Ring Opening by Nucleophiles

Ethers do not generally react with nucleophiles to displace an alkoxide ion. However, epoxides arc so strained that the C—O bond of the ring is cleaved even by nucleophiles such as OH, SH, or NH3 or the related organic species RO, RS , and RNH2. For example, hydroxide ion displaces an alkoxide of an epoxide. The alkoxide is not released, as are typical leaving groups of Sj 2 reactions, because the ether is cyclic. 

A mechanistically related reaction occurs when epoxides react with Grignard reagents to produce alcohols. The carbon skeleton contains two more carbon atoms than the starting alkyl hahde. The sequence of reactions is shown below. 

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Aziridinones undergo two types of selective ring opening by nucleophiles <68AG(E)25). Reaction with proton-containing nucleophiles, e.g. water, alcohols, thiols, amines and mineral acids, leads exclusively to amides (339), corresponding to an C —N bond rupture. 

The discovery of conditions under which glycosyl 1,2-orthoesters will ring open by nucleophilic attack at C-1 has led to the development of a l,2-glycoside synthesis devoid of many of the shortcomings of the... 

Selective ring opening by nucleophilic fluorination was observed in the case of a-halooxirane... 

The oxathiadiazines (106) (73TL2783) and (107) (77ZC222) are ring opened by nucleophilic attack at the sp2 carbons indicated. The oxathiazine dioxide (108) is reduced to the 3,4-dihydro derivative by 0.5 equivalent LAH (72JOC196), although the isomeric chlorooxathiazine dioxide (109). behaves differently towards nucleophiles. Nucleophilic attack at C-6 followed by elimination of SO3 and chloride ion occurs as shown (80AG(E)131). 

Therefore acceptor cyclopropanes 1 will be ring opened by nucleophiles N to provide products like 2 (homo Michael addition) as depicted in Eq. 1. On the other hand, electrophiles E+ cleave donor activated cyclopropanes 3 affording adducts 4 or 5 which demonstrates that the cyclopropane serves as a homoenolate equivalent in this sequence (Eq. 2). Seebach consequently classified these methods as umpolung with the cyclopropane trick 4. ... 

Hie preparation of allylic epoxides from conjugated dienes requires careful control of pH, since allylic epoxides undergo ring opening by nucleophiles at acidic pH. The allylic epoxide (12) has been prepared from the diene (11 equation 5) however, the ring opening of (12) cannot be totally suppressed. 

The most common reaction of epoxides in organic synthesis is their ring opening by nucleophiles. Here issues of regioselectivity and scope of the reaction continue to be topics of current interest. 

The coordinated epoxide is ring-opened by nucleophilic attack on the carbonate species, which leads to an oxy-anion species, which yields the corresponding cyclic carbonate as a product. 

The syntheses of the title compounds start mostly from 1,6-anhydro derivatives, using either the often regioselective course of the oxi-rane-ring opening by nucleophilic agents380,384,437,447,448,506"507,544,629,630,632 637 (see Sect. V), or the Sn2 replacement.632 Cyclization of deoxyhalo-... 

In a similar fashion, 3,6-dihydrothiazine 1-imines can be cleaved by several alkyl and aryl organometallic reagents. Dihydrothiazine imines have more steric and electronic constraints compared to the corresponding oxides, and hence some are very resilient to ring opening by nucleophiles. Treatment of imine (80a) with phenylmagnesium bromide at — 60°C gave a product which was... 

N-Alkyl-4,5,6,7-tetrahydroindoxazenium tetrafluoroborates (87 R = Me or Et), like the fully unsaturated systems, are easily ring-opened by nucleophiles. For example, triethylamine in methylene dichloride generates the moderately stable iminoketenes (88).93 The angular fused analog (88a R = Et) is isolable as a stable oil. 

The aziridine ring is destabilized by salt formation, and ring-opening by nucleophiles is favoured. Aziridine itself reacts with acids explosively to give polymeric products. 

Ring-opening by nucleophiles proceeds more slowly than with three-membered heterocycles and is catalysed by acids. 

By analogy with oxetanes, tetrahydrofurans are ring-opened by nucleophiles. For example, 4-chlorobutan-l-ol is obtained on heating tetrahydrofuran with hydrochloric acid ... 

Isothiazoles react more slowly with nucleophiles than isoxazoles. They are not affected by alkali hydroxides or alkoxides. 2-Alkylisothiazolium salts are more reactive. By the action of aqueous alkali hydroxide, ring-opening occurs with formation of polymeric products. Carbanions cause ring-opening by nucleophilic attack on the S-atom [109], e.g. ... 

Selective ring opening of cyclopropanes. Ring opening by nucleophiles of suitably activated cyclopropanes has gained importance during recent years. Sodium or potassium cyanide can be used for this purpose. An example is the conversion of 1 or 2 into 3, ant/-7-cyano-eni/o-5-bromobicyclo[2.2.1]heptane-2-one, by reaction with potassium cyanide in the presence of catalytic amounts of sodium methoxide (equation T). The intermediate 2 can be isolated in high yield by reaction of 1 with 1 equiv. of sodium hexamethyldisilazide (4, 407) in ether. ... 

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