The Baylis-Hillman chemistry in aqueous media: a convenient synthesis of 2-methylenealkanoates and alkanenitriles

A convenient, general and efficient synthesis of 2-methylenealkanoates and alkanenitriles is accomplished via the regioselective nucleophilic (S<SUB>N</SUB>2') addition of hydride ion from NaBH<SUB>4</SUB> to (2Z)-2-(bromomethyl)alk-2-enoates and 2-(bromomethyl)alk-2-enenitriles respectively in the presence of DABCO in environment friendly aqueous media. Synthesis of two hypoglycemic agents is also described

An expedient, facile and simple one-pot synthesis of 2-methylenealkanoates and alkanenitriles from the Baylis-Hillman bromides in aqueous media

This protocol is for an expedient and operationally simple one-pot synthesis of 2-methylenealkanoates and alkanenitriles in high yields from the corresponding Baylis-Hillman bromides. The reaction proceeds via the successive treatment with 1,4-diazabicyclo(2.2.2)octane (DABCO) for 15 min and sodium borohydride for 15 min in aqueous media [tetrahydrofuran (THF):H<SUB>2</SUB>O (1:1)] at room temperature

Baylis-Hillman chemistry: a novel synthesis of functionalized 1,4-pentadienes

A novel synthesis of functionalized 1,4-pentadienes via the reaction of acrylonitrile with allyl halides, derived from Baylis-Hillman adducts, in the presence of DABCO has been described, demonstrating for the first time the application of allyl halides as electrophiles in the Baylis-Hillman reaction

Stereoselective transformation of Baylis-Hillman adducts into (3E)-3-(alkoxymethyl)alk-3-en-2-ones

The pure (3E)-3-(methoxymethyl)alk-3-en-2-ones and (3E)-3-(ethoxymethyl)alk-3-en-2-ones are formed in the acid induced reaction of 4-hydroxy-3-methylenealkan-2-ones with methanol and ethanol, respectively

Applications of Baylis-Hillman chemistry: enantioselective synthesis of (-)-methyl 3-aryl-2-methylene-3-(prop-2-yn-1-yloxy)propanoates via chiral leaving group strategy

Asymmetric synthesis of (-)-methyl 3-aryl-2-methylene-3-(prop-2-yn-1-yloxy)propanoates in 25-40% enantiomeric purities via the reaction of methyl (2Z)-3-aryl-2-(bromomethyl)prop-2-enoates with prop-2-yn-1-ol in the presence of quinidine is described

Applications of Baylis-Hillman chemistry: one-pot convenient synthesis of functionalized (1H)-quinol-2-ones and quinolines

A simple synthesis of functionalized (1H)-quinol-2-ones and quinolines from the Baylis-Hillman adducts, i.e. alkyl 3-hydroxy-2-methylene-3-arylpropanoates and β-hydroxy-a-methylene-β-arylalkanones, respectively, has been described

A facile one-pot conversion of acetates of the Baylis-Hillman adducts to [E]-α-methylcinnamic acids

A simple and convenient stereoselective synthesis of [E]-α-methylcinnamic acids via the nucleophilic addition of hydride ion from sodium borohydride to methyl 3-acetoxy-3-aryl-2-methylenepropanoates followed by hydrolysis and crystallization is described. Efficacy of this methodology in the synthesis of [E]-p-(myristyloxy)-α-methylcinnamic acid, an active hypolipidemic agent, and [E]-p-(carbomethoxy)-α -methylcinnamic acid, a valuable synthon for an orally active serine protease inhibitor, is also demonstrated

Design, synthesis, and X-ray structural studies of BACE-1 inhibitors containing substituted 2-oxopiperazines as P1 '-P2 ' ligands

We report the design and synthesis of a series of BACE1 inhibitors incorporating mono- and bicyclic 6-substituted 2-oxopiperazines as novel P1â\u80² and P2â\u80² ligands and isophthalamide derivative as P2-P3 ligands. Among mono-substituted 2-oxopiperazines, inhibitor 5a with N-benzyl-2-oxopiperazine and isophthalamide showed potent BACE1 inhibitory activity (Ki = 2 nM). Inhibitor 5g, with N-benzyl-2-oxopiperazine and substituted indole-derived P2-ligand showed a reduction in potency. The X-ray crystal structure of 5g-bound BACE1 was determined and used to design a set of disubstituted 2-oxopiperazines and bicyclic derivatives that were subsequently investigated. Inhibitor 6j with an oxazolidinone derivative showed a BACE1 inhibitory activity of 23 nM and cellular EC50of 80 nM