Highly diastereoselective synthesis of enantioenriched <i>anti</i>-α-allyl-β-fluoroamines

Chevis, Philip J.; Wangngae, Sirilak; Thaima, Thanaphat; Carroll, Anthony W; Willis, Anthony C.; Pattarawarapan, Mookda; Pyne, Stephen G.

doi:10.1039/c9cc02765c

Cited by 13 publications

(19 citation statements)

References 36 publications

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“…All used enamine catalysis (secondary amine organocatalysts), and two of them (procedures by Beeson and MacMillan [61c] and Jørgensen et al [61d] ) are still the most commonly used methods for asymmetric α-fluorinations of aldehydes, due to their efficiency and excellent enantioselectivity. [63][64][65][66][67][68][69][70][71] Both the MacMillan and the Jørgensen catalysts (see Scheme 29 and Scheme 30) differentiate the nonfluorinated aldehyde substrates and the α-fluoroaldehyde products efficiently, despite the enhanced acidity of the product, which should promote enamine formation and racemization. [61d] The Jørgensen catalyst is also highly efficient in various other direct α-functionalizations of aldehydes.…”

Section: Fluorination Of Aldehydesmentioning

confidence: 99%

“…[72] However, fluorination of α-branched aldehydes with these methods is rarely efficient. [71c] Because simple α-fluorinations utilizing MacMillan's method or Jørgensen's procedure are lacking novelty, this chapter focuses on reaction cascades utilizing these methods [64][65][66][67][68][69][70]79] and alternative systems for aldehyde fluorination instead. [73][74][75][76][77][78][80][81][82] Brenner-Moyer and coworkers reported a one-pot α-chlorination/α-fluorination cascade.…”

Section: Fluorination Of Aldehydesmentioning

confidence: 99%

“…[64] α-Fluoroaldehydes are highly reactive and versatile synthetic intermediates. [65][66][67][68][69][70] For example, they can be transformed into β-fluoroamines. Simple reductive amination is sufficient to achieve this goal, [65] but there are other methods available.…”

Section: Fluorination Of Aldehydesmentioning

confidence: 99%

“…2 : 1 d.r.). [68] Jørgensen and coworkers reported that the Ohira-Bestmann modification of the Seyferth-Gilbert method is compatible with asymmetric organocatalytic fluorinations. This enabled efficient one-pot transformation of aldehydes into chiral propargylic fluorides via α-fluoroaldehyde intermediates, while utilization of Wittig reagents in a similar fashion yielded chiral allylic fluorides (Scheme 33).…”

Section: Fluorination Of Aldehydesmentioning

confidence: 99%

“…α‐Fluoroaldehydes are highly reactive and versatile synthetic intermediates [65–70] . For example, they can be transformed into β‐fluoroamines.…”

Section: Asymmetric C−f Bond‐forming Reactions Using Organocatalysismentioning

confidence: 99%

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Asymmetric Methods for Carbon‐Fluorine Bond Formation

et al. 2021

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In memory of Ferenc FülöpAs a consequence of the ever-increasing relevance of fluorinated drugs in medicinal chemistry, organofluorine chemistry has become a hot topic research area during the last decade. Asymmetric carbon-fluorine bond-forming reactions have enormously developed in recent years with considerable findings related to novel reactions and synthetic approaches. These new synthetic efforts have contributed to the access to a growing number of fluorinated molecules and complex natural or synthetic products of high relevance in medicinal chemistry and drug research. Illustrative examples of novel synthetic methodologies, including organocatalytic processes, asymmetric syntheses or phase-transfer catalytic methods for the enantioselective incorporation of fluorine atom(s) into versatile molecular entities, are covered in the current Review, focusing on main contributions of the last ten years.

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Section: Fluorination Of Aldehydesmentioning

confidence: 99%

Section: Fluorination Of Aldehydesmentioning

confidence: 99%

Section: Fluorination Of Aldehydesmentioning

confidence: 99%

Section: Fluorination Of Aldehydesmentioning

confidence: 99%

“…α‐Fluoroaldehydes are highly reactive and versatile synthetic intermediates [65–70] . For example, they can be transformed into β‐fluoroamines.…”

Section: Asymmetric C−f Bond‐forming Reactions Using Organocatalysismentioning

confidence: 99%

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Asymmetric Methods for Carbon‐Fluorine Bond Formation

et al. 2021

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Asymmetric Carbon–halogen Bond Forming Reactions (Excluding C–h Activation Processes)

Fustero¹,

Remete²,

Kiss³

et al. 2022

Catalytic Asymmetric Synthesis

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Diastereoselective Petasis‐Borono‐Mannich Crotylation Reactions of Chiral α‐Heteroatom (F, OBz, OH) Aldehydes: Rapid Access to Valuable Mono and Bicyclic Heterocyclic Scaffolds

Chevis

Chao

Richardson

et al. 2023

Chemistry A European J

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The crotylation reactions of chiral α‐F, α‐OBz and α‐OH aldehydes under Petasis‐borono‐Mannich conditions using (E)‐ or (Z)‐crotylboronates and primary amines resulted in γ‐addition products in high dr and high er. α‐F and α‐OBz aldehydes gave 1,2‐anti‐2,3‐syn and 1,2‐anti‐2,3‐anti, products, respectively while an α‐OH aldehyde gave 1,2‐syn‐2,3‐syn products. The stereochemical outcomes of reactions of the former aldehydes can be explained using a six‐membered ring transition state (TS) model in which a Cornforth‐like conformation around the imine intermediate is favoured resulting in 1,2‐anti products. The 2,3‐stereochemical outcome is dependent upon the geometry of the crotylboronate. These TS models were also supported by DFT calculations. The stereochemical outcomes of reactions employing an α‐OH aldehyde can be rationalised as occurring via an open‐TS involving H‐bonding in the imine intermediate between the α‐OH group and the imine N atom. Representative products were converted to highly functionalized 1,2,3,6‐tetrahydropyridines and 3H‐oxazolo[3,4‐a]pyridine‐3‐ones which will be valuable scaffolds in synthesis.

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Highly diastereoselective synthesis of enantioenriched anti-α-allyl-β-fluoroamines

Abstract: A highly diastereoselective synthesis (dr = 99 : 1 97 : 3) of enantioenriched anti-α-allyl-β-fluoroamines (ee = 86–92%) has been developed involving a highly diastereoselective Petasis allyl borono-Mannich reaction of (S)- or (R)-α-fluoroaldehydes.

Cited by 13 publications

References 36 publications

Asymmetric Methods for Carbon‐Fluorine Bond Formation

Asymmetric Methods for Carbon‐Fluorine Bond Formation

Asymmetric Carbon–halogen Bond Forming Reactions (Excluding C–h Activation Processes)

Diastereoselective Petasis‐Borono‐Mannich Crotylation Reactions of Chiral α‐Heteroatom (F, OBz, OH) Aldehydes: Rapid Access to Valuable Mono and Bicyclic Heterocyclic Scaffolds

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