A simple two steps ytterbium triflate‐catalysed preparation of 2,2‐dimethyl‐2h‐chromenes from salicylaldehydes and 2‐methylpropene

Abstract

The preparation of various 2,2-dimethyl-2H-chromenes was achieved in two steps via an ytterbium triflate-catalysed reaction between salicylaldehydes, trimethylorthoformate and 2-methylpropene. From salicylaldehyde, two reaction products were characterised: 4-methoxy-2,2-dimethylchroman and 2-(1,3-dimethoxy-3-methylbutyl)phenol. The former compound probably results from a Lewis acid-catalysed [2+4] cycloaddition between the intermediate quinonemethide and 2-methylpropene whereas the latter may occur via a reaction related to a carbonyl-ene reaction between the quinonemethide and 2-methylpropene. Both compounds were subjected to a catalytic acidic treatment leading to 2,2-dimethyl-2H-chromene. Starting from various salicylaldehydes, the scope of this method was investigated.J. Heterocyclic Chem., 43, 1605Chem., 43, (2006.In the course of synthesis of biologically active chromene derivatives, [1] our attention was drawn [2] to a patent [3] reporting a simple preparation of 2,2-dimethyl-2H-chromene (2) using a reaction between salicylaldehyde (1) and 2-methylpropene catalysed by acidic silicaalumina catalysts at 150 °C or zinc chloride at 75°C. More recently [4], the preparation of furo[2,3-b]benzopyran 5 was achieved in excellent yield using the ytterbium triflate-catalysed reaction between salicylaldehyde (1), trimethylorthoformate and dihydrofuran 4. As illustrated in Scheme 1, this reaction is an example [5][6][7][8][9][10][11] We wish to report here the synthesis of various 2,2-dimethylchromenes via an ytterbium triflate-catalysed reaction between salicylaldehydes, trimethylorthoformate and 2-methylpropene.From the overnight reaction between salicylaldehyde (1), trimethylorthoformate, 2-methylpropene and ytterbium triflate in a sealed flask at room temperature, we could isolate and characterise compounds 6 and 7 in 27 and 14% yield respectively. In a control experiment, compound 6 was subjected to the reaction conditions but no ring opening into 7 took place. Moreover, from salicylaldehyde (1), no reaction was seen if trimethylorthoformate was omitted. From the results of these negative control experiments, we suggest that compound 7 occurs via a reaction related to a carbonylene reaction between the o-quinonemethide intermediate 3 and 2-methylpropene followed by a methanol addition on the resulting double bond. Carbonyl-ene reactions catalysed by lanthanide triflate have been reported [13,14] and an example of a competition between this reaction and a Diels-Alder cycloaddition was also observed [13]. An excellent review describes all the reactions that can be catalysed by lanthanides triflates [15]. As related intramolecular cycloadditions have been reported previously [9], including an iodine-catalysed example [10], we also tried iodine on our substrates but without success. In order to obtain the corresponding chromene, compounds 6 and 7 were heated to reflux in toluene in the presence of a catalytic amount of p-toluenesulfonic acid (PTSA). It is noteworthy that allowing the resulting methanol to distil fr...

Simultaneous Synthesis of Both Rings of Chromenes via a Benzannulation/o-Quinone Methide Formation/Electrocyclization Cascade

“…2 Nearly all of the methods for the synthesis of chromenes involve the closure of the pyran ring on a substrate containing a pre-formed phenol unit of the type 2 . Recent representative methods include Claisen rearrangement 3 or electrophile induced cyclization of aryl propargyl ethers, 4 palladium-catalyzed 5 and selenium-mediated 2a cyclization of 2-butenylphenols, ring closing metathesis, 6 cyclization of salicylaldehydes with enamines, 7 Wittig olefination, 8 Petasis reaction of salicylaldehydes 9 and the reaction of salicylaldehydes with vinyltrifluoroborates, 10 palladium catalyzed oxidative cyclization of aryl-3-butenyl ethers, 11 ene 12 and Baylis-Hillman 13 reactions of salicylaldehydes, ylide induced annulation, 14 enolization of vinylquinones, 15 cyclization onto 3,4-epoxy alcohols, 16 the reactions of phenols with α, β-unsaturated aldehydes, 17 the oxa-Michael-aldol/Henry reaction of salicylaldehydes 18 and the dehydrative cyclizations of 2-(1-hydroxy-2-propenyl)phenols. 19 Of all the methods of the myriad, to the best of our knowledge, there is not a single one in which both rings of the chromene core are constructed at the same time.…”

Antimycobacterial Benzofuro[3,2-f]chromenes from a 5-Bromochromen-6-ol

“…4 We have reported an approach addressing this issue, the synthesis of the chromene ring system by an ytterbium triflate catalysed reaction between isobutene and various salicylaldehydes via the corresponding quinonemethides formed in situ. 6 In the course of this work, we observed that 2,5-dihydroxybenzaldehyde gave the corresponding chromene in low yield, along with unidentified side products. We also found more recently that, under the same reaction conditions, the readily available 2-bromo-3,6dihydroxybenzaldehyde (3) 7 led to the corresponding 5bromo-2,2-dimethyl-2H-chromen-6-ol (4) in 65% yield.…”

“…A previously described procedure was followed: 6 In a 300-mL thick bottle tube fitted with a PTFE-faced screw-cap, 2-bromo-3,6dihydroxybenzaldehyde 7 (3; 4.00 g, 29.0 mmol) was dissolved in CH 2 Cl 2 (185 mL). HC(OMe) 3 (4.25 mL, 37.7 mmol) and Yb(OTf) 3 •xH 2 O (0.78 g, 1.3 mmol) were then added.…”

“…14 g (65%). NMR (400 MHz, CDCl 3 ): d = 1.44 (s, 6 H, CH 3 ), 5.18 (s, 1 H, OH), 5.76 (d, J = 9.9 Hz, 1 H, H-3), 6.60 (d, J = 9.9 Hz, 1 H, H-4),6.71 (d, J = 8.7 Hz, 1 H, H-7), 6.83 (d, J = 8.7 Hz, 1 H, H-8) 13. C NMR (100 MHz, CDCl 3 ): d = 27.7, 76.0, 109.4, 115.5, 117.0, 121.3, 121.5, 133.5, 146.9, 147.6.…”

Applications of alkyl orthoesters as valuable substrates in organic transformations, focusing on reaction media

“…On the other hand, aldehydes including hydroxyl functional groups at the 3- and 5-positions could not be fully isolated because other unidentified compounds were formed with similar polarity that prevented a complete purification. 374 …”