Iridium‐Catalyzed Asymmetric Allylic Substitutions—Very High Regioselectivity and Air Stability with a Catalyst Derived from Dibenzo[a,e]cyclooctatetraene and a Phosphoramidite

Abstract

Transition-metal-catalyzed asymmetric allylic substitutions are widely employed. Steric course and regioselectivity of these reactions vary considerably, depending on the metal ion, ligands, the nucleophile, and the leaving group. Today, Pd catalysts [1] are usually employed for 1,3-disubstituted allylic substrates, while Ir catalysts [2] serve well for a broad range of monosubstituted allylic substrates.The currently best Ir catalysts are prepared from [{Ir-(cod)Cl} 2 ] (cod = cycloocta-1,5-diene) and a chiral phosphoramidite by C À H activation with base (Scheme 1). Although enantioselectivity is high, this catalyst system suffers from several deficiencies: 1) It is sensitive towards oxygen.2) Long-term stability is low. 3) High selectivities are obtained only with solvents of low polarity, preferably THF. The catalyst system is stable against water and alcohols; however, enantioselectivity in these solvents is lower than in THF. 4) Regioselectivity can be as low as 3:1 (2/3), for example, with substrates 1 b-e.[3]We have now developed a modified catalyst derived from dibenzo[a,e]cyclooctatetraene (dbcot) and L2, which allows substitutions to be run without inert gas for the first time. In addition, regioselectivities with the new catalyst are considerably improved over those with presently used catalysts. Furthermore, we have observed that catalyst preparation by CÀH activation is reversible for complexes of L2 under the standard reaction conditions.The ligand cod can be removed from iridium or altered by a number of reactions. For improvement, dbcot appeared promising because its bonding to Ir is stronger than that of cod, its Ir complexes do not undergo intramolecular CÀH activation at the dbcot moiety, and it is a better electron acceptor than cod. [4] Preparations of dbcot [5] and [{Ir(dbcot)Cl} 2 ][4] were straightforward. The latter was subjected to C À H activation under argon by treatment with 1,5,7-triazabicyclo-[4.4.0]dec-5-ene (TBD) [6] or n-propylamine (Scheme 3). [7] Substitution reactions were investigated with ligands L1-L3 (Scheme 1); the best results were obtained with L2.

Phosphoramidite: privilegierte Liganden in der asymmetrischen Katalyse

“…[285] Auch eine salzfreie Methode wurde entwickelt. [286] Des Weiteren wurden Phosphoramidite mit einer Amidgruppe eingesetzt, allerdings lieferten die Katalysatoren mit diesen Liganden nicht so hohe Enantioselektivitäten wie die zuvor genannten Katalysatoren.…”

Ir‐Catalysed Asymmetric Allylic Substitutions with Cyclometalated (Phosphoramidite)Ir Complexes—Resting States, Catalytically Active (π‐Allyl)Ir Complexes and Computational Exploration

“…Resting state of the allylic substitution upon use of an in situ catalyst: Some time ago we have shown [4] that treatment of in situ generated K2 with weak acids, for example acetic acid, effects the reformation of K1. Now we have found that reformation of K1 also proceeds with allylic substrates and that the catalytically inactive complex K1 constitutes the resting state of the allylic substitution.…”

“…Both K1 and K2 have been previously described. [4] Addition of an allylic substrate to the solution of K2 rapidly led to reformation of the complex K1. As examples, reactions with cinnamyl acetate (C) and cinnamyl diethyl phosphate (D) are illustrated by 31 P NMR spectra in Figure 1.…”

“…First, the complex K1, R= Ph, was prepared by mixing [{IrA C H T U N G T R E N N U N G (cod)Cl} 2 ] and L2 in THF (A in Figure 3). [4] Addition of AgClO 4 gave rise to a precipitate of AgCl. The corresponding solution displayed two singlets with an intensity ratio of 3:1 (B in Figure 3) in the 31 P NMR spectrum.…”

“…A broad range of C-, N-and O-nucleophiles can be employed. [1] After probing a variety of Ir complexes the presently best catalysts are generated by base-induced C À H activation from [{Ir-A C H T U N G T R E N N U N G (cod)Cl} 2 ] (cod = cycloocta-1,5-diene) [2,3] or [{IrA C H T U N G T R E N N U N G (dbcot)Cl} 2 ] (dbcot = dibenzocyclooctatetraene) [4] and a chiral phosphoramidite. Several experimental protocols have been developed for the reaction.…”