Organoboranes as a source of radicals.

A directed cross-aldol reaction of silyl enol ethers with carbonyl compounds, such as aldehydes and ketones, promoted by a Lewis acid, a reaction which is now widely known as the Mukaiyama aldol reaction. It was first reported in 1973, and this year marks the 40th anniversary. The directed cross-aldol reactions mediated by boron enolates and tin(II) enolates also emerged from the Mukaiyama laboratory. These directed cross-aldol reactions have become invaluable tools for the construction of stereochemically complex molecules from two carbonyl compounds. This Minireview provides a succinct historical overview of their discoveries and the early stages of their development.

The Mukaiyama aldol reaction: 40 years of continuous development.

This Review describes the basic concepts that have guided our exploration of new chemical reactions by giving examples of results from my research group. Our strategy of carrying out research is to investigate three to four different topics at a time so we can gather as many results as possible. These may at first appear unrelated to each other but may have the potential to be united into a greater hypothesis after repeated feedback. Three scenarios from our research are presented: the "oxidative-reductive condensation reaction" devised in 1960, which after an interval of nearly 40 years brought forth the new concept of using compounds of structure Ph(2)POR as reducing reagents; the "TiCl(4)-aldol reaction" of 1973 that eventually led to the present "base-promoted aldol reaction" through a chain of ideas; and the "glycosylation reaction using fluorosugars" from 1984 which recently bloomed into "stereocontrolled glycosylation". Thus, it can be said that by reviewing what we had done before, we were able to expand on it to achieve new outcomes.

Explorations into new reaction chemistry.

There are basically two kinds of hetero atoms in organic molecules: one kind confers electrophilic character upon the carbon atom to which it is bound, and the other kind turns it into a nucleophilic site. The development of methods permitting transitions between the two resulting categories of reagents has become an important task of modern organic synthesis. The scope of such umpolung of the reactivity of functional groups is discussed for the case of amines as an example. A method of preparing masked α-secondary amino carbanions consists in nitrosation of the secondary amine, followed by metalation of the resulting nitrosamine α-to the nitrogen, reaction with electrophiles, and subsequent denitrosation. Many examples are given for each of these steps which illustrate the wide scope of the overall synthetic operation (electrophilic substitution at the α-C atom of the secondary amine). Preliminary applications and a method for avoiding the handling of nitrosamines are presented, and the report concludes with a brief account of the significance of nitrosamines in the study of carcinogenesis and mutagenesis.

Umpolung of Amine Reactivity. Nucleophilic α-(Secondary Amino)-alkylation via Metalated Nitrosamines†‡

Steroselective Alkylation at C(α) of Serine, Clyceric Acid, Threonine, and Tartaric Acid Involving Heterocyclic Enolates with Evocyelic Double Bonds



The chiral, non-racemic title acids are converted to methyl dioxolane-(cf.13), oxazoline-(4) and oxazolidinecarboxylates (cf.9). Deprotonation by Li(i-Pr) 2N at dry-ice temperature gives solutions of the lithium enolates A–D With exocyclic enolate double bonds. These are stable crough with respect to β-elimination (Scheme 1) to be alkylated with or without cosolvents such as HMPA or DMPU The products are formed in good to excellent yields and, with the exception of the tartrate-derived acetonlde (see Scheme 2), with diastereoselectivities above 90%. While the tartrate-and threonine-derived enolates (A and B, resp.) are chiral due to the second stereogenic center of the precursors, the serine- and glyceric-acid-derived enolates (Aand B, resp.) are chiral due to the second sterogenic center of the precursors, the serine-nd glyceric-acid-derived enolates are non-racemic due to a tert butyl-substituted (pivalaldehyde-derived) acetal center (C and D, resp.). The products of alkylation can be hydrolyzed to give α-branched tartaric acid (Scheme 2), allothreonine (Scheme 3), serine (Scheme 4), and glyceric-acid derivatives (Scheme 5) with quaternary stereogenic centers. The configurations of the products are determined by NOE-NMR measurements and by chemical correlation. These show that the dioxolane-derived enolates A and D are alkylated preferentially from that face of the ring which is already substituted (‘syn’-attack), while the dihydrooxazol-and oxazolidine-derived enolates B and C are alkylated from the opposite face (‘anti’-attack). The ‘syn’-attack is postulated to arise from strong folding of the heterocyclic ring due to electronic repulsion between the enolate π-system and non-bonding electron pairs on the heteroatoms (see Scheme 6).

Stereoselektive Alkylierung an C(α) von Serin, Glycerinsäure, Threonin und Weinsäure über heterocyclische Enolate mit exocyclischer Doppelbindung†‡

Vinyloxyboranes as synthetic intermediates

It was found that the reaction of thioboronites with carbonyl compounds and ketene proceeds with the initial formation of vinyloxyboranes (VII). The boranes were found to be important intermediates for the formation of β-hydroxythiolesters by the reaction with various carbonyl compounds. Vinyloxyborane derivatives can be alternatively prepared by the reactions of trialkylboranes and α-diazocarbonyl compounds. The boranes similarly reacted with carbonyl compounds to give β-hydroxyketones and β-hydroxyesters.

Reactions of Vinyloxyboranes. A Convenient Method for the Preparation of β-Hydroxy Thiolesters, Esters and Ketones

Aminoaluminum hydride as new reducing agents. I. Selective reduction of carboxylic acids to aldehydes.

A new vinyloxyborane derivative, Id, was found to be formed in reaction of phenyl di-n-butylthioboronite (II) with methyl vinyl ketone. In order to explore its utilization in organic synthesis, the reactivity of Id and other known vinyloxyboranes was variously examined. Id and Ie gave β-hydroxyketones (IVa–c, Va–d) in fairly good yields when they were allowed to react with carbonyl compounds. The reaction of Ia′ and Ib with nitriles, followed by hydrolysis, afforded β-iminothioates (VIa–c) and β-ketoesters (VIIa–d) respectively. It was also found that the borane (Ib) reacted with formates or formamides at room temperature to give ethyl α-formylhexanoate.

Masayoshi Muraki

Papers

Vinyloxyboranes as synthetic intermediates

Reactions of Vinyloxyboranes. A Convenient Method for the Preparation of β-Hydroxy Thiolesters, Esters and Ketones

Aminoaluminum hydride as new reducing agents. I. Selective reduction of carboxylic acids to aldehydes.

Reactions of Vinyloxyboranes with Carbonyl Compounds, Nitriles, and Formates

Reactions of vinyloxyboranes with carbonyl compounds, nitriles, and formates