S-Orthoesters

O S-Orthoesters are much more stable to acid hydrolysis than their 0.0,0 analogues. Nevertheless they can be unleashed under essentially neutral conditions using mercury(II) catalysis [Scheme 2.116]241 or silver(I) catalysis [Scheme 2 117].144 Note that in both cases the labile ethoxyethyl and tetrahydropyranyl (THP) groups survived. 

S-Orthoesters seldom appear in organic synthesis but they do occupy one useful niche. In 1967 Seebach245-246 introduced tris(methylthio)methyhithium as an acyl anion equivalent of a carboxyl group. It was sufficiently stable and nucleophilic to react with a range of electrophiles. For example, nucleophilic substitution of the allylic chloride 121,1, followed by mercury(Il)-mediated hydrolysis of the SS-orthoester intermediate 121,2, gives the p,y-unsaturated car-... 

Ethylene ketals. The exchange reaction between dialkyl acetals or dialkyl ketals and 1,2-glycols as a route to cyclic acetals and ketals was first described by Delepine. This method in combination with Claisen s orthoester ketalization procedure (1, 1206) constitutes a convenient route to ethylene ketals (1, 376). The mixed orthoester 1 is probably the actual reagent involved in the Delepine method. It is convenient to prepare and use for ketalization of carbonyl compounds under mild conditions. A striking example is the ready conversion of the acid-sensitive 2 into 3, a reaction that proceeds by other known methods in yields of only 30%. 

The final SnCl2-mediated glycosidation of the 2-phenylseleno glycosyl fluoride 267 and the alcohol 311 gave the oligosaccharide 312 with complete stereocontrol, which was subjected to Sinay s orthoester formation to afford everninomicin 13,384-1 (314) after successful deprotections, including reductive debenzylation and TBAF-induced desilylation. 

The most commonly used protected derivatives of aldehydes and ketones are 1,3-dioxolanes and 1,3-oxathiolanes. They are obtained from the carbonyl compounds and 1,2-ethanediol or 2-mercaptoethanol, respectively, in aprotic solvents and in the presence of catalysts, e.g. BF, (L.F. Fieser, 1954 G.E. Wilson, Jr., 1968), and water scavengers, e.g. orthoesters (P. Doyle. 1965). Acid-catalyzed exchange dioxolanation with dioxolanes of low boiling ketones, e.g. acetone, which are distilled during the reaction, can also be applied (H. J. Dauben, Jr., 1954). Selective monoketalization of diketones is often used with good success (C. Mercier, 1973). Even from diketones with two keto groups of very similar reactivity monoketals may be obtained by repeated acid-catalyzed equilibration (W.S. Johnson, 1962 A.G. Hortmann, 1969). Most aldehydes are easily converted into acetals. The ketalization of ketones is more difficult for sterical reasons and often requires long reaction times at elevated temperatures. a, -Unsaturated ketones react more slowly than saturated ketones. 2-Mercaptoethanol is more reactive than 1,2-ethanediol (J. Romo, 1951 C. Djerassi, 1952 G.E. Wilson, Jr., 1968). 

Die durch Lithiumalanat nur schwer reduzierbaren Orthocarbonsaure-triester z.B. 2-Methoxy-l,3-dioxane und Zucker-orthoester werden mit Aluminiumhydrid oder Chloraluminiumdihydrid (s.S. 10) in hoher Ausbeute zu den entsprechenden Acetalen reduziert10. 

Choi, N. S., and Heller, J., Structured orthoesters and orthocarbonate drug delivery devices, U.S. Patent 4,131,648, December 26, 1978. 

Scheme 5.14 Prandi s strategy to oligoarabinofuranosides from internal orthoester 41.

In contrast to Mori s synthesis, Pawar and Chattapadhyay used enzymatically controlled enantiomeric separation as the final step [300]. Butanone H was converted into 3-methylpent-l-en-3-ol I. Reaction with trimethyl orthoacetate and subsequent Claisen-orthoester rearrangement yielded ethyl (E)-5-methyl-hept-4-enoate K. Transformation of K into the aldehyde L, followed by reaction with ethylmagnesium bromide furnished racemic ( )-7-methylnon-6-ene-3-ol M. Its enzyme-catalysed enantioselective transesterification using vinylacetate and lipase from Penicillium or Pseudomonas directly afforded 157, while its enantiomer was obtained from the separated alcohol by standard acetylation. 

Li S, Dory P. Hydrolysis of cyclic orthoesters experimental observations and theoretical rationalization. Tetrahedron 1996 52 14841. 

In order to obtain information concerning the hydrolysis of a S,6-0-orthoester such as 31, it was thus necessary to prevent the participation of OH-3. Starting (Figure 9) from compound J4 (obtained from 1,2 B,6-di-0-isopropylidene-a-D-glucofuranose throLigh acetylation and selective hydrolysis of the S,6-0-isopropylidene protec-... 

The different structures and seven-membered-r1ng orthoesters the C-n.m.r. chemical shift of atom as a probe for the assignment the now we 1 1 -e s t aii 1 i shed criteria references cited therein). Table T range- , for ethyl i dene acetals ( 13), (67), and o r t h OG n t f. r. As ex pec terl observed in goi rig from acetals to p.p.m. from isopropv1idene acetal derivatives). 

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