Highly enantioselective addition of linear alkyl alkynes to linear aldehydes

Du, Yuhao; Turlington, Mark; Zhou, Xiang; Pu, Lin

doi:10.1016/j.tetlet.2010.07.082

Cited by 29 publications

(19 citation statements)

References 19 publications

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“…Furthermore, the use of NMI as a Lewis base to form the alkynylzinc at room temperature for the addition of 1-hexyne to valeraldehyde produced the product with a drastically reduced enantioselectivity of 64% ee. 16 The lower enantioselectivity observed for the linear alkyne could be due to the smaller steric bias of the linear alkyne in the catalytic pocket.…”

Section: Catalysis By Binol-znet 2 -Ti(oi-pr) 4 -Cy 2 Nhmentioning

confidence: 99%

“…It was found that in the presence of 20 mol% (S)-BINOL, dicyclohexylamine (Cy 2 NH) could provide the product with a much improved enantioselectivity of 81% ee for the addition of 1-hexyne to valeraldehyde at room temperature over the use of NMI. 16 This catalyst system was successfully applied to the addition of a variety of linear alkyl alkynes to aliphatic aldehydes utilizing 20 mol% BINOL and 50 mol% Ti(Oi-Pr) 4 as shown in Scheme 11 and Table 6, resulting in yields of 57-77% and improved enantioselectivities of 77-89% ee. The addition of the Lewis base Cy 2 NH could not only facilitate the reaction at room temperature but also enhance the enantioselectivity.…”

Section: Catalysis By Binol-znet 2 -Ti(oi-pr) 4 -Cy 2 Nhmentioning

confidence: 99%

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Asymmetric Alkyne Addition to Aldehydes Catalyzed by BINOL and Its Derivatives

Turlington¹,

Pu²

2012

Synlett

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This Account describes our research over the past decade in the asymmetric alkyne addition to aldehydes to generate optically active propargylic alcohols. Our methods employ a dialkylzinc reagent to react with a terminal alkyne to form an alkynylzinc nucleophile, and can be grouped into the BINOL-catalyzed reactions and the functionalized BINOL catalyzed reactions. We first describe the development of the BINOL-ZnEt 2 -Ti(Oi-Pr) 4 catalyst system, and its modification through the use of Lewis base additives to form the alkynylzinc at room temperature. The substrate scope compatible with these methods and the enantioselectivities achieved are discussed. We then describe the functionalized BINOL and H 8 BINOL catalyst systems, which can be further divided into classes based on the manner in which the BINOL framework has been modified. Generally, these functionalized BINOL and H 8 BINOL derivatives contain internal Lewis basic sites which can both promote the formation of the nucleophilic alkynylzinc reagents at reduced temperature and modify the catalytic properties of the chiral biaryl unit. In a few cases, these catalysts also show good efficiency even without the use of the Ti(IV) reagent. The catalytic methods in this Account have demonstrated that a wide range of alkyne and aldehyde substrates can be subjected to the asymmetric addition reactions to generate structurally diverse chiral propargylic alcohols with high enantioselectivity. Some of these methods have exhibited high practicality in synthesis. 1 Introduction 2 BINOL-Based Catalytic Systems 2.1 Catalysis by BINOL-ZnEt 2 -Ti(Oi-Pr) 4 2.2 Catalysis by BINOL-ZnEt 2 -Ti(Oi-Pr) 4 -HMPA 2.3 Catalysis by BINOL-ZnEt 2 -Ti(Oi-Pr) 4 -NMI 2.4 Catalysis by BINOL-ZnEt 2 -Ti(Oi-Pr) 4 -Cy 2 NH 3 Functionalized BINOL-Based Catalytic Systems 3.1 Catalysis by 3,3¢-Dianisyl-BINOLs and -H 8 BINOLs 3.2 Catalysis by 3,3¢-Bis(diphenylmethoxy)methyl Substituted BINOLs 3.3 Catalysis by Acyclic and Macrocyclic Binaphthyl Salens 3.4 Catalysis by 3,3¢-Bismorpholinomethyl H 8 BINOL 3.5 Catalysis by C 1 -Symmetric BINOL-Terpyridine 4 Summary

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Section: Catalysis By Binol-znet 2 -Ti(oi-pr) 4 -Cy 2 Nhmentioning

confidence: 99%

Section: Catalysis By Binol-znet 2 -Ti(oi-pr) 4 -Cy 2 Nhmentioning

confidence: 99%

Asymmetric Alkyne Addition to Aldehydes Catalyzed by BINOL and Its Derivatives

Turlington¹,

Pu²

2012

Synlett

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“…1 In our laboratory, we have developed a number of catalytic systems for the asymmetric alkyne additions using 1,1′-bi-2-naphthol (BINOL) and its derivatives as the source of chirality. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] These catalytic systems have shown high enantioselectivity for the reaction of a wide range of aldehyde and alkyne substrates with good functional group tolerance. Using these catalytic systems has allowed us to obtain diverse chiral propargylic alcohols in excellent yields and with high enantiomeric purity.…”

Section: Introductionmentioning

confidence: 99%

Diverse Transformations of Chiral Propargylic Alcohols Generated by BINOL-Catalyzed Alkyne Addition to Aldehydes

Wang

2013

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Asymmetric alkyne addition to aldehydes catalyzed by our BINOL-based (BINOL = 1,1′-bi-2-naphthol) catalyst system has allowed easy access to a variety of functionalized chiral propargylic alcohols with high enantiomeric purity. This article summarizes our work on using these chiral propargylic alcohols for the synthesis of structurally diverse organic molecules.Optically active tetronic acids and aminofuranones have been synthesized by the regiospecific hydration and amine addition, respectively, of chiral γ-hydroxy-α,β-acetylenic esters, a type of functionalized propargylic alcohol. Ruthenium-carbene-catalyzed ring-closing metathesis and octacarbonyldicobalt(0)-mediated Pauson-Khand (PK) cycloadditions have been used to convert propargylic alcohol based enynes into optically active mono-and bicyclic products, respectively. A chiral propargylic alcohol derived dienediyne has been subjected to a rhodium(I)-catalyzed PK cycloaddition, followed by enyne metathesis catalyzed by the Grubbs II catalyst and a Diels-Alder reaction, leading to the formation of a polycyclic product with high chemo-and stereoselectivity. Finally, a highly chemo-and stereoselective domino PK/[4+2] cycloaddition of a series of optically active trienynes has been discovered to quickly generate tetracyclic products that contain a spirocyclic framework and a quaternary carbon center.This work demonstrates that the BINOL-catalyzed asymmetric addition of alkynes to aldehydes is a very useful process for the asymmetric synthesis of structurally diverse organic products.

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“…Addition of 10% N -methylimidazole (NMI) promptly restored reactivity, and screening could continue. 11 A range of solvents were found to be suitable including CH 2 Cl 2 , 1,4-dioxane, MeCN, PhCF 3 , i -PrOAc, and PhMe; although THF afforded a better purity profile and is readily available anhydrously. A concentration of 0.125 M was utilized to ensure all the zinc species remained in solution, and a slight excess of alkyne and ZnEt 2 were used to drive the reaction to completion.…”

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confidence: 99%

“…It is reasonable to assume from previous reports that the transformation passes through the initial metalation of the alkyne-H, mediated by the amine base, to form the zinc acetylide 5 . 9f , 9g , 11 Reversible precoordination between the azide and zinc acetylide could be expected to occur before the [3 + 2]-cycloaddition can take place, explaining the necessity for stoichiometric quantities of ZnEt 2 in the reaction and the formation of the aryl-zinc intermediate 4 . Harnessing the further reactivity of this aryl-zinc species ( 4 ) has been demonstrated by the trapping experiments set out in Table 1 .…”

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confidence: 99%