Base‐Induced Trifluoroethanolysis of Acyclic Di‐ and Trihalogeno Ketones: Favorskii Rearrangement and [4+3] Cycloaddition

Abstract

Reactions of five acyclic dihalogeno‐ and trihalogeno ketones, representing the α,α‐, α,α′‐, α,α,α‐ and α,α,α′‐di‐ and trihalogeno substitution pattern, with sodium 2,2,2‐trifluoroethoxide in 2,2,2‐trifluoroethanol (NaTFE/TFE) in the presence of furan were investigated with the aim of obtaining [4+3] cycloadducts of the corresponding oxyallyl intermediates. Preference of Favorskii rearrangement over cycloaddition was observed with dichloromethyl isobutyl ketone (1a) and 1,3‐dibromobutan‐2‐one (12) that formed mainly the trifluoroethyl esters of 3‐chloro‐2‐isopropylpropanoic acid (9a), and (Z)‐but‐2‐enoic acid (isocrotonic acid) (13), respectively. 9a was dehydrohalogenated to form trifluoroethyl 3‐isopropylacrylate (11a). [4+3] Cycloaddition was favored with the 1,1,3‐trihalogenobutan‐2‐ones 24 and 25, leading to 2,4‐dihalogenated 8‐oxabicyclo[3.2.1]oct‐6‐en‐3‐ones (26, 27) as a mixture of endo‐exo‐stereoisomers. With trichloromethyl isobutyl ketone (30) the isomeric 2,4‐dichloro‐substituted oxabicycles (34) were formed in lithium perchlorate/diethyl ether/furan/triethylamine, while in NaTFE/TFE solvolytic displacement of one chloro substituent occurred, providing 2‐chloro‐4‐trifluoroethoxy‐4‐isopropyl‐8‐oxabicyclo[3.2.1]oct‐6‐en‐3‐one (36). By analogy, 27 reacted with sodium methoxide/methanol to form the methoxy‐substituted oxabicycles 39a and 39b. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

The α,α‐Dihalocarbonyl Building Blocks: An Avenue for New Reaction Development in Organic Synthesis

“…Fohlisch et al., described the [4+3] cycloaddition reactions of in situ generated oxyallyl intermediate 100 (2 π component) from α,α‐dihalo‐α′‐halocarbonyl compounds 101 and furan (4 π system) in basic medium to afforded the stereoselective endo ‐, endo ‐bicyclic products 102 a – 102 c (Scheme D). During the reaction, two regioisomeric oxyallyl cations 100 a and 100 b were generated, which are responsible for the formation of a mixture of stereoisomers.…”

Synthetic Approaches to Hydroazulenes and Guaianes through [4 + 3] Cycloadditions of Oxyallyl Intermediates

“…Obviously trichloro ketone 20 was reacting in the same manner as with unsubstituted furan. [44] The unstable (under these conditions) product could be identified as the 2,4-dichlorooxabicycle 21 by allowing the compounds to react at a lower temperature (0°C). With the goal of directing the reaction course towards the "stable" compound, we added 2 equiv.…”

Catalyst-free formation of 1,4-diketones by addition of silyl enolates to oxyallyl zwitterions in situ generated from α-haloketones

“…Under typical Favorskii rearrangement conditions (Scheme 3), 21 strong bases induce the formation of cyclopentanone intermediates XV from a-haloketones and then the ring-contracted product XVII, 22 XVIII,23 or XIX 24 is produced depending on the p-nucleophile we used. 26 It is well known that oxyallyl zwitterions 27 tend to react with enes either in a stepwise or a concerted fashion so as to generate the [4 + 3] 28 or [3 + 2] 29 cycloadducts (Scheme 4). However, in the presence of a weaker base, such as sodium bicarbonate, or without any bases, most of the starting material remains unreacted, and only a trace of the substituted product XX is detected.…”

“…25 It should be noted that both oxyallyl zwitterions and cyclopentanone intermediates are formed in the reaction of a-haloketones with furan using sodium 2,2,2-triuoroethoxide as a base in 2,2,2-triuoroethanol (NaTFE/TFE), and that the two corresponding types of products, the ring-contracted products (XVIII, Scheme 3) and the [4 + 3] cycloadducts (Scheme 4) are eventually generated. 26 It is well known that oxyallyl zwitterions 27 tend to react with enes either in a stepwise or a concerted fashion so as to generate the [4 + 3] 28 or [3 + 2] 29 cycloadducts (Scheme 4). However, several valuable interrupted cycloadditions of oxyallyl zwitterions have been reported in recent years.…”