Spiroacetalization

In transforming bis-ketone 45 to keto-epoxide 46, the elevated stereoselectivity was believed to be a consequence of tbe molecular shape — tbe sulfur ylide attacked preferentially from tbe convex face of the strongly puckered molecule of 45. Moreover, the pronounced chemoselectivity was attributed to tbe increased electropbilicity of the furanone versus the pyranone carbonyl, as a result of an inductive effect generated by tbe pair of spiroacetal oxygen substituents at tbe furanone a-position. ... 

Additions of silylated ketene acetals to lactones such as valerolactone in the presence of triphenylmethyl perchlorate in combination with either allyltrimethylsilane 82, trimethylsilyl cyanide 18, or triethylsilane 84b, to afford substituted cyclic ethers in high yields have already been discussed in Section 4.8. Aldehydes or ketones such as cyclohexanone condense in a modified Sakurai-cyclization with the silylated homoallylic alcohol 640 in the presence of TMSOTf 20, via 641, to give unsaturated cyclic spiro ethers 642 and HMDSO 7, whereas the 0,0-diethyllactone acetal 643 gives, with 640, the spiroacetal 644 and ethoxytrimethylsilane 13b [176-181]... 

Succinic anhydride is dimerised to 1,6-dioxaspiro [4.4] nonane-2,7-dione by heating with sodium hydroxide. Modification of an existing procedure by adding further sodium hydroxide after the initial reaction led to a severe exothermic reaction after heating for some 30 h which fused the glass flask to the heating mantle, probably at a temperature approaching 550°C. The reason for this was not known [1], At elevated temperatures and under influence of alkali, succinic acid condenses decarboxylatively beyond the dimeric spiroacetal, sometimes explosively. Contamination of the anhydride with base is to be avoided [2],... 

Alder (hDA) reaction <00CEJ3755> and the electrochemical oxidation of m-hydroxyalkyl tetrahydropyrans offers a different approach to spiroketals <00TL4383>. The synthesis and stereochemistry of insect derived spiroacetals has been reviewed <00S1956>. 

Pikho and co-workers50 found that nonanomeric [6,5]-spiroketals (having a pyranoside moiety with an equatorial CO acetal bond) can be formed under conditions of kinetic control. For instance, 62 undergoes acid catalyzed spiroacetalization giving the anomeric (most stable) acetal 63... 

In TaHe and Kocienski s total synthesis of lacrimin A (272), methoxyallene 268 was easily prepared via consecutive alkylations and subjected to acidic conditions to afford the presumed enone intermediates 269 and 270 (Scheme 19.48) [57]. Enone 269 underwent spontaneous spiroacetal formation to give a single stereoisomer 271 in 78% yield from 268. This compound was taken on to complete a total synthesis of lacrimin A (272). 

Recordings from Staphylininae [115] include 3-methylbutanal, the corresponding alcohol, and its acetate, various ketones such as 4-methyl-3-hexanone, 4-methyl-3-heptanone, 5-methyl-3-hexanone (and the corresponding alcohol), 2-heptanone, 6-methyl-2-heptanone, 6-methyl-5-hepten-2-one as well as methyl-cyclopentene and methylfuran. In addition, the secretions of Ontholestes murinus contain the spiroacetals (2S,6R,8S)-2,8-dimethyl-l,7-dioxaspiro[5,5]-... 

All 12 thermodynamically stable enantiomers and traces of a few of the less stable enantiomers of the spiroacetals 27-30 depicted in Fig. 7 are present in the secretion. This is the first identification in a mammal of spiroacetals previously... 

Fig. 7 Basic structures of the spiroacetals of which all the stable enantiomers were identified in the preorbital secretion of the red duiker... 

The oxidation of alkoxides instead of alcohols is an alternative to achieve the desired oxidation. A spiro-cyclization of (5) occurred, when it was electrolyzed in EtOH containing both EtONa and LiBF4 to afford 61% of the spiroacetal (6)... 

The spiroacetal morpholine work of Scheme 38 subsequently inspired research on the preparation of a novel family of morpholino-glycosides from sucrose via lead tetraacetate cleavage and reductive amination (Scheme 40). Significantly, the latter work, which was done with the present author, unveiled a completely new structural class of sweeteners, more intense than sucrose but having a similar taste profile. 

Scheme 38. The Chan, Hough, and Richardson s enantioselective synthesis of spiroacetal derivatives from the chloroethyl pyranoside derived from D-fructose (1984).

The synthesis of bis-spiroacetal ring systems has been discussed <99T7661>. An enantioselective synthesis of reveromycin B has been achieved <99JA456> and fungal metabolites containing a 1,8-dihydroxynaphthalene derived spiroacetal unit have been synthesised <99JCS(P1)1073,99JOC1092>. 

The alkylation of metalated imines, hydrazones, 4,5-dihydrooxazoles, 4,5-dihydroisoxazoles, 5,6-dihydro-4/7-1,2-oxazines and 2,5-dialkoxy-3,6-dihydropyrazines (i.e., azaenolates) is a commonly used method in asymmetric synthesis of enantiomerically enriched aldehydes, ketones, spiroacetals, amines, /J-oxo esters, carboxylic acids, lactones, 1,3-amino alcohols, /(-hydroxy ketones and amino acids. 

The cleavage of a,a -disubstituted SAMP- or RAMP-hydrazones to spiroacetals is performed without racemization under acidic conditions (4-methylbenzenesulfonic acid in chloroform) by careful monitoring of the reaction by thin layer chromatography and immediate workup of the reaction after completion in order to avoid racemization. Racemic mixtures are obtained when the reaction mixture is stirred for a longer time20. 

Research Focus Synthesis of polycarbonates, poly(acetal carbonate)s, poly(spiroacetal)s, polyesters, and polyurethanes using dihydroxyacetone. 

Martin et al. (289) utilized the chiral bicyclic lactone 88 for a total synthesis of (+)-phyllanthocin (Scheme 6.62). Cycloaddition of 88 to acetonitrile oxide, generated in situ from hydroximoyl chloride (89), furnished cycloadduct 90 in 45% yield together with other regio- and stereoisomers. After several steps, methyl glycoside (91) could be obtained. From this, reduction-hydrolysis gave the aldol that was subjected to acid-catalyzed spiroacetalization to produce spiroketal (92), and eventually (+)-phyllanthocin (93) after two additional steps (289). The... 

In addition to these, however, a number of interesting 1,3-dioxane-containing polymers have been obtained (B-77MI11105) from spiroacetals (150) derived from pentaeryth-ritol and functionalized aldehydes (Scheme 47). These and other related spiro-1,3-dioxane polymers have attracted interest as fiber- and film-formers and as biodegradable matrices for drug delivery systems. 

The cyclofunctionalization of cycloalkenyl systems where the chain containing the nucleophilic functionality is attached at one end of the double bond leads to spirocyclic structures. Cyclizations of cyclic and acyclic enol ethers to generate spiroacetals are shown in equations (66)168 and (67).169 These reactions generate the thermodynamically more stable products based on anomeric and steric factors.170 Spiroacetal products have also been obtained using isoxazolines as the nucleophilic functionality (cf. Table 14).l4lb Studies of steric and stereoelectronic control in selenoetherification reactions which form spirocyclic tetrahydrofurans have been reported.38 An interesting example of stereoelectronic control in the formation of a spirocyclic lactone has been reported in a recent mevinolin synthesis (equation 68).171... 

This process has found occasional use in the synthesis of heterocycles. The major product resulting from the reaction of MeLi on the dibromocarbene adduct (51) is the tetrahydrofuran (52), as shown in equation (105).189 In a novel approach to the synthesis of spiroacetal pheromones, caibene insertion into an acetal C—H bond was studied (equation 106).252 Unfortunately, the reaction proceeds in low yield and the approach is further hampered by the lack of stereocontrol in the ring opening of the cyclopropane. Carbene insertions into N—H and C—H bonds adjacent to nitrogen have been shown to give azabicyclo systems, as shown in equations (107) and (108).188... 

Building block 10 also contains a PMB piotecting group. The resulting simplification of the protection for the hydroxy groups required for spiroacetalization pcnniis simultaneous cleavage with the formation of 1... 

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