Application of Tridentate Bis(oxazoline) Ligands in Catalytic Asymmetric Nozaki–Hiyama Allylation and Crotylation: An Example of High Enantioselection with a Non‐Symmetric Bis(oxazoline) Ligand

Abstract

A series of both symmetric and non-symmetric bis(oxazoline) ligands was applied in the Nozaki-Hiyama allylation and crotylation of benzaldehyde. It was found that both the magnitude and sense of the asymmetric induction depended strongly on the nature and combination of the oxazoline substituents. For both reactions, the non-symmetric tert-butyl/benzyl-substituted ligand proved to be the optimal ligand and was applied successfully in the allylation and crotylation of a range of aryl and aliphatic aldehydes. The enantioselectivities obtained in allylation were up to 91% ee and in crotylation up to 92% with typical syn:anti ratios of up to 80 : 20.

New Chemistry with Anionic NNN Pincer Ligands

“…99.5% ee) than the iodide. With BOPA ligands, rather than Cbzbox, higher anti/ syn ratios (up to 4/1) and enantioselectivities (up to 92% ee for the major isomer) were observed in the crotylation reactions [71]. Finally, the BOXMI ligand family, in combination with CrCl 2 , has also been exploited in the NHK reactions.…”

“…Crotylation reactions of benzaldehyde with crotyl bromide resulted in poorer results with an anti/syn ratio of 2.7/1 with the reaction being anti-selective from the attack of the nucleophile onto the Si-face of the aldehyde [11]. BOPA ligands were subsequently employed in NHK reactions with varying results depending upon the ligand employed [71,72]. The C 2 -symmetric BOPA bearing i Pr groups on the oxazoline rings resulted in an enantiomeric excess of 69%, whereas the non-C 2 -symmetrical ligand bearing two inequivalent oxazoline rings (one with a t Bu and one with a Bn substituent) gave an enantiomeric excess of 87% for the same reaction.…”

New Proline–Oxazoline Ligands and Their Application in the Asymmetric Nozaki–Hiyama–Kishi Reaction

“…Two such examples are the total synthesis of palytoxin and halichondrin B, which both involve extensive use of chromium additions. [15] To date there has been a limited range of ligand classes applied to the enantioselective process, with the most promising examples emerging from the groups of Sigman (3), [5] Cozzi and Umani-Ronchi (11), [16] Nakada (12, 13), [17] Berkessel (14), [18] Kishi (15) [19] and ourselves (4) [8,9] (Figure 5). Our new ligand class 5 was applied in the chromiumcatalysed reaction of allyl bromide with benzaldehyde (Table 1).…”

“…[6] We previously reported the synthesis of tridentate bis-(oxazoline) ligands 4 and their application in the enantioselective Nozaki-Hiyama-Kishi (NHK) allylation, crotylation and methallylation of a range of aromatic and aliphatic aldehydes. [7][8][9] The ligands were prepared by means of a palladium-catalysed aryl amination between the corresponding anilino-oxazoline and bromo-oxazoline. This convergent synthesis allowed the synthesis of both symmetric and nonsymmetric ligands.…”

New Thiazoline–Oxazoline Ligands and Their Application in the Asymmetric Friedel–Crafts Reaction

“…[4,5] The key step in their synthesis was a palladiumcatalyzed aryl amination which allowed us to prepare both C 2 -and non-C 2 -symmetric analogues. These ligands were synthesised by a Pd-catalyzed aryl amination.…”