; found 471.2293. N-(2-Hydroxyphenyl)-N-(1-(4-methoxyphenyl)-2-oxo-2(pentylamino)ethyl)-3-phenylpropiolamide (7i). Liquid (69 mg, 73% yield); Rf = (20% EtOAc/hexane) 0.75. 1H NMR (500 MHz, CDCl3) δ 0.83 (t, J = 9 Hz, 3H), 1.19−1.30 (m, 4H), 1.42−1.50 (m, 2H), 3.22−3.45 (m, 2H), 3.78 (s, 3H), 6.12 (s, 2H), 6.88−6.92 (m, 3H), 6.99 (s, 1H), 7.01 (d, J = 9.5 Hz, 2H), 7.15 (d, J = 10 Hz, 1H), 7.30 (t, J = 9.5 Hz, 1H), 7.37−7.42 (m, 4H), 7.83 (d, J = 9.5 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 14.0, 22.3, 29.0, 29.1, 40.1, 55.3, 61.4, 114.3, 114.5, 116.3, 116.5, 123.1, 124.3, 128.5, 128.6, 129.5, 130.2, 133.5, 141.0, 142.4, 158.6, 159.6, 167.7; HRMS (ESI-TOF) m/z [M +H]+ calcd for C29H31N2O4 471.2278; found 471.2287. N-(2-Hydroxyphenyl)-N-(2-oxo-1-phenyl-2-((2,4,4-trimethylpentan-2-yl)amino)ethyl)-3-phenylpropiolamide (5j). White solid (65 mg, 68% yield); mp 190−192 °C, Rf = (22% EtOAc/hexane) 0.75. 1H NMR (500 MHz, CDCl3) δ 0.90 (s, 9H), 1.40−1.42 (m, 6H), 1.59 (d, J = 15 Hz, 1H), 1.81 (d, J = 15 Hz, 1H), 6.03 (s, 1H), 6.46 (s, 1H), 6.62 (s, 1H), 6.88 (d, J = 7.5 Hz, 1H), 7.02 (d, J = 7 Hz, 2H), 7.08 (d, J = 5.5 Hz, 1H), 7.17 (s, 5H), 7.19 (d, J = 7.5 Hz, 2H), 7.28 (t, J = 7.5 Hz, 1H), 11.40 (s, 1H); 13C NMR (125 MHz, CDCl3 + DMSO-d6) δ 28.0, 28.8, 31.2, 51.8, 56.3, 65.2, 82.0, 90.5, 117.2, 118.5, 120.0, 125.4, 128.1, 128.2, 128.4, 128.7, 129.8, 129.9, 130.1, 132.3, 132.6, 132.7, 132.8, 155.6, 156.5, 171.1; HRMS (ESI-TOF) m/z [M+H]+ calcd for C31H35N2O3 483.2642; found 483.2663. 2-(4-Oxo-2-phenylbenzo[b][1,4]oxazepin-5(4H)-yl)-2-phenyl-N(2,4,4-trimethylpentan-2-yl)acetamide (6j). Pale yellow solid (65 mg, 68% yield); mp 140−142 °C, Rf = (15% EtOAc/hexane) 0.6. 1H NMR (500 MHz, CDCl3) δ 0.96 (s, 9H), 1.48−1.49 (m, 6H), 1.67 (q, J1 = 18.5 Hz, J2 = 38 Hz, 2H), 5.75 (s, 1H), 6.14 (s, 1H), 6.70 (s, 1H), 7.05−7.11 (s, 2H), 7.19−7.25 (m, 2H), 7.27−7.31 (m, 2H), 7.40 (d, J = 9.5 Hz, 2H), 7.43−7.47 (m, 3H), 7.53−7.56 (m, 1H), 7.84−7.87 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 28.4, 28.7, 31.5, 31.6, 52.8, 55.8, 105.3, 120.8, 125.3, 126.0, 126.4, 126.5, 127.8, 128.1, 128.5, 128.8, 131.0, 132.8, 134.8, 135.2, 154.2, 166.3, 167.0, 168.4; HRMS (ESITOF) m/z [M+H]+ calcd for C31H35N2O3 483.2642; found 483.2671. N-(5-(tert-Butyl)-2-hydroxyphenyl)-N-(2-(tert-butylamino)-2-oxo1-phenylethyl)-3-phenylpropiolamide (5k). White solid (62 mg, 64% 66


Article

The Journal of Organic Chemistry (125 MHz, CDCl3) δ 21.4, 28.6, 51.5, 55.1, 68.3, 104.4, 113.8, 120.6, 125.8, 126.3, 126.4, 127.0, 129.5, 129.36, 129.9, 141.5, 154.2, 158.9, 166.4, 167.1, 169.3; HRMS (ESI-TOF) m/z [M+H]+ calcd for C29H31N2O4 471.2278; found 471.2295. (Z)-N-(tert-Butyl)-2-(4-methoxyphenyl)-2-(2-(4-methylbenzylidene)-3-oxo-2,3-dihydro-4H-benzo[b][1,4]oxazin-4-yl)acetamide (7m). Pale yellow solid (62 mg, 66% yield); mp 85−88 °C, Rf = (10% EtOAc/hexane) 0.55. 1H NMR (500 MHz, CDCl3) δ 1.33 (s, 9H), 2.39 (s, 3H), 3.79 (s, 3H), 5.93 (s, 1H), 6.11 (s, 1H), 6.88−6.92 (m, 3H), 6.97−7.04 (m, 3H), 7.16 (d, J = 8 Hz, 1H), 7.21 (d, J = 7.5 Hz, 2H), 7.35 (d, J = 8 Hz, 2H), 7.74 (d, J = 8 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 21.5, 28.5, 51.8, 55.2, 61.8, 114.3, 114.4, 116.1, 116.6, 122.9, 124.1, 126.0, 126.5, 129.3, 130.1, 130.6, 138.6, 140.4, 142.4, 158.8, 159.3, 166.9; HRMS (ESI-TOF) m/z [M+H]+ calcd for C29H31N2O4 471.2278; found 471.2288. N-(2-(tert-Butylamino)-1-(4-methoxyphenyl)-2-oxoethyl)-N-(2hydroxyphenyl)-3-(4-methoxyphenyl)propiolamide (5n). White solid (76 mg, 78% yield); mp 215−218 °C, Rf = (25% EtOAc/ hexane) 0.5. 1H NMR (500 MHz, CDCl3) δ 1.36 (s, 9H), 3.71 (s, 3H), 3.74 (s, 3H), 5.67 (s, 1H), 5.92 (s, 1H), 6.47−6.52 (m, 2H), 6.69 (d, J = 8.5 Hz, 4H), 6.89 (d, J = 8 Hz, 1H), 6.96 (d, J = 8.5 Hz, 2H), 7.07−7.11 (m, 3H), 11.18 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 28.4, 52.6, 55.1, 55.2, 64.6, 81.4, 91.8, 112.1, 113.9, 114.1, 114.6, 117.4, 118.6, 124.8, 125.4, 130.1, 131.0, 132.5, 134.7, 156.2, 156.5, 159.9, 160.9, 171.9; HRMS (ESI-TOF) m/z [M+H]+ calcd for C29H31N2O5 487.2227; found 487.2232. N-(tert-Butyl)-2-(4-methoxyphenyl)-2-(2-(4-methoxyphenyl)-4oxobenzo[b][1,4]oxazepin-5(4H)-yl)acetamide (6n). liquid (50 mg, 51% yield); Rf = (25% EtOAc/hexane) 0.64. 1H NMR (500 MHz, CDCl3) δ 1.43 (s, 9H), 3.76 (s, 3H), 3.86 (s, 3H), 5.77 (s, 1H), 6.02 (s, 1H), 6.77−6.87 (m, 3H), 6.96 (d, J = 8.5 Hz, 2H), 7.07−7.09 (m, 2H), 7.17 (d, J = 6.5 Hz, 1H), 7.31 (d, J = 8 Hz, 2H), 7.55 (d, J = 6.5 Hz, 1H), 7.80 (d, J = 8.5 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 28.6, 51.5, 55.1, 55.4, 103.2, 113.8, 114.2, 120.6, 125.0, 125.5, 125.8, 126.3, 127.0, 128.1, 129.5, 154.1, 158.9, 161.9, 166.3, 167.2, 169.3; HRMS (ESI-TOF) m/z [M+H]+ calcd for C29H31N2O5 487.2227; found 487.2239. (Z)-N-(tert-Butyl)-2-(2-(4-methoxybenzylidene)-3-oxo-2,3-dihydro-4H-benzo[b][1,4]oxazin-4-yl)-2-(4-methoxyphenyl)acetamide (7n). liquid (65 mg, 67% yield); Rf = (22% EtOAc/hexane) 0.56. 1H NMR (500 MHz, CDCl3) δ 1.33 (s, 9H), 3.78 (s, 3H), 3.84 (s, 3H), 5.99 (s, 1H), 6.12 (s, 1H), 6.87−6.89 (m, 2H), 6.93−6.96 (m, 3H), 6.99 (d, J = 8 Hz, 1H), 7.03 (d, J = 8.5 Hz, 2H), 7.15 (d, J = 8 Hz, 1H), 7.35 (d, J = 8.5 Hz, 2H), 7.80 (d, J = 8.5 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 28.5, 51.8, 55.2, 55.3, 61.7, 114.0, 114.2, 116.1, 116.7, 117.3, 122.8, 124.0, 126.0, 126.3, 129.3, 129.9, 131.7, 139.6, 142.5, 158.9, 159.3, 159.7, 167.0; HRMS (ESI-TOF) m/z [M+H]+ calcd for C29H31N2O5 487.2227; found 487.2213.

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Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by grant from the DST-India in the form of INSPIRE Faculty (IFA-13, CH-116) to S.S. Authors acknowledge Prof. B. L. Ahuja (Dean Sciences, MLSUUdaipur) and Prof. Pinki B. Punjabi (Head, Department of Chemistry, MLSU-Udaipur) for constant encouragement. Authors are thankful to Prof. Palwinder Singh, from GNDUAmritsar for scientific guidance. Authors also acknowledge MLSU-Udaipur, Rajasthan, for giving infrastructure support. K.S. is registered Ph.D. scholar in GNDU, Amritsar. T.K.R thanks to the Central University of Jammu for the infrastructural facilities and for partially supporting this work through grant CUJ/Acad/Proj-PHY/2017/97.

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S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b02123. Copies of 1H NMR, 13C NMR, X-ray, and DFT calculations data of all the synthesized compounds (PDF) X-ray crystallographic data of compound 6f (CIF) X-ray crystallographic data of compound 7d (CIF)

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REFERENCES

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected] ORCID

Vimal K. Bhardwaj: 0000-0003-1387-6709 Swapandeep Singh Chimni: 0000-0001-9206-5845 Siddharth Sharma: 0000-0003-2759-4155 67


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Catalyst-Controlled Structural Divergence: Selective Intramolecular 7

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