Isopropylidene, formation

One instance where correlation with cuprammonium data appears possible is the reaction between adjacent cis glycol groups and acetone to form isopropylidene derivatives. Although data on the kinetics and equilibria of isopropylidene formation are too meager to prove that reactivity with acetone parallels reactivity with cuprammonium, isolated observations support such a supposition. Knauf, Hann, and Hudson12 have noted the ease of formation of the acetone derivatives of D-mannosan, and this is one of the substances most reactive toward cuprammonium.6 Tipson13 has noted that the optically active 2,3-butanediols react with acetone more readily than the meso form, and this is the order in which these substances react with cuprammonium.14... 

Diacetate Derivative, Isopropylidene Formation, and Mass Spectrometry. A particularly facile route to proof of structure of the glyceryl ether components is to use a combination of (a) purification by thin-layer chromatography and (b) separation into individual species of the isopropylidene or acetate derivatives by gas-liquid chromatography. As an example, the experimental protocol for examination of the diacetates will be described at this point and later that of the isopropylidene derivative. Inherent in such an experimental approach is to have synthetic standards of high purity available. It is possible to accomplish this task, but it is not necessarily quick and neat. The synthesis... 

Silylation, isopropylidene formation, and debenzylation gave compound 206 obtained from L-xylose (Scheme 27) and further transformed to ketophosphonate 187 by the same three steps. 

Activation of the disaccharide has been achieved via acetalization with isopropylidene formation followed by acylation using immobilized M miehei lipase (lipozyme IM-60) in the molten state. This technique has been utilized by Sarney and coworkers on numerous mono- and disaccharides, including glucose [49], sucrose [54], galactose [49], lactose [55], xylose [51], and maltose [55]. Regioselectivity was achieved at the 6 -OH position via isopropylidene intermediates to yield conversions of up to 80% in the monoester. Sarney and Vulfson [6] provide details for several routes of enzymatic synthesis in solvent free media via acetalization. Currently, the challenges of commercial manufacture by such a multi-step process has yet to justify the implementation of this methodology. 

A further improvement to the existing procedure involves the substitution of Tin(II) Chloride for the p-toluenesulfonic acid and 1,2-dimethoxyethane for DMF. Studies involving D-mannitol have shown that the tin(II) chloride does not act as a Lewis acid catalyst or as a source of HCl (by reaction with the hydroxy groups) since the use of zinc chloride under identical conditions gives no reaction. In this particular case, it was subsequently demonstrated that no catalyst is required and that isopropylidenation occurs under completely neutral conditions, presumably via acetal exchange. Tin(II) chloride has been used to catalyze isopropylidene formation in other carbohydrate systems. ... 

The formation of ethyl isopropylidene cyanoacetate is an example of the Knoevenagel reaction (see Discussion before Section IV,123). With higher ketones a mixture of ammonium acetate and acetic acid is an effective catalyst the water formed is removed by azeotropic distillation with benzene. The essential step in the reaction with aqueous potassium cyanide is the addition of the cyanide ion to the p-end of the ap-double bond ... 

O-isopropylidene derivative (57) must exist in pyridine solution in a conformation which favors anhydro-ring formation rather than elimination. Considerable degradation occurred when the 5-iodo derivative (63) was treated with silver fluoride in pyridine (36). The products, which were isolated in small yield, were identified as thymine and l-[2-(5-methylfuryl)]-thymine (65). This same compound (65) was formed in high yield when the 5 -mesylate 64 was treated with potassium tert-hx Xy -ate in dimethyl sulfoxide (16). The formation of 65 from 63 or 64 clearly involves the rearrangement of an intermediate 2, 4 -diene. In a different approach to the problem of introducing terminal unsaturation into pento-furanoid nucleosides, Robins and co-workers (32,37) have employed mild base catalyzed E2 elimination reactions. Thus, treatment of the 5 -tosylate (59) with potassium tert-butylate in tert-butyl alcohol afforded a high yield of the 4 -ene (60) (37). This reaction may proceed via the 2,5 ... 

The lower diastereoselectivity found with aldehyde 15 (R = CH3) can be explained by the steric influence of the two methyl substituents in close vicinity to the stereogenic center, which probably diminishes the ability of the ether oxygen to coordinate. In contrast, a significant difference in the diastereoselectivity was found in the additions of phenyllithium and phenylmagnesium bromide to isopropylidene glyceraldehyde (17)58 (see also Section 1.3.1.3.6.). Presumably the diastereo-sclcctivity of the phenyllithium addition is determined by the ratio of chelation-controlled to nonchelation-controlled attack of the nucleophile, whereas in the case of phenylmagnesium bromide additional chelation with the / -ether oxygen may occur. Formation of the -chelate 19 stabilizes the Felkin-Anh transition state and therefore increases the proportion of the anZz -diastereomeric addition product. 

I-Oialkoxy carbonyl compounds are a special class of chiral alkoxy carbonyl compounds because they combine the structural features, and, therefore, also the stereochemical behavior, of 7-alkoxy and /i-alkoxy carbonyl compounds. Prediction of the stereochemical outcome of nucleophilic additions to these substrates is very difficult and often impossible. As exemplified with isopropylidene glyceraldehyde (Table 15), one of the most widely investigated a,/J-di-alkoxy carbonyl compoundsI0S, the predominant formation of the syn-diastereomer 2 may be attributed to the formation of the a-chelate 1 A. The opposite stereochemistry can be rationalized by assuming the Felkin-Anh-type transition state IB. Formation of the /(-chelate 1C, which stabilizes the Felkin-Anh transition state, also leads to the predominant formation of the atm -diastereomeric reaction product. 

On the other hand, the a,0-isopropylidene-protected analog 13 gives predominant formation of the anO, am(-diastereomer 14 with nucleophiles such as 2-(trimcthylsilyl)thiazole and organo-... 

The two -OH groups in l,2 5,6-di-0-cyclohexylidene-wii/o-inositol and its di-O-isopropylidene analog are trans. The X-ray crystal structure of the latter compound suggests that the ring is in a skew conformation with the 0-3 and 0-4 -OH groups both in ax positions, but NMR studies and ab initio calculations indicate that a mixture of the skew and chair conformations, with 0-3 and 0-4 both in eq positions, is present. Formation of a dibutylstannylene acetal presumably locks these two compounds in the latter conformation. 

Quebrachitol was converted into iL-c/j/roinositol (105). Exhaustive O-isopropylidenation of 105 with 2,2-dimethoxypropane, selective removal of the 3,4-0-protective group, and preferential 3-0-benzylation gave compound 106. Oxidation of 106 with dimethyl sulfoxide-oxalyl chloride provided the inosose 107. Wittig reaction of 107 with methyl(triphenyl)phos-phonium bromide and butyllithium, and subsequent hydroboration and oxidation furnished compound 108. A series of reactions, namely, protection of the primary hydroxyl group, 0-debenzylation, formation of A-methyl dithiocarbonate, deoxygenation with tributyltin hydride, and removal of the protective groups, converted 108 into 7. 

Reacts with vapors of sodium with luminescence at about 260°C. Reacts explosively with thionyl chloride or potassium reacts violently with hexafluoro isopropylidene, amino lithium, ammonia, and strong acids reacts with tert-butyl azidoformate to form explosive carbide reacts with 24-hexadiyn-l, 6-diol to form 2, 4-hexadiyn-l, 6-bischloro-formate, a shock-sensitive compound reacts with isopropyl alcohol to form isopropyl chloroformate and hydrogen chloride thermal decomposition may occur in the presents of iron salts and result in explosion. 

Another example is provided by the observation of Ohle and Wilcke16 that whereas 3-tosyl-l,2-isopropylidene-D-glucofuranose (XXXV) is saponified without anhydro ring formation and without Walden inversion, the triacetate of methyl 3-tosyl-/3-D-glucofuranoside (XXXVI) is... 

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