4- alkyl-l,3-dioxanes

TABLE 9.2 Activation Energy of Forming 4-alkyl-l, 3-Dioxanes and Some Peculiarities of Electronic Structure of the Corresponding TS (lc-5c). 

Due to the analysis of the calculated data of the transition states structure of 4-alkyl-l,3-dioxane formation from formaldehyde oligomers and al-kenes, it is found that 1,3-dioxane structures are formed in the result of direct isomerization of re-cation on the first stage. A free o-cation formation is not observed here. 

The analysis of the IRC procedure results (i.e., Fig. 10.5 IRC plot for isobutylene) allows to estimate the degree of synchrony in adding FD by the double bond. To fulfill it, there were found the structures where the second bond order 01-C3 of 1,3-dioxane cycle becomes quite a appreciable value on the way of transforming transition states (Ic-5c) in the corresponding 4-alkyl-l,3-dioxanes ld-5d). The synchrony degree was calculated by the method suggested in the article [22]. The values of the parameters considered are presented in Table 10.2. 

Other liquid-crystalline materials that have been investigated by X-ray scattering include single- and double-chained pyridinium [33] and N-substituted 4-(5-alkyl-l,3-dioxan-2-yl)pyridinium salts [34]. In the former case, diffraction analysis allowed an explanation for the differences in mono- and di-substituted salts to be proposed. 

In asymmetric Strecker synthesis ( + )-(45,55 )-5-amino-2,2-dimethyl-4-phenyl-l,3-dioxane has been introduced as an alternative chiral auxiliary47. The compound is readily accessible from (lS,25)-2-amino-l-phcnyl-l,3-propancdioI, an intermediate in the industrial production of chloramphenicol, by acctalization with acetone. This chiral amine reacts smoothly with methyl ketones of the arylalkyl47 or alkyl series48 and sodium cyanide, after addition of acetic acid, to afford a-methyl-a-amino nitriles in high yield and in diastereomerically pure form. 

Alkylations of 4-cyano-l,3-dioxanes (cyanohydrin acetonides) represent a highly practical approach to syn-l,3-diol synthesis. Herein we present a comprehensive summary of cyanohydrin acetonide chemistry, with particular emphasis on practical aspects of couplings, as well as their utility in natural product synthesis. Both 4-acetoxy-l,3-dioxanes and 4-lithio-1,3-dioxanes have emerged as interesting anri-l,3-diol synthons. The preparation and utility of these two synthons are described. 

While the steric explanation is consistent with the observed selectivity, it nonetheless presents an incomplete explanation, as alkylation of 2-methyl-4-cyano-l,3-dioxane 17 also proceeded with very high syn-selectivity [11] (Eq. 5). The selective equatorial alkylation can be rationalized as an anfz-anomeric effect that disfavors axial alkylation of the ketene iminate through filled-shell repulsion. Simple lithiated nitriles are known to exist as ketene iminates, but it would be easy to rationalize the preference for equatorial alkylation by considering the relative stability of hypothetical equatorial and axial alkyllithium reagents, vide infra. Preferential equatorial alkylation was also observed by Beau... 

Leahy demonstrated that unsaturation at the 5-position of a 4-cyano-l,3-dioxane can lead to a reversal in selectivity [12] (Eq. 6). Alkylation of cyanohydrin acetonide 19 with benzyl bromide generated a 9 1 mixture of 20 and 21, with the flufz-isomer 20 predominating, in 57% overall yield. An alkylithium intermediate in which overlap with the methylidene tt orbital favors the axial configuration could account for this anomalous selectivity. 

Later work examined substituent effects on kinetically controlled alkylations [68, 69] (Scheme 32). Substitution at the 5-position is well tolerated in these reactions. Reductive lithiation of a series of 4-phenylthio-l,3-dioxanes and quenching of the axial alkyllithium intermediate with dimethyl sulfate provided the flzzfz -l,3-diols in good yield, with essentially complete selectivity. 

The study of the transformation of 5-alkoxyalkyl-5-alkyl-l,3-dioxanes provided the first experimental evidence that the conformation of the reactant molecule plays a determining role regarding the direction of the catalytic reaction. The reason for the differing reaction directions clearly indicates that the conformers adsorb in different ways.32 The 5-alkoxyethyl isomers can exist in their chair conformations (1 and 2 in Scheme 4.12). The main reaction of the adsorbed surface species is the formation of an ester (3) by the rupture of the C-O bond in the ring. In one of the two isomers (1) the R2-0 group can also be adsorbed and this adsorption leads to a smaller ester molecule (4). 

The equilibria of the diasteromers of 2-Alk-2,4,6-tri-Me-l,3-dioxanes and 2-Ph-2,4,6-tri-Me-l,3-dioxanes were studied by equilibration (in ether at 25°C (78JA2202) (Scheme 12) the more bulky 2-Alk substituent goes into the equatorial position in line with well-known conformational principles [78ACSA(B)769 95H2233]. The configuration and conformation of a multitude of 5-alkyl-, 5,5-dialkyE, 2,2,-di-Me-5-alkyl-, and 2,2,4,5-tetra-Me-5-alkyl-l,3-dioxanes were studied by H NMR spectroscopy (75T489) the... 

Displacement of a phenylthio group by lithium using LiDBB at —78°C was found to be effective for the preparation of a /ra r-4-lithio-l,3-dioxane configurationally stable at that temperature. Reaction with alkyl halides with retention of the configuration afforded the /ra r-dioxanes with 99 1 selectivity. Equilibration of the trans-configurated 4-lithio-l,3-dioxane to the thermodynamically more stable r-derivative was achieved upon warming the solution to —20 °C. The transjcis-ratio was approximately 1 5. This ratio was also found after alkylation with alkyl halides (Scheme 60) <1999JOC6849>. 

This reaction can also be used to convert 6-alkyl-l,3-dioxan-4-ones, available from P-hydroxy carboxylic acids,2 to ryn-l,3-diols. 

Dialkylzincs undergo formal substitution with 4-acetoxy-6-alkyl-l,3-dioxanes in the presence of trimethylsilyl triflate (TMSOTf) with excellent diastereoselectivity (Equations (61) and (62)).123,123a 123c The addition of TMSOTf triggers also the allylic substitution of glycal derivatives, providing the substitution product with excellent regio- and diastereoselectivity (Equation (63)). 

Comparison of the O-C-O with the S-C-S anomeric interaction has been effected (2, 4 ) as shown in Scheme 2. In this case one can tell, unequivocally, that the O-C-O anomeric effect is the larger, for the overall AG° in the two systems is nearly the same and from the known conformational energies of 2-alkyl-l,3-dioxanes and -1,3-dithianes (5) it is obvious that the countervailing... 

Scheme 5.2.28). Anticipated production of oxonium 133 leads to the C-1 alkylation products 134 and 135 in a 3 1 ratio, which can be rationalized via synclinal 136 and antiperiplanar 137, respectively. The lack of facial basis in the oxocarbenium 133 leads equally to attack from above and below the plane of the conjugated cation, yielding an additional pair of syn and anti adducts analogous to 134/135 in similar ratio (dr 4 1). In related fashion, Rychnovsky has described the allylation reactions of 4-acetoxy-l,3-dioxanes.43 The presence of the 5-methyl substituent in 138 requires treatment with reactive -2-butenyl tri-n-butylstannane, affording 139 as the major product (dr 4 1) via the antiperiplanar transition state arrangement analogous to 137. 

Treatment of 2,4,4-trimethyI-l,3-dioxan under acid conditions gave 5,6-dihydro-2,4-dimethylpyran, but related dioxans also gave some 2,3-dihydro-pyrans. Dihalogenocarbenes, generated by phase-transfer catalysis, effect a regiospecific insertion reaction in 1,3-dioxans (317 R — H, alkyl, or aryl), giving (318). When the methylene-1,3-dioxan (319) is treated with s-butyl-... 

A report has appeared of the H n.m.r. spectra of some 4-methyl-6-alkyl-and 4,5,5-trimethyl-6-alkyl-l, 3-dioxans with and without methylation at C-2. The authors suggested that 2,2-r-4-trimethyl-/-6-t-butyl-l,3-dioxan (12) is in a twist conformation. 

Alkyl-l,3-dioxane derivatives are acetals and are generated in an equilibrium mixture from 2-alkylpropan-1,3-diols, 4.1, and aldehydes (Scheme 4) and the yield of product is optimized by azeotropic removal of water from the reaction mixture. A cis-/trans-mixture of products, with the tranj-isomer predominating, is obtained and repeated recrystallization gives the pure traus-products 4.2 in 50-60% yield [55-57]. The 1,3-oxathiane, 4.3, [58, 59] and 1,3-dithiane, 4.4, [57, 59-61] analogues of 1.3, dioxanes... 

DialkyIzincs couple with 4-acetoxy-l,3-dioxane (49) in the presence of (la) to form 4-alkyl-1,3-dioxanes (50) with good to excellent trans diastereoselectivity [88]. A variety of functionalities can be introduced because of the stability of the C-Zn bond. The diastereoface selectivity is reasonably explained by the kinetically favored... 

Dioxans - Several syntheses of this ring are notable. In a modification of the Prins reaction, self-condensation of aliphatic aldehydes with styrene has given 4-phenyl-l,3-dioxans [such as ( 195)] in which the alkyl group is in the equatorial position. Good yields of the 1,3-dioxin-4-ones (196 and R alkyl or aryl) have been obtained by reaction of aldehydes or ketones with diketene and Aliquat 336 (MeN[ (CHa ) Me] 3CI) Condensation of... 

Cyclic Esters of Phosphorous Acid.—A large number of 2-substituted-4-methyl-l,3,2-dioxaphospholans (88) have been prepared and their stereochemistry and conformations investigated by 1H and 31P n.m.r.69 Unlike the corresponding 1,3-dioxans, the tra/w-isomer (88a) is favoured in all cases, and each isomer is best described in terms of two rapidly equilibrating half-chair conformers with the 4-alkyl group pseudo-axial or pseudo-equatorial. 

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