TBD‐Catalyzed Direct 5‐ and 6‐enolexo Aldolization of Ketoaldehydes

Abstract

Treatment of unfunctionalized acyclic ketoaldehydes with a catalytic amount of 1,5,7-triazabicyclo[4.4.0]dec-5-ene induces a direct intramolecular 5-and 6-enolexo aldolization, furnishing 2-ketocyclopentanols and 2-ketocyclohexanols in good-to-excellent yields.

Theoretical Mechanistic Study of the TBD-Catalyzed Intramolecular Aldol Reaction of Ketoaldehydes

“…6 The reactions performed with 8 mol % of TBD in THF at room temperature were complete after only 30 min and yielded 2-ketocyclopentanols and 2-ketocyclohexanols 3 in good to excellent yields as chromatographically separable trans/cis diastereoisomers. 6 Alternatively, such isomers could also be prepared in an indirect intramolecular aldol reaction of masked ketoaldehydes. However, these protocols are limited due to lengthy multistep procedures.…”

Lithiated anions derived from (alkenyl)pentamethyl phosphoric triamides: Useful synthons for the stereoselective synthesis of 9-oxo- and 10-hydroxy-2(E)-decenoic acids, important components of queen substance and royal jelly of honeybee Apis mellifera

“…In turn, the most convenient protocols leading to 8-hydroxy-octanal require: a) the use of 8-nonenoic acid as substrate, reduction of the carboxylic acid followed by hydroxylation of the terminal C]C and oxidative cleavage of the intermediate 1,2-diol [20] or b) selective bromination of octane-1,8-diol, protection of the free hydroxyl with THP group and oxidation at the halogenated carbon atom followed by deprotection [21]. Simple and efficient preparation of 7-oxooctanal and 8-hydroxy-octanal, their synthetic equivalents and analogues would not only facilitate the access to the pheromones 1 and 2 but also would be of great interest for the synthesis of cyclic compounds via intermolecular aldol reactions that use unmodified dialdehydes, ketoaldehydes and diketones [17,18,22].…”

“…An interesting solution is the copper catalyzed reaction to protected acrolein [16]. Most recent and effective syntheses of 7-oxo-octanal involve: a) preparation and reduction of 7-oxooctanoic acid to corresponding diol and oxidation with PCC [17]; b) preparation of 7,7-dimethoxy-heptanal followed by its methylenation, oxidation and deprotection [18] or c) the use of heptane-1,7-diol as substrate followed by its selective protection with THP group, and subsequent sequence oxidation, methylenation, oxidation and finally deprotection and again oxidation [19]. In turn, the most convenient protocols leading to 8-hydroxy-octanal require: a) the use of 8-nonenoic acid as substrate, reduction of the carboxylic acid followed by hydroxylation of the terminal C]C and oxidative cleavage of the intermediate 1,2-diol [20] or b) selective bromination of octane-1,8-diol, protection of the free hydroxyl with THP group and oxidation at the halogenated carbon atom followed by deprotection [21].…”

Synthesis of Tri-Arm Star Shaped 1, 3, 5-Triazines Catalyzed by 1,5,7-TRIAZABICYCLO[4.4.0] Dec-5-Ene (Tbd)

“…Among super bases, TBD has high pKa value (pKa = 24.97) and has been widely utilized in organic synthesis. 10 For example, it can promote diverse organic reactions including Wittig reaction, HornerWadsworth-Emmons reactions, 11 secondary amine alkylation, 12 carboxylation of propylene glycol with CO 2 , 13 synthesis of symmetrically N,N-substituted ureas, 14 5-and 6-enolexo aldolisation of acyclic ketoaldehydes, 15 intramolecular aldolization of acyclic ketoaldehydes 16 Techniques Mps were measured on an Electrothermal 9100 apparatus. 1 H-NMR and 13 C-NMR spectra were recorded on a Bruker 300 MHz instrument (Germany).…”