Dianions of glyoxylic acid thioketals: conventent α-keto acid equivalents

Abstract

. Can. J. Chem. 58,716 (1980). By varying the solvent, reaction temperature, and bases (i.e., gegenions present), optimum conditions for the alkylation of the dianions of glyoxylic acid derivatives 8 and 9 were established. It was found that the easily prepared, thermally stable, tetrahydrofuran-soluble potassium dianion of bis(ethy1thio)acetic acid was readily alkylated by alkyl halides. tosylates, epoxides, and N-tosyl aziridines. The latter alkylation is being used to develop a possible cytochalasin synthesis.The alkylated products may be readily converted into the corresponding a-keto acids or methyl 2,2-bismethoxycarboxylates. Chem. 58,716 (1980). On a etabli des conditions ideales d'alkylation des dianions de derives 8 et 9 de l'acide glyoxylique en faisant varier le solvant, la temperature et les bases (i.e., ions opposes). On a trouve que le dianion de potassium de l'acide bis(ethylthi0) acetique, soluble dans le tetrahydrofuranne que l'on peut preparer facilement et qui est thermiquement stable, peut &re alkyle facilement par les halogenures d'alkyles, les tosylates, les epoxydes et les N-tosyl-aziridines. On utilise la derniere alkylation pour developper une synthese realisable de la cytochalasine. Les produits alkyles peuvent etre transformes facilement en acides u cetoniques correspondants ou en carboxylates de bismethoxy-2,2 de methyle.[Traduit par le journal]In connection with a preliminary investigation directed at a synthesis of the microbial metabolites cytochalasins A, B, and F (1, 2)2 we required a glyoxylic acid (ester) anion equivalent (3).3 Our strategy involves alkylation of such an anion with an aziridine unit 1 which incorporates the chirality at C-3 of the cytochalasins, eventually followed by lactam formation to give compound 2. This inter-mediate contains an oxygen function at what will eventually become the C-9 position of the target molecules, and thus overcomes a possible difficulty arising from attempted oxidation at this hindered position later in the synthesis (2g). Cleavage of the aziridine by a nucleophile will result in a developing negative charge on the nitrogen atom. To facilitate the opening of the aziridine, the group R1 (attached to nitrogen) should thus be capable of stabilizing this negative charge, and in addition should not itself be very susceptible to nucleophilic attack. Thep-toluenesulphonyl group appeared to fulfil the necessary criteria (4).4 L-Phenylalanine was converted to the corresponding chiral amino alcohol ( 5 ) , which was subsequently ditosylated and cyclized to the desired crystalline chiral aziridine derivative B (R' = p-MeC,H,SO,-) which was used in our subsequent studies.The glyoxylic acid (ester) anion equivalent should possess a number of characteristics: ready availability, ease of preparation, high reactivity, and thermal stability. In addition, alkylation of this synthon should proceed in high yield to give a product which is stable and easily puj-ified and yet is readily convertible into the desired a-keto acid (ester). An investigation of t...

Studies on the Asymmetric Oxidation of Ester Derivatives of 1,3-Dithiane-2-carboxylates. Asymmetric Synthesis of trans-1,3-Dithiane 1,3-Dioxide

“…A range of esters of 1,3-dithiane-2-carboxylic acid were required for a study of the asymmetric oxidation process. The methyl ester 3 was prepared by a literature procedure, and the ethyl ester 4 was commercially available.…”

Anodic Oxidation of Dithiane Carboxylic Acids: A Rapid and Mild Way to Access Functionalized Orthoesters

“…Dithiane carboxylic acid 1, a bench stable crystalline solid, is readily prepared, on large scale, by treating glyoxylic acid 4 with 1,3-propanedithiol in the presence of a catalytic amount of PTSA (Scheme 3). 25…”

“…17,23,24 Dithiane carboxylic acid 1, a bench-stable crystalline solid, is readily prepared, on a large scale, by treating glyoxylic acid 4 with 1,3-propanedithiol in the presence of a catalytic amount of PTSA (Scheme 3). 25 The synthesis of the alkylated electrolysis precursors 5 is simple and rapid, with high yields obtained. This can be achieved in several ways.…”

Ring-opening reaction of Bus- and SES-protected aziridines using lithiated dithianes

“…[1][2][3] As an alternative method, nucleophilic ring opening of N-p-toluenesufonyl (=Ts) aziridine using lithiated dithianes has been reported. [4][5][6][7][8][9][10][11][12] The latter methodology is advantageous for several reasons: (1) because the carbonyl group is masked in the product, undesirable side reactions such as self-aldol condensation are suppressed. (2) The amino group in the product is protected by a p-tosyl group.…”