Acylacetylenes in multiple functionalization of hydroxyquinolines and quinolones

Abstract

The expected one-pot multiple functionalization of hydroxyquinolines and quinolones with acylacetylenes (20 mol% KOH, 5 equiv. H₂O, MeCN, 55–60 °C), which, according to the previous finding, might involve the addition of OH and NH-functions to the triple bond and insertion of acylacetylenes into the quinoline scaffold, retains mainly on the formation of chalcone-quinoline ensembles in up 99% yield. The higher functionalized quinolines can be obtained in a synthetically acceptable yield, when the above ensembles are treated with the second molecule of acylacetylenes. Thus, the further insertion of second molecule of the acetylenes into the quinoline scaffold occurs as a much slower process indicating a strong adverse substituent effect of the remote chalcone moiety.

Graphical abstract

Highlights

• •C-, O-, or N-functionalizations of quinoline core.
• •Broad scope, short reaction time.
• •Excellent product yields.

1. Introduction

Functionalized quinoline scaffold is a frequently met structural motif in a plethora of biologically important compounds, both of natural and synthetic origin. The wide spectrum of their biological activity covers anti-cancer [1,2], antibacteria^l−5 antioxidant [1], and antifungal [6]. Functionalized quinolines [7,8] and fluoroquinolines [[9], [10], [11], [12], [13], [14]] gave rise to a new generation of antibiotics. The modern antimalarial therapy cannot be imaged without the functionalized natural quinoline, quinine, and its later modifications such as chloroquine, amodiaquine, and mefloquine [[15], [16], [17]] (Fig. 1 ).

Fig. 1.

The modern antimalarial drugs on the quinoline platform.

The latter is now considered as a possible drug against coronavirus COVID-19 [18]. Therefore, further modifications of the quinine structure can be rated as requested by time. In this context, the recent modification of the quinine with acylacetylenes [19] (Scheme 1 ) looks timely.

Scheme 1.

Modification of the quinine with acylacetylenes.

Commonly, acetylenic compounds are widely employed for functionalization of the quinoline core. For this, two major approaches are being developed: (i) nucleophilic additions of hydroxyquinolines or quinolones to the triple bond; (ii) transformation of the quinoline ring via donor-acceptor adducts (zwitterions) with electron-deficient acetylenes. In the framework of the first approach, N- and O-vinyl derivatives of quinolines were synthesized using both acetylene gas under pressure [20] and electrophilic acetylenes, mostly esters of acetylene dicarboxylic acids [21] and also propiolic esters [21,22], cyanoacetylene [21,23] and cyanopropargylic alcohols [23]. The zwitterion approach allows a series of new quinoline-tailored functionalized heterocyclic systems to be designed. This series includes oxazinoquinolines [[24], [25], [26]], pyrimidoquinolinones [27], phosphorylated dihydroquinolines [28].

Recently, transition metal-free unique double functionalization of the quinoline ring with acylacetylenes has been discovered [29]. Formally, it represents the replacement of unsubstituted acetylene unit by the acetylenic ketone in the pyridine counterpart of the quinoline ring being in fact a multistep cascade transformation involving ring opening/ring closure/fragmentation processes (Scheme 2 ).

Scheme 2.

Double functionalization of the quinoline ring with acylacetylenes.

It might be thought that the combination of this reaction with the first approach when applied to hydroxyquinolines could lead to a one-pot triple functionalization of the quinoline core.

2. Results and discussion

This paper is a brief report on our efforts towards addressing this challenge.

The objects of the investigation were available hydroxyquinolines 1a-c, 2- and 4-quinolones 1d-f and acylacetylenes of aromatic and heteroaromatic series 2a-i (Fig. 2 ).

Fig. 2.

Objects of investigation.

When choosing the latter, we were guided by the following reasons: (i) the ability of the acylacetylenes to generate chalcone upon adding protogenic (OH or NH) functions to the triple bond; (ii) potential biological activity of the aromatic (aryl) or heteroaromatic (pyrrolyl, furyl, thienyl) substituents; (iii) synthetically suitable balance between high reactivity and stability (convenience to be handled). The merging of biological active chalcone [[30], [31], [32]] and quinoline [[1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17]] structures in a one molecule could result in a synergetic effect and extension of the scope of their pharmaceutically important properties. The acetylenic ketone with branched acetal substituents at the triple bond 2i, benzoyloxysecbutylbenzoylacetylene, was specially synthesized to provide additional possibilities for further functionalization (in particular, after deprotection of the hydroxyl group) of adducts as well as to evaluation steric effect of the reaction.

To verify the possibility of the above hypotized triple functionalization of hydroxyquinolines with acylacetylenes the reference reaction between 6-hydroxyquinoline 1b and benzoylphenylacetylene 2a under the optimum conditions (Scheme 2) has been tested. Disappointingly, the results did not entirely meet the expectations: mainly only nucleophilic addition of the hydroxyl group to the triple bond (even with two-fold excess of the ketone) occurred to afford benzoyl-1-phenyl-ethenyloxyquinoline 3b, no signs of 2,3-difunctionalization of the quinoline ring were observed. The expected product of triple functionalization 4b was detectable (¹H NMR) in the crude as a minor product in amount of ∼9% (Scheme 3 ).

Scheme 3.

The reaction of 6-hydroxyquinoline 1b with benzoylphenylacetylene 2a.

Notably, as previously shown [29], 6-methoxyquinoline, when reacted with ketone 2a under the same conditions, readily underwent the insertion of the ketone moiety into the quinoline ring to deliver 2-phenyl-3-benzoyl-6-methoxyquinoline in 62% yield. Since 2,3-difunctionalization starts with the formation of donor-acceptor adduct (zwitterion) between nitrogen atom and electron-deficient acetylene [29], obviously, here we face extraordinary long-range transmittance of electron-withdrawing effect of the carbonyl group over the nitrogen atom through the whole quinoline ring system. Eventually, we have managed to render the above triple functionalization of quinoline scaffold in a stepwise manner and synthesized trifunctionalized product 4b in modest 24% yield when preliminary prepared adduct 3b was treated with ketone 2a (Scheme 4 ) under the same conditions of Scheme 3.

Scheme 4.

2,3-Functionalization of adduct 3b with benzoylphenylacetylene 2a.

Thus, we have been edged to focus our study on optimization of the synthesis of monofunctionalized quinoline 3b. The selected experimental results illustrating the yield/reaction condition relationship are presented in Table 1 .

Table 1.

Monofunctionalized quinoline 3b produced viaScheme 3.^a.

No	Base [mol%]	H2O (equiv.)	Temp. (oC)	Time (min)	Yield (%)	E/Z ratio (%)b
1	none	none	rt	24	No reaction	No reaction
2	NaOH (20)	5	55–60	0.5	60	25/75
3	KOH (10)	5	55–60	4	84	60/40
4	KOH (20)	5	55–60	0.5	92	30/70
5	KOH (30)	5	55–60	0.5	76	17/83
6	KOH (20)	none	55–60	0.5	87	20/80
7	KOH (20)	55	55–60	2	79	15/85
8	KOH (20)	none	rt	24	80	26/74
9	KOH (20)	5	rt	48	86	20/80
10	K2CO3 (20)	5	55–60	0.5	84	48/52
11	K3PO4 (20)	5	55–60	0.5	35	50/50
12	NaHCO3 (20)	5	55–60	0.5	No reaction	No reaction
13	Et3N (20)	5	55–60	0.5	13	25/75
14	DBU (20)	5	55–60	0.5	78	42/58
15	Ph3P (20)	5	55–60	0.5	54	17/83

^aReaction conditions: 1b (0.5 mmol), 2a (0.5 mmol), 0.5 mL MeCN.

^b(E)- and (Z)-isomers were determined by comparison of their ¹H NMR chemical shifts of the olefin fragment β-hydrogen with the latter of (E)-3k or (E)-3l (see below).

¹H NMR chemical shifts of β-hydrogen of the olefinic fragment with those of (E)-3k or (E)-3l (see below).

The reaction was carried out at the equimolar ratio of the reactants, the variable parameters being the nature and concentration of a catalyst (inorganic or organic base), the content of water, and temperature. The process duration was determined by the full consumption of the acetylenic ketone 2a or by the moment when its concentration stopped changing. The progress of the reaction was monitored using the IR spectroscopy to follow the disappearance of the absorption band (С≡С bond) of acetylene 2а at 2198 cm⁻¹.

As anticipated, the reaction did not take place without the base catalyst (entry 1). The best result (92% yield of 3b, 70% of the (Z)-stereoselectivity, entry 4) was attained under the following conditions: 20 mol% KOH, 5 equiv. of water, MeCN, 55–60 °C, 0.5 h). The yield of the target product mostly depends on the nature of a basic catalyst being highest with KOH and being dropped in the order KOH > K₂CO₃ > DBU > NaOH > Ph₃P > K₃PO₄ > Et₃N. A lesser influence on the product yield and the reaction time was observed for concentration of KOH (entries 3, 4, 5) and water (entries 6, 7). A higher concentration of KOH likely facilitates the side base-catalyzed hydration of the acetylenic ketone. The presence of water had a slightly favorable effect on the yield of the target product and the reaction stereochemistry. Apparently, water molecules participate as a proton transfer agents in the reaction transition state as it commonly accepted for nucleophilic addition to acetylenes [33]. Consequently, such reactions are stereoselective leading to the (Z)-isomers exclusively. A partial deviation from this rule in this case is likely due to steric encumbrance in the (Z)-isomer of 3b (benzoyl and quinolynyl oxy moiety located on the same side of the double bond).

An advantageous feature of the reaction is that it can be efficiently realized at room temperature (entry 9) albeit in this case it lasted much longer (48 h) and to complete it for 30 min it required 55–60 °C (entry 4).

Basing on the data of Table 1, to evaluate the scope of monofunctionalization of quinolines 1a-c with acylacetylenes 2a-i we taken the conditions, which were found to be best (20 mol% of KOH, 5 equiv. of water, 55–60 °C), the process time being dependent on the reaction completion (Scheme 5 ).

Scheme 5.

Scope of the reaction. Reagents and conditions: 1 (0.5 mmol), 2 (0.5 mmol), KOH (20 mol%), H₂O (2.5 mmol), 0.5 mL MeCN, 55–60 ^оС. ^a (E):(Z)-isomer ratio; ^b 1.2 equiv. of KOH.

As follows from Scheme 5, the reaction well tolerates 3-, 6- and 8-hydroxyquinolines 1a-c and all the abovementioned series of acylacetylenes 2a-i. The process proceeded smoothly for a short time (15 min-2 h) to provide the target functionalized quinolines 3a-m, mostly in good-to-excellent yields. As far as the product yields do not differ considerably, the substituent effect can be roughly estimated from the reaction time. Using this criterion, the reactivity of hydroxyquinolines under question may be ordered as follows: 1b (6-OH) > 1c (8-OH) > 1a (3-OH) that approximately reflects nucleophilicity of the corresponding O-centered anions. The effect of substituents in the acylacetylenes is generally in consistence with character of the reaction as a nucleophilic addition to the triple bond. Indeed, electron-donating groups such as tolyl, pyrrolyl which reduce electrophilicity of the triple bond expectedly slow down the reaction rate (compounds 3j-l). On the contrary in case of nitrobenzoyl substituent (compound 3e), the syntheses completed faster. Comparatively low yield of the target product in this case (79%) is due to side base-catalyzed hydration of the triple bond, as previously observed [29].

Noteworthy that with benzoyl-(5-arylpyrrol-2-yl)acetylenes 2g,h, it was required to increase the alkali loading (up to 1.2 equiv.), since ∼ 1 equivalent of the base was spent for the pyrrolate formation.

In this case of compounds 3k,l, the intramolecular N–H⋯O C hydrogen bond is formed between hydrogen of the NH group and oxygen of the carbonyl group (Fig. 3 ). This is manifested by an extraordinary downfield shift (to 14.8 ppm) of the NH group hydrogen signal (vs 9.25 ppm). Therefore, compounds 3k,l adopts only the (E)-configuration stabilized by the intramolecular hydrogen bond. The chemical shift of the β-hydrogen of the olefin fragment (δH_β) in the (E)-isomers of 3k,l is 6.27 ppm. Basing on this, the isomers of the compounds 3a-m, where the δH_β value is within the range from 6.0 to 6.2 ppm, are assigned to the (E)-configuration, while the isomers of the compounds 3a-m, where the δH_β value ranges from 7.0 to 7.2 ppm, are assigned to the (Z)-configuration. At the same time the β-hydrogen signals of both isomers of the compound 3 m are shifted upfield by 0.3–0.5 ppm since no influence of the anisotropy of the phenyl ring takes place in this case.

Fig. 3.

(E)-3-(5-Aryl-1H-pyrrol-2-yl)-1-phenyl-3-(quinolin-6-yloxy)prop-2-en-1-ones 3k,l.

Compounds 3 are products of nucleophilic addition of hydroxyquinolines 1 to acetylene 2 (on the example of 6-hydroxyquinoline 1b and benzoylphenylacetylene 2a, Scheme 6 ). Formation of the compound 5b is shown [29] to begin from 1,3-dipole intermediate A, the adduct of the nucleophilic attack of the nitrogen atom of quinoline 3b to the triple bond of acetylene 2a. Intermediate A reacts with a water molecule leading to a hemiaminal B, in which the N-C(2) bond is cleaved. The N-vinyl aldehyde intermediate C undergoes a series of transformations to afford the dihydroquinoline D. After elimination of acetaldehyde, trifunctionalized quinoline 4b is formed (Scheme 6).

Scheme 6.

Possible mechanisms for the formation of compounds 3b and 4b.

Quinolines functionalized at the 2- and 4-position by a hydroxyl group are known to exist predominantly in the keto form [[34], [35], [36], [37]], i.e. as 2- and 4-quinolones 1d-f, respectively. Consequently, they reacted under the above conditions mostly as N-centered nucleophiles to deliver the hybrid molecules 5a-d, which combine the quinoline and enaminone entities (Scheme 7 ). The products yields were excellent ranging 85–95%. As anticipated, the reaction was regioselective. In this case products were obtained predominantly as (Z)-isomers.

Scheme 7.

Reaction of quinolones 1d-f with acylphenylacetylenes 2a,d. ^a (E):(Z)-isomer ratio

For the series of N-adducts 5a-d, only compound 5b was obtained as two isomers in which the β-hydrogen signals appear at 7.0 and 7.6 ppm. Based on the previous consideration, the isomer of 5b, where the δH_β value is 7.0 ppm, is assigned to the (E)-configuration, whereas the isomer of 5b, where the δH_β value is 7.6 ppm, is assigned to the (Z)-configuration. In addition, since the signal of the β-hydrogen of the olefin fragment resonates at 7.6–8.0 ppm in compounds (5a,c,d), their isomers are assigned to the (Z)-configuration.

The possibility of the further functionalization of the obtained products was exemplified by the reduction (NaBH₄) of adduct 3b to afford the allylic alcohol 6b (Scheme 8 ).

Scheme 8.

Reduction of chalcone moiety.

There are two characteristic pairs of the upfield doublets (5.76; 6.18 and 5.48; 5.60 ppm, respectively) splitting due to the vicinal spin-spin coupling (³ J _H,H = 8.8 and 9.9 Hz, respectively) in the ¹H NMR spectrum of the (Z)- and (E)-isomers as well as a broad absorption bond at 3200 cm⁻¹ in the IR spectrum of compound 6b.

3. Conclusion

In conclusion, the base-catalyzed reaction of acylacetylenes with hydroxyquinolines and quinolone gives rise to new representatives of highly functionalized quinolines containing chalcone and enaminone moieties in good to excellent yields. The triple functionalization by insertion of second molecule of acylacetylenes into the position 2 and 3 of quinoline scaffold, previously observed under the same conditions, occurs as a slower process than likely results from a long-range transmittance of the electron-acceptor effect of the chalcone substituent on quinoline nitrogen. The combination of biologically active entities such as quinoline ring and chalcone or enaminone fragment in a one molecule may be of interest in the synthesized compounds from specialists of bio- and medical chemistry.

4. Experimental

4.1. General information

Quinolines 1a-f and solvents were purchased from commercial sources and used without further purification. Samples of acylacetylenes 2a-f,i [38] and 2g,h [39], were obtained according to describe methods. Monitoring of the reaction was carried out using the method of IR spectroscopy to follow the disappearance of the C C bond intensity of acetylenes 2 at 2195-2264 cm⁻¹. The products 3a-m, 4b, 5a-d and 6b were separated and purified by column chromatography on silica gel (0.06–0.2 mm) with chloroform/toluene/ethanol (20:4:1) mixture as eluent. NMR spectra were recorded on a Bruker DPX-400 spectrometer (400.1 MHz for ¹H and 100.6 MHz for ¹³C) in CDCl₃. The internal standards were HMDS (for ¹H) or the residual solvent signals (for ¹³C). IR spectra were obtained with a Bruker Vertex 70 spectrometer (400–4000 cm⁻¹, microlayer). Mass spectra were recorded on Mass spectrometer HR-TOF-ESI-MS Agilent 6210 (USA) in the mode of recording positive results with acetonitrile as solvent and 0.1% perfluorobutyric acid as ionizing agent. Melting point (uncorrected) was determined on a Kofler micro hot stage apparatus.

4.2. General procedure for synthesis of quinolinyloxypropenones 3 and 5

A mixture of hydroxyquinoline 1 (0.5 mmol), acylacetylene 2 (0.5 mmol), KOH (20 mol%), H₂O (2.5 mmol) in acetonitrile (0.5 mL) was placed in a 10-mL round-bottom flask (air atmosphere) with stir bar and stirred at 55-60^оС for appropriate time. After the reaction completion the reaction mixture cooled, solvents were evaporated at a low pressure and the residue was passed through the chromatography column deliver to the target product 3 or 5.

4.2.1. 1,3-Diphenyl-3-(quinolin-3-yloxy)prop-2-en-1-one (3a)

Following the general procedure, 3a was prepared from 3-hydroxyquinoline 1a (73 mg, 0.5 mmol) and acetylene 2a (103 mg, 0.5 mmol); 3a was isolated as a dark-yellow oil (151 mg, 86% yield). E:Z-isomer ratio 15:85 (¹H NMR); (Z)-isomer ¹H NMR (400 MHz, CDCl₃): δ = 8.73 (m, 1H, H-2), 7.98 (d, ³ J _7,8 = 8.2 Hz, 1H, H-8), 7.87 (m, 2H, H_o’ from Ph), 7.70 (m, 2H, H_o from Ph), 7.53 (m, 1H, H-5), 7.48 (m, 1H, H-7), 7.45 (m, 1H, H-6), 7.43 (d, ⁴ J _2,4 = 2.5 Hz, 1H, H-4), 7.40-7.30 (m, 6H, H_{m,m’,p,p’} from Ph), 7.08 (s, 1H, H_β); ¹³C NMR (101 MHz, CDCl₃): δ = 189.1 (C O), 160.1 (C_α), 150.8 (C-3), 145.5 (C-8a), 143.5 (C-2), 138.4 (C_i’ from Ph), 133.5 (C_i from Ph), 132.9 (C_p’ from Ph), 131.1 (C-8), 129.4 (C-4a), 129.2 (C_p from Ph), 129.1 (C_m from Ph), 128.5 (C_m’ from Ph), 128.4 (C-7), 128.3 (C_o’ from Ph), 127.6 (C-6), 127.1 (C_o from Ph), 127.0 (C-5), 118.2 (C-4), 111.2 (C_β); (E)-isomer ¹H NMR (400 MHz, CDCl₃): δ = 8.88 (m, 1H, H-2), 8.11 (d, ³ J _7,8 = 8.2 Hz, 1H, H-8), 7.74 (m, 1H, H-5; 2H, H_o’ from Ph), 7.63 (m, 1H, H-4; m, 2H, H_o from Ph), 7.50 (m, 1H, H-7), 7.45 (m, 1H, H-6), 7.40-7.30 (m, 6H, H_{m,m’,p,p’} from Ph), 6.21 (s, 1H, H_β); ¹³C NMR (101 MHz, CDCl₃): δ = 190.6 (C O), 168.3 (C_α), 147.9 (C-3), 145.8 (C-8a), 144.4 (C-2), 138.5 (C_i’ from Ph), 133.2 (C_i from Ph), 132.7 (C_p’ from Ph), 130.7 (C-8), 129.5 (C-4a), 129.0 (C_p from Ph), 129.1 (C_m from Ph), 128.5 (C_m’ from Ph), 128.2 (C-7), 128.3 (C_o,o′ from Ph), 127.6 (C-6), 127.5 (C-5), 124.8 (C-4), 106.4 (C_β); IR (microlayer): 1662 (C O), 1601 (C C) cm⁻¹; HRMS (ESI): m/z calcd for C₂₄H₁₈NO₂ ⁺ [M + H]⁺: 352.1338; found: 352.1339.

4.2.2. 1,3-Diphenyl-3-(quinolin-6-yloxy)prop-2-en-1-one (3b)

Following the general procedure, 3b was prepared from 6-hydroxyquinoline 1b (73 mg, 0.5 mmol) and acetylene 2a (103 mg, 0.5 mmol); 3b was isolated as a brown oil (162 mg, 92% yield). E:Z-isomer 30:70 (¹H NMR); (Z)-isomer ¹H NMR (400 MHz, CDCl₃): δ = 8.71 (m, 1H, H-2), 7.95 (d, ³ J _3,4 = 9.2 Hz, 1H, H-4), 7.88 (d, ³ J _7,8 = 8.2 Hz, 1H, H-8; m, 2H, H_o’ from Ph), 7.72 (m, 2H, H_o from Ph), 7.47 (m, 1H, H_p from Ph), 7.45-7.35 (m, 6H, H-7, H_m,m’,p’ from Ph), 7.24 (m, 1H, H-3), 7.13 (m, 1H, H-5), 7.07 (s, 1H, H_β); ¹³C NMR (101 MHz, CDCl₃): δ = 189.6 (C O), 160.5 (C_α), 155.3 (C-6), 148.8 (C-2), 144.8 (C-8a), 138.6 (C_i’ from Ph), 135.3 (C-4), 134.1 (C_i from Ph), 132.9 (C_p’ from Ph), 131.2 (C-8), 131.0 (C_p from Ph), 129.1 (C_m from Ph), 129.0 (C-4a), 128.6 (C_m’ from Ph), 128.5 (C_o’ from Ph), 127.2 (C_o from Ph), 121.7 (C-7), 121.5 (C-3), 111.2 (C-5), 111.1 (C_β); (E)-isomer ¹H NMR (400 MHz, CDCl₃): δ = 8.87 (m, 1H, H-2), 8.07 (d, ³ J _3,4 = 9.2 Hz, 1H, H-4), 8.16 (d, ³ J _7,8 = 8.2 Hz, 1H, H-8), 7.73 (m, 2H, H_o’ from Ph), 7.64 (m, 2H, H_o from Ph), 7.59 (d, ³ J _7,8 = 8.2 Hz, 1H, H-7), 7.55 (m, 1H, H-5), 7.40-7.25 (m, 7H, H-3, H_{m,m’,p,p’} from Ph), 6.21 (s, 1H, H_β); ¹³C NMR (101 MHz, CDCl₃): δ = 190.6 (C O), 168.8 (C_α), 152.3 (C-6), 150.2 (C-2), 146.1 (C-8a), 138.7 (C_i’ from Ph), 135.6 (C-4), 133.6 (C_i from Ph), 132.6 (C_p’ from Ph), 132.0 (C_p from Ph), 130.6 (C-8), 129.5 (C_m from Ph), 129.1 (C-4a), 128.4 (C_m’ from Ph), 128.3 (C_o′ from Ph), 128.2 (C_o from Ph), 124.2 (C-7), 121.9 (C-3), 117.4 (C-5), 105.9 (C_β); IR (microlayer): 1662 (C O), 1600, 1576 (C C) cm⁻¹; HRMS (ESI): m/z calcd for C₂₄H₁₈NO₂ ⁺ [M + H]⁺: 352.1338; found: 352.1338.

4.2.3. 1,3-Diphenyl-3-(quinolin-8-yloxy)prop-2-en-1-one (3c)

Following the general procedure, 3c was prepared from 8-hydroxyquinoline 1c (73 mg, 0.5 mmol) and acetylene 2a (103 mg, 0.5 mmol); 3c was isolated as an yellow oil (165 mg, 94% yield). E:Z-isomer ratio 30:70 (¹H NMR); (Z)-isomer ¹H NMR (400 MHz, CDCl₃): δ = 8.89 (m, 1H, H-2), 7.92 (d, ³ J _3,4 = 9.2 Hz, 1H, H-4), 7.86 (m, 2H, H_o’ from Ph), 7.73 (m, 2H, H_o from Ph), 7.35-7.10 (m, 10H, H-3, H-5, H-6, H-7, H_{m,m’,p,p’} from Ph), 7.07 (s, 1H, H_β); ¹³C NMR (101 MHz, CDCl₃): δ = 188.9 (C O), 161.2 (C_α), 152.8 (C-8), 149.6 (C-2, C-7), 139.7 (C-8a), 138.5 (C_i’ from Ph), 135.6 (C-4), 134.1 (C_i from Ph), 132.3 (C_p’ from Ph), 130.5 (C_p from Ph), 129.4 (C-4a), 128.6 (C_m from Ph), 128.2 (C_m’ from Ph), 128.1 (C_o’ from Ph), 127.0 (C_o from Ph), 126.1 (C-6), 121.8 (C-5), 121.5 (C-3), 109.8 (C_β); (E)-isomer ¹H NMR (400 MHz, CDCl₃): δ = 8.92 (m, 1H, H-2), 8.03 (d, ³ J _3,4 = 9.2 Hz, 1H, H-4), 7.81 (m, 2H, H_o’ from Ph), 7.69 (m, 2H, H_o from Ph), 7.55 (m, 1H, H-5), 7.42 (m, 1H, H-6), 7.35-7.10 (m, 7H, H-3, H_{m,m’,p,p’} from Ph), 7.06 (m, 1H, H-7), 5.99 (s, 1H, H_β); ¹³C NMR (101 MHz, CDCl₃): δ = 188.9 (C O), 161.2 (C_α), 152.8 (C-8), 149.6 (C-2, C-7), 139.7 (C-8a), 138.5 (C_i’ from Ph), 135.6 (C-4), 134.1 (C_i from Ph), 132.3 (C_p’ from Ph), 130.5 (C_p from Ph), 129.4 (C-4a), 128.6 (C_m from Ph), 128.2 (C_m’ from Ph), 128.1 (C_o′ from Ph), 127.0 (C_o from Ph), 126.1 (C-6), 121.8 (C-5), 121.5 (C-3), 109.8 (C_β); IR (microlayer): 1662 (C O), 1601, 1572 (C C) cm⁻¹; HRMS (ESI): m/z calcd for C₂₄H₁₈NO₂ ⁺ [M + H]⁺: 352.1338; found: 352.1340.

4.2.4. 1-(3-Methoxyphenyl)-3-phenyl-3-(quinolin-6-yloxy)prop-2-en-1-one (3d)

Following the general procedure, 3d was prepared from 6-hydroxyquinoline 1b (73 mg, 0.5 mmol) and acetylene 2b (118 mg, 0.5 mmol); 3d was isolated as a brown oil (184 mg, 96% yield). E:Z-isomer ratio 40:60 (¹H NMR); (Z)-isomer ¹H NMR (400 MHz, CDCl₃): δ = 8.70 (m, 1H, H-2), 7.97 (d, ³ J _3,4 = 9.2 Hz, 1H, H-4), 7.86 (d, ³ J _7,8 = 8.2 Hz, 1H, H-8), 7.72 (m, 2H, H_o from Ph), 7.50 (m, 1H, H-2′), 7.44 (m, 1H, H-6′), 7.40-7.25 (m, 5H, H-7, H-5′, H_m,p from Ph), 7.18 (m, 1H, H-3), 7.14 (d, ⁴ J _5,7 = 2.4 Hz, 1H, H-5), 7.07 (s, 1H, H_β), 7.02 (m, 1H, H-4′), 3.70 (s, 3H, OMe); ¹³C NMR (101 MHz, CDCl₃): δ = 188.9 (C O), 160.5 (C_α), 159.8 (C-3′), 155.2 (C-6), 148.8 (C-2), 144.8 (C-8a), 139.9 (C-1′), 135.1 (C-4), 134.0 (C_i from Ph), 131.3 (C-8), 130.9 (C_p from Ph), 129.4 (C-5′), 129.0 (C_m from Ph), 128.9 (C-4a), 127.1 (C_o from Ph), 121.6 (C-7), 121.4 (C-3), 121.0 (C-6′), 119.4 (C-4′), 111.0 (C-2′), 112.5 (C-5), 105.9 (C_β), 55.4 (OMe); (E)-isomer ¹H NMR (400 MHz, CDCl₃): δ = 8.87 (m, 1H, H-2), 8.16 (d, ³ J _7,8 = 8.2 Hz, 1H, H-8), 8.07 (d, ³ J _3,4 = 9.2 Hz, 1H, H-4), 7.65 (m, 2H, H_o from Ph), 7.59 (m, 1H, H-6′), 7.55 (m, 1H, H-2′), 7.40-7.25 (m, 5H, H-7, H-5′, H_m,p from Ph), 7.28 (m, 1H, H-5), 7.22 (m, 1H, H-3), 6.21 (s, 1H, H_β), 6.95 (m, 1H, H-4′), 3.70 (s, 3H, OMe); ¹³C NMR (101 MHz, CDCl₃): δ = 190.1 (C O), 168.8 (C_α), 159.7 (C-3′), 152.3 (C-6), 150.2 (C-2), 146.1 (C-8a), 140.1 (C-1′), 135.5 (C-4), 133.6 (C_i from Ph), 131.9 (C-8), 130.5 (C_p from Ph), 129.3 (C-5′), 129.4 (C_m from Ph), 129.0 (C-4a), 128.1 (C_o from Ph), 124.2 (C-7), 121.8 (C-3), 120.9 (C-6′), 119.1 (C-4′), 117.3 (C-5), 112.6 (C-2′), 105.9 (C_β), 55.4 (OMe); IR (microlayer): 1661 (C O), 1600, 1583 (C C) cm⁻¹; HRMS (ESI): m/z calcd for C₂₅H₂₀NO₃ ⁺ [M + H]⁺: 382.1443; found: 382.1444.

4.2.5. 1-(4-Nitrophenyl)-3-phenyl-3-(quinolin-6-yloxy)prop-2-en-1-one (3e)

Following the general procedure, 3e was prepared from 6-hydroxyquinoline 1b (73 mg, 0.5 mmol) and acetylene 2c (126 mg, 0.5 mmol); 3e was isolated as a dark-yellow powder (157 mg, 79% yield), mp 148–150 °C (EtOH). E:Z-isomer ratio 20:80 (¹H NMR); (Z)-isomer ¹H NMR (400 MHz, CDCl₃): δ = 8.73 (m, 1H, H-2), 8.18 (m, 2H, H-3′, H-5′), 7.95 (d, ³ J _3,4 = 9.2 Hz, 1H, H-4; m, 2H, H-2′, H-6′), 7.88 (d, ³ J _7,8 = 8.2 Hz, 1H, H-8), 7.73 (m, 2H, H_o from Ph), 7.63 (m, 1H, H_p from Ph), 7.45-7.30 (m, 3H, H-7, H_m from Ph), 7.25 (m, 1H, H-3), 7.11 (d, ⁴ J _5,7 = 2.4 Hz, 1H, H-5), 7.00 (s, 1H, H_β); ¹³C NMR (101 MHz, CDCl₃): δ = 188.0 (C O), 162.4 (C_α), 154.9 (C-6), 149.2 (C-2, C-4′), 144.9 (C-8a), 143.5 (C-1′), 135.1 (C-4), 133.5 (C_i from Ph), 131.5 (C-8), 131.5 (C_p from Ph), 129.2 (C-2′, C-6′, C_m from Ph), 128.3 (C-4a), 127.4 (C_o from Ph), 123.6 (C-3′, C-5′), 121.6 (C-7), 121.3 (C-3), 111.2 (C-5), 110.3 (C_β); (E)-isomer ¹H NMR (400 MHz, CDCl₃): δ = 8.90 (m, 1H, H-2), 8.16 (d, ³ J _7,8 = 8.2 Hz, 1H, H-8), 8.10 (d, ³ J _3,4 = 9.2 Hz, 1H, H-4), 8.07 (m, 2H, H-2′, H-6′), 7.95 (m, 2H, H-3′, H-5′), 7.45-7.30 (m, 7H, H-3, H-7, H_o,m,p from Ph), 7.25 (m, 1H, H-5), 6.13 (s, 1H, H_β); ¹³C NMR (101 MHz, CDCl₃): δ = 188.9 (C O), 171.2 (C_α), 150.5 (C-6), 149.9 (C-2), 149.7 (C-4′), 146.2 (C-8a), 143.7 (C-1′), 135.6 (C-4), 133.2 (C_i from Ph), 131.1 (C-8), 132.2 (C_p from Ph), 129.5 (C_m from Ph), 129.0 (C-4a), 128.8 (C-2′, C-6′), 128.3 (C_o from Ph), 123.5 (C-3′, C-5′), 124.0 (C-7), 122.0 (C-3), 117.7 (C-5), 104.7 (C_β); IR (microlayer): 1665 (C O), 1598 (C C), 1211 (NO₂) cm⁻¹; HRMS (ESI): m/z calcd for C₂₄H₁₇N₂O₄ ⁺ [M + H]⁺: 397.1188; found: 397.1188.

4.2.6. 1-(2-Furyl)-3-phenyl-3-(quinolin-3-yloxy)prop-2-en-1-one (3f)

Following the general procedure, 3f was prepared from 3-hydroxyquinoline 1a (73 mg, 0.5 mmol) and acetylene 2d (98 mg, 0.5 mmol); 3f was isolated as an yellow oil (166 mg, 97% yield). E:Z-isomer ratio 70:30 (¹H NMR); (Z)-isomer ¹H NMR (400 MHz, CDCl₃): δ = 8.87 (m, 1H, H-2), 8.01 (d, ³ J _7,8 = 8.2 Hz, 1H, H-8), 7.72 (m, 2H, H-4, H-5), 7.71 (m, 2H, H_o from Ph), 7.55 (m, 2H, H-6, H-7), 7.45-7.35 (m, 3H, H_m,p from Ph), 7.42 (m, 1H, H-5′), 7.19 (s, 1H, H_β), 7.18 (m, 1H, H-3′), 6.50 (m, 1H, H-4′); ¹³C NMR (101 MHz, CDCl₃): δ = 175.9 (C O), 161.3 (C_α), 152.0 (C-2′), 151.0 (C-3), 146.1 (C-5′), 145.9 (C-2), 144.5 (C-8a), 133.7 (C_i from Ph), 131.4 (C-8), 129.6 (C_m from Ph), 129.3 (C-4a), 129.2 (C_p from Ph), 128.2 (C_o from Ph), 127.6 (C-7), 127.2 (C-6), 127.1 (C-5), 118.0 (C-4), 117.0 (C-4′), 112.7 (C-3′), 109.2 (C_β); (E)-isomer ¹H NMR (400 MHz, CDCl₃): δ = 8.85 (m, 1H, H-2), 8.14 (d, ³ J _7,8 = 8.2 Hz, 1H, H-8), 7.88 (d, ⁴ J _2,4 = 2.5 Hz, 1H, H-4), 7.88 (d, ³ J _5,6 = 9.0 Hz, 1H, H-5), 7.71 (m, 2H, H_o from Ph), 7.55 (m, 2H, H-6, H-7), 7.45-7.35 (m, 4H, H-5′, H_m,p from Ph), 7.00 (d, ³ J _3’,4’ = 4.5 Hz, 1H, H-3′), 6.38 (m, 1H, H-4′), 6.24 (s, 1H, H_β); ¹³C NMR (101 MHz, CDCl₃): δ = 177.5 (C O), 169.4 (C_α), 153.9 (C-2′), 147.9 (C-3), 145.9 (C-5′), 145.7 (C-2), 143.7 (C-8a), 133.2 (C_i from Ph), 130.9 (C-8), 129.6 (C_m from Ph), 129.18 (C_p from Ph), 129.16 (C-4a), 128.2 (C_o from Ph), 127.7 (C-7), 127.6 (C-6), 127.4 (C-5), 125.1 (C-4), 116.7 (C-4′), 112.4 (C-3′), 104.4 (C_β); IR (microlayer): 1657, 1601 (C O), 1581 (C C) cm⁻¹; HRMS (ESI): m/z calcd for C₂₂H₁₆NO₃ ⁺ [M + H]⁺: 342.1130; found: 342.1135.

4.2.7. 1-(2-Furyl)-3-phenyl-3-(quinolin-6-yloxy)prop-2-en-1-one (3g)

Following the general procedure, 3g was prepared from 6-hydroxyquinoline 1b (73 mg, 0.5 mmol) and acetylene 2d (98 mg, 0.5 mmol); 3g was isolated as a dark-yellow oil (164 mg, 96% yield). E:Z-isomer ratio 20:80 (¹H NMR); (Z)-isomer ¹H NMR (400 MHz, CDCl₃): δ = 8.70 (m, 1H, H-2), 8.01 (d, ³ J _7,8 = 8.2 Hz, 1H, H-8), 7.86 (d, ³ J _3,4 = 9.2 Hz, 1H, H-4), 7.73 (m, 2H, H_o from Ph), 7.53 (m, 1H, H_p from Ph), 7.37 (m, 3H, H-7, H_m from Ph), 7.50 (m, 2H, H-5, H-5′), 7.18 (m, 1H, H-3), 7.17 (m, 1H, H-3′), 7.17 (s, 1H, H_β), 6.45 (m, 1H, H-4′); ¹³C NMR (101 MHz, CDCl₃): δ = 176.0 (C O), 161.5 (C_α), 155.3 (C-6), 152.1 (C-2′), 148.7 (C-2), 146.1 (C-5′), 144.8 (C-8a), 135.1 (C-4), 134.0 (C_i from Ph), 131.3 (C-8), 131.1 (C_p from Ph), 129.0 (C_m from Ph), 128.3 (C-4a), 127.3 (C_o from Ph), 121.7 (C-7), 121.4 (C-3), 116.8 (C-4′), 112.6 (C-3′), 110.7 (C-5), 109.1 (C_β); (E)-isomer ¹H NMR (400 MHz, CDCl₃): δ = 8.88 (m, 1H, H-2), 8.16 (d, ³ J _7,8 = 8.2 Hz, 1H, H-8), 8.08 (d, ³ J _3,4 = 9.2 Hz, 1H, H-4), 7.71 (m, 2H, H_o from Ph), 7.50 (m, 2H, H-5, H-5′), 7.40-7.30 (m, 5H, H-3, H-7, H_m,p from Ph), 6.95 (m, 1H, H-3′), 6.35 (m, 1H, H-4′), 6.24 (s, 1H, H_β); ¹³C NMR (101 MHz, CDCl₃): δ = 177.6 (C O), 169.7 (C_α), 154.0 (C-6), 153.9 (C-2′), 150.2 (C-2), 145.7 (C-5′), 146.1 (C-8a), 135.6 (C-4), 133.5 (C_i from Ph), 131.9 (C-8), 130.6 (C_p from Ph), 129.5 (C_m from Ph), 128.9 (C-4a), 128.0 (C_o from Ph), 124.2 (C-7), 121.8 (C-3), 116.4 (C-4′), 112.3 (C-3′), 117.5 (C-5), 103.9 (C_β); IR (microlayer): 1656 (C O), 1597 (C C) cm⁻¹; HRMS (ESI): m/z calcd for C₂₂H₁₆NO₃ ⁺ [M + H]⁺: 342.1130; found: 342.1132.

4.2.8. 1-(2-Furyl)-3-phenyl-3-(quinolin-8-yloxy)prop-2-en-1-one (3h)

Following the general procedure, 3h was prepared from 8-hydroxyquinoline 1c (73 mg, 0.5 mmol) and acetylene 2d (98 mg, 0.5 mmol); 3h was isolated as a dark-yellow oil (161 mg, 94% yield). E:Z-isomer ratio 30:70 (¹H NMR); (Z)-isomer ¹H NMR (400 MHz, CDCl₃): δ = 8.95 (m, 1H, H-2), 7.97 (d, ³ J _3,4 = 9.2 Hz, 1H, H-4), 7.75 (m, 2H, H_o from Ph), 7.42 (m, 2H, H-5, H-6), 7.30-7.10 (m, 6H, H-3, H-7, H-5′, H_m,p from Ph), 7.15 (s, 1H, H_β), 7.00 (d, ³ J _3’,4’ = 4.5 Hz, 1H, H-3′), 6.36 (m, 1H, H-4′); ¹³C NMR (101 MHz, CDCl₃): δ = 175.7 (C O), 162.1 (C_α), 153.8 (C-8), 152.8 (C-2′), 149.6 (C-2), 145.6 (C-5′), 139.7 (C-8a), 135.6 (C-4), 134.1 (C_i from Ph), 130.6 (C_p from Ph), 129.4 (C-4a), 128.5 (C_m from Ph), 127.0 (C_o from Ph), 126.0 (C-6), 121.6 (C-5), 121.5 (C-3), 116.3 (C-4′), 113.1 (C-7), 112.2 (C-3′), 109.1 (C_β); (E)-isomer ¹H NMR (400 MHz, CDCl₃): δ = 8.88 (m, 1H, H-2), 8.04 (d, ³ J _3,4 = 9.2 Hz, 1H, H-4), 7.91 (m, 2H, H_o from Ph), 7.57 (m, 1H, H_p from Ph), 7.30-7.10 (m, 7H, H-3, H-5, H-6, H-7, H-5′, H_m from Ph), 6.85 (d, ³ J _3’,4’ = 4.5 Hz, 1H, H-3′), 6.22 (m, 1H, H-4′), 6.08 (s, 1H, H_β); ¹³C NMR (101 MHz, CDCl₃): δ = 177.8 (C O), 170.7 (C_α), 153.6 (C-2′), 150.4 (C-2), 150.2 (C-8), 145.3 (C-5′), 140.7 (C-8a), 135.8 (C-4), 133.7 (C_i from Ph), 130.2 (C_p from Ph), 129.7 (C-4a), 129.7 (C_m from Ph), 127.4 (C_o from Ph), 126.2 (C-6), 125.2 (C-5), 121.7 (C-3), 120.4 (C-7), 116.4 (C-4′), 111.8 (C-3′), 103.7 (C_β); IR (microlayer): 1656 (C O), 1598 (C C) cm⁻¹; HRMS (ESI): m/z calcd for C₂₂H₁₆NO₃ ⁺ [M + H]⁺: 342.1130; found: 342.1136.

4.2.9. 3-Phenyl-3-(quinolin-6-yloxy)-1-(2-thienyl)prop-2-en-1-one (3i)

Following the general procedure, 3i was prepared from 6-hydroxyquinoline 1b (73 mg, 0.5 mmol) and acetylene 2e (106 mg, 0.5 mmol); 3i was isolated as a dark-yellow oil (172 mg, 96% yield). E:Z-isomer ratio 30:70 (¹H NMR); (Z)-isomer ¹H NMR (400 MHz, CDCl₃): δ = 8.68 (m, 1H, H-2), 7.98 (d, ³ J _7,8 = 8.2 Hz, 1H, H-8), 7.83 (d, ³ J _3,4 = 9.2 Hz, 1H, H-4), 7.70 (m, 3H, H-3′, H_o from Ph), 7.50 (m, 1H, H_p from Ph), 7.40-7.30 (m, 4H, H-5′, H-7, H_m from Ph), 7.16 (d, ⁴ J _5,7 = 2.3 Hz, 1H, H-5), 7.15 (m, 1H, H-3), 7.06 (s, 1H, H_β), 7.03 (m, 1H, H-4′); ¹³C NMR (101 MHz, CDCl₃): δ = 180.3 (C O), 160.7 (C_α), 155.1 (C-6), 148.7 (C-2), 146.1 (C-2′), 144.8 (C-8a), 133.8 (C-5′), 131.5 (C-4), 133.9 (C_i from Ph), 131.5 (C-4′), 131.2 (C-8), 131.0 (C_p from Ph), 129.0 (C_m from Ph), 128.0 (C-4a, C-3′), 127.2 (C_o from Ph), 121.6 (C-7), 121.3 (C-3), 110.9 (C-5), 110.2 (C_β); (E)-isomer ¹H NMR (400 MHz, CDCl₃): δ = 8.85 (m, 1H, H-2), 8.15 (d, ³ J _7,8 = 8.2 Hz, 1H, H-8), 8.06 (d, ³ J _3,4 = 9.2 Hz, 1H, H-4), 7.52 (m, 1H, H-3′), 7.50 (m, 2H, H_o from Ph), 7.49 (d, ⁴ J _5,7 = 2.4 Hz, 1H, H-5), 7.40-7.35 (m, 5H, H-3, H-7, H_m,p from Ph), 7.36 (m, 1H, H-5′), 6.89 (m, 1H, H-4′), 6.19 (s, 1H, H_β); ¹³C NMR (101 MHz, CDCl₃): δ = 181.7 (C O), 168.8 (C_α), 152.1 (C-6), 150.2 (C-2), 146.3 (C-8a), 146.0 (C-2′), 135.6 (C-4), 133.4 (C_i from Ph), 133.3 (C-5′), 131.8 (C-8), 131.2 (C-4′), 130.6 (C_p from Ph), 129.5 (C_m from Ph), 128.9 (C-4a), 128.3 (C_o from Ph), 127.9 (C-3′), 124.1 (C-7), 121.8 (C-3), 117.4 (C-5), 104.9 (C_β); IR (microlayer): 1645 (C O), 1594 (C C) cm⁻¹; HRMS (ESI): m/z calcd for C₂₂H₁₆NO₂S⁺ [M + H]⁺: 358.0902; found: 358.0902.

4.2.10. 3-(4-Methylphenyl)-1-phenyl-3-(quinolin-6-yloxy)prop-2-en-1-one (3j)

Following the general procedure, 3j was prepared from 6-hydroxyquinoline 1b (73 mg, 0.5 mmol) and acetylene 2f (110 mg, 0.5 mmol); 3j was isolated as a brown oil (180 mg, 99% yield). E:Z-isomer ratio 20:80 (¹H NMR); (Z)-isomer ¹H NMR (400 MHz, CDCl₃): δ = 8.68 (m, 1H, H-2), 7.92 (d, ³ J _7,8 = 8.2 Hz, 1H, H-8), 7.85 (m, 2H, H_o’ from Ph), 7.83 (d, ³ J _3,4 = 9.2 Hz, 1H, H-4), 7.60 (m, 2H, H_o from Ph), 7.45-7.30 (m, 4H, H-7, H_m’,p’ from Ph), 7.19 (dd, ³ J _3,4 = 9.2 Hz, ³ J _2,3 = 4.6 Hz, 1H, H-3), 7.17 (m, 2H, H_m from Ph), 7.12 (m, 1H, H-5), 7.05 (s, 1H, H_β), 2.28 (s, 3H, Me); ¹³C NMR (101 MHz, CDCl₃): δ = 189.2 (C O), 160.7 (C_α), 155.3 (C-6), 148.7 (C-2), 144.8 (C-8a), 141.5 (C_p from Ph), 138.7 (C_i’ from Ph), 135.1 (C-4), 131.8 (C_i from Ph), 132.6 (C_p’ from Ph), 131.2 (C-8), 129.7 (C_m from Ph), 128.8 (C-4a), 128.4 (C_m’ from Ph), 128.3 (C_o’ from Ph), 127.1 (C_o from Ph), 121.6 (C-7), 121.3 (C-3), 110.8 (C-5), 110.2 (C_β), 21.4 (Me); (E)-isomer ¹H NMR (400 MHz, CDCl₃): δ = 8.84 (m, 1H, H-2), 8.14 (d, ³ J _7,8 = 8.2 Hz, 1H, H-8), 7.74 (m, 2H, H_o’ from Ph), 8.04 (d, ³ J _3,4 = 9.2 Hz, 1H, H-4), 7.55 (m, 3H, H-3, H_o from Ph), 7.52 (m, 1H, H-5), 7.45-7.30 (m, 4H, H-7, H_m’,p’ from Ph), 7.14 (m, 2H, H_m from Ph), 6.21 (s, 1H, H_β), 2.29 (s, 3H, Me) ppm. ¹³C NMR (101 MHz, CDCl₃): δ = 190.4 (C O), 168.9 (C_α), 152.4 (C-6), 150.0 (C-2), 146.0 (C-8a), 140.9 (C_p from Ph), 138.8 (C_i’ from Ph), 135.5 (C-4), 130.6 (C_i from Ph), 132.4 (C_p’ from Ph), 131.1 (C-8), 129.4 (C_m from Ph), 129.0 (C-4a), 128.4 (C_m’ from Ph), 128.3 (C_o′ from Ph), 128.1 (C_o from Ph), 124.1 (C-7), 121.8 (C-3), 117.2 (C-5), 105.5 (C_β), 21.5 (Me); IR (microlayer): 1661 (C O), 1597 (C C) cm⁻¹; HRMS (ESI): m/z calcd for C₂₅H₂₀NO₂ ⁺ [M + H]⁺: 366.1494; found: 366.1496.

4.2.11. (2E)-1-Phenyl-3-(5-phenyl-1H-pyrrol-2-yl)-3-(quinolin-6-yloxy)prop-2-en-1-one (3k)

Following the general procedure, 3k was prepared from 6-hydroxyquinoline 1b (73 mg, 0.5 mmol) and acetylene 2g (136 mg, 0.5 mmol). In this case 1.2 equivalents of KOH were used. 3k was isolated as a brown oil (182 mg, 87% yield); ¹H NMR (400 MHz, CDCl₃): δ = 14.76 (br. s, 1H, NH), 8.84 (m, 1H, H-2), 8.14 (d, ³ J _3,4 = 9.1 Hz, 1H, H-4), 8.02 (d, ³ J _7,8 = 8.8 Hz, 1H, H-8), 7.54 (dd, ³ J _7,8 = 8.8 Hz, ⁴ J _5,7 = 2.6 Hz, 1H, H-7), 7.46 (d, ⁴ J _5,7 = 2.6 Hz, 1H, H-5), 7.35-7.25 (m, 11H, H-3, H_{o,m,p,o’,m’,p’} from Ph and Bz), 7.11 (m, 1H, H-3′ from pyrrolyl), 6.74 (m, 1H, H-4′ from pyrrolyl), 6.27 (s, 1H, H_β); ¹³C NMR (101 MHz, CDCl₃): δ = 189.1 (C O), 162.0 (C_α, C-2), 153.4 (C-6), 145.8 (C-8a), 140.3 (C-5′ from pyrrolyl), 137.6 (C_i’ from Bz), 136.7 (C-4), 131.5 (C_i from Ph), 132.1 (C_p’ from Bz), 131.8 (C-8), 129.1 (C_m from Ph), 128.5 (C_m’ from Bz), 128.3 (C-2′ from pyrrolyl, C_p from Ph), 127.9 (C_o’ from Bz), 127.8 (C-4a), 124.8 (C_o from Ph), 121.9 (C-3′ from pyrrolyl), 118.3 (C-7), 123.8 (C-3), 116.0 (C-5), 109.4 (C-4′ from pyrrolyl), 100.3 (C_β); IR (microlayer): 1627 (C O), 1575 (C C) cm⁻¹; HRMS (ESI): m/z calcd for C₂₈H₂₁N₂O₂ ⁺ [M + H]⁺: 417.1603; found: 417.1603.

4.2.12. (E)-3-(5-(3-Fluorophenyl)-1H-pyrrol-2-yl)-1-phenyl-3-(quinolin-6-yloxy)prop-2-en-1-one (3l)

Following the general procedure, 3l was prepared from 6-hydroxyquinoline 1b (73 mg, 0.5 mmol) and acetylene 2h (145 mg, 0.5 mmol). In this case 1.2 equivalents of KOH were used. 3l was isolated as a brown oil (152 mg, 70% yield). ¹H NMR (400 MHz, CDCl₃): δ = 14.29 (br. s, 1H, NH), 8.86 (m, 1H, H-2), 8.16 (d, ³ J _3,4 = 9.0 Hz, 1H, H-4), 8.06 (d, ³ J _7,8 = 8.8 Hz, 1H, H-8), 7.72 (m, 2H, H_o from Bz), 7.57 (m, 1H, H-2 from 3-FC₆H₄), 7.54 (m, 1H, H-7), 7.49 (d, ⁴ J _5,7 = 2.5 Hz, 1H, H-5), 7.74 (m, 1H, H-6 from 3-FC₆H₄), 7.27 (m, 1H, H-3), 7.35-7.25 (m, 4H, H-5 from 3-FC₆H₄ and H_m,p from Bz), 7.10 (m, 1H, H-3′ from pyrrolyl), 6.97 (m, 1H, H-4 from 3-FC₆H₄), 6.72 (m, 1H, H-4′ from pyrrolyl), 6.29 (s, 1H, H_β); ¹³C NMR (101 MHz, CDCl₃): δ = 189.2 (C O), 163.3 (d, ¹ J _CF = 252.0 Hz, C-3 from 3-FC₆H₄), 162.1 (C_α), 153.2 (C-6), 150.1 (C-2), 145.9 (C-8a), 140.2 (C-5′ from pyrrolyl), 136.1 (C_i from Bz), 135.7 (C-4), 133.7 (d, ³ J _CF = 4.0 Hz, C-1 from 3-FC₆H₄), 132.6 (C_p from Bz), 132.3 (C-8), 130.8 (d, ³ J _CF = 8.0 Hz, C-5 from 3-FC₆H₄), 128.6 (C_m from Bz), 128.2 (C-2′ from pyrrolyl), 128.0 (C_o from Bz), 127.9 (C-4a), 124.4 (C-3), 121.9 (C-3′ from pyrrolyl), 120.4 (d, ⁴ J _CF = 3.0 Hz, C-6 from 3-FC₆H₄), 118.0 (C-7), 116.3 (C-5), 114.6 (d, ² J _CF = 21.0 Hz, C-2 from 3-FC₆H₄), 111.7 (d, ² J _CF = 23.0 Hz, C-4 from 3-FC₆H₄), 109.9 (C-4′ from pyrrolyl), 100.5 (C_β); IR (microlayer): 1625 (C O), 1616, 1578 (C C) cm⁻¹; HRMS (ESI): m/z calcd for C₂₈H₂₀FN₂O₂ ⁺ [M + H]⁺: 435.1509; found: 435.1509.

4.2.13. 1-Ethyl-1-methyl-4-oxo-4-phenyl-2-(quinolin-6-yloxy)but-2-en-1-yl benzoate (3m)

Following the general procedure, 3m was prepared from 6-hydroxyquinoline 1b (73 mg, 0.5 mmol) and acetylene 2i (153 mg, 0.5 mmol); 3m was isolated as an yellow oil (166 mg, 74% yield). E:Z-isomer ratio 65:35 (¹H NMR); (Z)-isomer ¹H NMR (400 MHz, CDCl₃): δ = 8.69 (m, 1H, H-2), 8.03 (d, ³ J _7,8 = 8.2 Hz, 1H, H-8), 8.03 (m, 2H, H_o’ from Ph), 7.94 (d, ³ J _3,4 = 9.2 Hz, 1H, H-4), 7.82 (m, 1H, H_p from Ph), 7.65 (m, 2H, H_o from Ph), 7.50 (m, 1H, H_p’ from Ph), 7.45-7.15 (m, 7H, H-3, H-5, H-7, H_m,m’ from Ph), 6.51 (s, 1H, H_β), 2.35, 2.24 (sxt, ² J _H,H(CH2) = 12.0 Hz, ³ J _H,H(CH2,Me) = 8.0 Hz, 2H, CH₂), 1.91 (s, 3H, Me), 1.14 (t, 3H, CHMe); ¹³C NMR (101 MHz, CDCl₃): δ = 190.3 (C O), 164.2 (C_α), 165.3 [-OC(O)], 155.1 (C-6), 148.9 (C-2), 144.8 (C-8a), 138.1 (C_i’ from Ph), 135.1 (C-4), 133.1 (C_p from Ph), 132.6 (C_p’ from Ph), 131.0 (C-8), 130.7 (C_i from Ph), 128.7 (C-4a), 128.3 (C_o’ from Ph), 128.2 (C_m,m’ from Ph), 128.1 (C_o from Ph), 121.4 (C-7), 121.3 (C-3), 111.6 (C-5), 107.7 (C_β), 83.6 (C_quat.), 31.9 (CH₂), 22.3 (Me), 8.18 (CH₂ Me); (E)-isomer ¹H NMR (400 MHz, CDCl₃): δ = 8.85 (m, 1H, H-2), 8.17 (d, ³ J _7,8 = 8.2 Hz, 1H, H-8), 8.07 (d, ³ J _3,4 = 9.2 Hz, 1H, H-4), 7.94 (m, 2H, H_o’ from Ph), 7.82 (m, 1H, H_p from Ph), 7.65 (m, 2H, H_o from Ph), 7.60 (d, ³ J _7,8 = 8.2 Hz, 1H, H-7), 7.56 (d, ⁴ J _5,7 = 2.4 Hz, 1H, H-5), 7.45-7.15 (m, 6H, H-3, H_m,m’,p’ from Ph), 5.74 (s, 1H, H_β), 2.57, 2.42 (sxt, ² J _H,H(CH2) = 12.0 Hz, ³ J _H,H(CH2,Me) = 8.0 Hz, 2H, CH₂), 1.96 (s, 3H, Me), 1.20 (t, 3H, CHMe); ¹³C NMR (101 MHz, CDCl₃): δ = 191.3 (C O), 168.7 (C_α), 165.4 [-OC(O)], 151.7 (C-6), 150.2 (C-2), 146.3 (C-8a), 138.3 (C_i’ from Ph), 135.5 (C-4), 132.7 (C_p from Ph), 132.6 (C_p’ from Ph), 131.0 (C-8), 130.7 (C_i from Ph), 129.6 (C_m from Ph), 129.0 (C-4a), 128.5 (C_o from Ph), 128.3 (C_o’ from Ph), 128.2 (C_m′ from Ph), 124.8 (C-7), 121.7 (C-3), 118.2 (C-5), 104.0 (C_β), 83.4 (C_quat.), 31.6 (CH₂), 22.5 (Me), 8.32 (CH₂ Me); IR (microlayer): 1716, 1661 (C O), 1602 (C C) cm⁻¹; HRMS (ESI): m/z calcd for C₂₉H₂₆NO₄ ⁺ [M + H]⁺: 452.1862; found: 452.1859.

4.2.14. (Z)-3-[(4-Methylquinolin-2-yl)oxy]-1,3-diphenylprop-2-en-1-one (5a)

Following the general procedure, 5a was prepared from 4-methylquinolin-2(1H)-one 1d (81 mg, 0.5 mmol) and acetylene 2a (103 mg, 0.5 mmol); 5a was isolated as a light-yellow powder (156 mg, 85% yield), mp 209–211 °C (EtOH). ¹H NMR (400 MHz, CDCl₃): δ = 7.87 (m, 2H, H_o’ from Ph), 7.83 (s, 1H, H_β), 7.67 (d, ³J_5,6 = 8.0 Hz, 1H, H-5), 7.53 (m, 2H, H_o from Ph), 7.47 (m, 1H, H_p’ from Ph), 7.40-7.32 (m, 5H, H_m,m’,p from Ph), 7.29 (m, 1H, H-7), 7.15 (m, 1H, H-6), 7.09 (d, ³J_7,8 = 8.4 Hz, 1H, H-8), 6.59 (s, 1H, H-3), 2.47 (s, 3H, Me); ¹³C NMR (101 MHz, CDCl₃): δ = 188.6 (C O), 161.2 (C-2), 148.1 (C_α), 146.3 (C-4), 139.6 (C-8a), 138.2 (C_i’ from Ph), 134.9 (C_i from Ph), 133.1 (C_p’ from Ph), 130.9 (C-7), 130.5 (C_p from Ph), 129.4 (C_m from Ph), 128.6 (C_m’ from Ph), 128.5 (C_o′ from Ph), 126.7 (C_o from Ph), 125.2 (C-5), 122.4 (C-6), 122.3 (C-3), 121.5 (C-8), 121.2 (C-4a), 115.8 (C_β), 19.4 (Me); IR (microlayer): 1662 (C O), 1597 (C C) cm⁻¹; HRMS (ESI): m/z calcd for C₂₅H₂₀NO₂ ⁺ [M + H]⁺: 366.1494; found: 366.1497.

4.2.15. 1-[3-Oxo-1,3-diphenylprop-1-en-1-yl]quinolin-4(1H)-one (5b)

Following the general procedure, 5b was prepared from quinolin-4(1H)-one 1e (73 mg, 0.5 mmol) and acetylene 2a (103 mg, 0.5 mmol); 5b was isolated as an yellow powder (157 mg, 89% yield), mp 150–154 °C (EtOH). E:Z-isomer ratio 15:85 (¹H NMR); (Z)-isomer ¹H NMR (400 MHz, CDCl₃): δ = 8.35 (d, ³ J _5,6 = 7.2 Hz, 1H, H-5), 7.84 (m, 2H, H_o’ from Ph), 7.60 (s, 1H, H_β), 7.52-7.35 (m, 9H, H-6, H-7, H-8, H_{o,m’,p’,p} from Ph), 7.25 (m, 2H, H_m from Ph), 7.10 (d, ³ J _2,3 = 7.8 Hz, 1H, H-2), 6.30 (d, ³ J _2,3 = 7.8 Hz, 1H, H-3); ¹³C NMR (101 MHz, CDCl₃): δ = 188.9 (C O), 178.5 (C-4), 149.2 (C_α), 142.6 (C-2), 140.4 (C-8a), 137.5 (C_i’ from Ph), 134.9 (C_i from Ph), 133.8 (C_p’ from Ph), 131.8 (C-7), 132.1 (C_p from Ph), 129.8 (C_m from Ph), 128.9 (C_m’ from Ph), 128.4 (C_o’ from Ph), 126.8 (C-4a, C-5, C_o from Ph), 124.1 (C-6), 122.1 (C-8), 117.7 (C-3), 110.9 (C_β); (E)-isomer ¹H NMR (400 MHz, CDCl₃): δ = 8.42 (d, ³ J _5,6 = 7.6 Hz, 1H, H-5), 7.97 (m, 2H, H_o’ from Ph), 7.73 (d, ³ J _7,8 = 7.8 Hz, 1H, H-8), 7.52-7.35 (m, 10H, H-6, H-7, H_{o,m,p,m’,p’} from Ph), 7.26 (m, 1H, H-2), 7.02 (s, 1H, H_β), 6.37 (d, ³ J _2,3 = 7.8 Hz, 1H, H-3); ¹³C NMR (101 MHz, CDCl₃): δ = 191.5 (C O), 178.5 (C-4), 149.8 (C_α), 142.5 (C-2), 140.4 (C-8a), 137.5 (C_i’ from Ph), 134.9 (C_i from Ph), 134.1 (C_p’ from Ph), 131.2 (C-7), 132.4 (C_p from Ph), 129.2 (C_m from Ph), 129.0 (C_m’ from Ph), 128.8 (C_o′ from Ph), 127.0 (C-4a), 126.8 (C-5, C_o from Ph), 124.5 (C-6), 122.1 (C-8), 117.9 (C-3), 111.0 (C_β); IR (microlayer): 1662, 1624 (C O), 1603 (C C) cm⁻¹; HRMS (ESI): m/z calcd for C₂₄H₁₈NO₂ ⁺ [M + H]⁺: 352.1338; found: 352.1333.

4.2.16. (Z)-3-[(2-Methylquinolin-4-yl)oxy]-1,3-diphenylprop-2-en-1-one (5c)

Following the general procedure, 5c was prepared from 2-methylquinolin-4(1H)-one 1f (81 mg, 0.5 mmol) and acetylene 2a (103 mg, 0.5 mmol); 5c was isolated as an yellow powder (174 mg, 95% yield), mp 218–220 °C (EtOH). ¹H NMR (400 MHz, CDCl₃): δ = 8.37 (d, ³ J _5,6 = 7.8 Hz, 1H, H-5), 8.03 (s, 1H, H_β), 7.89 (m, 2H, H_o’ from Ph), 7.53 (m, 1H, H-7), 7.50-7.35 (m, 7H, H-8, H_{o,m’,p’,p} from Ph), 7.34 (m, 1H, H-6), 7.21 (m, 2H, H_m from Ph), 6.33 (s, 1H, H-3), 2.22 (s, 3H, Me); ¹³C NMR (101 MHz, CDCl₃): δ = 187.8 (C O), 178.2 (C-4), 150.4 (C-2), 146.5 (C_α), 141.2 (C-8a), 137.4 (C_i’ from Ph), 134.5 (C_i from Ph), 133.8 (C_p’ from Ph), 132.0 (C_p from Ph), 131.8 (C-7), 129.9 (C_m from Ph), 129.0 (C_m’ from Ph), 128.3 (C_o′ from Ph), 126.5 (C-5), 126.4 (C_o from Ph), 126.0 (C-4a), 123.6 (C-6), 122.5 (C-8), 116.6 (C-3), 111.7 (C_β), 21.1 (Me); IR (microlayer): 1664, 1623 (C O), 1610 (C C) cm⁻¹; HRMS (ESI): m/z calcd for C₂₅H₂₀NO₂ ⁺ [M + H]⁺: 366.1494; found: 366.1493.

4.2.17. (Z)-1-(2-Furyl)-3-phenyl-3-(quinolin-4-yloxy)prop-2-en-1-one (5d)

Following the general procedure, 5d was prepared from quinolin-4(1H)-one 1g (73 mg, 0.5 mmol) and acetylene 2d (98 mg, 0.5 mmol); 5d was isolated as an yellow powder (148 mg, 87% yield), mp 206–207 °C (EtOH). ¹H NMR (400 MHz, CDCl₃): δ = 8.31 (d, ³ J _5,6 = 8.0 Hz, 1H, H-5), 7.59 (s, 1H, H_β), 7.49 (m, 1H, H-5′), 7.37 (m, 4H, H_o,m from Ph), 7.33 (m, 2H, H-7, H-8), 7.27 (m, 1H, H-6), 7.17 (m, 1H, H_p from Ph), 7.15 (m, 1H, H-3′), 6.94 (d, ³ J _2,3 = 8.6 Hz, 1H, H-2), 6.46 (m, 1H, H-4′), 6.28 (d, ³ J _2,3 = 8.6 Hz, 1H, H-3); ¹³C NMR (101 MHz, CDCl₃): δ = 178.7 (C-4), 175.2 (C O), 150.1 (C_α), 153.7 (C-2′), 146.9 (C-5′), 142.7 (C-2), 140.3 (C-8a), 134.9 (C_i from Ph), 132.1 (C_p from Ph), 132.0 (C-7), 129.7 (C_m from Ph), 127.0 (C_o from Ph), 127.0 (C-4a), 126.8 (C-5), 124.0 (C-6), 119.1 (C-8), 118.2 (C-3), 117.5 (C-4′), 113.3 (C-3′), 110.9 (C_β); IR (microlayer): 1657, 1623 (C O), 1602 (C C) cm⁻¹; HRMS (ESI): m/z calcd for C₂₂H₁₆NO₃ ⁺ [M + H]⁺: 342.113; found: 342.1133.

4.3. Procedure for synthesis of 3-((3-benzoyl-2-phenylquinolin-6-yl)oxy)-1,3-diphenylprop-2-en-1-one (4b)

A mixture of benzoylphenyl-ethenyloxyquinoline 3b (202 mg, 0.58 mmol), acetylene 2a (119 mg, 0.58 mmol), KOH (6 mg, 20 mol%), H₂O (574 mg, 32 mmol) and acetonitrile (1 mL) was placed in a 10-mL round-bottom flask (air atmosphere) with stir bar and stirred at 55-60^оС for 48 h. Then the reaction mixture was cooled, solvents were evaporated at a low pressure and the residue was passed through the chromatography column deliver to the target product 4b (73 mg, 24%) as an orange oil. E:Z-isomer ratio 15:85 (¹H NMR); (Z)-isomer ¹H NMR (CDCl₃): δ = 8.11 (d, ³ J _7,8 = 8.0 Hz, 1H, H-8), 8.05 (s, 1H, H-4), 7.90 (m, 2H, H_o from C_β-Bz), 7.73 (m, 2H, H_o from C_α-Ph), 7.63 [m, 2H, H_o from C(2)-Ph], 7.51 [m, 2H, H_o from C(3)-Bz], 7.49 (m, 1H, H-7), 7.45-7.20 [m, 12H, H_m,p from C(2)-Ph, C(3)-Bz, C_α-Ph, C_β-Bz], 7.19 (d, ⁴ J _5,7 = 2.5 Hz, 1H, H-5), 7.11 (s, 1H, H_β); ¹³C NMR (101 MHz, CDCl₃): δ = 197.0 (C_γ = O), 189.3 (C O), 160.3 (Cα), 155.9 (C-2, C-6), 145.0 (C-8a), 139.7 [C_i from C(2)-Ph], 138.6 (C_i from C_β-Bz), 137.0 [C_i from C(3)-Bz], 136.6 (C-4), 134.2 (C_i from C_α-Ph), 133.9 (C-3), 133.4 [C_p from C(3)-Bz], 133.0 (C_p from C_β-Bz), 131.6 (C_p from C_α-Ph), 131.1 (C-8), 130.0 [C_o from C(2)-Ph], 129.7 (C_m from C_α-Ph), 129.2 [C_m from C(2)-Ph], 128.7 [C_p from C(2)-Ph], 128.6 (C_m from C_β-Bz), 128.5 (C_o from C_β-Bz), 128.4 [C_o,m from C(3)-Bz], 127.2 (C_o from C_α-Ph), 126.6 (C-4a), 123.5 (C-7), 111.3 (C-5), 111.0 (C_β); (E)-isomer ¹H NMR (CDCl₃): δ = 8.26 (s, 1H, H-4), 8.20 (d, ³ J _7,8 = 8.0 Hz, 1H, H-8), 6.28 (s, 1H, H_β), other signals are overlapped with major isomer; IR (microlayer): 1663 (C O), 1595 (C C) cm⁻¹; HRMS (ESI): m/z calcd for C₃₇H₂₆NO₃ ⁺ [M + H]⁺: 532.1913; found: 532.1915.

4.4. Procedure for synthesis of 1,3-diphenyl-3-(quinolin-6-yloxy)prop-2-en-1-ol (6b)

A solution of benzoylphenylethenyloxyquinoline 3b (170 mg, 0.48 mmol), NaBH₄ (90 mg, 2.40 mmol) in 1 mL of EtOH was placed in a 10-mL round-bottom flask (air atmosphere) with stir bar and stirred at 20-25^оС for 4 h. Then the reaction mixture was concentrated under the low pressure, dissolved with Et₂O (2 mL) and washed with H₂O (3 × 1 mL). Organic layer was dried under MgSO₄, filtered and concentrated in vacuo. The crude mixture was purified via silica gel to afford the title compound 6b (116 mg, 64%) as beige gum. E:Z-isomer ratio 25:75 (¹H NMR); (Z)-isomer ¹H NMR (400 MHz, CDCl₃): δ = 8.57 (m, 1H, H-2), 7.91 (d, ³ J _7,8 = 7.6 Hz, 1H, H-8), 7.74 (d, ³ J _3,4 = 7.6 Hz, 1H, H-8), 7.49 (m, 2H, H_o from C_γ-Ph), 7.40-7.20 (m, 10H, H-3, H-7, H_o,m,p from Ph, H_m,p from C_γ-Ph), 7.03 (s, 1H, H-5), 6.18 (d, ³ J _β,γ = 8.8 Hz, 1H, H_β), 5.76 (d, ³ J _β,γ = 8.8 Hz, 1H, H_γ), 3.95 (br. S, 1H, OH); ¹³C NMR (101 MHz, CDCl₃): δ = 155.2 (C-6), 149.4 (C_α), 148.3 (C-2), 144.3 (C-8a), 143.5 (C_i from C_γ-Ph), 135.6 (C_i from C_α-Ph), 135.4 (C-4), 134.0 (C-8), 131.0 (C_p from C_α-Ph), 129.2 (C-4a), 128.7 (C_m from C_α-Ph), 128.6 (C_m from C_γ-Ph), 128.5 (C_p from C_γ-Ph), 127.7 (C_β), 126.2 (C_o from C_α-Ph), 125.9 (C_o from C_γ-Ph),121.8 (C-7), 121.5 (C-3), 110.0 (C-5), 68.8 (Cγ); (E)-isomer ¹H NMR (400 MHz, CDCl₃): δ = 8.54 (m, 1H, H-2), 7.86 (m, H-4, H-8), 7.61 (m, 2H, H_o from C_γ-Ph), 5.60 (d, ³ J _β,γ = 9.9 Hz, 1H, H_β), 5.48 (d, ³ J _β,γ = 9.9 Hz, 1H, H_γ). Other signals in ¹H NMR were overlapped with signals of major isomer. Signals in ¹³C NMR were poor registrated due to the low concentration of isomer. IR (microlayer): 3200 (OH), 1621 (C C) cm⁻¹; HRMS (ESI): m/z calcd for C₂₄H₂₀NO₂ ⁺ [M + H]⁺: 354.1494; found: 354.1496.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Appendix A. Supplementary data

The following is the Supplementary data to this article: