Remember Teruaki Mukaiyama. Born in 1927 he became one of Japan’s most prolific organic chemists of the 20th century. Mukaiyama helped establish organic chemistry in Japan after World War II. This Mukai-yama before you bears silent testimony to his work.
Mukaiyama earned his BSc in synthetic organic chemistry in 1948 from the Tokyo Institute of Technology. Later, he became an assistant professor at Gakushuin University in 1953. He received his Ph.D. in synthetic organic chemistry from the University of Tokyo in 1957.
In 1958 Mukaiyama became an assistant professor at the Tokyo Institute of Technology. He earned his full professorship in 1963. His early work focused on organophosphorus chemistry. Mukaiyama discovered that mercury acetate reacted with phosphorus compounds to produce acetic anhydride. This led to the redox condensation reaction. It became a primary research focus for much of his career.
The initial reaction involved phosphine as a reducing agent. Mercury served as the oxidation agent. Carboxylic acids condensed with the loss of water. This framework expanded to include esters and amides. The synthesis of phosphoric esters using DEAD and an alcohol in 1967 was most significant.
In the same year, Oyo Mitsunobu, Mukaiyama’s co-author, created the Mitsunobu reaction. He attacked the products of the reaction with carboxylic acid and triphenylphosphine to yield an ester.
The aldol reaction is an essential tool. It involves two carbonyl compounds joining to form a carbon-carbon bond. Mukaiyama modified it. In 1971 he reported that ketene reacted with thioboronite. This produced a beta-hydroxyalkanethioate via a vinyloxyborane intermediate. Boron enolates provide an alternative to metal enolates for cross-aldol reactions.
Mukaiyama also examined metallic catalysts for dehydrative Friedel-Crafts alkylation. In 1973 he reported that titanium chloride treated with zinc powder catalyzed a pinacol coupling of carbonyls. This formed an alkene after reflux with dioxane. It is now known as the McMurry reaction.
Mukaiyama sought a Lewis acid to activate aldehydes for reaction with silyl enol ethers. This became the Mukaiyama aldol reaction. Published in 1973 it is a cross-aldol reaction between a silyl enol ether and an aldehyde. A Lewis acid like titanium chloride is used.
Tin enolates formed from tin triflate could produce aldol products. In 1982 Mukaiyama showed that these were over 95% stereospecific. Tin has multiple empty orbitals. It can coordinate chiral ligands and induce enantioselectivity.
In 1975 Mukaiyama reported that N-methyl-2-chloropyridinium iodide allowed for a dehydration condensation. This was between a carboxylic acid and an alcohol to form an ester linkage. The family of 2-halo-N-alkylpyridinium salts are named the Mukaiyama reagents.
In the early 1990s, Mukaiyama retired from the University of Tokyo. He set up an academic lab at the Tokyo University of Science. His taxol total synthesis was published between 1997 and 1999.
Mukaiyama’s synthesis used L-serine as a starting material. It was the only total synthesis not to use the Ojima lactam to create the amide tail. He developed a room-temperature oxidation involving N-chlorosuccinimide and a catalytic amount of N-t-butylbenzenesulfenamide.
Mukaiyama published over 900 papers. After 1972, he only published in the Japanese journal Chemistry Letters. He believed that chemistry results should be published in journals of one’s country. 145 people earned doctorates under Mukaiyama. 54 eventually became professors.
Mukaiyama received numerous honors. He is the namesake of the Mukaiyama Award. This is awarded by the Society of Synthetic Organic Chemistry, Japan since 2005. Mukaiyama died November 17 2018. He was 91.