Some Typical Carbonyl-Addition Reactions

We turn now to discuss a few specific addition reactions of the carbonyl groups of aldehydes and ketones. We shall not attempt to provide an extensive catalog of reactions, but will try to emphasize the principles involved with especially important reactions that are useful in synthesis. 

Exercise 16-9 Write equations to show the steps involved in the following carbonyl-addition reactions (a) base-catalyzed addition of ethanol to ethanal to form the corresponding hemiacetal, 1-ethoxyethanol (b) formation of 1-ethoxyethanol from ethanol and ethanal, but under conditions of acid catalysis (c) formation of 1,1-diethoxyethane from 1-ethoxyethanol and ethanol with an acid catalyst and (d) formation of diethyl carbonate (CH3CH20)2C—0 from ethanol and carbonyl dichloride. 

16 Carbonyl Compounds I. Aldehydes and Ketones. Addition Reactions of the Carbonyl Group 

NC—H 1 NC—C—OH 1 basic catalysts synthesis of cyanoalkenes, carboxylic acids, Section 16-4A 

R—MgX R—Li 1 R—C—OMgX 1 R—C—OLi ether solvent, no catalyst needed synthesis of alcohols, Section 14-12A 

---

Okashi and Inoue are also dealing with the asymmetric addition to an unsaturated carbonyl compound [36—38]. The catalyst is poly-( S )-isobutylethylenimine (PIEI, XXXIV). Schemes 7 and 8 and Table VII show the reaction and some typical results. 

Evidence for such reactions in methylmethacrylate polymerizations was obtained by termination of polymerizations with acetic acid followed by measurements of methanol formed (119, 120). Fig. 6 shows typical results obtained. It is assumed that the methanol found corresponds to lithium methoxide in the reaction mixture. Some methanol might in fact be produced only in the termination reaction from pseudo-cyclized species (cf. p. 82). In addition the tertiary alkoxides formed by attack of the initiator or growing polymer chains on the carbonyl group of the monomer might not eliminate lithium methoxide immediately but would do so on termination with acetic acid. In any case much of the methanol formed corresponds to actual alkoxide in the reaction mixture and the results give a minimum value of the concentration of species inactive in polymerization. For brevity it will be referred to as lithium methoxide. 

Oxidation of enolizable nitro, carbonyl and dicarbonyl compounds with Fem MnnI and Celv reagents in the presence of electron rich aromatic (or heteroaromatic) rings often provides modest to good yields of substituted products. Typical examples are shown in Scheme 81.233 234 The oxidant functions both to generate the initial radical (Scheme 71) and to trap the adduct radical. Products of ortho substitution usually predominate but significant amounts of para and meta products are often formed, and in some cases, reversibility in the addition step may influence the product distribution. A recent paper by Citterio and Santi provides a nice introduction to these types of reactions.219... 

Michael-type addition of a suitable nucleophile, e.g. thiols, on to the a,f)-unsaturated lactone. Such alkylation reactions are believed to explain biological activity, and, indeed, activity is typically lost if either the double bond or the carbonyl group is chemically reduced. In some structures, additional electrophilic centres offer further scope for alkylation reactions. In parthenolide (Figure 5.31), an electrophilic epoxide group is also present, allowing transannular cyclization and generation of a... 

Acyl halides and alkynes also give lactones upon reaction with Ni(CO)4 in an aqueous acetone medium. The result in this system is typically a 3,y-unsaturated lactone, formed together with some product derived from condensation with molecules of solvent (equation 18). Lactones are also formed in low yield as byproducts from the reactions of acylnickel carbonyl anions (derived from addition of RLi to Ni(CO)4) with terminal alkynes at -30 A single example of y-aminolactone formation is reported from 2-butyne, CO and diethylamine, catalyzed by (Et2NH)2NiBr2. ... 

Lithiation of both A/-phenyl- and 0-phenyl-urethanes has been reported. The ortho lithiadon of /V-r-bu-toxycaibonylaniline and subsequent addition to carbonyls, nitriles and several other electrophiles was first reported by Muchowski in 1980. In some cases the adduct cyclized by attacking the urethane carbonyl. Typical examples are shown in Scheme 17. Lithiation of an /V-r-butoxycarbonylaniline derivative served as one of two directed lithiation steps in Snieckus synthesis of anthramycin (17 Scheme 18). Treatment of phenothiazines with 2 equiv. of butyllithium affords an A(,o-dilithium species, but reaction with electrophiles occurs at both sites. Katritzky has shown that the sequence of N-lithiadon, car-bonation and o-lithiation protects the nitrogen from alkylation (Scheme 19). ... 

---