13-Dipolar cycloaddition 1.4- Dithianes

The use of chiral 2-alkylidene-l,3-dithiane 1,3-dioxides in asymmetric cycloaddition reactions has been demonstrated. A highly enantioselective synthesis of (—)-cispentacin by an intramolecular 1,3-dipolar cycloaddition was reported (Scheme 52) <20020L1227, 20030BC684>. 

The 3 + 2-cycloaddition of nitrile oxides to 2-crotyl-l,3-dithiane 1-oxides produces exclusively 5-acyldihydroisoxazoles.92 Lewis acid addition to 1,3-dipole cycloaddition reactions of mesityl nitrile oxide with a, /i-unsaturated 2-acyl-1,3-dithiane 1-oxides can reverse the sense of induced stereoselectivity.93 The 1,3-dipolar cycloaddition of 4-t-butylbenzonitrile oxide with 6A-acrylainido-6A-deoxy-/i-cyclodextrin (68) in aqueous solution favours the formation of the 4-substituted isoxazoline (69) rather than the 5-substituted regioisomer (Scheme 24).94 Tandem intramolecular cycloadditions of silyl nitronate, synthons of nitrile oxides, yield functionalized hydrofurans.95... 

Burn at Hoffmann-La Roche chose to couple the two monomeric units via an intramolecular Wadsworth-Emmons reaction rather than lactonization (see Scheme 4.16). Thus dithiane 70, obtained by formylation of the anion derived from 69, underwent a regiospecific 1,3 dipolar cycloaddition with acetonitrile oxide to afford isoxazoline 71. Dibal reduction to the related amino alcohol followed by optical resolution with D-camphorsulfonic acid led to the isolation... 

The requisite dihydroxyketones are commonly assembled via iterative aldol coupling reactions [1], but other methods including Nef reactions [17,18], acetylide additions [19, 20], 1,3-dipolar nitrile oxide cycloadditions [21], iterative alkylation of dithianes [22-28], hydrazones [29], oximes [30], nitriles [31], or dihalomethylene species [32-34], cross-metathesis/hydroboration/oxidation [35], iterative substitution of a xanthate [36], dihydroxylation/desymmetrization of alkenes [37], Homer-Wadsworth-Emmons olehnations [38, 39], allylmetallations [40], and alkyne-alkyne cross-coupling [41] have also been reported. 

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