Asymmetric Carboxycyanation of Aldehydes by Cooperative AlF/Onium Salt Catalysts: from Cyanoformate to KCN as Cyanide Source.

Asymmetric 1,2-additions of cyanide yield enantioenriched cyanohydrins as versatile chiral building blocks. Next to HCN, volatile organic cyanide sources are usually used. Among them, cyanoformates are more attractive on technical scale than TMSCN for cost reasons, but catalytic productivity is usually lower. Here, the development of a new strategy for cyanations is described, in which this activity disadvantage is overcome. A Lewis acidic Al center cooperates with an aprotic onium moiety within a remarkably robust bifunctional Al-F-salen complex. This allowed for unprecedented turnover numbers of up to 104 . DFT studies suggest an unexpected unique trimolecular pathway in which the ammonium bound cyanide attacks the aldehyde, which itself is activated by the carbonyl group of the cyanoformate binding to the Al center. In addition, a novel practical carboxycyanation method was developed that makes use of KCN as the sole cyanide source. The use of a pyrocarbonate as carboxylating reagent provided the best results.

An Aluminum Fluoride Complex with an Appended Ammonium Salt as an Exceptionally Active Cooperative Catalyst for the Asymmetric Carboxycyanation of Aldehydes.

Al-F bonds are among the most stable σ bonds known, exhibiting an even higher bond energy than Si-F bonds. Despite a stability advantage and a potentially high Lewis acidity of Al-F complexes, they have not been described as structurally defined catalysts for enantioselective reactions. We show that Al-F salen complexes with appended ammonium moieties give exceptional catalytic activity in asymmetric carboxycyanations. In addition to aromatic aldehydes, enal and aliphatic substrates are well accepted. Turnover numbers up to around 104 were achieved, whereas with previous catalysts 101 -102 turnovers were typically attained. In contrast to Al-Me and Al-Cl salen complexes, the analogous Al-F species are remarkably stable towards air, water, and heat, and can be recovered unchanged after catalysis. They possess a considerably increased Lewis acidity as shown by DFT calculations.

Cooperative Al(salen)-pyridinium catalysts for the asymmetric synthesis of trans-configured ß-lactones by [2+2]-cyclocondensation of acylbromides and aldehydes: investigation of pyridinium substituent effects.

The trans-selective catalytic asymmetric formation of ß-lactones constitutes an attractive surrogate for anti-aldol additions. Recently, we have reported the first catalyst which is capable of forming trans-ß-lactones with high enantioselectivity from aliphatic (and aromatic) aldehyde substrates by cyclocondensation with acyl bromides. In that previous study the concepts of Lewis acid and organic aprotic ion pair catalysis were combined in a salen-type catalyst molecule. Since a pyridinium residue on the salen periphery is essential for high trans- and enantioselectivity, we were interested in the question of whether substituents on the pyridinium rings could be used to further improve the catalyst efficiency, as they might have a significant impact on the effective charges within the heterocycles. In the present study we have thus compared a small library of aluminum salen/bispyridinium catalysts mainly differing in the substituents on the pyridinium residues. As one result of these studies a new catalyst was identified which offers slightly superior stereoselectivity as compared to the previously reported best catalyst. NBO calculations have revealed that the higher stereoselectivity can arguably not be explained by the variation of the effective charge.

Cooperative Lewis acid-onium salt catalysis as tool for the desymmetrization of meso-epoxides.

Epoxide desymmetrizations by bromide are very rare despite the large synthetic potential of chiral bromohydrins. Herein we present a new concept for epoxide desymmetrizations in which a bifunctional Lewis acid/ammonium salt catalyst allows for efficient enantioselective epoxide ring openings by Br-. With acetylbromide as a Br- source bromohydrin esters are formed.