Asymmetric Allylic Substitution Catalyzed by C₁‐Symmetrical Complexes of Molybdenum: Structural Requirements of the Ligand and the Stereochemical Course of the Reaction

Abstract

Application of new chiral ligands (R)-(-)-12 a and (S)-(+)-12 c (VALDY), derived from amino acids, to the title reaction, involving cinnamyl (linear) and isocinnamyl (branched) type substrates (4 and 5 --> 6), led to excellent regio- and enantioselectivities (>30:1, < or =98 % ee), showing that ligands with a single chiral center are capable of high asymmetric induction. The structural requirements of the ligand and the mechanism are discussed. The application of single enantiomers of deuterium-labeled substrates (both linear 38 c and branched 37 c) and analysis of the products (41-43) by (2)H{(1)H} NMR spectroscopy in a chiral liquid crystal matrix allowed the stereochemical pathways of the reaction to be distinguished. With ligand (S)-(+)-12 c, the matched enantiomer of branched substrate was found to be (S)-5, which was converted into (R)-6 with very high regio- and stereoselectivity via a process that involves net retention of stereochemistry. The mismatched enantiomer of the branched substrate was found to be (R)-5, which was also converted into (R)-6, that is, with apparent net inversion, but at a lower rate and with lower overall enantioselectivity. This latter feature, which may be termed a "memory effect", reduced the global enantioselectivity in the reaction of the racemic substrate (+/-)-5. The stereochemical pathway of the mismatched manifold has been shown also to be one of net retention, the apparent inversion occurring through equilibration via an Mo-allyl intermediate prior to nucleophilic attack. Incomplete equilibration leads to the memory effect and thus to lower enantioselectivity. Analysis of the mismatched manifold over the course of the reaction revealed that the memory effect is progressively attenuated with the nascent global selectivity increasing substantially as the reaction proceeds. The origin of this effect is suggested to be the depletion of CO sources in the reaction mixture, which attenuates turnover rate and thus facilitates greater equilibrium. The linear substrate was also converted into the branched product with net syn stereochemistry, as shown by isotopic labeling. An analogous process operates in the generation of small quantities of linear product from branched substrate.

Metal‐Catalyzed Enantioselective Allylation in Asymmetric Synthesis

“…[259] Very recently, C 1 -symmetric pyridine-substituted diamine (S)-(+)-L194 was shown to be an efficient chiral ligand for the molybdenum-catalyzed asymmetric allylic alkylation of dimethyl malonate with isomeric carbonate 92 a and 269: the branched product 110 b was afforded with excellent regioand enantioselectivities (> 30:1, 97-98 % ee, Scheme 87). [260] 4. Iridium-Catalyzed Enantioselective Allylation The reaction of 5-phenyl-1-penten-3-yl acetate (94 f) with sodium malonate in the presence of chiral ligand L195 afforded the branched product (R)-271 a with 93 % ee and high regioselectivity.…”

Nonlinear Effects in Asymmetric Catalysis

“…(39)]. [116] A weak (+)-NLE was detected when scalemic 143 was employed. Since previous crystallographic studies indicated that the active intermediate in such reactions was a monocoordinated allylic complex [Mo(CO) 2 L(allyl)], [117] the authors suggested an equilibrium between the active Mo(L) and inactive (Mo) n (L) 2 complex (n = 1 or 2), which serves as a racemic trap.…”

Metallkatalysierte enantioselektive Allylierungen in der asymmetrischen Synthese

“…[259] Das C 1 -symmetrische pyridylsubstituierte Diamin (S)-(+)-L194 erwies sich erst kürzlich als effizienter chiraler Ligand in der molybdänkatalysierten asymmetrischen allylischen Alkylierung der isomeren Carbonate 92 a und 269 mit Dimethylmalonat, die mit ausgezeichneter Regio-und Enantioselektivität (> 30:1, 97-98 % ee) zum verzweigten Produkt 110 b führte (Schema 87). [260] 4. Iridiumkatalysierte enantioselektive Allylierungen [261] Iridiumkomplexe mit chiralen Liganden wie dem Phosphan-Oxazolin L196, [262] (S)-1,1'-Binaphthyl-2,2'-diylphenylphosphit L197, [263] oder den Phosphoramiditen L198 [264] [272] Han et al haben kürzlich die Synthese der Allylamine 282 (70-92 % Ausbeute, 92 bis über 99 % ee) durch regio-und enantioselektive decarboxylierende allylische Amidierung der Allylbenzylimidodicarbonate 281 beschrieben (Schema 91).…”