Enantioselective Synthesis of Primary 1-(Aryl)alkylamines by Nucleophilic 1,2-Addition of Organolithium Reagents to Hydroxyoxime Ethers and Application to Asymmetric Synthesis of G-Protein-Coupled Receptor Ligands

Atobe, Masakazu; Yamazaki, Naoki; Kibayashi, Chihiro

doi:10.1021/jo049517+

Cited by 62 publications

(31 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The volatile amine products were isolated as the HCl salts. [15] Although cleavage of hydroxylamines and hydrazides by zinc is well-known, [16,17] cleavage of hydrazones under these conditions is less established.…”

mentioning

confidence: 99%

Primary tert‐ and sec‐Allylamines via Palladium‐Catalyzed Hydroamination and Allylic Substitution with Hydrazine and Hydroxylamine Derivatives

2007

View full text Add to dashboard Cite

Keywords allylic substitution; homogeneous catalysis; hydroamination; palladium The challenge of controlling the regiochemistry of palladium-catalyzed allylic substitution by choice of ancillary ligand has a long history. Much attention has been focused on controlling regiochemistry because formation of the more substituted product could be developed into a mild route to sec-and even tert-alkylamines (Scheme 1). Åkermark and co-workers reported that attack can occur at the more substituted position of a prenyl complex, but that the reversibility of this attack ultimately leads to formation of the less substituted amine in many cases.[1] More recently, Hou and co-workers reported a ligand for palladium that causes benzylamine to add irreversibly to form secondary and tertiary N-alkyl sec-butylamines,[2] and Yudin and co-workers have shown that the attack by aziridine is irreversible and that tert-alkyl-substituted aziridines can be prepared by allylic substitution.[3,4] During studies to develop the scope of the hydroamination of dienes,[5-7] we found that the reactions of hydrazine and hydroxylamine derivatives occur irreversibly at the more substituted position of both prenyl and crotyl palladium intermediates. We explored this transformation further because, unlike the products from additions of aziridines,[3,4] the products from addition of hydrazine and hydroxylamine derivatives could be readily transformed into primary tert-alkylamines or sec-alkylamines. The synthesis of primary amines containing tertiary alkyl groups is challenging because many of the conventional methods, such as nucleophilic substitution and additions to imines, are difficult to conduct at tertiary electrophiles and at ketimines,[8,9] and few catalytic reactions have been developed that form tert-alkyl-substituted amines.[10,11] Herein we report our studies on the reactions of hydrazine and hydroxylamine derivatives to form allylamine products from reaction at the more hindered site of aliphatic dienes or allylic ** We are grateful to the NIH (NIGMS GM-55382) for support of this work and Johnson-Matthey for palladium.

show abstract

mentioning

confidence: 99%

Primary tert‐ and sec‐Allylamines via Palladium‐Catalyzed Hydroamination and Allylic Substitution with Hydrazine and Hydroxylamine Derivatives

2007

View full text Add to dashboard Cite

show abstract

“…With sodium amalgam in MeOH, both the pyridylsulfonyl and phenylsulfonyl groups can be removed in one step to give the 1-phenylpentane amine (62) in a nonoptimized yield of 43 % (Scheme 17). By comparison to literature reported optical rotation data, [52] the (R)-configuration was assigned to this product. 1 H NMR NOE experiments and the 1 H NMR J-coupling constants of the ring protons (ca.…”

Section: Since Lanthanide Ions Such As Ybmentioning

confidence: 66%

Catalytic Asymmetric Synthesis of β‐Sultams as Precursors for Taurine Derivatives

Zajac

Peters

2009

Chemistry A European J

View full text Add to dashboard Cite

Beta-sultams, biologically interesting sulfonyl analogues of beta-lactams, have been prepared by an organocatalytic asymmetric formal [2+2]-cycloaddition approach of non-nucleophilic imines with alkyl sulfonyl chlorides. In the case of very electron poor N-tosyl imines derived from chloral or ethylglyoxylate, this reaction type was catalyzed by cinchona alkaloids providing the heterocycles in high yield, with good diastereoselectivity and up to 94% ee. Mechanistic investigations suggested that the product formation proceeded via a zwitterionic imine-catalyst adduct. The scope was significantly extended by 2-pyridylsulfonyl imines derived from non-activated aromatic aldehydes employing Yb(OTf)3 as Lewis acid cocatalyst. The synthetic value of the strained enantioenriched beta-sultams was demonstrated by smooth nucleophilic ring opening reactions with O-, N- and C-nucleophiles yielding a variety of acyclic beta-aminosulfonyl (taurine) derivatives (sulfonates, sulfonamides, sulfones) without racemization or epimerization.

show abstract

“…[695] Scheme 200 Synthesis of an O,N-Dialkylhydroxylamine from Addition of a Grignard Reagent to (S)-(-)-O-(1-Phenylbutoxy)butan-1-imine [ Me H >72:28 76 [696] iBu H >95:5 89 [696] iBu Me >93:7 76 [696] Addition of vinyllithium to the (S)-2-hydroxy-1-phenylethyl benzaldehyde oxime ether 491 in toluene/cyclohexane at 0 8C results in the formation of the hydroxylamines 492 in a 5:1 selectivity favoring the R,S-epimer (Scheme 202). [698] Scheme 202 Synthesis of O,N-Disubstituted Hydroxylamines [698] [707] (CH 2 ) 5 (CH 2 ) 2 Ph H Me 94 [707] (CH 2 ) 5 (CH 2 ) 6 Me H Me 90 [707] (CH 2 ) 5 Me H Bn 72 [707] Me Me (CH 2 ) 5 Me 43 [707] 40.5.2.1.3…”

Section: Bno H N Phmentioning

confidence: 99%

Product Class 5: Hydroxylamines

Enders¹,

Schaumann²

2009

Category 5, Compounds With One Saturated Carbon Heteroatom Bond

View full text Add to dashboard Cite

Enantioselective Synthesis of Primary 1-(Aryl)alkylamines by Nucleophilic 1,2-Addition of Organolithium Reagents to Hydroxyoxime Ethers and Application to Asymmetric Synthesis of G-Protein-Coupled Receptor Ligands

Cited by 62 publications

References 31 publications

Primary tert‐ and sec‐Allylamines via Palladium‐Catalyzed Hydroamination and Allylic Substitution with Hydrazine and Hydroxylamine Derivatives

Primary tert‐ and sec‐Allylamines via Palladium‐Catalyzed Hydroamination and Allylic Substitution with Hydrazine and Hydroxylamine Derivatives

Catalytic Asymmetric Synthesis of β‐Sultams as Precursors for Taurine Derivatives

Product Class 5: Hydroxylamines

Contact Info

Product

Resources

About