Structure−Activity Relationships for Group 4 Biaryl Amidate Complexes in Catalytic Hydroamination/Cyclization of Aminoalkenes

Abstract

Synthesis of bis(carboxamide) proligands derived from (R,S)-2,2‘-diamino-6,6‘dimethylbiphenyl was readily achieved by treatment of the amine with acid chlorides. Direct reaction with homoleptic alkyls of the group 4 metals cleanly yielded amidate complexes. These complexes were shown by single-crystal X-ray diffraction to be monomeric in the case of titanium and dimeric in the case of zirconium. The complexes formed do not yield well-defined cations upon reaction with standard borate/borane activators, and although some hydroamination catalysis was observed, it was not at a rate that is useful. In-situ treatment of Zr(NMe2)4 with the proligands H2L1-4 yielded complexes of varying nuclearity depending on the steric bulk of the amide substituents, but in contrast to the metal alkyl series, mononuclear species are accessible; the mesityl derivative [(S)-L4Zr(NMe2)2] was found to be a highly enantioselective catalyst for the hydroamination/cyclization of 1-amino-2,2-dimethylpent-4-ene, with an enantiomeric excess of 91%.

Transition‐Metal‐Catalyzed Hydroamination Reactions

“…Asymmetric alkene hydroamination remains a long-standing goal in the field, and to date, there are only a handful of catalysts from across the periodic table that can achieve this reaction with enantioselectivities in excess of 90% [65][66][67][68][69][70][71]. Notably, all of these reported examples display significant substrate specificity whereby select substrates undergo cyclohydroamination with excellent enantioselectivity with some catalysts, while other substrates with the same catalyst system can give low enantioselectivities or even the opposite absolute configuration.…”

“…This focused topic has been comprehensively reviewed by Hultzsch [280] and is briefly summarized in the comprehensive review of 2008 [10]. Most published contributions have focused on the use of rare earth and early transition metal (Section 15.2.5) catalysts and indeed these have been some of the most successful examples reported to date [43,63,64,66,67,[74][75][76][77][78][79][80][81][82][83][84][85][281][282][283][284][285][286][287][288], likely because of the clear mechanistic requirement of a reactive M-N bond (single or double, depending on the mechanistic proposal) in the catalytic cycle. In late transition metals, where many reactions have been shown to proceed via outer-sphere amine addition to coordinated alkene, it is challenging to control such additions distal to the metal.…”

“…To realize expanded reactivity with unactivated alkenes, protected nitrogen substrates have been used to advantage and this will be summarized later in this section. Interestingly, while intramolecular enantioselective hydroamination of unactivated alkenes with alkylamines has been extensively reported for rare earth metals [85,[284][285][286][287] and early transition metals [43,63,64,66,67,[74][75][76][77][78][79][80][81][82][83][84]288], it was not until 2010 that late transition metals were reported to give comparable results. Buchwald [291] disclosed asymmetric intramolecular hydroamination of unprotected secondary aminoalkenes to give chiral pyrrolidine products with ee's up to 91%.…”

Asymmetric Hydroamination

“…Enantioselectivities of up to 93% ee may be achieved using chiral bis(amidate) zirconium complex (S)-55 (Scheme 11.16), first introduced by Schafer [89] and soon after by Scott [90].…”

Synthesis, structure, and catalytic activity of group 4 complexes with new chiral binaphthyldiamine-based ligands

“…One of the initial driving forces for this work is the interest in the development of catalysts for intramolecular asymmetric alkene hydroamination [10][11][12][13], because the hydroamination is a highly atomic economical process in which an amine N-H bond is added to an unsaturated carbon-carbon bond leading to the formation of nitrogen heterocycles that are found in numerous biologically and pharmacologically active compounds. Although chiral catalysts based on group 4 metals for asymmetric alkene hydroamination have been intensively studied in recent years [14][15][16][17][18][19][20][21][22][23][24], only a small number of highly enantioselective reactions (N90% ee) have been reported [19,20]. Thus, the development of new group 4 metal catalysts for asymmetric alkene hydroamination is a desirable and challenging goal.…”