Synthesis of α-hydroxyalkyl dehydroazepanes via catalytic enantioselective borylative migration of an enol nonaflate

Clement, Helen A.; Hall, Dennis G.

doi:10.1016/j.tetlet.2018.10.053

Cited by 10 publications

(5 citation statements)

References 24 publications

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“…Furthermore, this methodology was recently extended to the homologous dehydroazepane system, albeit with a lower selectivity. 11 The piperidinyl allylic boronate 4 has proven to be particularly versatile in the synthesis of bioactive compounds using either aldehyde allylboration or regiodivergent Suzuki− Miyaura cross-coupling with aryl and alkenyl halides. The borylative migration/allylboration platform was employed for the concise synthesis of all four stereoisomers of the antimalarial drug mefloquine (Lariam), which confirmed the absolute configuration of the commercial product for the first time using a chemical approach.…”

Section: ■ Introductionmentioning

confidence: 99%

“…The optimal enantioselective conditions employ the piperidinyl alkenyl nonaflate 2b as a substrate, with 3 mol % of Pd(OAc) 2 and 3.3 mol % of the chiral diphosphine Taniaphos in diethyl ether or cyclopentyl methyl ether (CPME). Furthermore, this methodology was recently extended to the homologous dehydroazepane system, albeit with a lower selectivity …”

Section: Introductionmentioning

confidence: 99%

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Mechanism of the Palladium-Catalyzed Asymmetric Borylative Migration of Enol Perfluorosulfonates: Insights into an Enantiofacial-Selective Transmetalation

et al. 2021

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In 2009, one of our laboratories described a palladium-catalyzed enantioselective borylative migration reaction of heterocyclic enol perfluorosulfonates that provides ready access to optically enriched, synthetically useful dihydropyranyl and dehydropiperidinyl allylic boronates 3 and 4. However, several aspects of the catalytic cycle and the mechanism of enantiomeric induction of the anomalous borylation reaction that produces 3 and 4 remain unknown or ambiguous. Herein, a combination of experimental and computational studies suggests that the reaction is initiated by a Miyaura-type borylation, followed by an alkene isomerization pathway involving an electrophilic cationic palladium species. According to reaction kinetics analysis and computations, the first step of oxidative addition to afford the alkenylpalladium-(II) triflate complex Int-2 is the rate-determining step of the overall reaction. Following the complexation of pinacolborane to the cationic alkenylpalladium Int-4 to form the hydride complex Int-5, a face-selective enantio-determining transmetallation via σ-bond metathesis affords the η-2 alkenylboronate-bound palladium(II) hydride Int-6. While formation of this chiral intermediate is key, the calculations suggest that the stereoinduction process is further complicated by a possible reversibility in formation of the intermediate Int-5 preceding the σ-bond metathesis. Moreover, the enantioselectivity is inversely proportional to the pK aH of the amine base owing to protonation of the dimethylamine moiety on the Taniaphos ligand. From Int-6, alkene insertion, β-hydride elimination, and subsequent deprotonation and decomplexation lead to the allylboronate product with regeneration of the palladium(0) catalyst. The ratio of allylboronate to alkenylboronate products depends primarily on the presence of the heteroatom, which provides relative π-stabilization of the palladium hydride complex obtained after alkene isomerization.

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Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mechanism of the Palladium-Catalyzed Asymmetric Borylative Migration of Enol Perfluorosulfonates: Insights into an Enantiofacial-Selective Transmetalation

et al. 2021

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“…Accordingly, significant efforts have been devoted to the development of catalytic, enantioselective synthetic routes to this class of allylboron compounds. Although many excellent procedures have already been reported, the scope of accessible cyclic allylboronates remains limited. , …”

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confidence: 99%

“…Optically active N -heterocyclic allylic boronates have attracted considerable interest, especially in the context of the allylboration of aldehydes. This provides stereocontrolled access to functionalized chiral aminoalcohols, which represent a highly prized class of synthetic intermediates for the construction of a wide variety of naturally occurring complex molecules . Hall and co-workers have reported that the palladium-catalyzed enantioselective borylative alkene isomerization of alkenyl triflates affords chiral N -heterocyclic allylboronates, which are useful allylation reagents for the efficient synthesis of drug molecules (Scheme b) .…”

mentioning

confidence: 99%

“…This provides stereocontrolled access to functionalized chiral aminoalcohols, which represent a highly prized class of synthetic intermediates for the construction of a wide variety of naturally occurring complex molecules . Hall and co-workers have reported that the palladium-catalyzed enantioselective borylative alkene isomerization of alkenyl triflates affords chiral N -heterocyclic allylboronates, which are useful allylation reagents for the efficient synthesis of drug molecules (Scheme b) . However, this protocol is limited to the preparation of six- or seven-membered N -heterocycles (Scheme b).…”

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Synthesis of Chiral N-Heterocyclic Allylboronates via the Enantioselective Borylative Dearomatization of Pyrroles

et al. 2020

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The first enantioselective synthesis of five-membered N-heterocyclic allylboronates has been accomplished by a C−B bond-forming dearomatization of pyrroles using a copper(I) catalyst. This reaction involves the regio-and enantioselective addition of a borylcopper(I) species to pyrrole-2-carboxylates, followed by the diastereoselective protonation of the resulting copper(I) enolate to afford pyrrolidine-type allylboronates. The products are highly attractive reagents for the rapid construction of pyrrolidine derivatives that bear five consecutive stereocenters via subsequent allylboration/oxidation processes.

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Recent Advances in the Stereoselective Additions of Allylic Boronates to Carbonyl Compounds

Clement

Hall

2020

Patai's Chemistry of Functional Groups

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The addition of allylboronates to carbonyl compounds remains an invaluable transformation in synthetic organic chemistry for the stereoselective synthesis of a wide variety of substituted homoallylic alcohols. The use of allylboronates is an exceptionally attractive tool, in part due to the stability of organoboron nucleophiles and the inherently high and predictable stereoselectivity consistently observed. Herein, key advances regarding the thermal and catalyzed allylboration of aldehydes and ketones from the past decade are summarized, with a focus on aspects concerning the scope, mechanism, and stereoselectivity. Notably, novel modes of activation are described for both enantioenriched α‐substituted allylboronates and catalytic enantioselective additions of achiral boronates using chiral protic acids and organocatalysts. A number of innovative metal‐catalyzed enantioselective borylation approaches to allylboronates and their subsequent use as substrates, including bimetallic double allylation reagents, are also highlighted. The current innovative progress and limitations in the field of carbonyl allylboration are discussed.

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Synthesis of α-hydroxyalkyl dehydroazepanes via catalytic enantioselective borylative migration of an enol nonaflate

Cited by 10 publications

References 24 publications

Mechanism of the Palladium-Catalyzed Asymmetric Borylative Migration of Enol Perfluorosulfonates: Insights into an Enantiofacial-Selective Transmetalation

Mechanism of the Palladium-Catalyzed Asymmetric Borylative Migration of Enol Perfluorosulfonates: Insights into an Enantiofacial-Selective Transmetalation

Synthesis of Chiral N-Heterocyclic Allylboronates via the Enantioselective Borylative Dearomatization of Pyrroles

Recent Advances in the Stereoselective Additions of Allylic Boronates to Carbonyl Compounds

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