Trans-Acetalization

In the companion experiment carried out on the trans stereoisomer of the ketone only the trans acetate was formed... 

Fully acetylated hexopyranoses react with thiols in the presence of Lewis acids, such as BF3-Et20.32,33 The reaction is faster with 1,2-trans acetates than with the corresponding 1,2-cij ones and 1,2-trans products predominate. Alkyl, alkenyl, and aryl thioglycosides are produced by this method. Variations on this method include the use of trimethylsilyl34 or stannyl derivatives35 of the thiols. 

More recently, the equilibration of the conformationally rigid cis and trans tricyclic acetals 7 and 8 was carried out (23). The cis acetal 7 is less stable (45% at equilibrium) than the trans acetal 8 by 0.14 kcal/mol. Taking... 

The trans acetate 25 is the pheromone used to trap pea moths.6 Changing the -alkene into the acetylene allows the disconnection next to what was the double bond. The only problem is how to make a mono-bromide from the symmetrical diol 30. 

Following the procedure for the transformation of acetate (12) to (16), the acetate (13) was converted to trans-acetate (18). Reduction of (18) with metal hydride followed by oxidation of the resulting alcohol with pyridinum chlorochromate produced ketone (11), which afforded alcohol (17) by reduction with lithium aluminium hydride. 

The poly(vinyl alcohol) made for commercial acetalization processes is atactic and a mixture of cis- and turns-1,3-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, cis-acetalization is more rapid than trans-acetalization (24). In addition, the rate of hydrolysis of the />mf-acetal is faster than for the ay-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). 

More recently, however, results with monooelfins indicate that trans addition can occur to both Pd(II) and Pt(II) n complexes. The first demonstration was the trans addition of amines to Pt(II) complexes 215), and more recently the trans attack of acetate on cyclohexene has been demonstrated (Section III, A, 2, a). However, cis attack can also occur such as the addition of phenylpalladium to cyclohexene (Section III, A, 4) or addition of PdCOOR to cyclic olefins (Section III, A, 3). Also, in the exchange studies (Section III, B, 1) the stereochemistry indicates that some nucleophiles can attack cis or trans. Thus chloride ion containing acetic acid can attack the Pd(II) olefin n complex from either inside or outside the coordination sphere. What are the factors involved The most important appears to be the ability of the nucleophile to coordinate to Pd(II). Thus, phenyl is covalently bonded to Pd(II) and is therefore always in the coordination sphere. Chloride is both inside the coordination sphere as well as outside the coordination sphere and can thus attack both cis and trans. Acetate is not complexed to Pd(II) in chloride-containing media, and thus can only attack trans. On the other hand, in chloride-free acetic acid, acetate is both inside and outside the coordination. Stereochemical results indicate that in this system acetate can attack in both a cis and trans fashion. 

However, it was later shown that a more rapid route to 1,2-/ra .v-linked furanosides is possible from 1,2-trans acetates with an alcohol, using promotion by trimethylsilyl triflate.59,60... 

In a molecule with two chiral centres, such as (13), cis tosylate gives trans acetate and vice-versa. These are diastereoisomers and are not chiral. 

The trans acetate (16) is the pheromone used to trap pea moths to tell the farmer exactly when to spray to eliminate these destructive pests. It can be made from trans alcohol (17) and hence from acetylene (18) by reduction. Disconnection of (18) eventually requires an unsymmetrical compound (19). Diol (20) is available in large quantities so the statistical method (Chapter 5) can be used as very high yields are not so important when the starting material is cheap and the TM required in only small amounts-... 

VIII. 3 Total Synthesis Trans-Acetalization Reaction 339... 

The importance of the syn relationship of hydrogen and the leaving group is seen in hydrindanes 227 and 228, which produced 229 upon pyrolysis. The cis-derivative (227) required temperatures at least 200°C higher than the trans-acetate (228).209b synthetic example that involves ester pyrolysis is taken from Fallis synthesis of (-t-)-longifolene (230), formed in 56% yield by pyrolysis of 231. 10... 

Both enantiomers of frontalin, an aggregation pheromone of the Western pine beetle, have been synthesized using chiral dioxolanones derived from (S)- or (i )-lactic acid [23]. Alkylation of 56 with the dimethyl acetal of 5-iodo-2-pentanone affords trisubstituted dioxolanone 67 in high yield. Reductive cleavage of the hetero ring followed by acid-catalyzed trans-acetalization leads to (R)-( + )-frontalin (69) in 73% overall yield from (S)-( + )-lactic acid... 

P. J. L. Daniels et synthesised 2 -epi-gentamicin Ci 225 and 2"-deoxy-gentamicin C2 226. Penta-N-acetylgentamicin Cj is mesylated at the 2 -hydroxyl group. Through solvolysis of the mesylate by participation of the vicinal trans acet-amido group, epimerisation at the 2"-C atom takes place. 

Nucleophilic substitution reactions of acetates 88 and 90 (Fig. 4.32) indicate that a single substituent at C2 is not the origin of stereoselectivity for acetal 83 (Fig. 4.32). Treatment of the trans acetate 88 with aUyltrimethylsilane in the presence of SnBr4 provided the 1,4-c/s product 89 with 67 33 stereoselectivity (Fig. 4.32). Use of BF30Et2 and Me3SiOTf as the Lewis acid provided similar selectivities. The reaction of the related cis acetate 90 also afforded a mixture of diastereoisomers. Low selectivity with C2 and C4-c/s-substituted five-membered ring oxocarbenium ions has been observed [108]. 

Both the cmifomiational preference of the oxocarbenium ion intermediate and steric interacti(His that arise in the transitimi structure for nucleophilic attack influence the stereochemical outcomes observed with acetates 88 and 90. While the two ground-state cOTiformers of the cation derived from trans acetate 88, namely, 92 and 93, are comparable in energy, developing steric interactions between the approaching nucleophile and the pseudoequatorial methyl of intermediate 93 slightly disfavor the fomiatitHi of 1,4-trans product (Fig. 4.33). The selectivity obtained from the reaction... 

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