Allyl cyanide, asymmetric hydroformylation

The asymmetric hydroformylation of allyl cyanide has recently focused the interest of researchers because the iso-aldehyde derivative can be easily transformed into 2-methyl-4-aminobutanol, a useful building block, for instance for the asymmetric synthesis of tachikinin (58), a novel NK1 receptor agonist developed by Takeda [82], It should be noticed that this aldehyde is not accessible via the hydroformylation of crotononitrile. 

Table 5 Rh-catalyzed asymmetric hydroformylation of allyl cyanide with ligands 2, 5, 59-62 ...

DSM reported that the asymmetric hydroformylation of unsaturated nitriles (Scheme 12.72) to provide a potential route to (/ )-4-amino-2-methyl-l-ol (180), which is a key intermediate for TAK-637 (181), a new Tachykinin NK, receptor antagonist, developed by Takeda (Scheme 12.73). Rhodium-BINAPHOS (4 equiv) has catalyzed the asymmetric hydroformylation of but-3-enenitrile (allyl cyanide) with regioselectivity of 72/28 (b/1) and 66% ee at 73% conversions.227... 

Klosin and co-workers at Dow Chemical have reported a parallel protocol for the screening of asymmetric hydroformylation reactions of styrene, vinyl acetate, and allyl cyanide.In a one-pot, multiple substrate screening method introduced by Kagan, an Endeavor eight-cell reactor was used to screen 48 different rhodium... 

An exception concerns probably the asymmetric hydroformylation of allyl cyanide with a chiral monodentate phos-phoramidite ligand, which gave 80%... 

Scheme 4.84 Asymmetric hydroformylation of allyl cyanide and subsequent steps to a building block with the potential for the construction of pharmaceutically interesting compounds.

Cobley CJ, Gardner K, Klosin J, Praquin C, HiU C, Whiteker GT, Zanotti-Gerosa A, Petersen JL, Abboud KA. Synthesis and application of a new bisphosphite ligand collection for asymmetric hydroformylation of allyl cyanide. J. Org. Chem. 2004 69 4031 040. 

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