Acid-catalyzed synthesis of functionalized arylthio cyclopropane carbaldehydes and ketones

Abstract

A general strategy for the synthesis of arylthio cyclopropyl carbaldehydes and ketones via acid catalysed arylthiol addition/ring contraction reaction sequence has been exploited. The procedure led to a wide panel of cyclopropyl carbonyl compounds in high yields and broad substrate scope.

Catalytic Tandem Friedel–Crafts Alkylation/C4–C3 Ring-Contraction Reaction: An Efficient Route for the Synthesis of Indolyl Cyclopropanecarbaldehydes and Ketones

“…On the basis of the above-described results, a plausible mechanism for the acid-catalyzed indole cyclopropanation reaction is proposed in Scheme . In our hypothesis, activation of cyclobutanone 1a by the acid catalyst favors the nucleophilic attack of 2a , leading to the formation of cyclobutane diol adduct I . , Subsequent acid-promoted C3–C4 ring contraction via carbocationic species II allows the attainment of carbaldehyde 3a…”

“…of cyclobutanone 1a by the acid catalyst favors the nucleophilic attack of 2a, leading to the formation of cyclobutane diol adduct I. 15,21 Subsequent acid-promoted C3−C4 ring contraction via carbocationic species II allows the attainment of carbaldehyde 3a. 22 Finally, in order to rationalize the formation of cyclobutanone species 4, carbaldehydes 3a,f,g,r,v,x were dissolved in toluene in the presence of TsOH (10 mol %) and reacted at 40 °C (Scheme 6).…”

“…In this context, a versatile one-pot catalytic procedure that is able to introduce a cyclopropane moiety chemoselectively would represent a significant advance for pharmaceutical purposes. We recently initiated studies on the preparation of cyclopropylcarbaldehydes and developed a tandem acid-catalyzed thiol addition/ring-contraction reaction of 2-hydroxycyclobutanones 1 . Continuing in this research field, we have successfully performed a new reaction between cyclobutanones 1 and a series of indoles 2 that furnishes indolylcyclopropyl carbonyl compounds with broad scope and high chemical yields.…”

“…To extend this protocol to the synthesis of more complex cyclopropyl derivatives, 2-functionalized hydroxycyclobutanones 1b – e were reacted with a series of indoles under the above-described operational conditions (Scheme ). Pleasingly, 1 H -indolylcyclopropyl ketones 5 were isolated in good to excellent yields after 8–24 h. Indeed, N -methylindole ( 2m ) was easily converted to the corresponding adducts 5mb and 5mc in 90% yield.…”

Z‐Selective Synthesis of α‐Sulfanyl Carbonyl Compounds from Internal Alkynes and Thiols via Photoredox Catalysis

“…In our mind, the development of a one-pot process that would allow us to obtain functionalized cyclobutanones in a single synthetic step starting from alkynes, appeared to be very attractive. [15] Therefore, we planned a series of experiments in which 1-phenylbutyne 1 a was submitted to photo-oxidation reactions (440 nm) in the presence of 4-chloro-benzene thiol 2 a and Eosin B (EB) (Scheme 1g). In these experimental conditions, we observed the formation of a sulfanyl-butenone derivative 3 aa in non-negligible yields (12%) while the main reaction product was represented by a 90:10 Z:E mixture of the alkene 4 a (37%).…”