Carbonyl compounds substitution reactions

Cycloaddition of COj with the dimethyl-substituted methylenecyclopropane 75 proceeds smoothly above 100 °C under pressure, yielding the five-membered ring lactone 76. The regiocheraistry of this reaction is different from that of above-mentioned diphenyl-substituted methylenecyclopropanes 66 and 67[61], This allylic lactone 76 is another source of trimethylenemethane when it is treated with Pd(0) catalyst coordinated by dppe in refluxing toluene to generate 77, and its reaction with aldehydes or ketones affords the 3-methylenetetrahy-drofuran derivative 78 as expected for this intermediate. Also, the lactone 76 reacts with a, /3-unsaturated carbonyl compounds. The reaction of coumarin (79) with 76 to give the chroman-2-one derivative 80 is an example[62]. 

Active Figure 22.3 MECHANISM General mechanism of a carbonyl a-substitution reaction. The initially formed cation loses H+ to regenerate a carbonyl compound. Sign in at www.thomsonedu.com to see a simulation based on this figure and to take a short quiz. 

Meyers and Ford (76JOCI735), and Hirai et al. (72CPB206) have used 2-(alkylthio)-2-oxazolines or thiazolines to prepare the corresponding thi-iranes upon treatment with bases and subsequently with carbonyl compounds. The reactions of 2-pyridyl sulfides are expected to proceed similarly as shown in Scheme 22, since the oxazoline ring is a good leaving group in the intramolecular substitution reaction. When optically active oxazolines are used, asymmetric induction takes place to afford the optically active thiiranes in 19-32% enantiomeric excess (ee). The process is shown in Scheme 23. 

A variety of macrocyclic complexes which have adjacent nitrogen atoms (cyclic hydrazines, hydrazones or diazines) are formed by condensations of hydrazine, substituted hydrazines or hydrazones with carbonyl compounds. The reactions parallel in diversity those of amines, but are often more facile since the reacting NH2 groups is generally not coordinated and the electrophile is thus not in competition with the metal ion. The resulting macrocycles may be capable of coordination isomerism, since either of the adjacent nitrogen atoms can act as donor atom. 

These substitution products A and B need not be the final product of the reaction of nucleophiles with carboxyl species. Sometimes they may be formed only as intermediates and continue to react with the nucleophile. Being carbonyl compounds (substitution products A) or carboxylic acid derivatives (substitution products B), they can in principle undergo, another addition or substitution reaction (see above). Thus, carboxylic acid derivatives can react with as many as two equivalents of nucleophiles, and carbonic acid derivatives can react with as many as three. 

The ring opening of enantiopure IV-tosyl aziridines 215 with 2-substituted 2-lithio-l,3-dithianes takes place at the less substituted carbon atom in good yields (59-92%)321. The corresponding adducts gave /9-tosylamino carbonyl compounds after reaction with methyl iodide under acetone reflux. 

As resonance hybrids of two nonet uivalent forms, enolate ions can. be looked at either as a-keto carbanioris I C OO) or as vinylic alkoxidiHi tOC- O"). Thus, unolatv ions can react with electrophiles either Od carbon or on oxygen. Reaction on coTbon yields an o-substituted carbonyl compound, while reaction on oxygen yields an enot derivative (Figure 22.6). Both kinds of reactivity are Xnown, but reaction on carbon is more common. 

General mechanism of a carbonyl a-substitution reaction. The initially formed cation loses H to regenerate a carbonyl compound. 

Perhaps the most successful approach for promoting the 47r participation of 1-oxabutadiene systems in intermolecular Diels-Alder reactions employs a,/8-unsaturated carbonyl compounds substituted with an additional C-3 (a) electron-withdrawing group. The addition of the C-3 electron-withdrawing substituent increases the electron-deficient character of the oxabutadiene system, decreases the LUM0oxabutadiene, and as expected, enhances the observed [4 + 2] cycloaddition rate and regioselec-... 

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