Epoxides with strong nucleophiles

Thus, the reaction of glycal epoxides with strong nucleophiles, such organocuprates, allylmagnesium bromide, and allyllithium, did not require the use of Lewis acid and proceeded with the formation of l,2-tra s-C-glycosides. 

In the previous section, v e sav f the reactions of epoxides with strong nucleophiles. The driving force for such reactions was the removal of ring strain associated with the three-membered ring of an epoxide. Ring-opening reactions can also occur under acidic conditions. As an example, consider the reaction between ethylene oxide and HX. 

When lithiated, the ring strain of the three-membered heterocycle remains important, and this strain, combined with a weakening of the a-C-O bond, due to its greater polarization, make metalated epoxides highly electrophilic species [2], They react with strong nucleophiles (often the base that was used to perform the a-deprotonation) to give olefins following the elimination of M2O (Scheme 5.2, Path B), a process often referred to as reductive alkylation . 

The chemistry of metalated aziridines is far less developed than the chemistry of metalated epoxides, although from what is known [lb], it is obvious that their chemistry is similar. Like metalated epoxides, metalated aziridines can act as classical nucleophiles with a variety of electrophiles to give more highly substituted aziridines (Scheme 5.56, Path A). A small amount is known about how they can act as electrophiles with strong nucleophiles to undergo reductive alkylation (Path B), and undergo C-H insertion reactions (Path C). 

A Opening of Epoxide Rings with Strong Nucleophiles... 

These two steps—protonation followed by nucleophilic attack—are the exact rever.se of the opening of epoxide rings with strong nucleophiles, where nucleophilic attack precedes protonation. 

Epoxidation of cyclohexene adds an O atom from either above or below the plane of the double bond to form a single achiral epoxide, so only one representation is shown. Opening of the epoxide ring then occurs with backside attack at either C—O bond. Because the epoxide is drawn above the plane of the six-membered ring, nucleophilic attack occurs from below the plane. This reaction is a specific example of the opening of epoxide rings with strong nucleophiles, first presented in Section 9.15. 

Epoxides react with strong nucleophiles such as hydroxide, alkoxides, and ammonia or amines via an mechanism at the less hindered carbon of unsymmetrical epoxides. 

In the previous section (ring opening with strong nucleophiles), the regiochemistry was more straightforward, because electronics was not a factor at all. The epoxide was attacked by a nucleophile before being protonated, so the epoxide did not bear a positive charge when it was attacked. In such a case, steric hindrance was the only consideration. 

Reaction of methyloxirane with strong nucleophile OH is characterized by lower activation barriers if compare to formiate trarrstition state in the latter case has rather late nature. Transition states corresponding to nucleophile attack on the primary carbon atom of epoxide cycle for both nucleophiles are tighter (Fig. 10.3). 

Opening of epoxide rings with strong nucleophiles was first discussed in Section 9.15A. 

Ester, anhydride, nitrile, chlorosilane and epoxide are the electrophilic functions most commonly used for grafting onto reactions with strongly nucleophilic carbanions. 

Epoxide opening with nucleophiles occurs at the less substituted carbon atom of the oxlrane ting. Cataiytic hydrogenolysis yields the more substituted alcohol. The scheme below contains also an example for trons-dibromination of a C—C double bond followed by dehy-drobromination with strong base for overall conversion into a conjugated diene. The bicycKc tetraene then isomerizes spontaneously to the aromatic l,6-oxido[l0]annulene (E. Vogel, 1964). 

One of the earliest useful methods for asymmetric opening of meso-epoxides with sulfur-centered nucleophiles was reported by Yamashita and Mukaiyama, who employed a heterogeneous zinc tartrate catalyst (Scheme 7.10) [20]. Epoxides other than cydohexene oxide were not investigated, and the enantioselectivity depended strongly on the identity of the thiol. 

Epoxides can react with alcohols via acidic or basic catalysed reaction mechanisms. However, since both strong acids and bases will degrade the cell wall polymers of wood, the reaction is usually catalysed via the use of amines, which are more strongly nucleophilic than the OH group. For example, whereas the production of epoxy-phenolic resins requires temperatures in the region of 180-205 °C, reaction between epoxides and primary or secondary amines takes place at 15 °C (Turner, 1967). Reaction of epoxides with wood often involves the use of tertiary amines as catalysts (Sherman etal., 1980). The sapwood is more reactive towards epoxides than heartwood (Ahmad and Harun, 1992). 

Strong nucleophiles applied under basic conditions attack epoxides 364a at C(2) with inversion of the configuration, leading to fraw5,rran5-2,3,4-trisubstituted y-lactols 375, which are easily oxidized to the corresponding y-lactones 376 (equation 100) . 

Fpr most substitution reactions of epoxides, then, regioselectivity is much higher if you give in to the epoxide s desire to open at the less substituted end, and enhance it with a strong nucleophile under basic conditions. 

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