Necic acid synthons. Part 2. Regioselectivity in the reactions of Z-2-bromomethyl-2-alkenoate esters with selected carbon nucleophiles

Abstract

The preparation of selected (Z) -2-bromomethyl-2-alkenoate esters and their subsequent reaction with acetoacetic ester-derived nucleophiles is described. Both the substrate structure and the solvent system have significant effects on the regioselectivity of these nucleophilic displacements.During the past few years there has been renewed interest in the preparation of necic acids *J and the development of a convenient ' general synthesis,' sufficiently versatile to afford closely related natural systems, as well as specific synthetic analogues, would be invaluable. Our interest in these compounds stems from a continuing study of Senecio alkaloids 4 * 5 and includes a recent description of the total synthesis of integerrinecic acid via ethyl 3-acetoxy-2-methylenebutanoate.'*t We now report the results of regioselectivity studies which clearly illustrate the potential of the title compounds as necic acid synthons.Bromination Studies.-Goldberg and Dreiding have obtained the (2)-bromo ester (4b) by treating the hydroxy ester (3b) with NBS-Me2S.'*$ We have found that reaction of the same hydroxy ester (3b) with conc. HBr-conc. H,SO, * at

A Mild Synthesis of New Aryl Vinyl Ethers and Diethyl 1-[(Alkyl)(cyano)methyl]vinylphosphonates via the Substitution of a 2,3-Difunctional Allyl Bromide

“…The development of new strategies for the synthesis of organic compounds containing an α -bromomethyl group as in product 1 continues to pose a challenge to organic chemists. It has resulted in a wide variety of applications in the preparation of several natural [ 1 – 4 ] as well as biologically active compounds [ 5 – 8 ]. Moreover, the utility of these versatile allyl brominated intermediates 1 [ 9 – 18 ] comes from their reaction with different nucleophilic species and additionally their ability to act as excellent Michael acceptors.…”

An effective new access to ethyl 2-[(alkylamino)(cyano)methyl] acrylates: first synthesis of ethyl 3-cyano-2-(hydroxymethyl) acrylate

“…Indeed, bromomethylation at the a position of these acrylic substrates reveals a range of useful products for organic synthesis, particularly in the preparation of natural [1][2][3][4] and biologically active compounds. [5][6][7][8] Bromomethylated esters of type 1 and their homologous difunctionalized products of type 2 are useful synthons in several synthetic applications.…”

Asymmetric chemo- and regiospecific addition of organozinc reagents to Baylis–Hillman derived allylic electrophiles

“…Compounds 2 are attractive as they are available in just two, chromatography-free, steps via known Baylis-Hillman chemistry (Scheme 1). 11 Additionally, bromination of 1 proceeds with very high (Z)-selectivity 12 to afford solid products which may be crystallised to high chemical and stereochemical purity. Simple mixture of THF solutions of 2 and ZnEt 2 in the presence of [Cu(MeCN) 4 ]BF 4 13 (3 mol%) at 220 °C leads to rapid formation of 4 (R = Et) as apparently the sole product (Scheme 1).…”