Stereospecific formation acetals

Bromination is less stereoselective, and the reactions of cis- and trans-olefins tend to be stereoconvergent. The stereospecific formation of the mixed bromoadducts in protic media, such as methanol or acetic acid, could be interpreted in the light of the recent finding (Ruasse et al., 1991) that these solvents assist the formation of the ionic intermediate nucleophilically. If a solvent molecule is close to the cationic part of the transition state in the rate-limiting step, the intermediate can be trapped by this solvent molecule in a necessarily trans mode with respect to the first bromine, before the two components of the ion-pair diffuse away from each other (15). This would... 

Stereospecific formation of a cis-fused octahydroquinoline (226 85%) is depicted in Scheme 47, which also shows the conversion of diallyl ether (227) into a 1 1 cisitrans mixture of tetrahydrofiirans (228 75%). It is worth noting that analogous nickel(0)-catalyzed cyclization of the corresponding acetate gave exclusively the trans isomer of (228). ... 

The total synthesis of (+)- -onocerin via four-component coupling and tetracyclization steps was achieved in the laboratory of E.J. Corey. The farnesyl acetate-derived acyl silane was treated with vinyllithium, which brought about the stereospecific formation of a (Z)-silyl enol ether as a result of a spontaneous Brook rearrangement. In the same pot, the solution of I2 was added to obtain the desired diepoxide via oxidative dimerization. 

The endocyclic and acetal intermediates were excluded since experiments conducted in CD3OD showed that anomerization was accompanied by >98% exchange of the methoxyl group and solvent. Stereospecific formation of a glycopyranosidic product from the acetal was excluded by the fact that acidic treatment of it produced only furanosides, which were converted only slowly into pyranosides. The exocyclic intermediate was considered to be the most likely... 

Dehydration of compounds (653 R = H or Ph) by toluene-p-sulphonic acid in benzene proceeds by homo-allylic rearrangement to give (654 R = H or Ph) some unrearranged olefin is obtained in the dehydration of (653 R = Ph). The cycliza-tion of ethyl (cyclo-oct-4-enylidene) acetate with BFajOEtj in hot benzene affords (655) and the corresponding acid (656). The bridgehead cation (657) is the presumed reaction intermediate. Aluminium chloride-catalysed cyclization of the lactone (658) resulted in the stereospecific formation of the carboxylic acid (660) the epimeric lactone (659) produced a mixture of a hexahydrofluorene carboxylic acid and the epimeric benzobicyclononene acid (661) mechanisms are discussed. 

Acetic anhydride I pyridine Stereospecific formation of O-bridges... 

N-Aminobenzoxazolin-2-one (4), which was readily prepared by animation of benzoxazolin-2-one with hydroxylamine-O-sulfonic acid, is also a useful nitrene precursor (Scheme 2.2). Oxidation of 4 with lead(iv) acetate in the presence of a conjugated diene resulted in exclusive 1,2-addition of nitrene 5, to yield vinylazir-idine (6) in 71 % yield [6]. The formation of vinylaziridines through 1,2-additions of methoxycarbonylnitrene (2) or amino nitrene 5 contrasts with the claimed 1,4-ad-dition of nitrene itself to butadiene [7]. Since the reaction proceeded stereospecif-ically even at high dilution, the nitrene 5 appears to be generated in a resonance-stabilized singlet state, which is probably the ground state [8]. 

Palladium(II) acetate was found to be a good catalyst for such cyclopropanations with ethyl diazoacetate (Scheme 19) by analogy with the same transformation using diazomethane (see Sect. 2.1). The best yields were obtained with monosubstituted alkenes such as acrylic esters and methyl vinyl ketone (64-85 %), whereas they dropped to 10-30% for a,p-unsaturated carbonyl compounds bearing alkyl groups in a- or p-position such as ethyl crotonate, isophorone and methyl methacrylate 141). In none of these reactions was formation of carbene dimers observed. 7>ms-benzalaceto-phenone was cyclopropanated stereospecifically in about 50% yield PdCl2 and palladium(II) acetylacetonate were less efficient catalysts 34 >. Diazoketones may be used instead of diazoesters, as the cyclopropanation of acrylonitrile by diazoacenaph-thenone/Pd(OAc)2 (75 % yield) shows142). 

To summarize, when the kinetic data predict that only bromonium ions or only bromocarbocations are formed, the bromination products are obtained stereospecifically and regiospecifically, respectively, whatever the solvent. Olefin brominations involving open intermediates lead to more solvent-incorporated products in methanol or acetic acid than those involving bridged ions. This chemoselectivity can be interpreted in terms of the hard and soft acid and base theory (Dubois and Chretien, 1978). Methanol assistance to intermediate formation also plays a role in determining product-selectivity (Ruasse et al, 1991). 

Treatment of trans,trans-2,6-ociddiene (122) with deuteriated formic acid HCO2D in the presence of deuteriosulphuric acid gave the cyclized formate ester 123. A concerted mechanism (equation 63) was proposed for this reaction73. The stereospecific ring-closure of the 1,4-cyclohexadiene derivative 124 in acetic anhydride/perchloric acid affords the octalin 125, which was isolated as the diacetate 126 (equation 64)74. 

This stereospecific oxidation does not occur for all dioximes, probably due to isomerisation of the dioxime during the reaction or to different reaction mechanisms involved in the use of different oxidants. When the lipophilic-hydrophilic balance of the two furoxan isomers is appropriate, they are easily separated by chromatography or fractional crystallisation. For example, the synthesis of 4-hydroxymethyl-3-furoxancarboxamide (CAS 1609), one of the most promising furoxancarboxamide vasodilators (see later), passes through the intermediate formation of a mixture of the two isomeric methyl hydroxymethylfuroxancarboxylic esters, which can easily be separated by recrystallisation from isopropyl acetate [18]. 

An interesting problem in stereoisomerism is found in the aldol reactions of the achiral aldehydes which are obtained by ozonolysis of the homoallylic alcohols 174. After stereospecific conversion by the FruA [230], the products can be readily induced to form an intramolecular glycoside 175 by acidic (R=OH) or alkaline treatment (R=C1), under which conditions the two equatorial ring hydroxyl groups completely direct the stereogenic acetal formation [234]. The corresponding RhuA catalyzed reactions deliver the enantiomeric... 

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