Regio- and Enantioselective Allylic Substitution with Less Active N- or O-Nucleophiles Catalyzed by Iridium-Complex of Bis(oxazolinyl)pyridine

Abstract

Enantioselective transition metal-catalyzed allylic substitutions have been developed as fundamentally important crosscoupling reactions. [1][2][3][4][5][6][7][8] In general, the heteroatom nucleophiles in these reactions have been largely limited to alkylamines, anilines, carboxylates and phenols. Our laboratory is interested in searching the synthetically useful heteroatom nucleophiles for the synthesis of functionalized allylic compounds (Fig. 1).9) As our successful examples, we have recently reported the utility of oximes 1 and guanidines 5 and 6 as nucleophiles in the transition metal-catalyzed allylic substitution. [10][11][12][13][14] Hydroxylamines are also attractive synthetic reagents for allylic substitution, since they have nitrogen and oxygen atoms as nucleophiles. However, the allylic substitution with hydroxylamines has not been studied well and is limited to a simple palladium-catalyzed amination 15,16) ; thus, there are no reports on asymmetric reactions. We have recently reported that hydroxylamines 2 and 3 having an N-electron-withdrawing substituent, also known as hydroxamic acids, act as reactive oxygen nucleophiles in the enantioselective allylic substitution ( Fig. 1). 17,18) As a part of our program directed toward searching the synthetically useful heteroatom nucleophiles, we describe in detail the study of hydroxylamines 4 as nitrogen nucleophiles in the regio-and enantioselective iridium-catalyzed allylic substitutions. 19) In this study, we also expected that comparison with alkylamines, p-anisidine, and 4-methoxyphenol would lead to informative suggestions regarding the asymmetric reaction using the iridium complex of pybox (bis(oxazolinyl)pyridine) ligand. Results and DiscussionControlling both regio-and enantioselectivities has been of great importance in the allylic substitution of unsymmetrical substrates with heteroatom nucleophiles. [20][21][22][23][24] The regioselectivities in reactions using rhodium, [25][26][27][28][29][30][31][32][33] iridium, [34][35][36][37][38] and ruthenium [39][40][41] complexes are quite different from those of palladium-catalyzed reaction. Therefore, chiral iridium complexes controlling regio-and enantioselectivities have been a subject of current interest. Recently, we reported that the iridium-complex of pybox catalyzed allylic substitution of unsymmetrical substrates to form branched products with good enantioselectivities. 13,14,17,19) Prior to exploring the enantioselective reaction, we first investigated the viability of hydroxylamine 4A having N-benzoyl and O-benzyl groups (Chart 1). Although the reaction of 4A with carbonate 7 was less effective in the absence of a base, the reaction of 4A with acetate 8 proceeded smoothly by employing Et 2 Zn as a base to give the branched product 9Aa in 60% yield without formation of the linear product.Based on these results, we next investigated iridium-catalyzed asymmetric allylic substitution with hydroxylamine 4A under basic conditions (Chart 2). In this study, phosphate 10a was employed as an unsymm...

A Water-Soluble Pybox Derivative and Its Highly Luminescent Lanthanide Ion Complexes

“…While its use as a sensitizer of Ln(III) ion luminescence remains scarce, since Pybox was first reported by Nishiyama in 1989, it has been extensively utilized in catalysis. − Nishiyama et al showed that Pybox can be synthesized with substituted oxazoline rings and used as a ligand in a Ru(IIII) catalyst for the asymmetric hydrosilylation of ketones . Recent reports of enantioselective catalysis using transition-metal complexes with oxazoline-derivatized Pybox ligands include cross-coupling reactions on racemic halides with aryl zinc reagents, − Nazarov cyclizations, asymmetric [3 + 2] cycloadditions of racemic cyclopropanes and aldehydes or alkynes with N -tosylaziridines, carbonyl-ene reactions, aminations, , Negishi cross-coupling, , Mukaiyama-aldol reactions, allylic substitutions with N or O nucleophiles, and copper-catalyzed reduction of secondary amines . Pybox complexes of transition metals have also successfully been immobilized on solid supports to be used in catalytic processes. − Pybox complexes of the rare earths have been used in Friedel–Crafts alkylations, Mukaiyama-aldol reactions, , and silylcyanation of aldehydes .…”

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

“…Whereas the above mentioned addition was highly diastereoselective, the same reaction under identical conditions but in the absence of CeCl 3 resulted in the formation of a small amount of the anti,anti diastereomer of 4 (anti,syn/anti,anti, 80:20). Subsequently, the treatment of anti,syn-4 with zinc in acetic acid at 40 °C gave the N-Cbz-protected amino diol 11 in a very good yield of 85% [20,26]. Next, we investigated the substrate-directed epoxidation that could deliver an oxygen atom from the same side of the double bond as the adjacent hydroxy group [27].…”

Recent Advances in the Creation of Asymmetric Carbon Centre(s) by Generation of Carbon‐Heteroatom Bond(s) Using Metal‐Pybox Complexes

“…Later the iridium‐pybox catalysis was extended for the regio‐ and stereoselective allyl substitution of nitrogen nucleophiles such as hydroxyl amines, aliphatic and aromatic amines in DCM with CsOH.H 2 O as the optimized base. The reaction also worked well with p ‐methoxy phenol using K 2 CO 3 as the base (Scheme ) …”