Synthesis of Trifluoromethyl-Substituted Arenes, Cyclohexenones and Pyran-4-ones by Cyclocondensation of 1,3-Bis(silyloxy)-1,3-butadienes with 4,4-Dimethoxy-1,1,1-trifluorobut-3-en-2-one: Influence of the Lewis Acid on the Product Distribution

Abstract

The TiCl(4)-mediated formal [3 + 3] cyclocondensation of 1,3-bis(trimethylsilyloxy)-1,3-butadienes with 4,4-dimethoxy-1,1,1-trifluorobut-3-en-2-one afforded a variety of functionalized 4-methoxy-6-(trifluoromethyl)salicylates and 3-methoxy-5-(trifluoromethyl)phenols with very good regioselectivity. The Me(3)SiOTf-mediated cyclization of 1,3-bis(trimethylsilyloxy)-1,3-butadienes, containing no substituent located at carbon atom C-4 of the diene (R(1) = H), resulted in the formation of trifluoromethyl-substituted pyran-4-ones. In contrast, trifluoromethylated cyclohexenones were formed when dienes were employed which do contain a substituent located at carbon C-4 (R(1) not equal H).

Synthesis of trifluoromethyl-substituted salicylates by cyclocondensation of 1,3-bis(silyloxy)-1,3-butadienes with 4,4-dimethylthio-1,1,1-trifluorobut-3-en-2-one

“…The terminal substituted diene 1h under AlCl 3 conditions gave the stable cyclohexenone 9h in 52% yield. Similar compounds have been observed earlier [9]. The X-ray crystal structure analysis of 9h allows to unambiguously prove the relative configuration of this molecule [16].…”

“…It should be emphasized that acetals 2 and 6 are quite similar in their reactivities with ammonia and primary amines [14], however, their reaction with 1,3-bis(silyl enol ethers) 1 gave completely different products. The reaction of 1 with dithioacetal 6 gave 4-(trifluoromethyl)salicylates 7, while the reaction of 1 with acetal 2 afforded 6-(trifluoromethyl)salicylates 3 [9].…”

“…In recent years, we have extended the scope of this chemistry and studied its application to the synthesis of a variety of functionalized arenes [5]. For example, formal [3+3] cyclocondensations of 1,3-bis(trimethylsilyloxy)-1,3-butadienes 1 with 3-alkoxy-1-alkyl-2-en-1-ones [6], 3-alkoxy-1-trifluoromethyl-2-en-1-ones [7], and related enones [8], in particular with 4,4-dimethoxy-1,1,1-trifluorobut-3-en-2-one 2 [9], to afford new aromatic compounds has been described. In most reactions developed so far, the products -functionalized salicylates -contain CF 3 group located at C-6 as in compounds 3.…”

2-(Trifluoromethyl)-4H-pyran-4-ones: Convenient, available and versatile building-blocks for regioselective syntheses of trifluoromethylated organic compounds

“…Reaction of 1,3-bis(silyloxy)-1,3-butadiene and some its derivatives 28 with 4,4-dimethoxy-1,1,1-trifluorobut-3-en-2-one 29 afforded CF 3 -pyrones 30 (12-69%) (Scheme 10) [21]. It was mentioned that the formation of 30 presumably proceeds through the formation of allylic cation A c c e p t e d M a n u s c r i p t …”

Atom-Economic Synthesis of 4-Pyrones from Diynones and Water

“…Particularly, phenoxans, funicones and rapicones possess potent anti-HIV actitivity ( Figure 1) [60][61][62]. In general, 4-pyrones are prepared via the well-known condensation cyclization reaction of carbonyl compounds with polystep reactions [63][64][65][66][67]. Additionally, a transformation of isoxazoles to substituted pyran-4-ones in the presence of Mo(CO)6 and HCO2H in a two-step procedure was established [68].…”