Stereochemistry acetal hydrolysis

Fragmentations linked to ester hydrolysis (contrast acetal hydrolysis in Problem 3) pin stereochemistry. 

Since the discovery of the illudane-type sesquiterpenoids, a number of related compounds have been isolated, viz., illudalic acid (167), illudinine (168), and dihydroilludin S (169, R = a-OH). The absolute stereochemistry of illudin S (169, R = =0) has been determined. A sequel to the successful stereospecific synthesis of illudin M (170) has been reported by Matsumoto et in which the diacetate (171, R = Ac), which had previously been prepared in the first synthesis, was selectively hydrolysed to the monoacetate (171, R = H). This compound was converted in three steps to the diacetate (172), which, after another selective hydrolysis, Jones oxidation, and acetate hydrolysis, yielded illudin M (170). 

Lithium trimethylsilyldiazomethane has proved particularly useful in the conversion of ketones into alkylidene carbenes, vide supra, that readily undergo 1,5 C-H insertion reactions to afford cyclopentenes (eq 56). Yields are generally good and the chemoselectivity of C-H insertion is predictable. The C-H insertion of the singlet carbene into heteroatom-bearing stereocenters proceeds with retention of stereochemistry (eqs 57 and 58). Reaction with acetals affords spiroketals (eq 59) or 2-cyclopentenones after acetal hydrolysis (eq 60). ... 

Now that we have seen examples of hydrolytic reactions and acetal hydrolysis by enzymes, we may wonder how important the stereochemistry of the products and reactants is in these transformations. 

Recall that the goal was to arrive at aminoketone 56. The projected Mannich reaction requires that the amino group be on the concave face surface of the m-decalin ring system. Notice that the alcohol stereochemistry in 67 is set such that an 8 2 reaction at the carbinol center would establish the required stereochemistry in 56 [We will see another approach to establishing this stereochemistry shortly]. Tosylate formation followed by acetal hydrolysis provided 68, but treatment of this material with azide failed to give any of the desired 8 2 product. Treatment of 68 with methylamine, however, gave 56 in excellent yield. Given the results with azide, it is probable that this displacement occurs with intramolecular delivery the nucleophile via involvement of an N,W-acetal (69). The final Mannich reaction proceeded as anticipated to provide luciduline (55). 

The wM-diacetate 363 can be transformed into either enantiomer of the 4-substituted 2-cyclohexen-l-ol 364 via the enzymatic hydrolysis. By changing the relative reactivity of the allylic leaving groups (acetate and the more reactive carbonate), either enantiomer of 4-substituted cyclohexenyl acetate is accessible by choice. Then the enantioselective synthesis of (7 )- and (S)-5-substituted 1,3-cyclohexadienes 365 and 367 can be achieved. The Pd(II)-cat-alyzed acetoxylactonization of the diene acids affords the lactones 366 and 368 of different stereochemistry[310]. The tropane alkaloid skeletons 370 and 371 have been constructed based on this chemoselective Pd-catalyzed reactions of 6-benzyloxy-l,3-cycloheptadiene (369)[311]. 

The poly(vinyl alcohol) made for commercial acetalization processes is atactic and a mixture of cis- and /n j -l,3-dioxane stereoisomers is formed during acetalization. The precise cis/trans ratio depends strongly on process kinetics (16,17) and small quantities of other system components (23). During formylation of poly(vinyl alcohol), for example, i j -acetalization is more rapid than /ra/ j -acetalization (24). In addition, the rate of hydrolysis of the trans-2iQ. -A is faster than for the <7 -acetal (25). Because hydrolysis competes with acetalization during acetal synthesis, a high cis/trans ratio is favored. The stereochemistry of PVF and PVB resins has been studied by proton and carbon nmr spectroscopy (26—29). 

A similar case of enolatc-controlled stereochemistry is found in aldol additions of the chiral acetate 2-hydroxy-2.2-triphenylethyl acetate (HYTRA) when both enantiomers of double deprotonated (R)- and (S)-HYTRA are combined with an enantiomerically pure aldehyde, e.g., (7 )-3-benzyloxybutanal. As in the case of achiral aldehydes, the deprotonated (tf)-HYTRA also attacks (independent of the chirality of the substrate) mainly from the /te-side to give predominantly the t/nii-carboxylic acid after hydrolysis. On the other hand, the (S)-reagcnt attacks the (/ )-aldebyde preferably from the. S7-side to give. s wz-carboxylic acids with comparable selectivity 6... 

Stereoinversion Stereoinversion can be achieved either using a chemoenzymatic approach or a purely biocatalytic method. As an example of the former case, deracemization of secondary alcohols via enzymatic hydrolysis of their acetates may be mentioned. Thus, after the first step, kinetic resolution of a racemate, the enantiomeric alcohol resulting from hydrolysis of the fast reacting enantiomer of the substrate is chemically transformed into an activated ester, for example, by mesylation. The mixture of both esters is then subjected to basic hydrolysis. Each hydrolysis proceeds with different stereochemistry - the acetate is hydrolyzed with retention of configuration due to the attack of the hydroxy anion on the carbonyl carbon, and the mesylate - with inversion as a result of the attack of the hydroxy anion on the stereogenic carbon atom. As a result, a single enantiomer of the secondary alcohol is obtained (Scheme 5.12) [8, 50a]. 

Cellulose differs from amylose principally in the stereochemistry of the acetal linkages, which are a in amylose but P in cellulose. a-Amylase is specific for al 4 bonds and is not able to hydrolyse pi 4 bonds. An alternative enzyme, termed cellulase, is required. Animals do not possess cellulase enzymes, and thus cannot digest wood and vegetable fibres that are predominantly composed of cellulose. Ruminants, such as cattle, are equipped to carry out cellulose hydrolysis, though this is dependent upon cellulase-producing bacteria in their digestive tracts. 

Of all the selective, deprotection procedures that are available to carbohydrate chemists, the partial hydrolysis of polyacetals is probably the most familiar. Articles by de Beider4,5 and Brady6 contained examples of this type of reaction for aldose and ketose derivatives, respectively, and an article by Barker and Bourne7 gave useful information from the early literature on the graded, acid hydrolysis of acetal derivatives of polyols. A discussion of the stereochemistry of cyclic acetals of carbohydrates was included in an article by Mills 70 and in one by Ferrier and Overend,76 and a survey of the formation and migration of carbohydrate cyclic acetals was made by Clode.7c... 

Neooxaline has been obtained (80CPB2987) from Aspergillus japonicus and identified as 231 (undefined stereochemistry). With acetic anhydride in DMSO, it gave mainly 232 which, on alkaline hydrolysis, gave 230. Compound 230, like oxaline, with diazomethane gave 14-methyloxaline. 

In previous studies, i,e. concurrent carbonyl-oxygen exchange in the hydrolysis of esters, acid hydrolysis of orthoesters and oxidation of acetals by ozone, the configuration of the tetrahedral intermediate was determined by the application of the principle of stereoelectronic control. There could be some ambiguity in these experiments as the theory of stereoelectronic control is used to predict both the stereochemistry of the tetrahedral intermediate as well as its breakdown. The oxidation cleavage of vinyl orthoesters can therefore be considered a more powerful experimental technique in that respect because the configuration of the hemi-orthoester... 

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