The Construction of All‐Carbon Quaternary Stereocenters by Use of Pd‐Catalyzed Asymmetric Allylic Alkylation Reactions in Total Synthesis

Hong, Allen Y.; Stoltz, Brian M.

doi:10.1002/ejoc.201201761

Cited by 333 publications

(77 citation statements)

References 113 publications

(64 reference statements)

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“…66 Since these initial disclosures, this method has been featured in several natural product total syntheses. 4 For example, a variety of chiral 3,3-disubstituted oxindoles have been prepared in this fashion with good enantioselectivity, 67,68 as exemplified by the enantioselective and regioselective prenylation ( 78→79 ) utilized in the synthesis of ent -flustramines A ( 80 ) and B (Fig. 8a).…”

Section: Coupling Of Chiral Carbon Electrophilesmentioning

confidence: 99%

Catalytic enantioselective synthesis of quaternary carbon stereocentres

Quasdorf

Overman

2014

Nature

883

341

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Preface Quaternary carbon stereocenters–carbon atoms to which four distinct carbon substituents are attached–are common features of molecules found in nature. However, prior to recent advances in chemical catalysis, there were few methods available for constructing single stereoisomers of this important structural motif. Here we discuss the many catalytic enantioselective reactions developed during the past decade for synthesizing organic molecules containing such carbon atoms. This progress now makes it possible to selectively incorporate quaternary stereocenters in many high-value organic molecules for use in medicine, agriculture, and other areas.

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Section: Coupling Of Chiral Carbon Electrophilesmentioning

confidence: 99%

Catalytic enantioselective synthesis of quaternary carbon stereocentres

Quasdorf

Overman

2014

Nature

883

341

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“…This situation becomes more problematic when generation of all-carbon quaternary stereocenters is pursued. 8 Both reactivity attenuation by steric constraints and difficulties in controlling face selectivity in prostereogenic trisubstituted trigonal centers make this goal to be a hot topic yet. In this study we describe a new enoyl template model for asymmetric organocatalysis in which the bidentate substrate might engage as either H-bond donor or acceptor or both (ambivalency) during activation by the bifunctional catalyst ( Figure 1b).…”

Section: ■Introductionmentioning

confidence: 99%

Enantioselective Construction of Tetrasubstituted Stereogenic Carbons through Brønsted Base Catalyzed Michael Reactions: α′-Hydroxy Enones as Key Enoate Equivalent

et al. 2014

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Catalytic and asymmetric Michael reactions constitute very powerful tools for the construction of new C-C bonds in synthesis, but most of the reports claiming high selectivity are limited to some specific combinations of nucleophile/electrophile compound types, and only few successful methods deal with the generation of all-carbon quaternary stereocenters. A contribution to solve this gap is presented here based on chiral bifunctional Brønsted base (BB) catalysis and the use of α'-oxy enones as enabling Michael acceptors with ambivalent H-bond acceptor/donor character, a yet unreported design element for bidentate enoate equivalents. It is found that the Michael addition of a range of enolizable carbonyl compounds that have previously demonstrated challenging (i.e., α-substituted 2-oxindoles, cyanoesters, oxazolones, thiazolones, and azlactones) to α'-oxy enones can afford the corresponding tetrasubstituted carbon stereocenters in high diastereo- and enantioselectivity in the presence of standard BB catalysts. Experiments show that the α'-oxy ketone moiety plays a key role in the above realizations, as parallel reactions under identical conditions but using the parent α,β-unsaturated ketones or esters instead proceed sluggish and/or with poor stereoselectivity. A series of trivial chemical manipulations of the ketol moiety in adducts can produce the corresponding carboxy, aldehyde, and ketone compounds under very mild conditions, giving access to a variety of enantioenriched densely functionalized building blocks containing a fully substituted carbon stereocenter. A computational investigation to rationalize the mode of substrate activation and the reaction stereochemistry is also provided, and the proposed models are compared with related systems in the literature.

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“…1 A powerful approach for the synthesis of all-carbon quaternary stereocenters is an allylic substitution reaction. 1e, 2 Such a reaction not only delivers the desired stereocenter, but also includes a versatile alkene substituent that provides multiple opportunities for further elaboration. 3 Recognizing the potential of such an approach, many elegant enantioselective additions to allylic electrophiles have been developed to deliver quaternary stereocenters substituted with terminal alkenes ( 2 , Scheme 1A).…”

mentioning

confidence: 99%

Stereospecific, Nickel-Catalyzed Suzuki–Miyaura Cross-Coupling of Allylic Pivalates To Deliver Quaternary Stereocenters

et al. 2017

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Recognizing the importance of all-carbon, quaternary stereocenters in complex molecule synthesis, a stereospecific, nickel-catalyzed cross-coupling of allylic pivalates with arylboroxines to deliver products equipped with quaternary stereocenters and internal alkenes was developed. The enantioenriched allylic pivalate starting materials are readily prepared, and a variety of functional groups can be incorporated on both the allylic pivalate and the arylboroxine. Additional advantages include the use of a commercially available and air-stable Ni(II) salt and BISBI ligand, mild reaction conditions, and high yields and ee’s. The observed stereoinversion of this reaction is consistent with an open transition state in the oxidative addition step.

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The Construction of All‐Carbon Quaternary Stereocenters by Use of Pd‐Catalyzed Asymmetric Allylic Alkylation Reactions in Total Synthesis

Cited by 333 publications

References 113 publications

Catalytic enantioselective synthesis of quaternary carbon stereocentres

Catalytic enantioselective synthesis of quaternary carbon stereocentres

Enantioselective Construction of Tetrasubstituted Stereogenic Carbons through Brønsted Base Catalyzed Michael Reactions: α′-Hydroxy Enones as Key Enoate Equivalent

Stereospecific, Nickel-Catalyzed Suzuki–Miyaura Cross-Coupling of Allylic Pivalates To Deliver Quaternary Stereocenters

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