Reactions with Other Carbonyl Components

Chapter 24 concentrates on the second general reaction of enolates—reaction with other carbonyl compounds. In these reactions, one carbonyl component serves as the nucleophile and one serves as the electrophile, and a new carbon-carbon bond is formed. 

Friedlander condensation is considered as an atom-economic reaction proceeding through double condensation between 2-aminoaryl carbonyl compoimds with other carbonyl components that show enolizable hydrogens. 

Other components in the feed gas may react with and degrade the amine solution. Many of these latter reactions can be reversed by appHcation of heat, as in a reclaimer. Some reaction products cannot be reclaimed, however. Thus to keep the concentration of these materials at an acceptable level, the solution must be purged and fresh amine added periodically. The principal sources of degradation products are the reactions with carbon dioxide, carbonyl sulfide, and carbon disulfide. In refineries, sour gas streams from vacuum distillation or from fluidized catalytic cracking (FCC) units can contain oxygen or sulfur dioxide which form heat-stable salts with the amine solution (see Fluidization Petroleum). 

The first cyclization of a-hydroxyalkoxyallenes goes back to the pioneering experiments of Brandsma, Hoff and Arens, who found that dihydrofuran derivatives 102 are formed by treatment of 101 with KOtBu in DMSO (Scheme 8.26) [12c], This reaction protocol was successfully applied by others [61, 63, 64, 80-83], for example in the preparation of spiro compound 104 (Eq. 8.19) [83] and in the cyclization of 64 leading to a-amino acid-derived dihydrofurans 105 (Scheme 8.27) [61, 63], Acidic hydrolysis of dihydrofurans furnished 3(2H)-dihydrofuranones, which could be used again as carbonyl components in the repetitive addition of lithiated methoxyal-lene 42. This concept was employed in syntheses of racemic [82] and enantiomeri-cally pure [64] primary helical spirocycles. 

The amide ions are powerful bases and may be used (i) to dehydrohalogenate halo-compounds to alkenes and alkynes, and (ii) to generate reactive anions from terminal acetylenes, and compounds having reactive a-hydrogens (e.g. carbonyl compounds, nitriles, 2-alkylpyridines, etc.) these anions may then be used in a variety of synthetic procedures, e.g. alkylations, reactions with carbonyl components, etc. A further use of the metal amides in liquid ammonia is the formation of other important bases such as sodium triphenylmethide (from sodamide and triphenylmethane). 

While the above stepwise bimolecular process was well suited for reactions with paraformaldehyde, other aldehydes and ketones did not behave similarly, presumably because of incomplete reactions between the amine and the carbonyl components. To overcome these difficulties, we invented a three-component process (Scheme 7.6) based on the one-step reaction between various amines 38, carbonyls 39, and boronic acids or boronates 40 to give the corresponding amine derivatives... 

Three different carbonyl components are assembled to tetrahydropyran-2,4-diols by two successive diastereose-lective aldol reactions. Tin(rv) enolates provide high selectivity as compared with other metals (Equation (74)).227,228... 

The reaction conditions for the methanol carbonylation reaction are even milder than the commercial conditions indicate. Indeed, the complete catalytic cycle can be realized at room temperature and 1 atm of carbon monoxide This allowed Forster to specifically interpret the macroscopic kinetic observations in mechanistic terms (14) by demonstrating the component reactions under ambient conditions. Since then, a great deal of effort has been directed to determining the generality of this mechanism with other alcohols. In fact, a wide array of alcohols can be carbonylated by this catalyst system (e.g., Table I), though not necessarily by the same mechanistic pathways. 

A modified Ugi reaction was used in the synthesis of lactams of type 191 (Scheme 80 <1997T5591>). The acid and carbonyl functionalities required for the Ugi reaction are tethered with the appropriate spacing to afford the eight-membered ring in good yields, and the other two components - the amine and the nitrile - are introduced stepwise. Methanol plays a crucial catalytic role in the reaction as it adds to the acyl center and facilitates the lactam formation. 

Excess diamine (ODA) component on the other hand leads to undesirable chemical reactions. For instance, it was proposed that under conditions of excess ODA, following imidization, the free amino groups react with imide carbonyl groups resulting in the formation of imine links. These imine links are unstable beyond 300°C, consequently, the films also exhibit poor thermal stability. The optimum relative fluxes need to be determined for each polymer separately taking into consideration the differences in the surface residence time of the species. 

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