Base-mediated reactions

For polyhalogenated alkanes, the most general elimination reaction is the 1,2 elimination (Equation (8)). These reactions can be mediated by water, acid, or base. However, base-mediated reactions are studied most widely. 

The hydrolysis of epoxides can occur through neutral, acid-, or base- mediated reactions. Because the add and neutral processes generally dominate over the range of environmental pH, the base-mediated reaction often can be ignored. The products of hydrolysis are usually the corresponding diol and sometimes rearranged products (Equation (12)). 

Jha, S. C. Joshi, N. N. Intramolecular dehy-drohalogenation during base-mediated reaction of diols with dihaloalkanes./. Org. Chem. 2002, 67, 3897-3899. 

In general, reactions involving prochiral nucleophiles are rare however, examples using activated dicarbonyl compounds and carbonyl compounds that can form only a single enolate under the base-mediated reaction conditions have recently been reported. 

A synthesis of 2-oxazolidinones has been reported by a base-mediated reaction between epichlorohydrin and primary amines. This reaction proceeded via an intermediate hydroxy-l,3-oxazinan-2-one 300, which rearranged to the more stable 2-oxazolidinone product under the reaction conditions (Scheme 84) <2005JOC5737>. 

Condensations of acetophenones with aliphatic aldehydes are often complicated by side reactions, although some simple cases are known to proceed in good yield (e.g. equation 84). An example of the kind of complications that may arise in such cases is seen in the reaction of acetophenone with isobutyr-aldehyde. Base-mediated reaction at low temperature gives a crude aldol that is dehydrated by heating with phosphoric acid to obtain a 3 1 mixture of a,p- and p,7-unsaturated ketones (equation 85). If the reaction is carried out under more traditional conditions, by heating an alcoholic solution of the reactants... 

Remarkable improvements in chiral base-mediated reactions of prochiral ketones under external quench (EQ) conditions with TMS-Cl, furnishing enantiomerically pure enol silanes, were found upon deprotonation in the presence of LiCl. [22, 24] Simpkins et al. studied for instance the conversion of 4-tert-butylcyclohexanone 9 into enol silane 10 by employing the chiral amide base 11 (Scheme 9). [24] Applying the TMS-Cl in situ quench (TMS-Cl-ISQ) protocol a higher level of enantiomeric excess was observed compared to external quench conditions (EQ). However, under external quench conditions in the presence of LiCl (EQ-i-LiCl procedure) significantly higher levels of asymme-... 

Clark, A.J., Al-Faiyz, Y.S.S., Patel, D. and Broadhurst, M.J. (2001) Rearrangement of unactivated A-alkyl-O-benzoyl hydroxamic acid derivatives with phosphazene bases. Tetrahedron Letters, 42, 2007-2009 Clark, A.J., Patel, D. and Broadhurst, M.J. (2003) Base-mediated reaction of A-alkyl-O-acyl hydroxamic acids synthesis of 3-oxo-2,3-dihydro-4-isoxazole carboxylic ester derivatives. Tetrahedron Letters, 44, 7763-7765. 

In their synthesis of ( )-perophoramidine, Funk and Fuchs [27] use the base-mediated reaction of a 3-siloxyalkyl-substituted indole with a 3-bromoindolin-2-one to produce an indolenine derivative as a key step. The formation and subsequent IDA cycloaddition of an indole-2-one derivative followed by ring opening of the cycloadduct is proposed as one possible mechanism for the above reaction. A similar approach was also used by Dalko and coworkers in the total synthesis of the bis-pyrroloindoline alkaloid ( )-A b-desmethyl-/ncso-chimonanthine [28]. 

Scheme 6.31 Stoichiometry-dependent product distribution in base-mediated reactions of a-silyl allylalcohols.

Ynals have also been substrates for similar reactions via the intermediacy of a,p-unsaturated acyl azoliums (126) generated by the base-mediated reaction between ynals (125) and acyl azolium (124). All derivatives have been unambiguously characterized by spectroscopic means (Scheme 15), and hemiacetals of (126) have been demonstrated to be the kinetically important intermediates not only in the annulation reactions but also in the acylation reactions of (125). 

Calcined barium hydroxide is an efficient catalyst for a number of base-mediated reactions. Among these, the Claisen-Schmidt condensation of acetophenones with benzaldehydes occurs in times as short as 10 min at room temperature (Eq. 15). The acetophenone enolate (detected by IR spectroscopy) is formed on the catalyst surface, where the reaction with the aldehyde takes place. The higher activity of the ketone enolate is interpreted by the authors as the result of "an increased vibrational state of the lattice", a formulation close to the mechano-chemical explanation. With the help of selective poisoning experiments, it is concluded that the enolate forms via a SET mechanism. 

The above synthesis gives an example of the high synthetic value of 1-substituted TosMICs (p-toluenesulfonyl methylisocyanides). TosMIC 1600 has been created by van Leusen, who describes syntheses of some chiral sulfonylmethyl isocyanides as TosMIC analogues [1201]. Most of the isocyanides 1600-1605 are prepared by dehydration of the corresponding formamides with phosphoryl chloride, whereby yields of 60-85% are obtained. The chiral isocyanides are compared in terms of their ability to achieve asymmetric induction in base-mediated reactions with... 

The reaction mechanism of the initial Knoevenagel condensation strongly depends on the conditions applied [3]. The base-mediated reaction is shown in Scheme 13.1. Bases... 

Thiol Substitution Reactions. Vital to the usefulness of 2-(trimethylsilyl)ethanethiol is that it behaves as a typical thiol. Base mediated reactions that proceed as expected include alkylation and nucleophilic ring openings. Moreover, addition-eliminations on unsaturated systems, Michael additions, and c -additions to triple bonds (eq 2) are all routine. To access 2-(trimethylsilyl)ethyl thioethers, a useful procedure is hydrolysis of 2-(trimethylsilyl)ethyl thiolacetate and alkylation of the thiolate in a single pot. ... 

A similar base-mediated reaction of 130 with diethyl malonate gave carboxylates... 

Although the details are not clear, there are some examples of lithium bases mediated reactions that show interesting switch of reaction selectivity by changing the reaction conditions, especially the kind of base. Probably, the variation of the selectivity arises from same type change of aggregation structure of lithium bases. Some examples are shown here. 

---