1,2,4-Dithiazolidine-3,5-dione as an isocyanate equivalent in the Mitsunobu reaction

Abstract

Dithiazolidine-3,5-dione 1 can be used as a nitrogen nucleophile in a modified Mitsunobu procedure to give N-alkylated products 2 which can be converted via isocyanates, into amine derivatives, under very mild conditions.

Recent Advances in the Mitsunobu Reaction: Modified Reagents and the Quest for Chromatography‐Free Separation

“…[54] Triphenylphosphane-cyclic sulfonamide betaine (11, Figure 7) [55] gives better results for the synthesis of alkyl aryl ethers than Ph 3 P with DEAD or DIAD. [55,56] This reagent is especially useful for reactions where sensitivity of the heterocyclic substrates such as thiazolidine-2,4-dione [57] or 1,2,4-dithiazolidine-3,5-dione [58] precludes the use of traditional reagents. The betaine 11 reduces the number of components in the reaction mixture and flash chromatography is sufficient for product purification.…”

“…The betaine 11 reduces the number of components in the reaction mixture and flash chromatography is sufficient for product purification. [55,58] Applications of (cyanomethylene)trialkyl-or triphenylphosphoranes (12, Figure 7), spearheaded by Itô and Tsunoda, have extended CϪC bond formation reactions. [4e,41,42,59,60] With the use of cyanomethylenetrimethylphosphorane 12 (R ϭ Me) primary and secondary alcohols can be transformed into nitriles with acetone cyanohydrin, [41] primary alcohols can be converted into amines [61] or into one-carbon-atom extended nitriles, [62] and primary, secondary, and tertiary alcohols can be used for alkylation of 1H-indole and 9H-carbazole derivatives.…”

The Mitsunobu reaction in the chemistry of nitrogen-containing heterocyclic compounds. The formation of heterocyclic systems (review)

“…The diazepanone 106 is formed with a yield of only 32%, while the main product is the bicyclic compound 107 in the form of a mixture of diastereomers in a ratio of 15 The synthesis of tetrahydrodiazepinopurines, which are analogs of the marine alkaloids asmarines and have antitumor activity, was reported [18]. Closure of the diazepine ring was achieved under Mitsunobu reaction conditions.…”

“…The betaine 8 proved particularly effective for substrates sensitive to phosphines [17,18]. -+ A large number of oxidation-reduction systems that facilitate the isolation of the product from the reaction mixture have also been proposed [7,19].…”

Phosphines and Related Tervalent Phosphorus Systems

“…550 The betaine (186) has been used in a modified Mitsunobu procedure with 1,2,4-dithiazolidine-3,5dione as the source of the nucleophile in reactions with alcohols to give the related N-alkyldithiazolidinones, which are easily transformed into amine derivatives under very mild conditions. 551 The Staudinger reaction of phosphines with azides to form aza-ylides, R 3 P¼NR, has found widespread use in synthetic organic chemistry. However, in recent years, the potential of the reaction as a highly chemoselective ligation method in chemical biology for the synthesis of bioconjugates has started to be recognised, the reaction being applicable even in living cells.…”