The Nazarov Reaction of 1‐Acryloyl‐1,3,5‐cycloheptatriene; a Novel Synthetic Pathway from 1,3,5‐Cycloheptatriene to Dihydro‐1(2H)‐azulenone

Abstract

The title compound, l-acryloyl-1,3,5-cycloheptatriene (3), phosphoric acid and formic acid at room temp. produced was prepared from 1,3,5-~ycloheptatriene in four steps, and 3,8-dihydro-l(2H)-azulenone (6) and 3,3a-dihydro-l(2H)-subsequently its Nazarov cyclization of 3 was studied in or-azulenone (7) in yields of 46 and 13% respectively. Using der to develop a novel synthetic pathway to dihydro-l(2H)-stannic chloride as the acid in the reaction gave 6 and 7 in a azulenone. While the reaction of 3 in sulfuric acid afforded slightly better combined yield. 1-tetralone (5) in a low yield, the reaction in a mixture of The Nazarov reaction ['] is an electrocyclization involving the distribution of 4 7t electrons along a five-carbon atom chain. In the case of the ring closure of 3-hydroxypentadienylic cations, generated commonly from divinyl ketone derivatives in the presence of a protic or Lewis acid, this leads specifically to cyclopentenone derivatives. Because of its applicability to a wide variety of substrates, this reaction is one of the most convenient methods for constructing cyclopentenone-annelated carbocycles. L2] It is puzzling that, whilst there are several methods for the preparation of the azulene ~keleton, [~] has not yet been reported. In view of the synthetic importance of dihydroazulenones, we have directed our interests toward development of a new synthetic pathway to these compounds. Herein we describe both the convenient synthesis of 1 -acryloyl-1,3,5-cycloheptatriene (3) and its Nazarov reaction, resulting in the formation of two new dihydroazulenones. Results and DiscussionAmong several possible isomers for the purpose we chose l-acryloyl-1,3,5-cycloheptatriene (3) as a substrate for the Nazarov reaction. This choice was made from viewpoint of synthetic accessibility (vide infra). It was prepared in three steps starting from l-acetyl-l,3,5-cycloheptatriene (l), which is readily available in a large quantities via the Results of the Nazarov cyclization of 3 are summarized in Table 1. Attempts to carry out the reaction in the presence of sulfuric acid met with little success; in methanol the addition product 4 was obtained in a yield of 81 'YO, and in sulfuric acid 1-tetralone (5) was formed as the sole isolable product in a yield of 10%. Under less acidic conditions the expected products were obtained; in a mixture of phosphoric acid and formic acid at room temp. 3 gave the 3,8-and 3,3a-dihydro-l(2H)-azulenones (6 and 7) in yields of 46% and 13%, respectively. We have also examined the use of Lewis acids in the reaction instead of protic acids. While using stannic chloride in dichloromethane as the solvent at 0°C gave 6 and 7, in yields of 47% and 27% respectively, the reactions in the presence of other Lewis acids, such as boron trifluoride -diethyl ether, aluminium chloride and ferric chloride at 0°C gave a complex mixture of products, which included dihydroazulenones and 1-tetralone.The structures of 6 and 7 were supported by their spectroscopic data, and comparison of this data with that of

An Efficient Synthetic Pathway from Cyclohepta-1,3,5-triene to 2,3-Disubstituted 1,2,3,8-Tetrahydroazulen-1-ones

“…IR (film): ν =1720s, 1650s, 1590s, 1300s, 1250s, 1230s, 1150s, 1130s cm Ð1 . 1 -3-phenyl-1,2,3,8-tetrahydroazulen-1-one (4a…”

“…Reaction of 1-acetylcyclohepta-1,3,5-triene ( 1 ), which can be easily prepared from cyclohepta-1,3,5-triene by FriedelÐCrafts acylation, 8 with diethyl carbonate in the presence of sodium hydride gave the ester derivative 2 in 77 % yield. The Knoevenagel condensation of 2 with aryl aldehydes under the influence of piperidine and p -toluenesulfonic acid 9 gave the arylidene derivatives 3aÐd in good yields (81Ð93%).…”

“…The formation of the sole product in the Nazarov cyclizations of 3aÐd was a contrast to the case of 1-acryloylcyclohepta-1,3,5-triene which gave two double bond regioisomers under similar conditions. 1 In various examples of the Nazarov cyclization, the reaction of substitued divinyl ketones gives the thermodynamically favored double bond regioisomer, i.e., the more highly substituted cyclopentenone. 6 The result of this study, therefore, belongs to one of the typical examples in which only one of the regioisomers is formed.…”

“…Particularly, the formation of the sole product in the cyclization and the short step sequence from cyclohepta-1,3,5-triene to azulenones gain an advantage over our previous result. 1 Also, in view of the fact that various kinds of aldehyde can be employed in the Knoevenagel condensation of 2 and that further alkylation at the 2 position of 4 is a promising method for introducing suitable alkyl substituents, the present method is applicable for synthesizing a wide variety of azulen-1-one derivatives.…”

“…After drying (MgSO 4 ) and removal of the solvent, the residue was purified by column chromatography (silica gel; hexane/EtOAc, 7:3) to give 182 mg of 4a (73%) as colorless leaflets; mp 97Ð98¡C. IR (KBr): ν = 1735s, 1690s, 1150s, 705s cm Ð1 1. H NMR: δ = 1.29 (t, J = 7.2 Hz, 3 H), 2.79 (dd, J = 14.4, 6.4 Hz, 1 H), 2.88 (dd, J = 14.4, 6.4 Hz, 1 H), 3.45 (d, J = 2.8 Hz, 1 H), 4.22 (q, J = 7.2 Hz, 2 H), 4.48 (d, J = 2.8 Hz, 1 H), 5.71 (dt, J = 10.0, 6.4 Hz, 1 H), 6.17 (dd, J = 10.0, 6.0 Hz, 1 H), 6.35 (d, J = 11.2 Hz, 1 H), 6.71 (dd, J = 11.2, 6.4 Hz, 1 H), 7.07 (d, J = 7.2 Hz, 2 H), 7.29 (m, 3 H).…”