1.3- Dioxolane 2- -, isomers

Chemicals responsible for odor in some PUR foams were synthesised by polymerisation of PO in CH2CI2 with Bp2(C2H )20 catalyst (114). The yield was 25% volatile material and 75% polymeric material. The 25% fraction consisted of dimethyldioxane isomers, dioxolane isomers, DPG, TPG, crown ethers, tetramers, pentamers, etc, and 2-ethy1-4,7-dimethyl-1,3,6-trioxacane (acetal of DPG and propionaldehyde). The latter compound is mainly responsible for the musty odor found in some PUR foams. This material is not formed under basic conditions but probably arises during the workup when acidic clays are used for catalyst removal. 

More sterically demanding ketones can influence the selectivity of dioxolane formation. For example, butane-1,2,4-triol reacts with 3-pentanone43 44 or 3,3-dimethoxypentane45 46 to give a mixture of the dioxolane 2SA and dioxane 28 5 in a ratio of 45 1 respectively [Scheme 3.28]. Enhanced preference for the dioxolane isomer is also observed in the reaction of 2-0-p-methoxybenzyl-t-threitol (29 1) with 3-pentanone [Scheme 3.29].47 48... 

Cyclooligomerization of substituted oxiranes has been found to be highly stereo-specific Cis-2,3-dimethyloxirane gave only one dioxolane-type dimer namely 2,cis-4,trans-5-trimethyl-2-ethyl-l,3-dioxolane isomer (plus other cyclic- and linear oligomers) ... 

The isopropylidenation of propane-l, 3 triols provides a very sensitive measure of the relative stability of various dioxolane isomers. For example, the preference for the formation of isopropylidene derivatives of secondary alcohols in propane-1,2,3-triols is illustrated by the isopropylidenatin in Scheme 3.32 in which the more highly substituted /rnn -dioxolane is favoured at equilibrium. Mulzer and co-workers showed that isomerisation occurred easily when the dioxolane 33 1 [Scheme 3.33] was treated with mineral acid to give the rm/i -dioxolane 33 2. However, attempted isomerisation of the diastereoisomeric dioxolane 33 3 failed to occur under similar conditions demonstrating the penalty incurred on formation of the less stable cu-dioxolane 33 4. The isomerisation of the /rn/i5-fused dioxolane 34 1 to the m-fused dioxolane 34.2 is driven by the relief of strain [Scheme 3.34]. According to MM2 calculations, the difference in total energy between the cis- and rmm-fused dioxolanes is ca. 5 kcal/mol. 

In some cases the formation of a dioxolane or dioxan -can result in the generation of a new stereogenic center, either with complete selectivity or as a mixture of the two possible isomers. Since the new center is removed on deprotection, it should not seriously complicate the use of those protective groups that generate a new stereogenic center. 

Unsaturated substituents of dioxolanes 36-38 and dioxanes 39-41 are prone to prototropic isomerization under the reaction conditions. According to IR spectroscopy, the isomer ratio in the reaction mixture depends on the temperature and duration of the experiment. However, in all cases, isomers with terminal acetylenic (36, 39) or allenic (37, 40) groups prevail. An attempt to displace the equilibrium toward the formation of disubstituted acetylene 41 by carrying out the reaction at a higher temperature (140°C) was unsuccessful From the reaction mixture, the diacetal of acetoacetaldehyde 42, formed via addition of propane-1,3-diol to unsaturated substituents of 1,3-dioxanes 39-41, was isolated (74ZOR953). 

To synthesize 3-substituted isoxazoles directly, Kochetkov and Khomutova have used the reaction of ethyleneacetals of )S-keto-aldehydes (readily available from jS-chlorovinylketones) with hydroxylamine. Owing to the comparative stability of the dioxolane group, this reaction yields unequivocally the pure 3-substituted isomers (22—>23). The use of noncyclic alkyl )S-ketoacetals in this reaction results in a mixture of 3- and 5-substituted isomers. ... 

Several titanium(IV) complexes are efficient and reliable Lewis acid catalysts and they have been applied to numerous reactions, especially in combination with the so-called TADDOL (a, a,a, a -tetraaryl-l,3-dioxolane-4,5-dimethanol) (22) ligands [53-55]. In the first study on normal electron-demand 1,3-dipolar cycloaddition reactions between nitrones and alkenes, which appeared in 1994, the catalytic reaction of a series of chiral TiCl2-TADDOLates on the reaction of nitrones 1 with al-kenoyloxazolidinones 19 was developed (Scheme 6.18) [56]. These substrates have turned out be the model system of choice for most studies on metal-catalyzed normal electron-demand 1,3-dipolar cycloaddition reactions of nitrones as it will appear from this chapter. When 10 mol% of the catalyst 23a was applied in the reaction depicted in Scheme 6.18 the reaction proceeded to give a yield of up to 94% ee after 20 h. The reaction led primarily to exo-21 and in the best case an endo/ exo ratio of 10 90 was obtained. The chiral information of the catalyst was transferred with a fair efficiency to the substrates as up to 60% ee of one of the isomers of exo3 was obtained [56]. 

O-Isopropylidene derivatives of carbohydrates form structural isomers from carbohydrates which themselves are epimers. Since structural isomers often fragment differently whereas epimers do not, mass spectra of these derivatives may permit interpretation in terms of stereochemistry. Although molecular-ion peaks are not observed, the molecular weight can be determined readily from a relatively intense M-CH/ peak, resulting from loss of a methyl radical from a 1, 3-dioxolane ring (12). 

Dioxolanes 39 derived from a, 3-unsaturated aldehydes react with nitrile oxides R2CNO to give the corresponding isoxazolines 40 with the 1,3-dioxolan-2-yl substituent in position 4 as main products, and their 5-isomers as minor products with good regioselectivity and synthetically useful yields. The corresponding... 

Under analogous conditions, carbonylation of chloral affords cis or trans 2,5-bis(trichloromethyl)-l,3-dioxolan-4-ones. The stereochemical outcome of the reactions can be controlled by the concentration of the employed sulfuric acid (90-99%) and the reaction time. The cis isomer is predominantly formed under more acidic conditions after 10 min (cis/trans 95/5 48% yield), whereas complete isomerization to the trans isomer (cisltrans 0/100 65% yield) takes place at lower acidity (90%) and prolonged reaction time (7 h) [63]. 

Optically active icco-nucleosides of type 1.1 of 2-nitromidazole were prepared from tartaric acid ester by conversion to the dioxolan followed by reduction and acylation to give 1154, which was converted to 1155. Its coupling and deacylation gave 1156 (94MIP1). All the optically active isomers showed a radiation-sensitization effect equivalent to that of the racemate. 

The slightly unexpected behaviour of the dioxolanes 9, i.e., alkylation of the enolate on the face syn to the substituents has also been observed with the tert-butyl thioester of (2R,4,V)-2-ferf-butyl-1,3-dioxolane-4-carboxylic acid (16)76-78. Treatment of 16 with 1 equivalent of LDA in tetrahy-drofuran. in the presence of HMPA and RX at —78 °C preferentially furnished the isomer 17. 

In the case of lactic acid and trimethylacetaldehyde the crude product is a ca. 4 1 mixture of the cis- and the trans-isomers, 4 and 5 (R = /-Bu). respectively75,77 from which pure 4 can be isolated with d.r. 98 2 after one recrystallization at — 78 °C11. Similarly, with 2-/er/-butyl-5-phenyl-1,3-dioxolan-4-one (1, Rl = C6H5 Rz = f-Bu) the crude product is already formed with a d.r. >99 1 75 77 in favor of the m-isomer, giving the pure cw-compound after recrystallization77,79. 

There have been a number of reports where alicyclic-bridged precursors underwent an IAAC reaction. Thus, the dioxolane (203b), formed from triflate (203a), cyclized in situ to a tricyclic triazoline (Scheme 63).113 Treatment of this triazoline with sodium ethoxide converted it to a diazopyrrolidine in 86% yield, which underwent smooth catalytic hydrogenation in 89% yield. The (Z)-azidoalkene (204), bridged by a (3-lactam, cyclized at 20 °C to triazoline (205).114 The triazoline (205) extruded nitrogen at 80 C providing a tricyclic aziridine. The ( )-isomer of (204) did not cyclize to a triazoline but instead produced an azirine, presumably via a nitrene intermediate. 

For sodium cyanoborohydride — hydrogen chloride reagent the direction of the reductive opening of the dioxolane acetals obeys the same rule, it depends on the stereochemistry at the asymetric, benzylidene acetal carbon [168, 169]. Methyl exo-2,3 4,6-di-0-benzylidene-a-D-mannopyranoside is cleaved in oxolane solution to give 50 % of the 3,6-di-O-benzyl derivative, which is also the major product in the reaction of methyl 3-0-benzyl-4,6-0-benzylidene-a-D-mannopyranoside. The 2-O-benzyl isomer (20) was cleaved nonselectively, indicating again the effect of the bulk of the C-3 substituent [169]. A compatibility of this reagent, as well as of borane — tri-... 

Among these, the d-alio derivative 48 is more stable toward acid hydrolysis than the L-gulo 49a and D-manno 49b isomers, which undergo deprotection with extreme ease under mild acid conditions owing to steric compression between the endo-dioxolane ring and the more stable 1,6-anhydro bond. 

Methylcyclopentene ozonide 51 can also be allylated via this S -type reaction forming in good yields a 3,5,5-trisubstituted dioxolane 65 as a single regioisomer constituted by two separate cis- (35% each) and two trans-(15% each) isomers. The assignments were confirmed by transformation of the secondary alcohol into the acetate 66 or by its oxidation with PDC to the corresponding ketone 67 (Scheme 15). 

---