Enantiospecific Synthesis of ortho‐Substituted 1,1‐Diarylalkanes by a 1,2‐Metalate Rearrangement/anti‐SN2′ Elimination/Rearomatizing Allylic Suzuki–Miyaura Reaction Sequence

Rubial, Belén; Collins, Beatrice S. L.; Bigler, Raphael; Aichhorn, Stefan; Noble, Adam; Aggarwal, Varinder K.

doi:10.1002/ange.201811343

Cited by 7 publications

(3 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A related reactivity of alternative allylboron compounds was disclosed by the Aggarwal group (Scheme 8 D). 33 The chiral allylboron species was generated in situ through a stereospecific 1,2-metalate rearrangement/ anti -S N 2′ elimination sequence of the boron ate complex prepared from an o -lithiated benzylamine and a boronic ester. The allylic boron intermediate engaged in a subsequent Pd-catalyzed stereospecific cross-coupling with aryl iodides.…”

Section: Cross-coupling Of Allyl- and Propargylboron Compoundsmentioning

confidence: 99%

Stereospecific Palladium-Catalyzed Cross-Coupling of Alkylboron Compounds: A Short Account

Lee,

Roh

2024

Synthesis

View full text Add to dashboard Cite

Stereospecific approaches allow the introduction of a stereogenic center into complex organic molecules using optically active reagents. Among these, the Pd-catalyzed stereospecific cross-coupling of chiral alkylboron compounds stands out as a highly effective tool for organic synthesis. In parallel with advances in the development of borylation technology, the strategy has recently witnessed a growth in its applicability. This account aims to review the progress on Pd-catalyzed stereospecific B-alkyl Suzuki–Miyaura cross-coupling, tracing its evolution from early breakthroughs to the most recent advances.1 Introduction2 Cross-Coupling of 1° Alkylboron Compounds3 Cross-Coupling of Benzylboron Compounds4 Cross-Coupling of Allyl- and Propargylboron Compounds5 Cross-Coupling of Other Types of Activated 2° Alkylboron Compounds6 Cross-Coupling of Unactivated 2° Alkylboron Compounds7 Conclusion and Outlook

show abstract

Section: Cross-coupling Of Allyl- and Propargylboron Compoundsmentioning

confidence: 99%

Stereospecific Palladium-Catalyzed Cross-Coupling of Alkylboron Compounds: A Short Account

Lee,

Roh

2024

Synthesis

View full text Add to dashboard Cite

show abstract

“…Since Crudden’s first demonstration of stereospecific Suzuki–Miyaura cross-coupling of acyclic chiral nonracemic Csp 3 boronates in 2009, many important advances in this space have been made . This substantial and accelerating progress suggests that a simple, generalized, and broadly accessible Lego-like process for making stereochemically complex Csp 3 -rich small molecules may be within reach .…”

Section: Introductionmentioning

confidence: 99%

Stereospecific Csp³ Suzuki–Miyaura Cross-Coupling That Evades β-Oxygen Elimination

et al. 2022

View full text Add to dashboard Cite

cross-coupling could transform stereochemically complex small molecule synthesis into a simple and broadly accessible process. However, most current methods are not compatible with complex building blocks that represent densely packed, multistereogenic center-containing motifs commonly found in natural products and other complex targets. Here, we report a method that enables the α-methyl-β-hydroxyl motif, which is found in >18 000 natural products as well as other Csp 3 -rich organic fragments, to be embedded within stereochemically defined secondary alkyl boronic ester building blocks that are readily cross-coupled in a stereospecific manner. The steric effect-mediated decrease in reactivity toward transmetalation and deleterious side reactions associated with the cross-coupling of β-oxygen-containing Csp 3 boronic esters are concomitantly addressed using β-aryloxysilyl groups as dual-purpose transmetalation-promoting groups and stable β-oxygen surrogates. Mechanistic studies including real-time HPLC analysis show that a five-membered pinacol siloxaborolate generated in situ is then hydrolyzed to a dihydroxysiloxaborolate that acts as an activated transmetalation partner in a stereospecific process that proceeds with retention of configuration.

show abstract

“…The Biscoe/Sigman laboratories and the Burke laboratory have each reported approaches toward stereospecific Pd-catalyzed Suzuki reactions using unactivated enantioenriched secondary alkyltrifluoroborates (i.e., without α-heteroatom substitution, α-C(sp 2 ) substitution, or remote coordinating groups). − Our study resulted in the development of a stereodivergent Suzuki process in which the preferred stereochemical course was intimately tied to the electronic properties of the supporting phosphine ligand (Figure a). In these cross-coupling reactions, the bulky electron-deficient ligand bis-CF 3 PhXPhos ( 1 ) promoted a stereoretentive transmetalation pathway, whereas bulky electron-rich ligands P t Bu 3 and PAd 3 ( 2 ) promoted a stereoinvertive transmetalation pathway.…”

mentioning

confidence: 97%

The Stereochemical Course of Pd-Catalyzed Suzuki Reactions Using Primary Alkyltrifluoroborate Nucleophiles

et al. 2021

View full text Add to dashboard Cite

Using deuterium-labeled stereochemical probes, we show that primary alkyltrifluoroborate nucleophiles undergo transmetalation to palladium exclusively via a stereoretentive pathway and that the resulting stereospecificity is broadly independent of electronic and steric effects. This stands in stark contrast to the stereochemical course of transmetalation for secondary alkyltrifluoroborates, which varies between net stereoretention and net stereoinversion depending upon the electronic properties of the supporting phosphine ligand, the electronic properties of the aryl electrophile, and the steric properties of the alkylboron nucleophile. In this study, we additionally show that the stereochemical course of transmetalation for secondary alkylboron reagents can be under reagent steric control, while no such steric control exists for analogous primary alkylboron nucleophiles. The combined study reveals fundamental mechanistic differences between transmetalations of primary and secondary alkylboron reagents in Pd-catalyzed Suzuki reactions.

show abstract

Enantiospecific Synthesis of ortho‐Substituted 1,1‐Diarylalkanes by a 1,2‐Metalate Rearrangement/anti‐S_N2′ Elimination/Rearomatizing Allylic Suzuki–Miyaura Reaction Sequence

Cited by 7 publications

References 68 publications

Stereospecific Palladium-Catalyzed Cross-Coupling of Alkylboron Compounds: A Short Account

Stereospecific Palladium-Catalyzed Cross-Coupling of Alkylboron Compounds: A Short Account

Stereospecific Csp³ Suzuki–Miyaura Cross-Coupling That Evades β-Oxygen Elimination

The Stereochemical Course of Pd-Catalyzed Suzuki Reactions Using Primary Alkyltrifluoroborate Nucleophiles

Contact Info

Product

Resources

About

Enantiospecific Synthesis of ortho‐Substituted 1,1‐Diarylalkanes by a 1,2‐Metalate Rearrangement/anti‐SN2′ Elimination/Rearomatizing Allylic Suzuki–Miyaura Reaction Sequence

Cited by 7 publications

References 68 publications

Stereospecific Palladium-Catalyzed Cross-Coupling of Alkylboron Compounds: A Short Account

Stereospecific Palladium-Catalyzed Cross-Coupling of Alkylboron Compounds: A Short Account

Stereospecific Csp3 Suzuki–Miyaura Cross-Coupling That Evades β-Oxygen Elimination

The Stereochemical Course of Pd-Catalyzed Suzuki Reactions Using Primary Alkyltrifluoroborate Nucleophiles

Contact Info

Product

Resources

About

Enantiospecific Synthesis of ortho‐Substituted 1,1‐Diarylalkanes by a 1,2‐Metalate Rearrangement/anti‐S_N2′ Elimination/Rearomatizing Allylic Suzuki–Miyaura Reaction Sequence

Stereospecific Csp³ Suzuki–Miyaura Cross-Coupling That Evades β-Oxygen Elimination