Stereoselective synthesis of vitamin

These topics are discussed in more detail in other chapters of this text. Formally, the pyrolytic elimination of sulphur dioxide from a sulphone, with the concomitant formation of a new carbon-carbon bond, constitutes a reduction at sulphur. These reductions have been valuable in the formation of new molecules, especially macrocycles and cyclophanes, and have been reviewed by Vogtle and Rossa205. Pyrolytic elimination of sulphur dioxide has been used by Julia and co workers in the formation of mixtures of isoprenoids206, and by Takayama and collaborators in the stereoselective synthesis of vitamin D, 19-alkanoic acids207. 

Fig. 13.17. Alkenylation of a dienylboronic acid with an iodinated triene stereoselective synthesis of vitamin A. The enyne (top left) is added to catecholborane to prepare the tra/rs-configured boronic ester in a chemoselective fashion. The latter affords trans-dienylboronic acid A upon acid-catalyzed hydrolysis.

A highly (>98%) stereoselective synthesis of vitamin A [116a, 127] employing an alkyne ZMA-Pd-catalyzed alkenylation protocol (Eq. (1), Scheme 3.27) was followed by an exceedingly efficient and selective synthesis of fS- and y-carotenes [116a] (Eqs. (2) and (3), Scheme 3.27). In the latter, the use of ( )-ICH=CHBr as a two-carbon linchpin should be noted. Although no rigorous comparisons were attempted, the overall superiority of the Pd-catalyzed alkenylation route over the conventional carbonyl olefination route [128] appears to be rather clear. 

A -tritylaziridine-2-(5)-carboxaldehyde. The application of a novel, sequential, trans-acetalation oxonium ene cyclization has delivered a stereoselective synthesis of the C-aromatic taxane skeleton, and a combinatorial sequence of the regioselective propiolate-ene, catalytic enantioselective epoxidation and carbonyl-ene cyclization reactions has been used to complete the synthesis of the A-ring of a vitamin D hybrid analogue. 

Some examples of the synthetic value of the Eschenmoser fragmentation should be given. Kocienski s economical and highly stereoselective synthesis of both endo- and exo-brevicomin (140) uses the alky-none (139) as an intermediate, easily accessible by fragmentation of the keto epoxide (138 Scheme 45). Stevens used this fragmentation during the course of studies on the synthesis of vitamin B12 precursors. 

These ylids are classified as semi-stabilised or of intermediate reactivity, and their stereoselectivity may be poor.43 If the stereochemistry of the double bond in the ylid (from 167) is E, this is generally retained in the product, but if it is Z, as in the ylid derived from 170, low temperatures are needed to stop rotation at the allyl ylid stage. At -25 °C less than 5% -171 is formed in the synthesis of vitamin D metabolites.44 The stereochemistry of the new double bond is generally not well controlled, 1 1 ratios of E Z are not uncommon, but Vedejs finds that phosphonium salts such as 172 with two phenyl and two allyl groups give good yields of T-dicncs45 such as 173. 

A high degree of (E)-selectivity is observed in the synthesis of the vitamin D precursor (237) from a Wittig reaction of bromomethylene-phosphonium ylide with the corresponding ketone. 23 xhe chiral ylide (238) has been used to introduce the side chain in a stereoselective synthesis of the 25-hydroxyergost-22-ene derivative (239) which can be converted to various hydroxylated vitamin D2 analogues. 24... 

Isopropylidene glyceraldehyde 305 submitted to orthoester rearrangement was used by Suzuki in the initial steps of the synthesis of intermediate 333 leading to vitamin Dj [74] (Scheme 6.54). Still in the field of vitamin D, a stereoselective synthesis of steroid side chain and CD rings has been described by Takahashi and Tsuji [75]. Triethylorthohexenoate 335 was used as an orthoester. The stereochemical control of carbon fi to ester was good but as in other cases the a center was obtained as a mixture of diastereomers in ester 336 (Scheme 6.54). 

The total synthesis of vitamin Bn is arguably the most difficult challenge so far presented to synthetic organic chemists. It is therefore surprising that the application of a photocyclization reaction to a solution of this problem has escaped the attention of photochemistry reviewers. Irradiation of the optically active seco-corrin cadmium complex (120) in methanol gave the corrin (121), isolated as its Co complex, with a stereoselectivity of 95% (Scheme 38). Model... 

Numerous substrate variations can be explored as a com-plemoit to the ether transfer. Therefore, 1,1-disubstitution in the homoallylic alcohol starting material was envisioned as an avenue to access tertiary ethers. The synthesis of such fimctionahty from stereoselective C—O bond formation is rare. To access the issue of the stereoselective synthesis of calcitriol lactone, a major metabolite of vitamin D3 developed by Hoffmann-La Roche U.C. Riverside, Jonhson and Chan synthesized tertiary ethers in high stereocontrol through iodocyclization of the coiresponding tert-butyl carbonate 161 using Barlett s procedure (Scheme 37.32). ... 

The compatibility with different functional groups, the remarkable regio-and stereoselectivity, and the development of asymmetric procedures have made benzannulation an attractive methodology for the synthesis of natural products with densely functionalized quinoid or fused phenolic substructures [13-20], Some pertinent examples are the syntheses of vitamins K and E [17], and the production of anthracyclinones or naphtoquinone antibiotics [13, 14a, 15, 21]. 

Intramolecular cycloaddition of the nitrile oxide intermediate generated from the unsaturated oxime 221 was used for an evenmal synthesis of la,2p,25-trihydroxy-vitamin D3 (262) (Scheme 6.90). Oxime 221, prepared from tri-O-isopropyhdene-d-mannitol (220), was processed as usual to give isoxazoline 222 in good yield and with excellent stereoselectivity. Conversion of 222 to the aldol 223 proceeded in the normal manner and further elaboration gave the desired diene intermediate 224 (262). 

Few examples of total syntheses have been reported that involve an intramolecular nitrile oxide cycloaddition and ensuing reduction to an aminoalcohol. The very first example was reported by Confalone et al. (334) and involved a synthesis of the naturally occurring vitamin biotin (287). The nitro precursor 284 was easily prepared from cycloheptene. When treated with phenyl isocyanate-triethylamine, cycloaddition led to the all-cis-fused tricyclic isoxazoline 285 with high stereoselectivity (Scheme 6.102). Reduction with LiAlFLj afforded aminoalcohol 286 as a... 

The rigidity of the allene and its facile formation were imaginatively exploited in a synthesis of the vitamin E side chain alcohol, in which an overall transfer of 1,4 to 1,5 acyclic stereoselection process was achieved (Scheme 8).162... 

Acetals result from oxidative coupling of alcohols with electron-poor terminal olefins followed by a second, redox-neutral addition of alcohol [11-13]. Acrylonitrile (41) is converted to 3,3-dimethoxypropionitrile (42), an intermediate in the industrial synthesis of thiamin (vitamin Bl), by use of an alkyl nitrite oxidant [57]. A stereoselective acetalization was performed with methacrylates 43 to yield 44 with variable de [58]. Rare examples of intermolecular acetalization with nonactivated olefins are observed with chelating allyl and homoallyl amines and thioethers (45, give acetals 46) [46]. As opposed to intermolecular acetalizations, the intramolecular variety do not require activated olefins, but a suitable spatial relationship of hydroxy groups and the alkene[13]. Thus, Wacker oxidation of enediol 47 gave bicyclic acetal 48 as a precursor of a fluorinated analogue of the pheromone fron-talin[59]. 

Heathcock, C.H., Finkelstein, B.L., Jarvi, E.T., Radel, PA. and Hadley, C.R. (1988). 1,4-and 1,5-Stereoselection by sequential Aldol addition to a,6-unstaurated aldehydes followed by Claisen rearrangement. Application to total synthesis of the vitamin E side chain and the archaebacterial C40 diol. J. Org. Chem., 53,1922-1942. 

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