New chiral ligands based on (+)-α-pinene

Abstract

A number of new chiral ligands were synthesized starting from an accessible monoterpene, (+)-α-pinene. The new ligands were used in the vanadium-catalyzed oxidation of sulfides to chiral sufoxides. R 1 = R 3 = t-Bu, R 2 = H (a); R 1 = R 2 = R 3 = H (b); R 1 = 1,7,7-trimethylbicyclo[2.2.1]hept-2-yl, R 2 = H, R 3 = Me (c); R 1 = R 3 = CMe 2 Ph, R 2 = H (d); R 1 = R 2 = H, R 3 = NO 2 (e); R 1 = R 3 = NO 2 , R 2 = H (f); R 1 = R 2 = H, R 3 = OMe (g); R 1 = OMe, R 2 = R 3 = H (h); R 1 = R 3 = H, R 2 = NEt 2 (i); R 1 = Br, R 2 = H, R 3 = NO 2 (j).Optically active monoterpenes and their derivatives are widely used as source of chirality in asymmetric synthesis [1]. In the recent time, application of ligands derived from monoterpenes in asymmetric oxidation of prochiral sulfides to optically active sulfoxides has been reported [2-6]. Chiral sulfoxides play an important role in asymmetric synthesis [7,8], and many of these compounds exhibit strong biological activity [9].We recently synthesized a large series of new chiral Schiff bases Ia-Ij on the basis of an accessible monoterpene, α-pinene [3]. These compounds were used as ligands in vanadium-catalyzed asymmetric oxidation of sulfides. It was found that the largest enantiomeric excess (ee) in the oxidation of thioanisole (II) to sulfoxide III was attained in the presence of ligand Ia (ee 32%) [3] (Scheme 1). In the oxidation of sulfide V as precursor of effective antiulcer drug Esomeprazole (VI), the most efficient was ligand Ib (ee up to 31%)[4]. Hydrogenation of Schiff bases derived from chiral α-diamines and substituted salicylaldehydes gave the corresponding amines which were used as ligands in asymmetric oxidation of thioanisole (II). As a result, enantiomeric excess was raised to 95% (in the presence of initial Schiff bases enantiomeric excess did not exceed 20%) [10]. Although these data were not reproduced (the largest enantiomeric excess of sulfoxide III was 26% [11]), it is obvious that replacement of Schiff bases by the corresponding amines should affect the yield and enantioselectivity of the above transformations to an appreciable extent.The goal of the present work was to synthesize new chiral amines from Schiff bases derived from α-pinene, and estimate their potential as ligands in vanadiumcatalyzed asymmetric oxidation of sulfides. In addition to ligands Ia-Ij synthesized previously, by reaction of amino alcohol (-)-VII with 3-tert-butyl-2-hydroxy-5-(2-methoxyethyl)benzaldehyde (VIII) we obtained in quantitative yield new Schiff base Ik having a methoxyethyl group in the para position with respect to the phenolic hydroxy group (Scheme 2).By slow evaporation of a solution of compound Ia in chloroform we succeeded in obtaining for the first time single crystals of the corresponding hydrate, and the molecular and crystalline structure of Schiff base Ia was studied by X-ray analysis (Fig. 1). The hydroxyphenylmethylidene fragment C 3 N 1 C 12-18 is planar within ± 0.059 Å. The C 4 atom in the pinane fragment deviates from the C 2 C 3 C 5 C 6 plane by 0.180(...

Stereoselective Synthesis and Modelling‐Driven Optimisation of Carane‐Based Aminodiols and 1,3‐Oxazines as Catalysts for the Enantioselective Addition of Diethylzinc to Benzaldehyde

“…A large majority of these compounds is derived from readily available natural products, naturally occurring optically active monoterpenes being on obvious choice, because their chiral nature can determine the absolute configuration of the newly generated functional groups . A large variety of chiral amino alcohol ligands derived from monoterpenes such as (+)‐pulegone, α‐ and β‐pinene and fenchone camphor have been reported as successful chiral catalysts. Both monoterpene‐based 1,2‐ and 1,3‐amino alcohols have been demonstrated to be excellent catalysts in a wide range of stereoselective transformations, for example, the asymmetric alkylation of aldehydes by organozinc compounds, Pd‐catalysed allylation or alkylation, the stereoselective reduction of ketones or the synthesis of chiral sulfoxides …”

Chiral schiff bases synthesized from terpenes of pinane series in asymmetric metall complex oxidation of sulfides

“…One among the most effi cient and general synthetic procedures for the synthesis of optically active sulfoxides is the asymmetric metal complex oxidation of prochiral sulfi des. During recent years a constant attention was paid to the use as ligands in the asymmetric vanadium-catalyzed oxidation of sulfi des of compounds prepared from monoterpenoids [15][16][17][18][19][20][21][22] preferably with pinane skeleton [15][16][17][19][20][21].…”

“…One among the most effi cient and general synthetic procedures for the synthesis of optically active sulfoxides is the asymmetric metal complex oxidation of prochiral sulfi des. During recent years a constant attention was paid to the use as ligands in the asymmetric vanadium-catalyzed oxidation of sulfi des of compounds prepared from monoterpenoids [15][16][17][18][19][20][21][22] preferably with pinane skeleton [15][16][17][19][20][21].We showed recently [16] that the use of ligands Ia-Ic in the vanadium-catalyzed oxidation of methyl phenyl sulfi de (II) led to the formation of the corresponding sulfoxide III with the enantiomeric excess (ee) up to 32% (Scheme 1).The aim of this study was the synthesis of new ligands on the basis of the terpenoid of the pinane series, verbenol epoxide (V) and the investigation of the applicability of these ligands to the vanadium-catalyzed asymmetric Scheme 1.oxidation of several sulfi des as compared with the previously obtained ligands Ia-Ic.In the isomerization of verbenol epoxide (V) alongside diol VI and hydroxyketone VII α-hydroxyaldehyde VIII with a cyclopentane skeleton formed as a minor product [23-25] (Scheme 2). Although the confi guration at the atom C 6 was not established, it was shown [23] that the isomerization of epoxide V into compound VIII proceeded stereospecifi cally giving a single diastereomer.…”

Stereoselective Synthesis and Antiproliferative Activity of Monoterpene-Fused 2- Imino-1,3-oxazines

“…The transformation of enantiomerically purepinene to -amino acid derivatives such as 1,3-aminoalcohols was recently reported [3,10,15,16], and these synthons have proved to be useful chiral auxiliaries in the enantioselective synthesis of secondary alcohols or pharmacons, e.g. esomeprasol [17][18][19][20][21].…”