The Acid Test

Figure 1.(a) The planar carbocation. (b) The concept of the asymmetric addition described in this work. (c)Asymmetric hydroamination. Taken from Ref. [1]

Bronsted acid catalysis is an interesting field and it is very important. Not only we can achieve useful reactions by the judicious choice of the right counterion, but also asymmetric reactions are possible if we have a chiral counterion as our comrade. On the other hand, the ‘textbook-ish’ planar carbocation intermediate, which is generated either from a SN1 reaction or the electrophilic addition of an acid to an alkene [1], is notorious (literally) because of its planar structure, and the inevitable consequence of generating enantiomeric products in subsequent reactions.

These 2 aspects have led to an impressive achievement of a chiral Bronsted acid calaysis by Professor Toste and his group (Figure 1, 2) [2]. The protagonist is an acid known as ‘dithiophosphoric acid’. The concept is to add a chiral Bronsted acid catalyst to an diene precursor. This results in the generation of a chiral intermediate. Upon the SN2’ reaction that follows, the result is a chiral cyclic product, with the re-generation of the acid catalyst [1,2].


Figure 2. The asymmetric hydroamination. Taken from Ref. [2].

A prime example for this approach is the extremely useful asymmetric hydroamination [1, 2], which are catalyzed by many transition metal salts. An analogous useful reaction, which I also want to draw your attention to, is an hydroarylation reaction involving an ‘indole-allene’ precursor by the acid catalyst (Figure 3) [2]. Allenes have proved to be useful building blocks and the work of the catalyst leads to the useful tricyclic structure, with the double bond intact for further manipulations. As always, the group has carried out further experiments to verify the mechanisms [2].


Figure 3. Useful indole analogue sythesis. Taken from Ref. [2].

The Toste group has also carried out innovative ‘chiral counterion’ catalysis with transition metal salts in their past research [3], and this publication is indeed relevant to their engagements in that field, too.

-Ed Law 11/02/2011


This work is covered in a NATURE article by Gaunt in the same issue [1].

References:

1. Organic chemistry: Metals are not the only catalysts
Matthew Gaunt
Nature, 470, 183–185

2. Asymmetric additions to dienes catalysed by a dithiophosphoric acid
Nathan D. Shapiro, Vivek Rauniyar, Gregory L. Hamilton, Jeffrey Wu & F. Dean Toste.
Nature, 470, 245–249.

3. (a) A Powerful Chiral Counterion Strategy for Asymmetric Transition Metal Catalysis.
Gregory L. Hamilton, Eun Joo Kang, Miriam Mba, and F. Dean Toste
Science 2007, 496-499

(b) Chiral Anion-Mediated Asymmetric Ring Opening of meso-Aziridinium and Episulfonium Ions
Gregory L. Hamilton, Toshio Kanai and F. Dean Toste
J. Am. Chem. Soc., 2008, 130 (45), 14984–14986.