Asymmetric synthesis of α-substituted nitriles and cyanohydrins by oxidative cleavage of chiral aldehyde hydrazones with magnesium monoperoxyphthalate

Enders, Dieter; Plant, Andrew; Backhaus, Dirk; Reinhold, Ulrich

doi:10.1016/0040-4020(95)00647-q

Cited by 43 publications

(20 citation statements)

References 39 publications

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“…Additionally, the oxidative transformation of the hydrazone moiety of 191 into β-nitronitriles 193 was also accomplished cleanly by applying the method previously developed for simple N,N-dimethylhydrazones. [89,96] The method uses commercially available magnesium monoperoxyphthalate hexahydrate (MMPP·6H 2 O) as the oxidant and proceeded under very mild conditions (MeOH, 0°C) to afford nearly quantitative yields of products 193. The proposed mechanism consists of the N-oxidation of the amino nitrogen atom followed by an aza-Cope-type elimination, supported by the detection of N,N-dimethylhydroxylamine 194 in the reaction mixtures.…”

Section: Michael Addition To Nitroalkenesmentioning

confidence: 99%

Aldehyde N,N‐Dialkylhydrazones as Neutral Acyl Anion Equivalents: Umpolung of the Imine Reactivity

et al. 2007

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The isoelectronic replacement of the α‐carbon of enamines by nitrogen leads to the corresponding hydrazones, and thus, they can be termed “aza‐enamines”. Hence, aldehyde N,N‐dialkylhydrazones enable analogous electrophilic substitutions at the imine carbon that corresponds to the β‐carbon of enamines. In addition, after hydrolysis of the product hydrazones to the parent ketones or aldehydes, these reactions constitute an umpolung of the classical carbonyl reactivity and overall a nucleophilic acylation or formylation. This review covers the aza‐enamine chemistry from its very beginning in the late 1960s up to this year. In the first part, reactions of aromatic, aliphatic, and heterocyclic aldehyde N,N‐dialkylhydrazones with highly reactive substrates such as the Vilsmeier and Mannich reagents, sulfonyl isocyanates, perfluoroacetic anhydride, and inorganic electrophiles such as halogens and phosphorus tribromide are described. The hydrazones of α,β‐unsaturated aldehydes react as vinylogous aza‐enamines at the terminal carbon providing unsaturated aldehydes. As electron‐rich dienes and dienophiles, they also form Diels–Alder adducts and thus interesting N‐heterocycles. The second part covers carbon–carbon bond formations of the sterically less‐demanding formaldehyde N,N‐dialkylhydrazones with synthetically very useful electrophiles such as various Michael acceptors and carbonyl compounds. Formaldehyde SAMP‐hydrazone and related derivatives generally give excellent asymmetric inductions. Finally, first organocatalytic versions of the aza‐enamine chemistry are presented. In summary, the rich chemistry of aldehyde N,N‐dialkylhydrazones as neutral acyl anion, formyl anion, and cyanide equivalents is demonstrated. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

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Section: Michael Addition To Nitroalkenesmentioning

confidence: 99%

Aldehyde N,N‐Dialkylhydrazones as Neutral Acyl Anion Equivalents: Umpolung of the Imine Reactivity

et al. 2007

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“…Oxidative cleavage of (249) yields the acid (250) which was deprotected to afford (S)-(6) which can be converted to (S)-(7) in two steps [180]. A second route involves an asymmetric Mukaiyama-type aldol reaction on (247) providing the tert-butyldimethylsilyl (TBDMS)-protected hemiketal (251) which undergoes elimination to the alkene (252) and subsequent reduction to give the all synsubstituted oxazine (253). Deprotection affords (R)-(6) which can undergo conversion to (R)-(7) [181].…”

Section: B-hydroxy-g-amino Acidsmentioning

confidence: 99%

“…a-Alkylation and subsequent reaction with excess Grignard reagent and the acetyl chloride gives the N-acetyl hydrazides (323). Removal of the chiral auxiliary with concomitant deprotection of the alcohol, ozonolysis of the terminal alkene, and hydrolysis of the acetamide affords (R,R)- (8) in 38% overall yield [253,254].…”

Section: B-hydroxy-g-substituted G-amino Acidsmentioning

confidence: 99%

Synthesis of γ‐Aminobutyric Acid Analogs

Hanrahan

Johnston

2009

Amino Acids, Peptides and Proteins in Organic Chemistry

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“…However, accessing optically active nitriles without other functional groups remains a challenge. A few examples of asymmetric synthesis and enzymatic methods have been reported to access non‐functionalized nitriles in their optically active form, but these methods suffer from multiple reaction steps, the use of complex chiral ligands, and low activity . Despite many studies on host–guest inclusion crystals, enantioseparation of α‐alkylated chiral nitriles without any other functional groups has not been reported to date, as far as we know.…”

Section: Introductionmentioning

confidence: 99%

Enantioseparation of Sulfoxides and Nitriles by Inclusion Crystallization with Chiral Organic Salts Based on l‐Phenylalanine

2018

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Enantioselective inclusion of aromatic sulfoxides and nitriles was achieved in a host framework created by organic salts comprising achiral benzoic acids and a chiral primary amine (1a) derived from l‐phenylalanine. Tuning of the combined achiral acid component successfully changed the chiral recognition ability of the organic salts. The guest molecules were hydrogen‐bonded to form three‐component inclusion crystals, and the enantiomers of nitriles and sulfoxides were separated with high selectivity up to 92 and 98 % ee. As far as we know, this is the first example of the enantioseparation of non‐functionalized aromatic nitriles.

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Asymmetric synthesis of α-substituted nitriles and cyanohydrins by oxidative cleavage of chiral aldehyde hydrazones with magnesium monoperoxyphthalate

Cited by 43 publications

References 39 publications

Aldehyde N,N‐Dialkylhydrazones as Neutral Acyl Anion Equivalents: Umpolung of the Imine Reactivity

Aldehyde N,N‐Dialkylhydrazones as Neutral Acyl Anion Equivalents: Umpolung of the Imine Reactivity

Synthesis of γ‐Aminobutyric Acid Analogs

Enantioseparation of Sulfoxides and Nitriles by Inclusion Crystallization with Chiral Organic Salts Based on l‐Phenylalanine

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