Enantioselective Markovnikov Addition of Carbamates to Allylic Alcohols for the Construction of α-Secondary and α-Tertiary Amines

Bahamonde, Ana; Rifaie, Buthainah Al; Martín-Heras, Víctor; Allen, Jamie R.; Sigman, Matthew S.

doi:10.1021/jacs.9b03438

Cited by 33 publications

(19 citation statements)

References 39 publications

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“…Metal-catalyzed hydrofunctionalization of readily available alkenes with nitrogen sources is one of the most efficient methods for the synthesis of nitrogen-containing molecules; however, to achieve the high regio-and enantioselectivities of this transformation is still a challenge ( Fig. 2a) [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] . Among several activation strategies for alkene hydroamination, metal-catalyzed hydrogen atom transfer (HAT) reaction exhibits great Markovnikov selectivity and chemoselectivity (Fig.…”

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confidence: 99%

Ligand-promoted cobalt-catalyzed radical hydroamination of alkenes

Shen

Chen

et al. 2020

Nat Commun

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Highly regio-and enantioselective intermolecular hydroamination of alkenes is a challenging process potentially leading to valuable chiral amines. Hydroamination of alkenes via metalcatalyzed hydrogen atom transfer (HAT) with good regioselectivity and functional group tolerance has been reported, however, high enantioselectivity has not been achieved due to the lack of suitable ligands. Here we report a ligand-promoted cobalt-catalyzed Markovnikovtype selective radical hydroamination of alkenes with diazo compounds. This operationally simple protocol uses unsymmetric NNN-tridentate (UNT) ligand, readily available alkenes and hydrosilanes to construct hydrazones with good functional group tolerance. The hydrazones can undergo nitrogen-nitrogen bond cleavage smoothly to deliver valuable amine derivatives. Additionally, asymmetric intermolecular hydroamination of unactivated aliphatic terminal alkenes using chiral N-imidazolinylphenyl 8-aminoquinoline (IPAQ) ligands has also been achieved to afford chiral amine derivatives with good enantioselectivities.

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confidence: 99%

Ligand-promoted cobalt-catalyzed radical hydroamination of alkenes

Shen

Chen

et al. 2020

Nat Commun

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“…[73] Another limitation is the synthesis of quaternary stereocenters, which is currently restrained by the steric hindrance of the alkene substituents. [8d, 56] It is worth noting that there have been multiple reports on redoxrelay (oxidative) Heck b-functionalization using carbamates as coupling partners; [74] protected alcohols to furnish the corresponding carbonyl products, via in situ deprotections trategies; [61,75] or alkynes to generate C sp -C sp 3 stereocenters. [76] Expansiono ft hesem ethodologies for more remote functionali-zation would also be of great value.…”

Section: Discussionmentioning

confidence: 99%

Stereoselective Remote Functionalization via Palladium‐Catalyzed Redox‐Relay Heck Methodologies

Bonfield

Valette

Lindsay

et al. 2020

Chemistry A European J

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Exploration of novel, three-dimensional chemical space is of growing interesti nt he drug discoveryc ommunity and with this comest he challenge for synthetic chemists to devisen ew stereoselective methods to introduce chirality in ar apid and efficient manner.T his Minireview provides a timely summary of the development of palladium-catalyzed asymmetric redox-relay Heck-type processes. These reactions represent an important class of transformation for the selective introduction of remote stereocenters, and have risen to prominence overt he past decade. Within this Minireview, the vast scope of theset ransformationsw ill be showcased, alongside applications to pharmaceutically relevant chiral buildingb locks and drug substances.T oc omplementt his overview,amechanistic summary and discussion of the current limitations of the transformation are presented, followed by an outlook on future areas of investigation. Scheme1.Scopeo fr edox-relay Heck-type transformations coveredi nthis Minireview.

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“…Contrasting with the numerous reports of enantioselective intramolecular Wacker and aza-Wacker transformations, the intermolecular variants of these reactions are scarce [57][58][59][60]. There are only two reports regarding the addition of oxygen nucleophiles [57,58].…”

Section: Trends Trends In In Chemistry Chemistrymentioning

confidence: 99%

“…The only two examples of enantioselective intermolecular aza-Wacker reactions have been recently reported by the Sigman group [59,60]. Carbamates have been added to allylic alcohols to afford β-amino aldehydes in moderate yields with moderate to good enantioselectivity, albeit with the requirement of high ligand loadings due to the poor stability of the Pd-PyrOx complex under the reaction conditions [60]. This reaction is the only example of an intermolecular Wacker-type reaction that enables the formation of fully substituted enantioenriched chiral centers.…”

Section: Trends Trends In In Chemistry Chemistrymentioning

confidence: 99%

Mechanistically guided survey of enantioselective palladium-catalyzed alkene functionalization

Bahamonde

2021

Trends in Chemistry

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Palladium-catalyzed alkene functionalization was discovered more than 60 years ago and is now a commonly used strategy for the synthesis of pharmaceuticals and materials. The development of asymmetric variants of this reaction is described in this short review. The review is organized around the mechanistic challenges that have hampered the development of these transformations for various substrate classes, as well as the strategies, ligand classes, and additives that have been introduced to overcome them. New methodologies for Heck, oxidative Heck, dehydrogenative Heck, and Wacker-type reactions are highlighted, with a special focus on the progression from cyclic to acyclic to electronically unbiased olefin substrates.Historical background: Mizoroki-Heck-and Wacker-type chemistry Palladium-catalyzed methodologies are ubiquitous in synthetic chemistry and key to their successful implementation has been obtaining a detailed mechanistic understanding of these reactions. Specifically, the two-electron nature of oxidative addition (see Glossary) and reductive elimination, facile β-hydrogen elimination, and high π-Lewis acidity have enabled the organometallic community to rationally design a myriad of Pd-catalyzed strategies to efficiently build molecular complexity [1][2][3][4][5][6][7][8]. The versatility of Pd catalysis has been described in many reviews [9][10][11][12][13][14], but herein we focus on Pd-mediated enantioselective functionalization of alkenes. In particular, this review highlights the different strategies developed to control the regio-and stereoselectivity of the key elementary steps in these processes.The discovery of the Pd(II)-catalyzed water addition to ethylene to give acetaldehyde by researchers in Wacker Chemie in 1959 [15,16] inspired numerous chemists to study the use of transition-metal complexes to catalyze organic transformations. Shortly after, in 1970, the laboratories of Mizoroki and Heck reported the use of Pd(0) complexes to promote olefin arylations and alkylations [17,18]. The general mechanism of Heck-type transformations is outlined in Figure 1 (Key figure), where a Pd(0) complex (A) engages in oxidative addition with an alkenyl or aryl halide to generate Pd(II) intermediate B. Migratory insertion of the alkene into the Pd-C bond forges the new C−C bond and yields Pd-alkyl intermediate C. Subsequently, a β-hydrogen elimination delivers the alkene product 3, and a base-mediated reductive elimination of the Pd-hydride species (D) regenerates the Pd(0) catalyst to restart the cycle. Key to the development of asymmetric variants of this transformation is to favor the β-hydrogen elimination of H b , away from the newly formed stereocenter to render chiral product 3a, over H a , which would deliver achiral product 3b. Although early Heck reaction development attracted the attention of numerous research groups, asymmetric variants of these methodologies remained elusive until 1989, when the groups of Overman and Shibasaki described the use of bisphosphine HighlightsThe mechanistic rat...

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Enantioselective Markovnikov Addition of Carbamates to Allylic Alcohols for the Construction of α-Secondary and α-Tertiary Amines

Cited by 33 publications

References 39 publications

Ligand-promoted cobalt-catalyzed radical hydroamination of alkenes

Ligand-promoted cobalt-catalyzed radical hydroamination of alkenes

Stereoselective Remote Functionalization via Palladium‐Catalyzed Redox‐Relay Heck Methodologies

Mechanistically guided survey of enantioselective palladium-catalyzed alkene functionalization

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