Palladium-Catalysed Asymmetric Addition of Pronucleophiles to Allenes

Barry Trost has reported an atom economic method for adding pronucleophiles to benzyloxyallene with high regio- and enantioselectivity. The exact conditions depend on the pronucleophile used.

For example with Meldrum's acid as the pronucleophile (the anion of Meldrum’s acid would be the nucleophile) the reaction is carried out in dichloromethane, using 1 mol % ρ allylpalladium chloride dimmer, 1.25 mol % ligand and 1 mol % trifluoroacetic acid, giving the addition product in 81% yield, 100% regioselectivity and 94% ee.

The regioselectivity drops in alternative solvents such as THF (3:1 in favour of the branched product).< >However, when the pronucleophile is the azlactone shown below, the best conditions require 2 mol % potassium tert-butoxide in place of 1 mol % trifluoroacetic acid.

Under these conditions the product is formed in 80% yield, 7:1 dr and 73% ee. However if the reaction is buffered by addition of 20 mol % hippuric acid, the results are 85% yield, 20:1 dr, and 93% ee. A number of examples with other azlactones are reported with similar results. (J. Am. Chem. Soc. , 2003, 125, 4438-4439).

Highly Enantioselective Catalytic Conjugate Addition of Cyanide to a,b-unsaturated Imides

Jacobsen and Sammis have published the first examples of asymmetric 1,4-conjugate addition to a,b-unsaturated carbonyl compounds with cyanide ion.  Chiral aluminium salen catalysts were found to give good enantioselectivity under optimum conditions.  The cyanide source is important, with best results being obtained when HCN is generated in situ from trimethylsilyl cyanide and isopropanol.  If HCN alone is used as the cyanide source no reaction is observed.  Yields over 90% and ee’s over 95% are obtained.  Examples are included where R = Me, Et, ⁿPr, ⁱPr, ⁱBu, (CH₂)₃CHCH₂, ^tBu, and CH₂OBn.  (J. Am. Chem. Soc., 2003, 125, 4442-4443).