Alcohol carbonylation specific reactivities

Similarly, allenes [32] and alkynols [33] were used as starting materials and their carbonylation provides /3,y-unsaturated acids and unsaturated diacids, respectively. The specific reactivity of alkynols is explained by three formal steps during nickel catalysis (i) carbonylation of the triple bond leading to an acid containing an allylic alcohol moiety (ii) second carbonylation of the double bond to provide a hydroxydiacid and (iii) a dehydration step giving the corresponding unsaturated diacid (Scheme 2). 

In HO -catalyzed hydrolysis (specific base catalyzed hydrolysis), the tetrahedral intermediate is formed by the addition of a nucleophilic HO ion (Fig. 3.1, Pathway b). This reaction is irreversible for both esters and amides, since the carboxylate ion formed is deprotonated in basic solution and, hence, is not receptive to attack by the nucleophilic alcohol, phenol, or amine. The reactivity of the carboxylic acid derivative toward a particular nucleophile depends on a) the relative electron-donating or -withdrawing power of the substituents on the carbonyl group, and b) the relative ability of the -OR or -NR R" moiety to act as a leaving group. Thus, electronegative substituents accelerate hydrolysis, and esters are more readily hydrolyzed than amides. 

As anticipated, Sheldon and coworkers attempted to revise the Cu/TEMPO system, and suggested that a piperidinyloxycopper(II) adduct, rather than the oxoammonium ion, is instead formed as an intermediate species that adduct would be responsible for turning the alcohol into the carbonyl product. Sheldon and coworkers proposed the radical mechanism outlined in Scheme 17, and supported it with a Hammett p value of —0.16 (vs. a) and with a KIE of 5.4 . They also suggested that steric hindrance arising from interaction of secondary alcohols with the active-TEiMPO species, whatever it can be, are possibly responsible for the lower, or lack of, reactivity displayed by these substrates . Accordingly, a novel TEMPO-like system has been recently developed in order to specifically bypass this steric interference , as we are going to see below. 

---