Asymmetric Synthesis of 2,6-Methylated Piperazines

Mickelson, John W.; Belonga, K. L.; Jacobsen, E. J.

doi:10.1021/jo00118a039

Cited by 51 publications

(32 citation statements)

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“…Sakai and coworkers reported on the reduction of secondary amides to secondary amines using a TMDS/InI 3 system (Eqs. [17][18][19]. 27 Preliminary studies showed that Et 3 SiH/InBr 3 , PhSiH 3 /InBr 3 , and PMHS/InBr 3 among others failed to bring about useful yields of the amine.…”

Section: The Tmds Reduction Of Amides To Aminesmentioning

confidence: 99%

Tetramethyldisiloxane: A Practical Organosilane Reducing Agent

Pesti

Larson

2016

Org. Process Res. Dev.

104

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The chemistry of tetramethyldisiloxane (TMDS) is largely composed of the reduction of functional groups with increasing applications for carboncarbon bond formation. This reagent can be a safe alternative to H 2 , LiAlH 4 , and other reactive reagents. Notable are the amide conversion to amines and aldehydes, nitro group reductions, nitrile reductions, hydrogenolysis of arylchlorine bonds, reductive formation of sulfides, reductive etherification, reductive opening of ketals, reductive demethoxylation, and formation of nitriles with homologation. Selectivity can be carried out by the choice of catalysts. This review of recent chemistry will focus on synthetically applied reactions of the recent past. Displayed reactions are chosen to be representative of the referenced work, but are also chosen to illustrate a new viewpoint. Finally, where applicable, the results of competing hydrosilanes are presented to compare to the results obtained with TMDS.

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Section: The Tmds Reduction Of Amides To Aminesmentioning

confidence: 99%

Tetramethyldisiloxane: A Practical Organosilane Reducing Agent

Pesti

Larson

2016

Org. Process Res. Dev.

104

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“…57 Its reaction with methyl (R)-2-[(trifluoromethylsulfonyl)oxy]propionate proceeded uneventfully with inversion of configuration to produce a 94% yield of the ester 64. Hydrogenolytic monodebenzylation and subsequent acid-catalyzed cyclization provided 3,5-disubstituted piperazin-2-one 65 in 81% yield.…”

Section: Cyclization At N 1 -Cmentioning

confidence: 99%

“…58 This chemistry has also been applied to the enantioselective synthesis of (R)-3,5,5-trimethylpiperazin-2-one 69. 57 Similarly, the corresponding enantiomer was prepared using methyl (R)-2-[(trifluoromethanesulfonyl)oxy]propionate as the alkylating agent.…”

Section: Cyclization At N 1 -Cmentioning

confidence: 99%

“…The N 4 -C 5 bond-forming strategy centered on an intramolecular Mitsunobu reaction was firstly used by Jacobsen et al 57 for the preparation of (3R)-1-benzyl-3-methyl-piperazin-2-one 229 starting from amide 227 prepared by coupling Boc-D-alanine and N-benzylethanolamine (Scheme 43). Removal of the Boc-protecting group produced an intermediate amine 228, which underwent Mitsunobu cyclization (PPh 3 , DEAD) to give 229.…”

Section: Nucleophilic Substitutionmentioning

confidence: 99%

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Mastering chiral substituted 2-oxopiperazines

Risi¹,

Pelà²,

Pollini³

et al. 2010

Tetrahedron: Asymmetry

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“…The yield was improved up to 43% with NaBH 4 as reagent and with AlCl 3 as catalyst in chloroform to reflux [Burgess and Meyers, 1992;Fox et al, 1991]. A better yield was found when LiAlH 4 was used in refluxing THF for 24 h, furnishing 8a in 55% yield [Aston et al, 1994;Mickelson et al, 1995]. Because of the low yields, an alternative route was investigated that included the incorporation of the ethylamino chain by substitution of the chlorine atom in 2-chloroethylamine (16) by the phenoxide ion of eugenol (14), under phase-transfer conditions [Jensen et al, 2001], to give 8a in 90% yield (Fig.…”

mentioning

confidence: 98%

Potent hypolipidemic activity of mimetic amides of fibrates based on the 2‐methoxy‐4‐(2‐propenyl)phenoxyacetic scaffold

Hernández¹,

Bernal²,

Cruz³

et al. 2003

Drug Development Research

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A series of bioisosteric analogues of fibrates, such as clofibrate (2) and bezafibrate (3), was designed, considering the pharmacophore potential of phenoxyacetic derivatives 4 related to a-asarone (1) in their structure. Thus, the hypolipidemic activity of the series of amides 5a-5j, 6a-6d, and 7a-7c, amines 8b-8d, and amino acids 9a-9e has been evaluated. A significant decrease in serum cholesterol was observed in mice for a number of these compounds. Some of them also showed a lowering of low-density lipoprotein cholesterol, and a few had an effect on increasing the high-density lipoprotein cholesterol levels, and on reducing the triglyceride serum contents. Phenoxyacetic, phenoxyethyl-amido and -amino moieties, as well as the presence of a chlorine atom in their aromatic rings, were identified as potential pharmacophores. Unexpectedly, derivatives 9a-9e, bearing an amino acid group, did not exhibit any hypolipidemic activity under a similar pharmacological protocol. Drug Dev.

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Asymmetric Synthesis of 2,6-Methylated Piperazines

Cited by 51 publications

References 0 publications

Tetramethyldisiloxane: A Practical Organosilane Reducing Agent

Tetramethyldisiloxane: A Practical Organosilane Reducing Agent

Mastering chiral substituted 2-oxopiperazines

Potent hypolipidemic activity of mimetic amides of fibrates based on the 2‐methoxy‐4‐(2‐propenyl)phenoxyacetic scaffold

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