With Oxygen Nucleophiles

Nippon Shokubai Kagaku Kogyo Co. Ltd., Jpn. Kokai Tokkyo Koho 81 92 228. 

The acid-catalysed hydrolysis reactions of vinyl epoxides (140 = 1-4) have been shown to follow an A-l mechanism, via the intermediate allylic cations (141). ° The distributions of products from both (140 = 1) and (140 = 3) were similar, comprising all four possible cis- and trans-1,2- and -1,4-diols, whereas cyclohexadiene oxide (140 = 2) gave mainly the trans- 

2- and -1,4-diols. The reactivity of cyclo-octadiene oxide (140 n = 4) was some 10 times less than that of the other epoxides, and it yielded, in addition to 1,2- and 1,4-diols, the dienol (141) (35%) these results were attributed to steric effects in the medium-sized ring. A similar anomaly in the reactivity of cyclo-octane derivatives has been noted in the opening of a,/3-epoxy-silanes. While these reactions normally proceed with nucleophilic attack at the carbon which is a to silicon, to give (144 R = H, OMe, OH, 0CH2CH=CH2, Br, I, or SCN) (70-92%) from (143 = 2), the acid-catalysed methanolysis of (143 n =4) gave (145) by a transannular reaction. 

The furanones (149 R = Me, Et, Pr, Bu, Pr, or Bu ) are obtained in 36-59% yields by hydrolysis of the diepoxides (148) in boiling 5% H2S04. Nafion-H sulphonated resin has been found to catalyse both the hydrolysis and the alcoholysis of cycloalkene oxides to yield (150 = 1 or 2 R = H, Me, or PhCHa).  

6-Di-t-butylphenol reacts with terminal epoxides via 0- or C-alkylation at the least substituted epoxide carbon atom to give (151 R = H, Me, Et, n-octyl, Ph, or CHaPh) and (152 same The ratio of C- to 0-alkylation increases with the complexity of the group R (cyclohexene oxide gives entirely C-alkylation) and is also increased with the alkali-metal catalyst that is used, in the order K Na li. 

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Displacement reactions with oxygen nucleophiles are of potential commercial interest. Alkaline hydrolysis provides 2-fluoro-6-hydroxypyridine [55758-32-2], a precursor to 6-fluoropyridyl phosphoms ester insecticides (410—412). Other oxygen nucleophiles such as bisphenol A and hydroquinone have been used to form aryl—pyridine copolymers (413). 

Reaction with Oxygen Nucleophiles. In the presence of strong acids, eg, H2SO4, HBF, or BF, aziridines react with alcohols to form P-amino ethers (93) ... 

With Oxygen Nucleophiles Aziridine ring-opening of 111 (Scheme 3.42) with water in the presence of a catalytic amount of TsOH gave the corresponding (3-hydrox-yphenylalanine derivative 121 in 72% yield as the major isomer [74], Treatment of N-(p-tolylsulfmyl) aziridine-2-carboxylates with TFA and subsequent aqueous workup resulted in the formation of j3-substituted serine derivatives [62, 63, 101]. Under these reaction conditions, not only was the aziridine ring opened, but also the N-sulfmyl group was removed treatment of 122 (Scheme 3.43) with TFA at 73 °C, for example, afforded 123 in 75% yield [101],... 

The regioselective ring-opening of vinyloxiranes by nitrogen nucleophiles offers an attractive route to vie-amino alcohols, compounds of much recent interest. As with oxygen nucleophiles, the stereochemistry of the reaction can be controlled by choice of reaction conditions aminolysis of 25, for example, affords anti-amino alcohol 26 in excellent yield and diastereoselectivity (Scheme 9.21) [48, 96, 97], and... 

Sulfur compounds " are better nucleophiles than their oxygen analogs (p. 439), so in most cases these reactions take place faster and more smoothly than the corresponding reactions with oxygen nucleophiles. There is evidence that some of these reactions take place by SET mechanisms. ... 

C. Palladium-catalyzed reactions with oxygen nucleophiles. 

Both dienyl- and 7r-allylmetal complexes of Fe,492 Mo,493,494 and W374 have also been prepared and undergone similar reactions with oxygen nucleophiles. One pertinent example is the reaction of 7r-allylmolybdenum complexes with internal alcohols leading to THFs (Equation (128)) 493 additional examples of this chemistry have appeared in a... 

These facts indicate that an a-trifluoromethyl group remarkably promotes anodic substitutions with oxygen nucleophiles. Since these are very few successful examples of anodic methoxylation of phenylalkyl sulfides are known, it is notable that an a-trifluoromethyl group facilitates the anodic methoxylation. Therefore, such anodic substitutions have been systematically investigated from both mechanistic and synthetic aspects [42]. 

NL Benoiton, FMF Chen. Unexpected dimerization in the reactions of activated Boc-amino acids with oxygen nucleophiles in the absence of tertiary amine, in JE Rivier, GR Marshall, eds. Peptides, Structure and Function. Proceedings of the 11th American Peptide Symposium, Escom, Leiden, 1990, pp 889-891. 

Substituents can play a part in the reaction of 1,2,4-trioxolanes with oxygen nucleophiles, for example 3-acyl or 3-aldehydic substituents can lead to fragmentation pathways via attack at the carbonyl (Section 4.16.6.2). Also, it is possible to displace suitable leaving groups in the 3-position with alcohol nucleophiles (Sections 4.16.6.3 and 4.16.9.4). 

Reaction with oxygen nucleophiles provides a simple route for the oxidation (Fig. 88) [229] and alkoxylation [230] (Fig. 89) of pyridine and related heteroaromatics. 

Most reactions with oxygen nucleophiles that have been reported have involved displacement of a 4-halogen substituent. 

One of the earliest uses of palladium(II) salts to activate alkenes towards additions with oxygen nucleophiles is the industrially important Wacker process, wherein ethylene is oxidized to acetaldehyde using a palladium(II) chloride catalyst system in aqueous solution under an oxygen atmosphere with cop-per(II) chloride as a co-oxidant.1,2 The key step in this process is nucleophilic addition of water to the palladium(II)-complexed ethylene. As expected from the regioselectivity of palladium(II)-assisted addition of nucleophiles to alkenes, simple terminal alkenes are efficiently converted to methyl ketones rather than aldehydes under Wacker conditions. 

An intermolecular example of this process was also shown to proceed with a high degree of chirality transfer (equation 341).426 The chirality transfer process can also function with oxygen nucleophiles as shown in equations (342) and (343).427... 

Oxy- and oxosulfenylation of alkenes.6 Similar reactions can be effected with oxygen nucleophiles such as OH or OAc, resulting in oxysulfenylation. DMSO also reacts to give an adduct that is converted to the /i-kcto sulfide on addition of d i i sopropylethylamine. 

Although cyclization using an amine is more common, there are examples with oxygen nucleophiles. An alcohol was employed37 to give both five- and six-membered lactones (Fig. 12). In a similar vein are the... 

Scheme4.8. Reaction of benzylphosphonium salts with oxygen nucleophiles [47].

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