Asymmetric synthesis of 2-alkyl pyrrolidines and piperidines. Synthesis of (+)-metazocine

Meyers, A. I.; Dickman, Daniel A.; Bailey, T. R.

doi:10.1021/ja00312a029

Cited by 92 publications

(35 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…( S )‐ N ‐Isopropyl‐ O ‐methyl‐valinol : The ( S )‐ N ‐isopropyl‐ O ‐methyl‐valinol was prepared according to published procedures: LiAlH 4 reduction of D ‐valine to D ‐valinol,10 methylation by MeI to afford the amino methyl ether,11 condensation with acetone to the corresponding imine and finally reduction using H 2 /Pd/C in a Parr apparatus at 4 atm 12…”

Section: Methodsmentioning

confidence: 99%

Mixed Dimer and Mixed Trimer Complexes ofnBuLi and a Chiral Lithium Amide

Hilmersson

Malmros

2001

Chem. Eur. J.

View full text Add to dashboard Cite

Multinuclear and multidimensional NMR spectroscopy have shown that lithium (S)-N-isopropyl-O-methyl-valinol (1-[6Li]) exists in a mixed 2:1 complex with nBu[6Li], (1-[6Li])2/nBu[6Li], in non-coordinating solvents such as hexane or toluene. A 6Li,1H-HOESY NMR spectrum indicates that the complex is a cyclic trimer with a large distance between the di-coordinated lithium and the carbanion of nBu[6Li]. Such arrangements are present in the solid state as previously reported by Williard and Sun. The exchange of lithium atoms within the trimer is slow at -33 degrees C. The exchange barrier (deltaG++) was determined to be 14.7 kcal x mol(-1) from quantitative 6Li,6Li-EXSY spectra. Addition of diethyl ether results in the formation of mixed dimers of (1-[6Li])/nBu[6Li], tetramers of nBu[6Li], and homodimers (1-[6Li])2. The apparent equilibrium constant of the mixed dimer was determined from the 6Li NMR integrals as K = 7.

show abstract

Section: Methodsmentioning

confidence: 99%

Mixed Dimer and Mixed Trimer Complexes ofnBuLi and a Chiral Lithium Amide

Hilmersson

Malmros

2001

Chem. Eur. J.

View full text Add to dashboard Cite

show abstract

“…The transformation of 4a؊f into (R)-2-methylpyrrolidine, [23] (R)-2-ethylpyrrolidine, [24] (R)-2-propylpyrrolidine, [25] (S)-2-isopropylpyrrolidine, [26] (R)-2-butylpirrolidine, [27] and (R)-2-phenethylpyrrolidine, [28] isolated as tosylates, was carried out by removal of the N-benzyl moiety by hydrogenolysis over palladium on carbon and treatment with to- de [b] Yield (%) [a] de [b] Yield (%) syl chloride. The enantiomeric purity of the corresponding pyrrolidines was measured by 19 F NMR spectroscopy of the MTPA derivatives and the configuration of the final products was determined by comparison of the sign of the optical rotation previously described.…”

Section: Introductionmentioning

confidence: 99%

A Simple Stereoselective Synthesis of Enantiopure 2-Substituted Pyrrolidines and Piperidines from Chiral (R)-Phenylglycinol-Derived Bicyclic 1,3-Oxazolidines

Andrés

Herráiz-Sierra

Pedrosa³

et al. 2000

Eur. J. Org. Chem.

View full text Add to dashboard Cite

show abstract

“…The majority of these compounds are obtained through the reaction of bamino alcohols with borane-etherates or borane-thioetherates. [13][14][15][16][17] On a different note, b-amino alcohols are usually synthesized either by the direct reduction of free amino acids, [18][19][20][21][22][23][24][25][26] or indirectly from activated amino acid esters [27][28][29] and amino acid anhydrides. 30,31 Reagents employed for the reduction of free amino acids are usually metal hydrides, such as lithium aluminum hydride or lithium borohydride, in combination with various organic reagents such as trimethylchlorosilane, borane-methyl sulfide complex activated by trimethylborate, or boron trifluoride-diethyl ether complex.…”

mentioning

confidence: 99%

A Convenient One-Step Synthesis of Stable β-Amino Alcohol N-Boranes from α-Amino Acids

Pinaka¹,

Vougioukalakis²,

Dimotikali³

et al. 2012

Synthesis

View full text Add to dashboard Cite

Novel, non-cyclic b-amino alcohol N-boranes are isolated from the sodium borohydride-sulfuric acid assisted direct reduction of a series of a-amino acids. The reduction takes place in one step under mild conditions and affords the products in good yields.The importance of amine-borane adducts is profound both in industry and academia. These compounds, characterized by thermal and hydrolytic stability and solubility in a wide variety of solvents, 1 are utilized in a large number of applications including, but not limited to, asymmetric synthesis, 2-5 chemical hydrogen storage, 6-8 the synthesis of cyclic azaboranes and borazines, 9,10 and coordination chemistry. 11,12 A survey of the literature showed that there are a large number of publications on the synthesis of amine-borane adducts. In sharp contrast, there are only a few reports on the synthesis of b-amino alcohol boranes. The majority of these compounds are obtained through the reaction of bamino alcohols with borane-etherates or borane-thioetherates. [13][14][15][16][17] On a different note, b-amino alcohols are usually synthesized either by the direct reduction of free amino acids, [18][19][20][21][22][23][24][25][26] or indirectly from activated amino acid esters 27-29 and amino acid anhydrides. 30,31 Reagents employed for the reduction of free amino acids are usually metal hydrides, such as lithium aluminum hydride or lithium borohydride, in combination with various organic reagents such as trimethylchlorosilane, borane-methyl sulfide complex activated by trimethylborate, or boron trifluoride-diethyl ether complex. The utilization of sodium borohydride has also been reported in combination with inorganic compounds such as transition metal complexes, iodine, or sulfuric acid.While implementing a project aimed toward the synthesis of optically pure b-amino alcohols, which were intended for use as organocatalysts in asymmetric reactions, we employed the sodium borohydride-sulfuric acid assisted direct reduction of a-amino acids. 26 Our choice was based on the fact that this was a safe, cheap and reliable synthetic method toward b-amino alcohols. However, during the course of our experiments, we noticed that apart from the targeted b-amino alcohols, unexpected side products were also formed in significant amounts. These side products were observed in all the amino acid reductions we performed. The characterization of these compounds was carried out utilizing a variety of techniques (vide infra) and eventually led to the conclusion that they were the corresponding non-cyclic b-amino alcohol N-borane adducts 3a-f shown in Scheme 1.Scheme 1 b-Amino alcohol N-boranes obtained by the sodium borohydride-sulfuric acid assisted direct reduction of a-amino acids As mentioned above, amino alcohol-borane adducts are relatively stable compounds which are gaining considerable attention, especially in asymmetric organic reactions where they serve as chiral reducing agents. Considering their increasing importance, we decided to investigate the scope and limitations of the...

show abstract

Asymmetric synthesis of 2-alkyl pyrrolidines and piperidines. Synthesis of (+)-metazocine

Cited by 92 publications

References 0 publications

Mixed Dimer and Mixed Trimer Complexes ofnBuLi and a Chiral Lithium Amide

Mixed Dimer and Mixed Trimer Complexes ofnBuLi and a Chiral Lithium Amide

A Simple Stereoselective Synthesis of Enantiopure 2-Substituted Pyrrolidines and Piperidines from Chiral (R)-Phenylglycinol-Derived Bicyclic 1,3-Oxazolidines

A Convenient One-Step Synthesis of Stable β-Amino Alcohol N-Boranes from α-Amino Acids

Contact Info

Product

Resources

About