Proton abstraction intramolecular

In an attempt to metalate a MEM-protected phenol with BuLi, the methoxy group was eliminated, forming the vinyloxymethyl ether. This was attributed to intramolecular proton abstraction. ... 

It has been suggested that the kinetic preference for formation of (3,y-unsaturated ketones results from an intramolecular deprotonation, as shown in the mechanism above.51 The carbonyl-ene and alkene acylation reactions have several similarities. Both reactions occur most effectively in intramolecular circumstances and provide a useful method for ring closure. Although both reactions appear to occur through highly polarized TSs, there is a strong tendency toward specificity in the proton abstraction step. This specificity and other similarities in the reaction are consistent with a cyclic formulation of the mechanism. 

FIGURE 7.34 Decomposition of the symmetrical anhydride of A-methoxycarbonyl-valine (R1 = CH3) in basic media.2 (A) The anhydride is in equilibrium with the acid anion and the 2-alkoxy-5(4//)-oxazolone. (B) The anhydride undergoes intramolecular acyl transfer to the urethane nitrogen, producing thelV.AT-fcwmethoxycarbonyldipeptide. (A) and (B) are initiated by proton abstraction. Double insertion of glycine can be explained by aminolysis of the AA -diprotected peptide that is activated by conversion to anhydride Moc-Gly-(Moc)Gly-0-Gly-Moc by reaction with the oxazolone. (C) The A,A -diacylated peptide eventually cyclizes to the IV.AT-disubstituted hydantoin as it ejects methoxy anion or (D) releases methoxycarbonyl from the peptide bond leading to formation of the -substituted dipeptide ester. 

It has been pointed out (75TL213) that path A behavior might be more complex in some instances, and involve initial ylide formation followed by intramolecular proton abstraction (Scheme 202). The aryloxy quaternary salt (274), formed by reaction of pyridine 1-oxide with an arenediazonium salt, undergoes an interesting base-catalyzed rearrangement that is believed to take the course (path E) indicated (Scheme 203) (71JA3074). 

Treatment of the /J-hydroxy complex 15 with two equivalents of strong base followed by alkylation produces a mixture of the diastereomers 20 and 21 with an anomalously low d.r.27. The low degree of diastereofacial discrimination has been rationalized by invoking the formation of both rotamers of the initially formed alkoxide, 16 and 17. Rotamer 16 undergoes a-proton abstraction by a second equivalent of base to form the chelated dianionic Tf-enolate 18 which upon alkylation affords the usual diastereomer 20. Rotamer 17 is thought to rapidly transform to a metallo-lactone species by intramolecular attack of the alkoxide upon the proximate carbon monoxide ligand, which must occur faster than conversion to the less sterically encumbered conformer 16. Subsequent deprotonation to generate dianion 19, which is constrained to exist as the unusual Z-enolate, followed by alkylation provides the other diastereomer 21, which is formed in an amount nearly equal to 20. 

Phenyl azides (azidoarenes), introduced by Knowles and co-workers,[8 9] are the most abundantly used class of photophores. Examples include 4-azidophenylalanine (1) and 4-azido-3-nitrophenylalanine (4) (Scheme 1). Irradiation (<300 nm) of phenyl azide (13) generates nitrene 14, electrophilic in nature, which prefers insertion into O—H and N—H bonds over C—H bonds. Nitrenes are considerably less reactive and, therefore, more selective than carbenes. Nevertheless, due to their short life span (0.1-1 ms) they react indiscriminately with virtually any amino add residue in the target protein.1101 Intramolecular rearrangements do not compete effectively with intermolecular proton abstraction and insertion reactions (Scheme 4). 

Phenyltrimethyldisilene (15) and (E)- and (Z)-l,2-dimethyl-l,2-diphenyldisilene (16) were also observed as transient absorption spectra by laser flash photolysis of the precursors in methylcyclohexanes28. The absorption band at 380 nm, assigned to the disilene 15, reached maximum intensity at ca 10 ns after the excitation and then started to decrease. The half-life assigned to 15 was 700 ns. The logarithm of the decay profile of the transient absorption at 380 nm versus time shows a very good linear relationship, indicating that the decay of the transient absorption fits first-order kinetics. This result shows that intramolecular isomerization or proton abstraction from the solvent is the origin for the decay of the disilene 15, which survives in solution only for several nanoseconds. 

Methyl thiosalicylate provides both electrophilic and nucleophilic sites for annulation of arynes generated from silylaryl triflates in the presence of CsF. An initial intermolecular nucleophilic coupling to afford a diaryl sulfide 529 is followed by an intramolecular electrophilic cyclization and thioxanthones result. The use of THF as solvent suppresses the competitive proton abstraction which leads to methyl 2-thiophenoxybenzoate (Scheme 211) <2005OL4273>. 

Quaternary ammonium hydroxides anchored on MCM-41 provide stronger base catalysts than amine analogues11731 and were able to catalyse the same reaction as previously reported namely for the intermolecular Michael reaction leading to flavanone.[181] Moreover, this catalyst induced the successive intramolecular olefinic attack of the phenolic group from the Knoevenagel condensation product of salicylaldehyde and diethyl glutaconate (Scheme 9.6). This fast cyclization leads to chromene derivatives (1) from which subsequent conversions induced by proton abstraction from the alpha position of the ester function gives coumarin... 

A 1,6-silyl migration from C to O was also observed in the reaction of allylepoxysi-lane 326 with t-BuLi in a THF/HMPA (25 1) mixed solvent at low temperature, which afforded 5-silylpentenal 327 (equation 200). It was proposed that an initial proton abstraction from 326 gave w-silyl alkoxide 328, which underwent 1,2-silyl and then 1,6-silyl migrations to afford dienolate 329. Hydrolysis of 329 provided 327 (equation 201). The intramolecular nature of the transformation was suggested because the facile reaction occurred even in very dilute (0.02 lmol-1) and low-temperature (—78°C) conditions467. 

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