With Oxygen and Nitrogen Nucleophiles

Nucleophilic Ring-opening Reactions of Oxirans.—Reactions with Oxygen and Nitrogen Nucleophiles. A series of papers have appeared that deal with the reactions of lower aliphatic alcohols (R OH) with (120 = Me) to yield (121  

R = Me) and (122). An Sn2 mechanism has been confirmed by kinetic studies, which showed that the ratio of products (121 R = Me) to (122) decreases as the temperature of the reaction is raised but increases with complexity of alkyl group R. A mathematical model for the reaction was developed. 

The effect of temperature on the stereochemistry of the acid-catalysed ethanolysis of rran5-stilbene oxide has revealed two reaction mechanisms, operating concurrently. The oxiran ring may open either (a) by nucleophilic 

Sallay, J. Morgos, L. Farklas, B. Bartha, and I. Rusznak, Period. Polytech., Chem. Eng., 1979, 23, 

With internal nucleophilic ring-opening, cyclization may occur thus the epox-idation of (125) by 3-CIC6H4CO3H produces an epoxide which cyclizes and, after oxidation in situ, gives (126). Reduction of (127 R = H or Me, R = H or OMe, R = H or OMe) with LiAlH4 and AICI3 (1 7) leads, via cyclization, to 

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Intermolecular Opening with Oxygen and Nitrogen Nucleophiles... 

The reactions that have been described above have indicated that sulphones interact poorly with electrophiles. However, in 1970, Whiting and coworkers announced the synthesis of aryloxysulphoxonium salts , by the reaction of sulphones with the potent electrophile produced in the thermolysis of aryldiazonium tetrafluoroborates or hexaflu-orophosphates. Fluorobenzenes are by-products of the reaction. In a subsequent paper , Whiting described the reactions of the aryloxysulphoxonium salts, 5, with oxygen and nitrogen nucleophiles. The fundamentals of these are outlined in equations (34) (oxygen nucleophile) and (35) (nitrogen nucleophile). 

Aldehydes and ketones undergo nucleophilic addition-elimination reactions with oxygen and nitrogen nucleophiles. 

Hetzheim" summarized her investigations of ring transformations of 2-amino-3-phenacyloxazolium salts with oxygen and nitrogen nucleophiles to prepare substituted imidazolinones, imidazoles, imidazo[l,2-a]imidazoles, and 1,4-di-hydro-imidazo[2, -b [, 2,4]triazines. 

Additions of oxygen and nitrogen nucleophiles to vinyloxiranes can be achieved with Pd(0) catalysis [103, 104]. Acetate, silanols, amines, sulfonamides, and azide have been used as nucleophiles, and the stereochemical outcome of these additions, where applicable, is normally the result of two consecutive SN2 reactions. This is demonstrated by the additions of NaNHTs to vinylepoxides 29 and 30, affording syn- and anti-amino alcohols 31 and 32, respectively, in good yields and with high diastereoselectivities (Scheme 9.22) [105]. 

Further investigation of the original QM1 also demonstrated that simple thiols could react reversibly although regeneration of QM1 was very slow.25 In contrast, a later model of anthracycline was shown to form stable adducts with a thiol despite the lability of corresponding adducts formed by oxygen and nitrogen nucleophiles.26... 

DNBF (68) readily forms stable Meisenheimer complexes (71) with numerous oxygen and nitrogen nucleophiles and some of these are primary explosives with useful initiating properties. 

The most-studied compounds in this class are l,3-diazetidine-2,4-diones l,3-diazetidine-2,4-diones 134 react with a number of nucleophiles, especially oxygen and nitrogen nucleophiles, leading to ring-opened products. The preferred attack by the nucleophile occurs from the most hindered side of the ring. A few representative examples are summarized in Scheme 16. 

Fused dihydrooxazolium compounds react readily by nucleophilic displacement of the oxygen from the azine ring. Thus, 2-carboxy-2,3-dihydrooxazolo[2,3-a]pyridinium bromide reacts with oxygen or nitrogen nucleophiles to form 2-oxo- or 2-imino-l(2ff)-pyridinelactic acids (204) (52JA4906). Similarly, the pyridinium salt (205) reacts by substitution in potassium hydroxide solution, whereas potassium t-butoxide causes proton abstraction and formation of the JV-vinyl derivative (206) (79JA3607). 

Both oxygen and nitrogen nucleophiles react more rapidly with fluoroaromatics than corresponding sulphur and carbon nucleophiles, in accordance with Hard-Soft Acid-Base principles [51]. It should be remembered, however, that the situation can become more complex with, for example, base catalysis, where the rate of the second stage becomes important under these rather unusual conditions, an order of replacement Br > Cl > F has been observed [52]. 

The overall result of addition of a nucleophile and elimination of a leaving group is substitution of the nucleophile for the leaving group. Recall from Chapter 20 that nucleophilic substitution occurs with carbanions (R ) and hydride (H ) as nucleophiles. A variety of oxygen and nitrogen nucleophiles also participate in this reaction. 

In general, nucleophilic addition reactions of arene oxides with nonpolarizable oxygen and nitrogen nucleophiles are very slow. Thus both NH3 and NHj nucleophiles failed to add to benzene oxides under a range of conditions. Amine nucleophiles have, however, been found to react very slowly with benzene oxide. 

Conjugated dienes coordinated to palladium(Il) undergo nucleophilic addition of oxygen and nitrogen nucleophiles from the opposite side of the palladium center to give Ti-allylpalladium complexes. Subsequent reaction of the 7C-allyl complexes with another molecule of nucleophile results in the 1.4-addition of two kinds of nucleophiles to dienes. The direction of the second nucleophilic attack is dependent on the nature of the nucleophiles as well as the reaction conditions. Representative examples... 

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