Exogenous‐Base‐Free Palladacycle‐Catalyzed Highly Enantioselective Arylation of Imines with Arylboroxines

Abstract

Enantiomerically pure benzylic amines are important for the development of new drugs. A readily accessible planar-chiral ferrocene-derived palladacycle is shown to be a highly efficient catalyst for the formation of N-substituted benzylic stereocenters; this catalyst accelerates the 1,2-addition of arylboroxines to aromatic and aliphatic imines with exceptional levels of enantioselectivity. Using aldimines an exogenous base was not necessary for the activation of the boroxines, when acetate was used as an anionic ligand. Common problems such as aryl-aryl homocouplings and imine hydrolysis were fully overcome, the latter even in the absence of molecular sieves.

Ni(II)-catalyzed asymmetric alkenylations of ketimines

“…The stereochemical outcome can be explained using the model shown in Fig. 4 , similar to that of Rh- and Pd-catalysis 30 – 36 , 50 – 57 . The substrate coordinates with nickel and the sulfonyl group lies on the opposite side of diphenyl substituents on the oxazoline ring.…”

“…1b ) 45 – 47 . The Pd-catalyzed addition of alkenylboron reagents to double bonds, including imines, has not been described 50 – 57 . This may be due to potential side-reactions, such as homocouplings, Heck reactions, and aza-Wacker-type reactions.…”

Planar chiral palladacycle precatalysts for asymmetric synthesis

“…4 In addition, related chiral non-racemic palladacycles have been applied successfully to the catalysis of asymmetric reactions. 5 Examples include the allylic imidate rearrangement, 6 hydrophosphination, 7 imine arylation, 8 the aza-Morita-Baylis-Hillman reaction 9 and Michael type reactions. 10 Palladium(II) mediated activation of the substrate and retention of the palladacycle C-Pd bond in the chiral catalyst is either demonstrated 11 or invoked.…”

“…10 Palladium(II) mediated activation of the substrate and retention of the palladacycle C-Pd bond in the chiral catalyst is either demonstrated 11 or invoked. [7][8][9][10] A recent report on palladacycle catalysed asymmetric Suzuki cross-coupling was explained by the operation of a Pd(II)/Pd(IV) catalytic cycle. 12 In contrast, the use of chiral non-racemic palladacycles as precatalysts for asymmetric reactions proceeding via a Pd(0)/Pd(II) catalytic cycle does not appear to have been demonstrated.…”

Conversion of anilines to chiral benzylic amines via formal one-carbon insertion into aromatic C–N bonds

“…Chiral α-branched benzylic amines are important structural motifs found in a wide range of natural products and biologically active compounds 34 – 37 . Driven by the value of active pharmaceutical ingredients, the asymmetric arylation of aldimines by arylmetallic reagents, including lithium 38 , 39 , zinc 40 , titanium 41 , tin 42 , and boron reagents 43 , 44 , has been established as an efficient method for the synthesis of enantiopure benzylic amines. Enantioselective one-carbon insertion into the aromatic carbon–nitrogen bonds is an appealing route with which to establish nitrogen-substituted benzylic stereocenters, and this reaction could satisfy an unmet need in reaction design (Fig.…”