A new, bifunctional catalyst for anti-Markovnikov hydration of terminal alkynes to aldehydes (6) allows practical room-temperature hydration of alkyl-substituted alkynes. Other outstanding features include near-quantitative aldehyde yields from both alkyl- and aryl-substituted alkynes and wide functional group tolerance. The uncatalyzed rate of alkyne hydration is measured for the first time, showing the enzyme-like rate and selectivity enhancements of aldehyde formation by 6. For aldehyde formation, an uncatalyzed rate <1 x 10-10 mol h-1 means a half-life >600 000 years. The catalyzed rate is up to 23.8 mol (mol 6)-1 h-1 and 10 000:1 ratio in favor of aldehyde. Changes in rate and selectivity induced by 6 are thus >2.4 x 1011 and 300 000, respectively.

The secondary structure of a bifunctional catalyst positions a crucial reactive proton in the final intermediate of anti-Markovnikov alkyne hydration to give an aldehyde. NMR coupling and isotopic labeling studies elucidate the location of this proton and its involvement in hydrogen bonding.

Experiment and theory have been used to study reactive alkyne pi complexes, intermediates in anti-Markovnikov alkyne hydration by CpRu bis(phosphine) catalysts with heterocyclic substituents. Each heterocycle accepts a hydrogen bond from an acetylene C-H, as revealed by NMR coupling constants between alkyne 13C and 1H nuclei as well as between alkyne 13C and pyridine 15N (2hJCN). Moreover, further alkyne transformations occur at temperatures from 50 to 90 degrees C below what is needed to convert a control compound without the heterocycles.

Syntheses of pyrazoles featuring a functionalized side chain attached to carbon 3 and varying alkyl and aryl substituents attached to carbon 5 are presented. Installation of R = methyl, isopropyl, tert-butyl, adamantyl, or phenyl groups at C5 is reported here, starting by coupling protected alkynols with acid chlorides RCOCl, forming alkynyl ketones, which are reacted with hydrazine to form the pyrazole nucleus. Alcohol deprotection and conversion to a chloride gave 5-substituted 3-(chloromethyl)- or 3-(2-chloroethyl)pyrazoles. This sequence can be done within 2 d on a 30 g scale in excellent overall yield. Through nucleophilic substitution reactions, the chlorides are useful precursors to other polyfunctional pyrazoles. In the work here, derivatives with side chains LCH(2)- and LCH(2)CH(2)- at C3 (L = thioether or phosphine) were made as ligands. The significance of the ligands made here is that by placing a ligating side chain on a ring carbon (C3), rather than on a ring nitrogen, the ring nitrogen not bound to the metal and its attached proton will be available for hydrogen bonding, depending on the steric environment created by R at C5.