Conformationally restricted analogues of both (S)-β-homoserine and (S)-aspartic acid from chiral 3-acylamino pyrrolidin-2-ones

Starting from chiral 3,4-trans-disubstituted pyrrolidin-2-ones 11a and 11b, obtained from a Baylis-Hillman adduct, conformationally restricted analogues of both (S)-β-homoserine, 17, and (S)-aspartic acid, 21, were synthesized, respectively, and these compounds are suitable either for introduction in peptidomimetics or for synthesis of novel β-foldamers.     

Organic reactions in water: an efficient one-pot synthesis of acyloxiranes from Baylis-Hillman adducts using hypervalent iodine

Treatment of Baylis-Hillman adducts with iodosobenzene (PhIO) in the presence of a catalytic amount of KBr in water at room temperature afforded the corresponding acyloxiranes in good yields.     

One-pot easy conversion of Baylis-Hillman adducts into carbamates of unsaturated β-amino acids

An easy, one-pot transformation of Baylis-Hillman adducts into carbamates of unsaturated β-amino acids, for example, 2-(aryl(methoxycarbonylamino)methyl)acrylic acid methyl esters 7 and 2-(methoxycarbonyl aminomethyl)-3-arylacrylic acid methyl esters 8 via reaction with the Burgess reagent is described.     

Stereoselective synthesis of functionalized pyroglutamates

Novel stereoselective synthesis of α-methylene-β-substituted pyroglutamates, and α-alkylidene-pyroglutamates has been achieved via substrate controlled asymmetric alkylation of l-threonine derived oxazole with Baylis-Hillman reaction based allyl bromides and acetates, respectively. The synthesized compounds were evaluated for their proteasome inhibition and cytotoxicity on multiple myeloma cells.     

Highly regio- and stereoselective synthesis of tricyclic frameworks using Baylis-Hillman derivatives

A simple and convenient synthetic route for the synthesis of tricyclic chromeno[4,3-b]pyrrolidine frameworks using Baylis-Hillman bromides involving in situ formation of an imine, decarboxylation and a [3+2] cycloaddition sequence is described.     

Base-free amination of BH acetates of 2-chloroquinolinyl-3-carboxaldehydes: a facile route to the synthesis of N-substituted-1,2-dihydrobenzo[b][1,8]naphthyridines

An efficient base-free one-pot synthesis of 1,2-dihydrobenzo[b][1,8]naphthyridines from BH acetates of 2-chloro-3-formylquinolines and activated alkenes followed by their acetylation, with different amines have been reported. These reactions are completed in very short time and provided the products in good to excellent yields. We further explored the scope of BH acetate with carbon nucleophile providing a new route to the synthesis of acridine derivative in excellent yield under mild condition.     

Direct one-pot introduction of 2-methylpyridines to Baylis-Hillman adducts via base-mediated 3-aza-Cope rearrangement

An efficient and regioselective introduction method of 2-methylpyridines to the secondary position of Baylis-Hillman adducts has been developed. A base treatment of 2-methylpyridinium salt of Baylis-Hillman bromide generated N-allylenamine intermediate which underwent a facile 3-aza-Cope rearrangement under mild conditions to produce the product.     

Reductive Heck cyclization versus δ-carbon elimination/decarboxylation: synthesis of dihydroindole and indoles from Baylis-Hillman adducts

Modified Baylis-Hillman adducts having 2-bromoaniline moiety at the primary position underwent Pd-mediated reductive Heck type cyclization to produce dihydroindole derivatives. The same starting materials can also be used for the synthesis of indole derivatives under slightly different conditions via the concomitant δ-carbon elimination and decarboxylation process.     

A concise α-amino acid-based synthetic approach to [1,4]oxazepin-2-ones from Baylis-Hillman adducts

An original two-step process for the synthesis of [1,4]oxazepin-2-ones starting from Baylis-Hillman (BH) adducts is reported. The protocol involves a nucleophilic substitution of the acetates of BH adducts with renewable natural α-amino esters followed by base-catalyzed intramolecular Michael addition. These sequential reactions are operationally simple, performed under ambient conditions, and give 81-93% yields of the target [1,4]oxazepin-2-ones. Thus, the present invention opens up a new aspect for the synthetic utility of BH adducts.     

Solid phase synthesis of allylic alcohols via the Baylis-Hillman reaction

An efficient method for the solid phase synthesis of allylic alcohols via the Baylis-Hillman reaction has been developed. In the presence of DABCO® or 3-quinuclidinol the coupling of resin bound acrylic acid with different aldehydes yields allylic alcohols. Aldehydes with different reactivity were used and gave modest to excellent yields upon simply varying the base or the reaction time. The allylic alcohols were reacted with primary amines to form 1,3-aminoalcohols.