Olefmic 1,3-diols

An efficient and highly enantio- and diastereoselective bromocycliza-tion-desymmetrization of olefmic 1,3-diols used a cyclic sulfide as catalyst. Olefmic 1,3-diols as substrates gave substituted THFs with up to three ste-reogenic centers, with two tetra-substituted carbons. This protocol represents the first case of a monofunctional C2-symmetric Lewis basic sulfide-catalyzed enantioselective bromoetherification reaction, which was applicable to the synthesis of a key intermediate to the orally active antifungal drug posaconazole (Noxafil) (14JA5627). 

An interesting application of the cydization of alkenyl thioacetals is the stereoselective preparation of olefmic diols. Thus, oxidative cleavage of the silicon—carbon bond [32] in the ring-closed metathesis products, i.e. cyclic allylsilanes such as 35 and 36, affords (Z)-alk-2-ene-1,5-diols 37 and 38 (Scheme 14.18) [33],... 

The procedure is outlined in Scheme 8.33, starting from the generic allylic alcohol 125. SAE on 125 would provide epoxide 126, which could easily be transformed into the unsaturated epoxy ester 127 by oxidation/Horner-Emmonds olefmation (two-carbon extension). This operation makes the oxirane carbon adjacent to the double bond more susceptible to nucleophilic attack by a hydride, so reductive opening (DIBAL) of 127 provides, with concomitant ester reduction, diol 128. Pro-... 

Transformation of diols to the corresponding olefins by sequential treatment with l,r-thiocarbonyldiimidazole and trimethylphosphite. Also known as Corey-Winter reductive elimination, or Corey-Winter reductive olefmation. 

Terminal olefins are easily hydrogenated. Their hydrogenation is much faster than the hydrogenation of double bonds in cyclic systems or internal double bonds. c/5-Olefms are hydrogenated faster than tran -olefins. Conjugated diole-... 

Reduction of the olefmic bond in 12 and Swem oxidation of the free carbinol function provided ketone 53, onto which installation of the methyl group was performed by reaction with methylmagnesium chloride in THF. After protection of the resulting tertiary alcohol as a TBS-ether, fully protected triol 54 was obtained with a useful 80% diastereomeric excess. Acetonide deblocking and oxidative fission of the diol formed led to aldehyde 55, ready for the planned cyclization step. Exposure of aldehyde 55 to TBSOTf/DIPEA reagent system smoothly resulted in formation of the desired bicyclic adducts 56 and 57 which were isolated in a 82% combined yield (60 40 ratio). 

The mixture was taken on further, and the PMB ether removed to form the corresponding diol (Scheme 16). After selective oxidation of the primary hydroxyl with IBX, a Wittig olefination was used to form the C13-C14 bond, completing the carbon skeleton of myriaporone 4. Once the (Z)-olefm was installed, the two diastereomers 45a and 45b were now easily separated and each diastereomer was taken on independently. 

The reaction conditions applied are usually heating the amine with a slight excess of aldehyde and a considerable.excess of 20-30% hydrochloric acid at 100 °C for a few hours, but much milder ( physiological ) conditions can be used with good success. Diols, olefmic double bonds, enol ethers, and glycosidic bonds survive a Pictet-Spengler reaction very well, since phenol and indole systems are much more reactive than any of these acid sensitive functional groups (W.M. Whaley, 1951 J.E.D. Barton, 1965 A.R. Battersby, 1969). 

The complexes AuCl(olefin) and Au2Cl4(olefm) ( = 1-3) are formed from AuCls, H[AuCl4], or Na[AuCl4] as a result of oxidation of excess olefin. Ketones, 1,2-dioles, jS-chloroalcohols, or chloroalkanes are the oxidation products. 

Prior to hydroboration of the olefmic double bond, the lactone carbonyl was reduced by diisobutyl aluminium hydride to the corresponding lactol which was treated with HCl in methanol to give the protected lactol (166). Hydroboration afforded the diol (167). The latter was oxidized to the diketone (168). Elaboration of the disphenol units was achieved in a two-step sequence. The diketone (168) was treated with LDA and the resulted di-anion was submitted to the M0O5PH reagent 104) to give in 35% yield the bis-a-hydroxy ketone (169), which was smoothly transformed with sodium methoxide in dimethylsulfoxide into diosphenol (170). Upon methylation (170) gave (171) which was selectively hydrolysed to the racemic neoquassin (172). Oxidation with Fetizon s reagent yielded racemic quassin. Overall yield from the enone (162) was more than 3%. 

Dehydrogenative lactonization of diols is an efficient way to various lactones (Scheme 22). ° The lactone formation is found to be catalyzed by a recoverable stable dicationic iridium complex with 6,6 -dihydroxy-2,2 -bipyridine ligands, and employs a variety of benzylic and aliphatic diols in aqueous media. In comparison with the esterification of hydroxyl acids, hydroacyloxylation of olefmic acids and Baeyer-ViUiger reaction of cyclic ketones, the dehydrogenative lactonization of diols proceeds without any oxidant hence, it is more environmentally benign and atom economical. 

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