Highlights
G. Richard Stephenson University of East Anglia, UK
Organic chemistry
Asymmetric Fischer-type indoline synthesis Classic reactions can be reborn in asymmetric processes. Indoles, for example, are not chiral, so the famous Fischer indole synthesis – the reaction between a hydrazine and a ketone – is not one of the well established methods to prepare enantiopure samples of chiral compounds. However, the simple device of putting a substituent beside the ketone functional group, switches the mechanism to a synthesis of indolines, and provided regioselectivity of the reaction of the unsymmetrical ketone is well controlled, the reaction is now a good way to make chiral heterocycles. Scheme 1 shows recent results with
chiral auxiliaries such as 1 or 2 (Figure 1) that give the chiral product 3 in up to 87% e.e. (A. Martínez, M. J. Webber, S. Müller, B. List, Angew. Chem. Int. Ed., 2013, 52, 9486).
Chiral products by dearomatising pyrroles Reactions of flat achiral heterocycles can also produce chiral compounds. Turning to Chemical Communications (K.-J. Wu, L.-X. Dai and S.-L. You, Chem. Commun., 2013, 49, 8620), we find a very nice modern example employing palladium catalysis to dearomatise pyrroles such as 5 (Scheme 2). So far, achiral and racemic ligands have been employed, but the way is now open to develop the enantioselective variants of this process. The TRIP ligand class (based on BINOL), which has recently become extremely popular in organocatalysis (see, for example, 2 in Figure 1), is represented here as the phosphoramide 4 in this transition metal catalysed chemistry.
New functionalisation of internal alkynes Alkynes are useful functional groups because they are highly reactive, which gives great scope to perform a wide range of bond-forming processes. The ‘downside’ to high reactivity, however, is issues of control when the alkyne is
52 Chemistry&Industry • November 2013
Figure 1 Examples of BIONOL-derived chiral auxiliaries
1
OH OH
BINOL
Scheme 1 Reagents a: ligand 1 or 2 (Figure 1), Amberlite CG50 resin, toluene, 60o
(for the corresponding Fischer indole from cyclohexanone: see box). reagents b: ligand (rac)-4 (see Figure 1), [Pd(n3
1 (R = 3,5-(CF3 C6 -C3
)2 H5 H3 )Cl]2 , K2
): e.r. = 68:32; 2 (R = 3,5-(CF3 CO3
. toluene, reflux, 10-14h O N NH2 Bu Br
N Ph H
5 Ph c + 6
Scheme 2 Reagents c: CuCl, DCE, DTBP, 50o 24h
C,
unsymmetrically substituted. Copper catalysis has proved helpful
in alkyne chemistry, as, for example, in the immensely versatile CuAAC ‘click’ reaction, which gave regiocontrol to the Huisgen cycloaddition between terminal alkynes and organic azides. The
TfO I 7
conversion of 6 into 7 has now also been performed with the simple, inexpensive catalyst copper chloride. The outcome is a useful new arylation of an unsymmetrical internal alkyne (A. J. Walkinshaw, W. Xu, M. G. Suero, and M. J. Gaunt, J. Am. Chem. Soc., 2013, 135, 12532).
b (rac) Ph N N Ph Bu + Ph Ph a N
Bu 3
)2 C6 H3 4 ): e.r. = 64:36; 2 (R = 9-anthracenyl): e.r. = 87:13 C, 20h; 1 (R = SiPh3 : e.r. = 60:40; R
O O P
R 2
O O
P N Ph Ph
O OH R
O O
R P O OH
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