Relay Redox and Lewis Acid Catalysis in the Titanocene‐ Catalyzed Multicomponent Assembly of 1,5‐Enynes

Lepore, Antonio J.; Pinkerton, David M.; Ashfeld, Brandon L.

doi:10.1002/adsc.201300359

Cited by 16 publications

(8 citation statements)

References 58 publications

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“…Ashfeld advanced Ti-promoted redox–Lewis acid relay catalysis for the three-component coupling of aldehydes ( 54 ), iodoacetylides ( 55 ), and nucleophiles ( 56 ; Scheme ). − In this reaction, the Ti catalyst is proposed to take on multiple roles in the mechanism by behaving as both a Lewis acid and a single-electron reductant. The reaction begins with the reductive activation of 55 by Cp 2 Ti III Cl to form Ti IV -acetylide 58 .…”

Section: Net-reducing Methodologymentioning

confidence: 99%

“…For example, chromones and quinolones with pendent nitrile groups (41) can undergo reductive ketone− nitrile cyclization to yield product 42 (Scheme 5B). 42−44 developed an enantioselective variant of the reductive ketone− nitrile cyclization using Brintzinger's ansa-titanocene complex (48), providing efficient access to enantioenriched αhydroxyketones (49) with a fully substituted stereocenter (Scheme 6). 45,46 2.3.…”

Section: Introductionmentioning

confidence: 99%

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Recent Advances in Titanium Radical Redox Catalysis

McCallum

Lin

2019

J. Org. Chem.

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New catalytic strategies that leverage single-electron redox events have provided chemists with useful tools for solving synthetic problems. In this context, Ti offers opportunities that are complementary to late transition metals for reaction discovery. Following foundational work on epoxide reductive functionalization, recent methodological advances have significantly expanded the repertoire of Ti radical chemistry. This Synopsis summarizes recent developments in the burgeoning area of Ti radical catalysis with a focus on innovative catalytic strategies such as radical redox-relay and dual catalysis.

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Section: Net-reducing Methodologymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Recent Advances in Titanium Radical Redox Catalysis

McCallum

Lin

2019

J. Org. Chem.

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“…The combined organic layers were washed with brine, dried under anhydrous Na 2 SO 4 , and concentrated under reduced pressure to yield the crude product, which was purified by column chromatography on silica gel (eluent: hexane/EtOAc = 20:1) to afford a yellow solid (71 mg, 81% yield): 1 H NMR (CDCl 3 , 400 MHz, δ) 7.36 (d, J = 8.9 Hz, 2H), 6.59 (d, J = 8.9 Hz, 2H), 2.99 (s, 6H, N(CH 3 ) 2 ); 13 C{ 1 H} NMR (CDCl 3 , 100.6 MHz, δ) 150.9 (q), 134.5 (t), 111.7 (t), 106.8 (q), 79.2 (q), 75.8 (q), 73.6 (q), 40.2 (p), 0.4 (q); IR (cm (Iodobuta-1,3-diyn-1-yl)benzene (7d). 146 This compound was synthesized in accordance with method B from buta-1,3-diyn-1ylbenzene (5d) (300.0 mg, 2.38 mmol). The crude product was purified by column chromatography (eluent: hexane/acetone = 100:1) to afford a light brown solid (443 mg, 74% yield): 1 H NMR (CDCl 3 , 400.13 MHz, δ) 7.55−7.45 (m, 2H, Ar), 7.34 (m, 3H, Ar).…”

Section: Scheme 7 Electrophile-induced Cyclization Of Bis(ethynyl)tri...mentioning

confidence: 99%

1-Iodobuta-1,3-diynes in Copper-Catalyzed Azide–Alkyne Cycloaddition: A One-Step Route to 4-Ethynyl-5-iodo-1,2,3-triazoles

et al. 2019

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Cu-catalyzed 1,3-dipolar cycloaddition of iododiacetylenes with organic azides using iodotris(triphenylphosphine)copper(I) as a catalyst was found to be an efficient one-step synthetic route to 5-iodo-4-ethynyltriazoles. The reaction is tolerant to various functional groups in both butadiyne and azide moieties. The synthetic application of 5-iodo-4-ethynyl triazoles obtained was also evaluated: the Sonogashira coupling with alkynes resulted in unsymmetrically substituted triazole-fused enediyne systems, while the Suzuki reaction yielded the corresponding 5-aryl-4-ethynyl triazoles.

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“…Nevertheless, the main challenge with the proposed strategy resided in the enantioselective synthesis of enyne 1 . Most synthetic methods known to access 1,5-enynes take advantage of the reactivity of a propargylic cation generated through either catalytic or stoichiometric Lewis acid activation, allowing access only to racemic material . Morken et al showed recently that a Pd-catalyzed enantiospecific cross-coupling reaction gave 1,5-enynes with high enantiomeric excess starting from enantioenriched activated propargylic alcohols and allyl boronic esters .…”

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confidence: 99%

Enantioselective Synthesis of Polycyclic Carbocycles via an Alkynylation–Allylation–Cyclization Strategy

2014

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ABSTRACT:A new general three-stage strategy to access polycyclic ring systems bearing all-carbon quaternary centers with high enantioselectivity is reported. The required starting materials were readily accessed in racemic form through the -alkynylation of ketoesters with EBX (Ethynyl BenziodoXolone) hypervalent iodine reagents. A Pd-catalyzed asymmetric decarboxylation allylation was then achieved in high yields and enantioselectivities with Trost's biphosphine ligands. Finally, transition-metal catalyzed cyclization of the obtained chiral enynes gave access to fused and spiro polycyclic ring systems constituting the core of many bioactive natural products.The fascinating structure of natural products is the result of millions of years of evolution in interaction with biological targets. Particularly striking is the high occurrence of complex polycyclic ring systems with numerous stereocenters. An interesting substructure present in natural products is constituted by a benzene ring fused to at least two further saturated carbocycles. Both fused and spiro ring systems can be found in important bioactive compounds such as steroids like estradiol or alkaloids like buprenorphine.1 The presence of all-carbon quaternary centers embedded in the polycyclic core of many of these molecules represents a formidable challenge for synthetic chemistry.2 In this context, we envisioned that ketone 1 bearing a 1,5 enyne substructure around an all-carbon quaternary center would be an ideal precursor for both fused and spiro ring systems (Scheme 1). Addition of an allyl Grignard reagent, followed by olefin ring-closing metathesis (RCM) would give an easy access to fused ring systems. The 1,5-enyne itself can be used to access spiro or rearranged ringsystems based on transition-metal catalysis.3 Whereas RCM is now a mature method, cyclisomerization reactions to access spiro ring systems have been much less investigated. Indeed, there are only two examples of such transformations so far, both occurring on unsubstituted alkane rings. 3h,3k Nevertheless, the main challenge with the proposed strategy resided in the enantioselective synthesis of enyne 1. Most synthetic methods known to access 1,5 enynes take advantage of the reactivity of a propargylic cation generated through either catalytic or stoichiometric Lewis acid activation, allowing access only to racemic material. 4 Morken and co-workers showed recently that a Pd-catalyzed enantiospecific crosscoupling reaction gave 1,5-enynes with high enantiomeric excess starting from enantioenriched activated propargylic alcohols and allyl boronic esters. 5a In this report only one example leading to all-carbon quaternary centers in a non-cyclic product was presented. In 2013, the same group reported a kinetic resolution of racemic propargylic esters using chiral ligands. Clearly, none of the reported methods to access 1,5-enynes appeared promising in the context of our synthetic goal, and we decided to developed a new strategy based on the enantioselective decarboxylative allylation...

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Relay Redox and Lewis Acid Catalysis in the Titanocene‐ Catalyzed Multicomponent Assembly of 1,5‐Enynes

Abstract: Herein we describe a direct, multicomponent assembly of 1,5-enynes. The titanocene-catalyzed coupling of an aryl aldehyde, iodoalkyne, and allylsilane enables the convergent and rapid synthesis of this versatile architectural motif in good to excellent yields.

Cited by 16 publications

References 58 publications

Recent Advances in Titanium Radical Redox Catalysis

Recent Advances in Titanium Radical Redox Catalysis

1-Iodobuta-1,3-diynes in Copper-Catalyzed Azide–Alkyne Cycloaddition: A One-Step Route to 4-Ethynyl-5-iodo-1,2,3-triazoles

Enantioselective Synthesis of Polycyclic Carbocycles via an Alkynylation–Allylation–Cyclization Strategy

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