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Monodentate Phosphoramidites: A Breakthrough in Rhodium‐Catalysed Asymmetric Hydrogenation of Olefins
Author(s) -
van den Berg Michel,
Minnaard Adriaan J.,
Haak Robert M.,
Leeman Michel,
Schudde Ebe P.,
Meetsma Auke,
Feringa Ben L.,
de Vries André H. M.,
Maljaars C. Elizabeth P.,
Willans Charlotte E.,
Hyett David,
Boogers Jeroen A. F.,
Henderickx Hubertus J. W.,
de Vries Johannes G.
Publication year - 2003
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.200390026
Subject(s) - chemistry , asymmetric hydrogenation , denticity , rhodium , phosphoramidite , ligand (biochemistry) , catalysis , medicinal chemistry , enantiopure drug , solvent , itaconic acid , organic chemistry , enantioselective synthesis , copolymer , crystal structure , polymer , receptor , dna , biochemistry , oligonucleotide
Monodentate phosphoramidites based on BINOL or substituted BINOL are excellent ligands for the rhodium‐catalysed asymmetric hydrogenation of olefins. Very high enantioselectivities were obtained with MonoPhos ( 7a ) the simplest member of this class, a ligand that is prepared in a single step from BINOL and HMPT. Turnover numbers up to 6000 have been obtained in the hydrogenation of dehydroamino acid derivatives. Enantioselectivities in the hydrogenation of dehydroamino acids are solvent dependent; in non‐protic solvents they range from 95–99%. Itaconic acid and its dimethyl ester could be hydrogenated with 96 and 94% e.e., respectively. Hydrogenation of aromatic enamides gave the corresponding acylated amines in 86–94% e.e. Several analogous phosphoramidite ligands have been prepared. Surprisingly, bidentate ligands gave poorer results, both in terms of rate as well as enantioselectivity. Taddol‐based phosphoramidites led to poor e.e. and slow rates. Methyl substituents at the 3,3′‐position of BINOL led to a sharply reduced rate and a somewhat lower enantioselectivity. Bromo substituents at the 6,6′‐position led to a slightly reduced rate but little effect was seen on enantioselectivity. Use of octahydro‐MonoPhos ( 11 ) gave results that were very similar to those obtained with 7a . The rate of the reaction is dependent on the hydrogen pressure, however, the enantioselectivity is not affected. The rate of the dehydroamino acid hydrogenation also increases if the ligand to rhodium ratio is reduced from 2.2 to 1.5 or even to 1.0; yet, there is no deleterious effect on the enantioselectivity. Catalytic activity ceases with L/Rh=3 when dehydroamino acid derivatives were used as substrate. The reaction shows a positive non‐linear effect, which confirms the presence of Rh‐complexes with more than one ligand. Following the hydrogenation of methyl 2‐acetamidocinnnamate with Rh(nbd) 2 BF 4 / 7a by electrospray mass spectrometry showed the presence of several rhodium species. Notable are the presence of [Rh( 7a )] 3 + and [Rh( 7a )] 4 + . There is at present insufficient evidence to conclude if the active catalytic species carries one or two ligands. In view of the low cost of MonoPhos this invention might well lead to a broader application of asymmetric olefin hydrogenation for the production of enantiopure amino acids and amines.