Development of β-keto 1,3-dithianes as versatile intermediates for organic synthesis

Abstract

beta-Keto 1,3-dithianes can be generated by the double conjugate addition of dithiols to propargylic ketones, esters and aldehydes in excellent yields. As masked 1,3-dicarbonyl systems these substrates can be converted to a range of functionalised oxygen-containing heterocycles that can be used in natural product synthesis.

From 3,3,4,4-tetraethoxybutyne to carbohydrate mimics

“…As mentioned previously, Ley and coworkers have found that α,β-unsaturated alkynones generally undergo a double Michael addition and form 1,3-dithianes when treated with propane-1,3-dithiol under basic conditions [10]. Ketone 5, obtained in excellent yield by deketalization of 3,3,4,4-tetraethoxybutyne (Scheme 4), appears to be no exception to this rule and furnished 2-(3,3-diethoxy-2-oxopropyl)-1,3-dithiane (20) in excellent yield when reacted as outlined (Scheme 13).…”

“…Due to the reluctance of dithiane 22 to react even with aldehydes, it was decided to change strategy and follow a route involving protection of propargylic alcohols 8, deprotection of their ketal moiety to obtain the corresponding α,β-unsaturated alkynones, which were expected to undergo a double Michael addition and form 1,3-dithianes when treated with propane-1,3-dithiol under basic conditions [10]. As indicated by examples based on 4,4,5,5-tetraethoxypent-2-yn-1-ol (Scheme 14), this approach appeared to be successful provided the right protecting group was used.…”

“…In a similar fashion, the ketal moiety was anticipated to give the keto function, which conceivably could be transformed to a methylene group or secondary and tertiary alcohols, or afford hemiketals under the proper conditions (routes f and g). Finally, on the basis of the work of Ley and coworkers [10], it was also envisaged that 4, after having been converted to the corresponding conjugated acetylenic ketone, would undergo a double Michael addition when treated with propane-1,3-dithiol under basic conditions and give 2-substituted 1,3-ditiethanes (route h), which conceivably could be converted to 2,2-disubstituted 1,3-ditiethanes by treatment with butyllithium followed by an alkylating agent [11].…”

Dihydrosulfenylation of Alkynes with Thiols Using a Nickel Catalyst through a Radical Process

“…[2,3] On the other hand, a convenient synthesis of dithioacetals from alkynes is quite limited. [5,6,7] As a general rule, the reaction of alkynes with thiols usually affords the corresponding vinyl sulfides in excellent yields. [8,9] Although monohydrosulfenylation proceeds smoothly, dihydrosulfenylation is only slightly promoted.…”

On the PPh3 catalyzed reaction between dibenzoylacetylene and vicinal -OH and -SH acids. One-pot synthesis of 1,3-dioxolane derivative

“…On the other hand, different products are obtained from the reaction between activated alkynes and trivalent phosphorus nucleophiles in the presence of a proton source such as an alcohol or thiol [4]. The dithiol addition chemistry provides a useful general and versatile method to generate sulfur-containing compounds [5,6].…”