A short and versatile route to chiral spiroketal skeletons

Abstract

Different chiral spiroketal skeletons are obtained, in a versatile manner, by iterative alkylations of acetone N,N-dimethylhydrazone with iodides 2 followed by a one-pot deprotection/spirocyclization sequence. This methodology has been applied successfully to the synthesis of 1,7-dioxaspiro[5.5]undecane and 1,6-dioxaspiro[4.5]decane system

Synthetic Approaches to Spiroaminals

“…Treatment of 74 with p ‐TsOH in methanol led, as expected, to deprotection of both dioxolane and oxazolidine moieties and promoted the spiroketalization in 63 % yield. As we had observed in the spiroketal series,30 two isomers 75 and 76 – resulting from a cyclization according to path B – were detected in a 8:17 ratio, each existing as a mixture of C‐5 or C‐6 epimers. However, in this aza series, the spiro[5.5]undecanes 76 existed in equilibrium with the spiro[4.5]decanes 75 , and their separation could not be achieved 29b…”

N,N-Dialkylhydrazones in Organic Synthesis. From Simple N,N-Dimethylhydrazones to Supported Chiral Auxiliaries

“…A one-pot acidic deprotection/spirocyclization sequence (Amberlyst 15, MeOH) provided spiroketal 44. 107 The same convergent approach via a double alkylation of acetone N,N-dimethylhydrazone was also used for synthesis of a spiroheterocycle, 1-oxa-7-azaspiro[5.5]undecane (45). 108…”

Synthesis of 5,6- and 6,6-Spirocyclic Compounds

“…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][23][24][25][26][27][28], hydrazones [29], oximes [30], nitriles [31], or dihalomethylene species [32][33][34], cross-metathesis/hydroboration/oxidation [35], iterative substitution of a xanthate [36], dihydroxylation/desymmetrization of alkenes [37], Horner-Wadsworth-Emmons olefinations [38,39], allylmetallations [40], and alkyne-alkyne cross-coupling [41] have also been reported.…”