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

The efficient synthesis of orthogonally protected glycerols, 2-aminopropane-1,3-diols and 2-aminobutane-1,4-diols that can constitute useful tools in heterocyclic chemistry, is reported. These interesting tri-functionalized small synthons were easily prepared from serine or aspartic acid. In addition, these substrates can be readily transformed into their iodide derivatives in very good yields.

Pyridine derivatives R 0380A Rapid Access to the Spiroaminoketal Framework. -The efficient procedure opens the way to the construction of different spiroaminoketal types present in various natural compounds. -(TURSUN, A.; ABOAB, B.; MARTIN, A.-S.; SINIBALDI*, M.-E.; CANET, I.; Synlett 2005, 15, 2397-2399; Lab. Synth. Etud. Syst. Interet Biol., Univ. Blaise Pascal, F-63177 Aubiere, Fr.; Eng.) -Nuesgen 05-132

A convergent and stereoselective synthesis of 1-oxa-7-azaspiro[5.5]undecane is described. This functional new spiroheterocycle is readily available from acetone N,N-dimethylhydrazone via a double alkylation and subsequent spiroannulation process.Molecules possessing heterocycles fused by a spirocarbon atom are ubiquitous in nature, with many of them displaying interesting biological properties. 1,7-Dioxaspiro[5.5]undecane (6,6-spiroketal) moieties have received particular attention as they are found in a wide and diverse series of natural products such as polyether ionophores, marine alkaloids, or insect pheromones. Approaches for the elaboration of this ring system have been extensively reported in the literature. 1On the contrary, synthesis of spiroaminoketals, key intermediates in the preparation of biologically active compounds such as hydantocidin, 2 spironucleosides, 3 azaspiracid, 4 sanglifehrin, 5 or solanum alkaloids, 6 have been less explored. 7 As part of our continued interest in the synthesis of homochiral spiroheterocycles of biological interest, we wish to report herein an efficient approach to spiroaminoketal 1 using the spiroannulation methodology we have previously reported for the preparation of spiroketals 8a (Scheme 1).Our synthetic strategy lies in the use of iodides 3 and 4 as key precursors for the iterative alkylation of acetone N,Ndimethylhydrazone. 8b,c,d Upon synthesis of the dissymmetric ketone 2, cyclization should provide an efficient access to the [5.5]azaoxaspiranic core.Synthesis of (S)-3 has been previously reported. 8a Preparation of (S)-4 was accomplished from L-aspartic acid (Scheme 2). L-Aspartic acid was transformed by classical procedures into its N-Boc methylester 5 in two steps and 79% yield. The reduction of the carboxylic function of 5, via its activated ester, led efficiently to 6 9 (89% yield). Protection of the resulting alcohol using TBDPSCl in the presence of imidazole in CH 2 Cl 2 gave, nearly quantitatively, the tert-butyldiphenylsilyl ether 7. The ester function was then reduced by treatment with a 2 M solution of LiBH 4 in THF, resulting in the formation of alcohol 8 in 94% yield. Finally, conversion of 8 into the required iodide 4 10 was cleanly realized by treatment with iodine and triphenylphosphine/imidazole in toluene at room temperature in 82% yield. Thus (S)-4 was obtained in six steps and 54% overall yield from L-aspartic acid.With synthons 3 and 4 in hand, we then began the alkylation process (Scheme 3). We first used the experimental protocol developed for the synthesis of spiroketals, 8a namely: initial alkylation of acetone N,N-dimethylhydrazone using LDA as base and iodide (S)-3 followed by the second using BuLi as base and (S)-4. The first step resulted in quantitative formation of compound 9, however, and Scheme 2 Synthesis of iodide 4. Reagents and conditions: a) SOCl 2 , MeOH, -10°C then r.t., 25 min; b) (t-BuOCO) 2 O, Na 2 CO 3 , dioxane-H 2 O, r.t.,12 h; c) N-hydroxysuccinimide (1.2 equiv), DCC (1.2 equiv), CH 2 Cl 2 , r.t., 3 h, NaBH 4 (1.0...