Asymmetric Synthesis of (α<i>R</i>)-Polyfluoroalkylated Prolinols Based on the Perfluoroalkyl-Induced Highly Stereoselective Reduction of Perfluoroalkyl <i>N</i>-Boc-pyrrolidyl Ketones

Funabiki, Kazumasa; Shibata, Akitsugu; Iwata, Hiroki; Hatano, K.; Kubota, Yasuhiro; Komura, Kenichi; Ebihara, Masahiro; Matsui, Masaki

doi:10.1021/jo8004952

Cited by 12 publications

(28 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results, along with those of Kumadaki et al 12. and our8c previous reports, suggest that long fluoroalkyl groups are bulkier than n ‐octyl and phenyl groups.…”

Section: Resultssupporting

confidence: 88%

Conditions Favoring the Formation of Monomeric Pt^III Derivatives in the Electrochemical Oxidation of trans‐[Pt^II{(p‐BrC₆F₄)NCH₂CH₂NEt₂}Cl(py)]

et al. 2015

View full text Add to dashboard Cite

Characterization of the anticancer active compound trans‐[PtII{(p‐BrC6F4)NCH2CH2NEt2}Cl(py)] is described along with identification of electrochemical conditions that favor formation of a monomeric one‐electron‐oxidized PtIII derivative. The square‐planar organoamidoplatinum(II) compound was synthesized through a carbon dioxide elimination reaction. Structural characterization by using single‐crystal X‐Ray diffraction reveals a trans configuration with respect to donor atoms of like charges. As PtIII intermediates have been implicated in the reactions of platinum anticancer agents, electrochemical conditions favoring the formation of one‐electron‐oxidized species were sought. Transient cyclic voltammetry at fast scan rates or steady‐state rotating disc and microelectrode techniques in a range of molecular solvents and an ionic liquid confirm the existence of a well‐defined, chemically and electrochemically reversible one‐electron oxidation process that, under suitable conditions, generates a PtIII complex, which is proposed to be monomeric [PtIII{(p‐BrC6F4)NCH2CH2NEt2}Cl(py)]+. Electron paramagnetic resonance spectra obtained from highly non‐coordinating dichloromethane/([Bu4N][B(C6F5)4]) solutions, frozen to liquid nitrogen temperature immediately after bulk electrolysis in a glove box, support the PtIII assignment rather than formation of a PtII cation radical. However, the voltammetric behavior is highly dependent on the timescale of the experiments, temperature, concentration of trans‐[PtII{(p‐BrC6F4)NCH2CH2NEt2}‐ Cl(py)], and the solvent/electrolyte. In the low‐polarity solvent CH2Cl2 containing the very weakly coordinating electrolyte [Bu4N][B(C6F5)4], a well‐defined reversible one‐electron oxidation process is observed on relatively long timescales, which is consistent with the stabilization of the cationic platinum(III) complex in non‐coordinating media. Bulk electrolysis of low concentrations of [Pt{(p‐BrC6F4)NCH2CH2NEt2}Cl(py)] favors the formation of monomeric [PtIII{(p‐BrC6F4)NCH2CH2NEt2}Cl(py)]+. Simulations allow the reversible potential of the PtII/PtIII process and the diffusion coefficient of [PtIII{(p‐BrC6F4)‐ NCH2CH2NEt2}Cl(py)]+ to be calculated. Reversible electrochemical behavior, giving rise to monomeric platinum(III) derivatives, is rare in the field of platinum chemistry.

show abstract

“…These results, along with those of Kumadaki et al 12. and our8c previous reports, suggest that long fluoroalkyl groups are bulkier than n ‐octyl and phenyl groups.…”

Section: Resultssupporting

confidence: 88%

Conditions Favoring the Formation of Monomeric Pt^III Derivatives in the Electrochemical Oxidation of trans‐[Pt^II{(p‐BrC₆F₄)NCH₂CH₂NEt₂}Cl(py)]

et al. 2015

View full text Add to dashboard Cite

show abstract

“…The aza-nucleophile could be the benzyl amine (intermolecular reaction) or the benzyl amide resulting from the transamidation of the Weinreb amide (intramolecular reaction) . According to the stereochemical outcome of the reaction, regardless of the nucleophile, the addition to the trifluoromethyl ketone would happen via the Felkin-Anh transition state TS-2 , , as shown in Figure . Cyclization toward hemiaminals 4a – c is made possible thanks to the syn stereochemical relationship of the acetonide-protected diol.…”

Section: Resultsmentioning

confidence: 99%

cis-Dihydroxylated α-Trifluoromethylated N,O-Acetal from l-Tartaric Acid: Synthesis of Tetrasubstituted Stereocenter via Diastereoselective Pictet-Spengler Cyclization of N-Acyliminium Ions

et al. 2020

View full text Add to dashboard Cite

The synthesis of cyclic, chiral α-trifluoromethylated N,O-acetals having a protected cis-diol moiety has been readily achieved in two steps from a known bis-Weinreb amide derived from l-tartaric acid. The reaction of O-acetyl analogues of these N,O-acetals with triflic acid in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) at 0 °C generated in situ the corresponding electrophilic α-trifluoromethyl N-acyliminium ions that undergo Pictet-Spengler-type cyclizations. After only 10 min of reaction, the original enantiopure aza-tricyclic scaffolds bearing a trifluoromethyl substituent at the bridgehead position were obtained with diastereoselectivities ranging from 75:25 to 97:3.

show abstract

“…Perfluorobutyl pyrrolidines 26 and 27 were synthetized in 4 steps from the pyrrolidino‐ester 11 (Scheme ). At first, the pyrrolidino‐ester 11 was treated with perfluoro butyllithium (perfluorobutyl iodide, MeLi · LiBr, THF, –78 °C) to form a perfluorobutyl ketone intermediate, which is subsequently reduced with NaBH 4 to form the two diastereomeric perfluorobutyl alcohols 25 and 25′ . After cleavage of the carbamate by hydrogenolysis and N ‐benzylation, the two diastereomers, N ‐benzyl perfluorobutyl pyrrolidines 26 and 27 , were obtained in 62 % and 68 % yield respectively (Scheme ).…”

Section: Resultsmentioning

confidence: 99%

Synthesis of 2‐Fluoroalkyl 4‐Substituted Azepanes

et al. 2019

View full text Add to dashboard Cite

Synthesis of di‐ and tri‐substituted fluoroalkylated azepanes was achieved by ring expansion of pyrrolidines via a regioselective attack of nucleophiles on a bicyclic azetidinium intermediate. A broad scope of azepanes, substituted at C4 and bearing a α‐trifluoromethyl, α‐difluoromethyl or α‐perfluorobutyl group, can be synthesized by this method by using a wide variety of nucleophiles.

show abstract

Asymmetric Synthesis of (αR)-Polyfluoroalkylated Prolinols Based on the Perfluoroalkyl-Induced Highly Stereoselective Reduction of Perfluoroalkyl N-Boc-pyrrolidyl Ketones

Cited by 12 publications

References 69 publications

Conditions Favoring the Formation of Monomeric Pt^III Derivatives in the Electrochemical Oxidation of trans‐[Pt^II{(p‐BrC₆F₄)NCH₂CH₂NEt₂}Cl(py)]

Conditions Favoring the Formation of Monomeric Pt^III Derivatives in the Electrochemical Oxidation of trans‐[Pt^II{(p‐BrC₆F₄)NCH₂CH₂NEt₂}Cl(py)]

cis-Dihydroxylated α-Trifluoromethylated N,O-Acetal from l-Tartaric Acid: Synthesis of Tetrasubstituted Stereocenter via Diastereoselective Pictet-Spengler Cyclization of N-Acyliminium Ions

Synthesis of 2‐Fluoroalkyl 4‐Substituted Azepanes

Contact Info

Product

Resources

About

Asymmetric Synthesis of (αR)-Polyfluoroalkylated Prolinols Based on the Perfluoroalkyl-Induced Highly Stereoselective Reduction of Perfluoroalkyl N-Boc-pyrrolidyl Ketones

Cited by 12 publications

References 69 publications

Conditions Favoring the Formation of Monomeric PtIII Derivatives in the Electrochemical Oxidation of trans‐[PtII{(p‐BrC6F4)NCH2CH2NEt2}Cl(py)]

Conditions Favoring the Formation of Monomeric PtIII Derivatives in the Electrochemical Oxidation of trans‐[PtII{(p‐BrC6F4)NCH2CH2NEt2}Cl(py)]

cis-Dihydroxylated α-Trifluoromethylated N,O-Acetal from l-Tartaric Acid: Synthesis of Tetrasubstituted Stereocenter via Diastereoselective Pictet-Spengler Cyclization of N-Acyliminium Ions

Synthesis of 2‐Fluoroalkyl 4‐Substituted Azepanes

Contact Info

Product

Resources

About

Conditions Favoring the Formation of Monomeric Pt^III Derivatives in the Electrochemical Oxidation of trans‐[Pt^II{(p‐BrC₆F₄)NCH₂CH₂NEt₂}Cl(py)]

Conditions Favoring the Formation of Monomeric Pt^III Derivatives in the Electrochemical Oxidation of trans‐[Pt^II{(p‐BrC₆F₄)NCH₂CH₂NEt₂}Cl(py)]