Highly Enantio- and Regioselective Allylic Alkylations Catalyzed by Chiral [Bis(dihydrooxazole)]molybdenum Complexes

Abstract

In memory of Luigi M. VenanziA series of chiral C 2 -symmetric bis[dihydrooxazoles] with a trans-1,2-diaminocyclohexane backbone was synthesized. In view of the promising results obtained by Trost et al. with related bis[pyridine] ligands, we tested these new ligands in the enantioselective molybdenum-catalyzed allylic alkylation of 1-and 3-monosubstituted allylic substrates. Enantiomer excesses of up to 98% and branched/linear ratios of up to 11 : 1 were obtained with (E)-3-(alkyl)allyl carbonates. (E)-3-Phenoxyallyl acetate gave a branched/linear ratio of b 20 : 1 and an ee of 98%. Crystal structures of the free ligand 7a and of its tricarbonylmolybdenum(0) complex 28 are reported.Introduction. ± Transition-metal-catalyzed allylic substitution is one of the most efficient and most versatile methods for enantioselective CÀC and CÀheteroatom bond formation [1]. A number of chiral catalysts are available which afford high enantiomer excesses (ee) with many prochiral or racemic substrates. However, there are still classes of substrates which give unsatisfactory results with the known catalysts and, therefore, the search for new chiral ligands and catalyst systems continues.Unsymmetrically substituted allyl derivatives are particularly demanding substrates, because, in addition to the requirement of enantiocontrol, the problem of regioselectivity has to be addressed. With most Pd-catalysts, monosubstituted allyl systems such as 1-or 3-arylallyl derivatives react with C-nucleophiles preferentially at the unsubstituted terminus, giving rise to a linear, achiral product. It is only recently that catalysts have been discovered which allow the preparation of branched, chiral regioisomers from 1-or 3-arylallyl esters, with good enantio-and regioselectivity. Such a reversal of regioselectivity has been achieved by means of Pd complexes with certain chiral ligands such as 1 [2], W [3] and Ir [4] complexes derived from phosphinodihydrooxazoles 2, an Ir catalyst containing the phosphoramidite 3 [5] and, most recently, with a Mo complex [6] derived from the bis[pyridine] 4 [7]. In terms of regio-and enantioselectivity, the latter of these, developed by Trost et al. [6a,b], is the most selective catalyst available today, giving a branched/linear ratio of 49 : 1 and an ee of 99% in the reaction of methyl (E)-1-phenylallyl carbonate with dimethyl malonate.

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

“…Although the mode of coordination of 8 and 11 to Mo in the active catalyst has not been firmly established,10, 15, 16 there is a growing body of evidence that a tridentate, anionic, fac ‐binding mode is involved. By analogy, it can be argued that the R group in ligands 12 could act as an anchor, presumably occupying an “equatorial” position in the cyclic complex, thereby mimicking the rigid scaffold of 8 .…”

“…Trost originally proposed a bidentate coordination of ligand 8 to molybdenum with trans ‐configuration of the ligating nitrogens about the metal center ( A , see below) 10 Pfaltz has reported an X‐ray structure of the complex obtained from ligand 11 and [(EtCN) 3 Mo(CO) 3 ], which shows a tridentate coordination B (with two sp 2 nitrogens and one carbonyl group involved in the coordination) 16. Most recently, Krska, Hughes and Trost have reported on the X‐ray structure of the Mo–η 3 ‐complex C (Ar = Ph), in which the binding to the deprotonated amidic nitrogen has been confirmed by solution 15 N NMR spectroscopy 15.…”

Synthesis of new chiral hydroxy oxazolines and their use in the catalytic asymmetric phenyl transfer to aldehydes

“…After a brief survey of the literature, it was found that ethyl oxazoline-2-carboxylates 10 could be prepared in a single step starting from ethyl oxamate 9, following a procedure reported by Pfaltz and co-workers. 15 This involved an activation of the starting material by a triethyloxonium salt, followed by transamidation and ring closure. Thus, compounds 10a and 10b bearing a phenyl and a tert-butyl group, respectively, on the oxazoline ring were readily synthesized.…”

Mechanistic studies of the molybdenum-catalyzed asymmetric alkylation reaction

“…These reactions may proceed by means of intermediates in which isomerization (K eq in Scheme 1) is slow relative to nucleophilic reaction. In contrast, Mo-based catalysis (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39) proceeds with loss of substrate stereochemistry and provides the opportunity in reactions with asymmetric ligands to obtain high product ee, starting with either the linear substrate or racemic branched product (Scheme 1). These reactions proceed by a dynamic kinetic asymmetric transformation (40) with rapid equilibration of the two diastereomeric -allyl complexes before nucleophilic attack (Scheme 1).…”