Synthesis of Vitamin A via Sulfones: A C₁₅ Sulfone Route

Abstract

Reaction of vinyl-fl-ionol (1) [6] with the lithium or sodium salt of a sulfinic acid, essentially as described by Julia [5], gave the Cl5-sulfones 2 (a-k) 1) which on alkylation with l-acetoxy-3-chlormethyl-2-butene (3) [7] afforded the Czo-sulfones 4 (a-i) ; certain of these on base treatment furnished vitamin A (5). Table I lists the C15-and Czo-sulfones which were used in the present study.It was recognized at the onset that a major problem in this synthesis would be the elimination of the sulfinic acid from the Czo-sulfone. To this end we have explored some of the factors which were expected to influence the elimination reaction, namely electronic and steric factors associated with the sulfone group, as well as the effect of various bases and solvents.Preparation of Cis-Sulfones. -The C15-sulfones 2 were conveniently prepared[5] by reacting vinyl-fl-ionol (1) with the sodium or lithium salt of the sulfinic acid [S] in acetic acid. In general there was a rapid disappearance of starting material with the initial formation of several products, however, as the reaction proceeded, one of these was further converted into the all-tram primary sulfone which becomes the main product. Scheme 2 8 I 9By terminating the reaction at an early stage it was possible to isolate the primary all-trans-and Ag.10-cis-sulfones, 2 and 6 respectively (see Scheme 2). In addition, the 1)Numbering system: CIS and CZO refer to the isoprenoid skeleton.

Synthesis of 4-Nitrophenyl Sulfones and Application in the Modified Julia Olefination

“…It showed that 2,4-dinitrophenyl sulfone 1a was not suitable for the desired transformation, presumably due to an internal oxidation of the anion by the ortho nitro group that was also observed by Manchand et al 18 However, 4-nitrophenyl sulfones 1b-d were successfully applied in the modified Julia olefination (Scheme 1). Extensive investigations of different reaction conditions indicated that sodium hydride was the most efficient base for the reaction of unstabilized NP sulfone 1b and semistabilized NP sulfone 1c with aldehydes.…”

Allylic Sulfones Containing Triene Moieties as Key Synthons for Carotenoid Synthesis

“…The mixture was stirred for 30 min, and then bis(chloroallylic) sulfide 3 (2.53 g, 10.6 mmol) and NaI (3.81 g, 25.4 (d, J 10.6, 2 H); 6.06 (d, J 15.2, 2 H); 6.30 (dd, J 15.2, 10.6, 2 H); 7.43 ± 7.55 (m, 4 H); 7.55 ± 7.66 (m, 2 H); 7.73 ± 7.86 (m, 4 H). 15.9;16.9;17.7;25.7;26.5;28.1;37.5;40.1;63.8;110.0;121.8;123.8;124.7;124.8;126.2;128.8;129.1;131.7;133.2;133.5;137.7;140.9 [3,7,11,6,8,10,. Method A (Oxidation of 8).…”

“…608, respectively, according to the Karplus correlation [13]. Base-promoted anti-elimination of the H-atom and the PhSO 2 group then produced the (E)-CC bond at C(4) in conjugation with the other two CC bonds [7]. The (E)/(Z) stereoisomer ratios of the CC bond at C(2) in 7, however, deteriorated during this elimination process presumably due to an allylic migration of the anion at C(4), which might be formed under the harsh conditions in boiling EtOH.…”

“…Among the numerous approaches that have appeared in the literature to build the conjugated polyene chains of carotenoids [2], methods based on acetylide coupling/ partial hydrogenation [3] and Wittig olefination [4] have been the two main synthetic approaches. The Julia sulfone olefination protocol [5], which has been applied to retinol synthesis [6], is presumed to be the best method to produce double bonds with the (E)-configuration [7]. We have introduced the C 10 bis(chloroallylic) sulfide 3 as a stable substitute for the highly unstable 1,8-dichloro-2,7-dimethylocta-2,4,6-triene, and successfully accomplished total syntheses of b-carotene (1a) and lycopene (1b) based on the Julia sulfone-olefination protocol [8].…”

Synthesis of Configurational Isomers of Verbenyl Carboxylic Acid and Related Compounds

“…1. As the next synthetic strategy, a key intermediate which is assumed to produce an anion 7 ) useful for the generation of a C-C bond at the C-4 position of the pinene framework was considered. In our case, phenyl verbenyl sulfone 9 was adopted as the useful key intermediate.…”