Highly Stereoselective Cobalt(III)‐Catalyzed Three‐Component C−H Bond Addition Cascade

Abstract

A highly stereoselective three-component C(sp 2 )ÀH bond addition across alkene and polarized p-bonds is reported for which Co III catalysis was shown to be much more effective than Rh III . The reaction proceeds at ambient temperature with both aryl and alkyl enones employed as efficient coupling partners. Moreover, the reaction exhibits extremely broad scope with respect to the aldehyde input; electron rich and poor aromatic, alkenyl, and branched and unbranched alkyl aldehydes all couple in good yield and with high diastereoselectivity. Multiple directing groups participate in this transformation, including pyrazole, pyridine, and imine functional groups. Both aromatic and alkenyl C(sp 2 ) À H bonds undergo the three-component addition cascade, and the alkenyl addition product can readily be converted into diastereomerically pure five-membered lactones. Additionally, the first asymmetric reactions with Co III -catalyzed CÀH functionalization are demonstrated with three-component C À H bond addition cascades employing N-tert-butanesulfinyl imines. These examples represent the first transition metal catalyzed CÀH bond additions to N-tert-butanesulfinyl imines, which are versatile and extensively used intermediates for the asymmetric synthesis of amines.C À H functionalization has emerged as a core strategy to access synthetically useful structural motifs, many of which are found in drugs and natural products. [1,2] Of the many transition-metal catalysts that facilitate this process, Rh III catalysts have been demonstrated to be among the most useful because of their unique reactivity and high functional group compatibility.[3] Following the seminal reports of Co III -catalyzed C À H functionalization [4] by Kanai and Matsunaga in 2013, [5ac] a number of groups (including our own) have demonstrated that earth abundant Co III catalysts can provide analogous reactivity to their second row Rh III congeners. [4,5] For some transformations divergent reactivity is displayed between Cp*Co III and Cp*Rh III catalysts, [6] but significant differences in non-annulative redox-neutral couplings have yet to be reported. Recently, we described preliminary results on a three-component CÀH functionalization cascade by Rh III -catalysis (Figure 1 a). [7] Though the transformation proceeded in good yield, very poor diastereoselectivity was observed. After thorough investigation, only ethyl glyoxylate was reactive in the three-component transformation (Figure 1 a,b). Herein we report that Cp*Co III -catalysts not only facilitate three-component additions to a wide array of aldehydes, including electron poor and rich aromatic, alkenyl, and branched and unbranched alkyl derivatives, but that the transformation also proceeds with high diastereoselectivities ranging from 87:13 to > 98:2 d.r. (Figure 1 c). [8,9] Moreover, we disclose the first asymmetric C À H bond functionalization reaction employing Cp*Co III catalysts, with three-component CÀH bond addition cascades to N-tert-butanesulfinyl imines (Figure 1 d).Our initi...

Transition-Metal-Catalyzed C–H Bond Addition to Carbonyls, Imines, and Related Polarized π Bonds

“…This approach provides an exciting opportunity for accessing complex structures from simple precursors particularly when one considers the number and diversity of possible permutations for combining C=C π-bond inputs such as alkenes, alkynes, dienes and allenes with polarized π-bond electrophiles such as carbonyls, imines, isocyanates, isocyanides and nitriles. 189,190 The initial reports reviewed here provide key proof-of-principle examples, which demonstrated that this approach can be achieved with high levels of regiocontrol, and when stereocenters are introduced, also diastereocontrol.…”

“…190 Moreover, the reactions proceeded with high diastereoselectivity. Air-stable [Cp*Co(C 6 H 6 )][B(C 6 F 5 ) 4 ] 2 54 in combination with lithium acetate provided the highest yield and diastereoselectivity.…”

Intermolecular 1,4‐Carboamination of Conjugated Dienes Enabled by Cp*RhIII‐Catalyzed C−H Activation

“…[5] Despite considerable efforts in this area, most of the protocols developed to date remain limited to two-component reactions.M ulticomponent reactions provide an attractive alternative to streamline the synthesis of complex organic scaffolds. [6,7] Thus,modular three-component carboamination reactions with independent carbon and nitrogen sources are highly desirable. [8] In this regard, Engle and co-workers developed an elegant protocol for the regioselective carboamination of unactivated alkenes involving various nitrogen nucleophiles and carbon Scheme 1.…”

Mild Cobalt(III)‐Catalyzed C–H Hydroarylation of Conjugated C=C/C=O Bonds

“…However, among a number of analogous Cp*Co(III) complexes, only [Cp*Co(benzene)](PF 6 ) 2 displayed high efficacy for the addition of 2‐arylpyridines onto multiple bonds in α,β‐unsaturated enones and imines (Scheme a) . Very recently, a remarkable two‐step sequence consisting of cobalt(III)‐catalyzed C–H hydroarylation of α,β‐unsaturated enones and subsequent diastereoselective addition of the cobalt enolate to aldehydes was developed, as was reported by Ellman (Scheme b) . However, the substrate scope of the reaction needs to be further extended.…”