Chiral Quaternary Ammoniums Derived from Dehydroabietylamine: Synthesis and Application to Alkynylation of Isatin Derivatives Catalyzed by Silver

Abstract

Abietic acid and its derivatives have broadly been used in fine chemicals and are renewable resources. Its inherent chiral rigid tricyclic phenanthrene skeleton is unique. Its utilities in asymmetric catalysis remain to be explored. A series new amide-type chiral quaternary ammoniums bearing dehydroabietylamine were designed, and prepared by two convenient steps. Acylation of dehydroabietylamine with bromoacetyl chloride afforded amide holding bromoacetyl group in higher yields using triethyl amine as base. Subsequent quaternization reaction gave the desired amide-type chiral quaternary ammoniums. The new chiral quaternary ammoniums can be used as phase-transfer catalyst (PTC) for the transition metal-catalysed alkynylation of isatin derivatives.

Enantioselective Synthesis of Chiral 3‐Alkynyl‐3‐Hydroxyindolin‐ 2‐Ones by Zn/bis(Sulfonamide)‐Diamine Catalyzed Asymmetric Addition of Alkynes to Isatins

“…In 2016, Liu reported an asymmetric alkynalation of isatins catalyzed by a CuI/guanidine catalyst [12a] . Followed by this pioneered work, vairous efficent catalytic systems were developed, such as CuI/chiral phosphine ligand, [12b] CuOTf/bisoxazolidine, [12c] CuOTf/chiral aminophenol sulfonamide ligand, [12d] AgOAc/chiral phase‐transfer catalyst, [12e,f] AgBF 4 /bifunctional amidophosphine‐urea catalyst [12g] and Co(OAc) 2 /bisoxazolinephosphine catalyst [12h] . Besides, our group coined a Zn(OTf) 2 /chiral hydroxyl oxazoline ligand catalyst system to catalyze the generation of 3‐alkynyl‐3‐hydroxy‐2‐oxindoles [12i] .…”

Alkynylation of Isatin Derivatives Catalyzed by a Silver–Chiral Quaternary Ammonium Salt Derived from Quinine

“…It was found that N-benzyl isatin 2k can be employed in this transformation, affording the corresponding products 4ka and 4kb in high yields with good enantioselectivities. The mechanism of this Ag-catalyzed alkynylation of isatin derivatives was proposed on the basis of the experimental results as well as a working hypothesis from the literature, 12,13,15 as shown in Scheme 3. We speculated that a silver alkynilide ion pair intermediate A with a chiral quaternary ammonium catalyst (Q + Br − ) can be formed by the coordination of terminal alkyne 3a with Ag(I) and deprotonation.…”

“…■ EXPERIMENTAL SECTION General Information. 1 H and 13 C NMR data were acquired on a Bruker AV-500 MHz spectrometer. HRMS were obtained from an Agilent 6520 Q-TOF LC/MS instrument.…”

“…(R)-3-Hydroxy-1-(4-methoxybenzyl)-3-(phenylethynyl)indolin-2one (4aa). Silica gel column chromatography (10/1 petroleum ether/ AcOEt) gave 4aa as a white solid (60.5 mg, 82%): mp 160−162 °C; 1 H NMR (500 MHz, CDCl 3 ) δ 7.60 (d, J = 7.4 Hz, 1H), 7.46 (d, J = 6.6 Hz, 2H), 7.38−7.20 (m, 6H), 7.12 (t, J = 7.5 Hz, 1H), 6.85 (d, J = 8.3 Hz, 2H), 6.75 (d, J = 7.9 Hz, 1H), 4.87 (s, 2H), 3.77 (s, 3H), 3.63 (s, 1H); 13 C{ 1 H} NMR (126 MHz, CDCl 3 ) δ 174.0, 159. 2, 142.2, 132.1, 130.4, 129.1, 128.8, 128.6, 128.3, 127.0, 124.8, 123.7, 121.6, 114.3, 110.0, 86.5, 82.0, 69.6, 55.3, 43.7 2one (4ab).…”

“…(R)-3-[(4-Ethylphenyl)ethynyl]-3-hydroxy-1-(4-methoxybenzyl)indolin-2-one (4ac). Silica gel column chromatography (10/1 petroleum ether/AcOEt) gave 4ac as a white solid (61.9 mg, 78%): mp 158−160 °C; 1 H NMR (500 MHz, CDCl 3 ) δ 7.60 (d, J = 7.4 Hz, 1H), 7.37 (d, J = 7.9 Hz, 2H), 7.26−7.23 (m, 3H), 7.11 (t, J = 8.1 Hz, 3H), 6.84 (d, J = 8.6 Hz, 2H), 6.74 (d, J = 7.9 Hz, 1H), 4.86 (s, 2H), 3.76 (s, 3H), 3.66 (s, 1H), 2.63 (q, J = 7.6 Hz, 2H), 1.21 (t, J = 7.6 Hz, 3H); 13 C{ 1 H} NMR (126 MHz, CDCl 3 ) δ 174.1, 159. 2, 145.6, 142.2, 132.1, 130.3, 129.0, 128.6, 127.8, 127.1, 124.8, 123.7, 118.7, 114.3, 109.9, 86.8, 84.8, 69.6, 55.3, 43.6, 28.8, 15. Reaction conditions: isatin 5 (0.2 mmol), phenylacetylene 6a (0.4 mmol), a base (0.4 mmol), 5 mol % metal catalyst, 5.5 mol % PTC, and a solvent (2 mL) at 60 °C for t h. b Isolated yield.…”