Organocatalytic Asymmetric Alkylation of Aldehydes by S<sub>N</sub>1‐Type Reaction of Alcohols

Cozzi, Pier Giorgio; Benfatti, Fides; Zoli, Luca

doi:10.1002/anie.200805423

Cited by 257 publications

(86 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…31 Previous direct organocatalytic methods to form α-benzylated aldehydes require multiple and/or electron-rich aryl rings on the electrophilic coupling partner to stabilize intermediate benzylic carbocations. 32 Since photoredox organocatalysis relies on the formation of electron-deficient radicals, this strategy complements existing benzylation protocols. The α-benzylation of aldehydes proceeds through a slightly different photoredox catalytic cycle than described above.…”

Section: Carbonyl α-Functionalizationmentioning

confidence: 99%

Synergistic catalysis: A powerful synthetic strategy for new reaction development

2012

View full text Add to dashboard Cite

Synergistic catalysis is a synthetic strategy wherein both the nucleophile and the electrophile are simultaneously activated by two separate and distinct catalysts to afford a single chemical transformation. This powerful catalysis strategy leads to several benefits, specifically synergistic catalysis can (i) introduce new, previously unattainable chemical transformations, (ii) improve the efficiency of existing transformations, and (iii) create or improve catalytic enantioselectivity where stereocontrol was previously absent or challenging. This perspective aims to highlight these benefits using many of the successful examples of synergistic catalysis found in the literature.

show abstract

Section: Carbonyl α-Functionalizationmentioning

confidence: 99%

Synergistic catalysis: A powerful synthetic strategy for new reaction development

2012

View full text Add to dashboard Cite

show abstract

“…They have since reported a range of bases and nucleophiles to effect the elimination and subsequent addition 10. A variety of indolenine precursors have also been reported to be generated using both acidic11 and basic12 reaction conditions. Though a broad scope of additions has already been demonstrated (Grignard, nitroalkane, malonate, malononitriles), there have been very few asymmetric variations reported 13,14,15,16.…”

mentioning

confidence: 99%

Chiral Brønsted Base-Promoted Nitroalkane Alkylation: Enantioselective Synthesis of sec-Alkyl-3-Substituted Indoles

Dobish

Johnston

2010

Org. Lett.

View full text Add to dashboard Cite

A Brønsted base-catalyzed reaction of nitroalkanes with alkyl electrophiles provides indole heterocycles substituted at C3 bearing a sec-alkyl group with good enantioselectivity (up to 90% ee). Denitration by hydrogenolysis provides a product with equally high ee. An indolenine intermediate is implicated in the addition step, and surprisingly, water cosolvent was found to have a beneficial effect in this step, leading to a one-pot protocol for elimination/enantioselective addition using PBAM, a bis(amidine) chiral nonracemic base.Indole and pyrrole-derived small molecules bearing an n-alkyl substituent at C3 are very common, but the emergence of small molecules exhibiting a sec-alkyl substituent at C3 is more recent. Compelling biological activity can be associated with these congeners ( Figure 1): the gonadotropin releasing hormone antagonist developed by Merck (1), 1 the antiobitic roseophilin (2), 2 and inhibitors of MDM2 in the spirotryprostatin class (3). 3 Synthetic methods that provide for functionalization of the C3 indole carbon do not often translate to the production of chiral nonracemic products, though an exception to this is the Friedel-Craft alkylation 4 of indole where asymmetric versions have been reported. 5 While both metal-based chiral complexes and organocatalysts have been used to catalyze the addition of indoles to nitro alkenes, 6 there are currently no asymmetric additions to nonactivated α,β-substituted nitro alkenes, which would deliver highly substituted sec-alkyl substituents at the indole 3-position. 7,8 In 2006, Petrini described an innovative solution to this structural motif using 3-(1-arylsulfonylalkyl) indole precursors to indolenine reactive intermediates. 9 They have since reported a range of bases and nucleophiles to effect the elimination and subsequent addition. 10 A variety of indolenine precursors have also been reported to be generated using both acidic 11 and basic 12 reaction conditions. Though a broad scope of additions has already been demonstrated (Grignard, nitroalkane, malonate, malononitriles), there have been very few asymmetric variations reported. 13,14,15,16 More recently, a Brønsted-base catalyzed asymmetric addition of malononitrile using a cinchona based thiourea catalyst was reported with high selectivity.

show abstract

“…In 2009 the group of Cozzi used a MacMillan-type catalyst to carry out the enantioselective S N 1-type alkylation of bisarylmethanols with aldehydes. 86 When the TFA-salt of the catalyst was used, the cation formed smoothly and was subsequently trapped by the aldehyde via an enamine catalysis pathway. When 2-methylindol-3-yl(phenyl) methanol was used as the starting material, a 1.5:1 to 3:1 mixture of anti/syn diastereomers was obtained in low to good yield.…”

Section: -Indolyl(aryl)methanolsmentioning

confidence: 99%

Imine and iminium precursors as versatile intermediates in enantioselective organocatalysis

Kataja

Masson

2014

Tetrahedron

View full text Add to dashboard Cite

Organocatalytic Asymmetric Alkylation of Aldehydes by S_N1‐Type Reaction of Alcohols

Abstract: Work-alcoholic! The elusive enantioselective catalytic alpha-alkylation of aldehydes, a widely sought transformation, was brought to execution by the use of alcohols capable of forming stabilized carbocations (see scheme, TFA = trifluoroacetic acid).

Cited by 257 publications

References 78 publications

Synergistic catalysis: A powerful synthetic strategy for new reaction development

Synergistic catalysis: A powerful synthetic strategy for new reaction development

Chiral Brønsted Base-Promoted Nitroalkane Alkylation: Enantioselective Synthesis of sec-Alkyl-3-Substituted Indoles

Imine and iminium precursors as versatile intermediates in enantioselective organocatalysis

Contact Info

Product

Resources

About

Organocatalytic Asymmetric Alkylation of Aldehydes by SN1‐Type Reaction of Alcohols

Abstract: Work-alcoholic! The elusive enantioselective catalytic alpha-alkylation of aldehydes, a widely sought transformation, was brought to execution by the use of alcohols capable of forming stabilized carbocations (see scheme, TFA = trifluoroacetic acid).

Cited by 257 publications

References 78 publications

Synergistic catalysis: A powerful synthetic strategy for new reaction development

Synergistic catalysis: A powerful synthetic strategy for new reaction development

Chiral Brønsted Base-Promoted Nitroalkane Alkylation: Enantioselective Synthesis of sec-Alkyl-3-Substituted Indoles

Imine and iminium precursors as versatile intermediates in enantioselective organocatalysis

Contact Info

Product

Resources

About

Organocatalytic Asymmetric Alkylation of Aldehydes by S_N1‐Type Reaction of Alcohols