text: The aldol reaction is an essential tool for synthetic chemists. At its simplest, the aldol reaction involves two carbonyl compounds which join, forming a carbon-carbon bond. Depending on whether it is performed in acidic or basic conditions, the reaction proceeds by one of the carbonyls attacking the other, which has tautomerized into either an enol or enolate. However, when both carbonyls are similar in pKa they may both function as either the nucleophile or the electrophile, meaning the reaction may form either cross-products or self-products.
  While investigating sulfur-boron compounds in 1971, Mukaiyama reported that the reaction of ketene with thioboronite produced a beta-hydroxyalkanethioate via a vinyloxyborane intermediate that would perform an aldol reaction with formaldehyde leftover from the synthesis of ketene. These vinyloxyboranes proved straightforward to synthesize directly from the desired ketones using DBBT, which has a more electron-withdrawing triflate group in place of the sulfur. Boron enolates provide an alternative to metal enolates for performing cross-aldol reactions.
  As an extension of his earlier research with trivalent phosphorus as an oxygen acceptor, Mukaiyama began to examine the role of metallic catalysts for the dehydrative Friedel-Crafts alkylation and in particular titanium(IV) tetrachloride. In 1973, he reported that titanium(IV) chloride treated with zinc powder catalyzed a pinacol coupling of carbonyls in THF which formed an alkene after reflux with 1,4-dioxane. This is what is now known as the McMurry reaction - McMurry published a year later and cited both Mukaiyama and the group of Tyrlik in Poland in his paper, but Japan's position in the international organic chemistry community was not yet fully developed and the naming persists.
  Mukaiyama again turned to titanium(IV) chloride while seeking an appropriate Lewis acid to activate aldehydes for reaction with silyl enol ethers in what became known as the Mukaiyama aldol reaction. Published in 1973 as Mukaiyama was in the process of migrating to the University of Tokyo, it is a cross-aldol reaction between a silyl enol ether (typically derived from a carbonyl of choice using the method of Stork) and an aldehyde of choice in the presence of a Lewis acid like titanium(IV) chloride. The reaction is a landmark case on how activating aldehydes can allow even electronically neutral and weakly nucleophilic compounds like silyl enol ethers to be used as reagents.
  A Lewis acid must be added to use silyl enol ethers but not boron enolates because boron has an empty orbital but silicon does not, allowing boron to act as an electron acceptor. Tin(II) goes a step further by having multiple empty orbitals, allowing it to coordinate chiral ligands and induce enantioselectivity. In 1982 Mukaiyama showed that tin(II) enolates formed from tin(II) triflate could produce aldol products that were over 95% stereospecific. In a time when asymmetric reactions largely relied on chiral auxiliaries to be covalently bound to the reactants, tin(II) enolates formed from chiral diamine ligands derived from L-proline could achieve over 90% ee.