Divergent Chemical Synthesis of Prolines Bearing Fluorinated One-Carbon Units at the 4-Position via Nucleophilic 5-Endo-Trig Cyclizations

• Published in: Journal of organic chemistry Vol. 71; no. 23; pp. 8748 - 8754
• Main Authors: Nadano, Ryo, Iwai, Yu, Mori, Takashi, Ichikawa, Junji
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 10.11.2006; Amer Chemical Soc
• Subjects: Carbon - chemistry; Chemistry; Chemistry, Organic; Cyclization; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Hydrocarbons, Fluorinated - chemistry; Molecular Structure; Organic chemistry; Physical Sciences; Preparations and properties; Proline - analogs & derivatives; Proline - chemical synthesis; Proline - chemistry; Science & Technology; Stereoisomerism; Sulfonamides - chemical synthesis; Sulfonamides - chemistry; TRANSFORMATION; ALDOL; ACIDS; TRIPLE-HELIX; ORGANOCATALYSIS; CONVERTING ENZYME-INHIBITORS; BUILDING-BLOCK; DERIVATIVES; RING-CLOSURE; DIFLUOROMETHYLENE; Intramolecular reaction; Endo stereoisomer; Sulfonamide; Ether; Nitrogen heterocycle; Proline; SN2 mechanism; Selectivity; Hydrogenation; Ring cleavage; Pyrrolidine derivatives; α-Aminoacid; Cyclization; Aminoacid; Organic fluorine compounds; Aromatic compound; Oxidation; Fluorine Organic compounds; Chemical synthesis; Homoallylic compound; Nucleophile
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo061421n

N-[3-(Trifluoromethyl)homoallyl]sulfonamides, prepared via ring opening of (S)-glycidyl ethers or 2-aryloxiranes with 1-(trifluoromethyl)vinyllithium, underwent intramolecular addition or SN2‘-type reaction in the normally disfavored 5-endo-trig fashion, leading to 2-substituted 4-(trifluoromethyl)- or 4-(difluoromethylene)pyrrolidines. Both α- and β-face-selective hydrogenation of the 4-difluoromethylene group afforded syn- and anti-4-(difluoromethyl)pyrrolidines, respectively. These sequences, followed by the oxidation of a 2-hydroxymethyl or 2-aryl group, successfully provided prolines with a trifluoromethyl, difluoromethylene, or difluoromethyl group at the 4-position, including optically active prolines.