A-Pyrone sulfone

Posner and Kinter have demonstrated MAD-promoted highly stereoselective [4 + 2] cycloaddition under mild conditions in the asymmetric total synthesis of an A-ring precursor 171 to hormonally active la,25-dihydroxyvitamin D3 [172]. Reaction of a pyrone sulfone 168 and an enantiomerically pure vinyl ether 169 under the influence of MAD in toluene-CH2Cl2 at -45 °C for 12 h afforded cycloadduct 170 in 93 % isolated yield as a 98 2 ratio of the endo diastereomers. From 170, the synthesis of 171 required 13 steps and proceeded in 34.6 % overall yield as indicated in Sch. 133. 

The Chiron (-)-(lOa) was obtained with very high diastereoselectivity from a-pyrone sulfone and optically active vinyl ether (Scheme 69). This lactone was later used in the asymmetric synthesis of (-)-methyltriacetyl-4-epishikimate (10b). 3-Sulfonylnitroalkenes were also shown to be reactive alkyne equivalents in Diels-Alder reactions. ... 

Methanesulfonyl chloride reacts with enamino ketones (104), (e.g., 151) to give good yields of the enol sulfones (e.g., 152). The analogy with ketene addition to form a-pyrones (Section IV.A) is obvious. 

Diels-Alder reactions of thiete 1,1-dioxides occur readily as exemplified by the syntheses of 151 ° and 152. Adducts of thiete 1,1-dioxide with tetraphenylcyclopentadienone or a-pyrone ° are thermally unstable. Thiete 1,1-dioxides also undergo 1,3-dipolar additions with diazoalkanes, (e.g., the formation of 153 from which the strained bicyclic thietane sulfone 154 is obtained) " nitrile oxides, and cycloadditions with the MA -dimethylenamine of isobutyraldehyde (e.g., the formation of 155). ° ... 

Diels-Alder cycloadditions involving thiete sulfones as dienophiles occur with butadiene,cyclopentadiene, 1,2,3,4-tetraphenylcyclopentadiene, anthracene. tetraphenylcyclopentadienone, l,3-diphenyl-2H-cyclopenta[l]-phen-anthrene-2-one, a-pyrone, l-(Af,Af-dimethyl)- and l-(7V,A -diethyl)-l,3-butadiene, furan, 2,5-dimethylfuran, l,3-diphenylisobenzofuran, isobenzofuran," and l,3-diphenylnaphtho[2,3-c]furan. Generally, thiete... 

An interesting observation was reported by Posner who showed that a-pyrone substituted by a sulfoxide or a sulfone reacts rapidly with vinyl ethers, giving a diastereoselective [2 + 4] cycloaddition (Scheme 45). Racemic sulfide, sulfoxide or sulfone was introduced on a-pyrone via 3-cuprio-... 

Cycloaddition Yamamoto s MAD Lewis acid promoted very mild and highly stereocontrolled [4-1-2] cycloaddition between the pyrone sulfone and enantiomerically pure vinyl ether 56 by use of 50 mol% MAD, cycloadducts were isolated on a 1.5-g scale in 93% yield as a 98 2 ratio of endo diastereomers with 57 being a major isomer (Scheme 6.37) [59]. 

Stereochemical Control Element on the Dienophile. Pyrone sulfone 47 undergoes asymmetrical cycloaddition with a number of homochiral dienophiles at room temperature and gives modest to good diastereomeric excesses. The results, shown in Table 7, were best with benzylic vinyl ethers. This methodology was employed to synthesize (-)-methyl triacetyl-4-epishikimate and an A-ring precursor to la,25-dihydroxy vitamin Dj. ... 

Irradiation of 4,6-dimethyl-a-pyrone immobilized in a guanidinium-sulfonate-calixarene gives rise to a 4,6-dimethyl-Dewar-p-lactone, a carboxyl zwitterion and 1,3-dimethylcyclobutadiene, both in the solid crystalline state and in aqueous solution. Diarylmethyl carbocations have been generated within the cavities of non-protic zeolites (LiY, NaY, KY, RbY, CsY, and NaX) via laser-mediated decarboxylation of diarylacetic acids. 

Dimerization of sulfene yields disulfone 546, whose protons are readily replaced by deuterium, bromine, or trimethylsilyl groups. Sulfone 546 reacts with 2,6-dimethyl-4-pyrone to give an exo-methylene derivative and it may be tetra-methylated. Other disulfones are obtained by oxidation of 1,3-dithietanes with potassium permanganate or chromium trioxide-fuming nitric acid for resistant dithietanes. As mentioned above, peracetic acid oxidizes a disulfoxide, mono-sulfone, or a monosulfone-monosulfoxide to the disulfone 546. 57b,iii3a 2,2,4,4-Tetra(trifluoromethyl)-l,3-dithietane 537 is oxidized only to the monosulfone 547, even with chromium trioxide-hot, fuming nitric acid the disulfone is only... 

Reaction of sulfone pyrone 164c with enantiomerically pure vinyl ether (5)-355b in the presence of a Lewis add such as [4-Me-2,6-(r-Bu)2QH20]2-MeAl at -45°C in 1 1 toluene/methylene chloride gives the cycloadduct 356b in 93% yield as a 98 2 ratio of the endo diastereomers. This reaction is applied to the synthesis of la,25-dihydroxyvitamin D3 (354b) (90JOC3967). 

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