ChemInform Abstract: Asymmetric Synthesis of (αR)‐Polyfluoroalkylated Prolinols Based on the Perfluoroalkyl‐Induced Highly Stereoselective Reduction of Perfluoroalkyl N‐Boc‐pyrrolidyl Ketones.

Abstract

Amino acids U 0400Asymmetric Synthesis of (αR)-Polyfluoroalkylated Prolinols Based on the Perfluoroalkyl-Induced Highly Stereoselective Reduction of Perfluoroalkyl N-Boc-pyrrolidyl Ketones. -Treatment of fluoroalkylated pyrrolidyl ketones like (III) and (V) with NaBH4 allows efficient and highly stereoselective access to fluoroalkylated prolinols. In contrast, reduction of the nonfluorinated analogue (VII) proceeds only with low to moderate stereoselectivity. -(FUNABIKI*, K.; SHIBATA, A.; IWATA, H.; HATANO, K.; KUBOTA, Y.; KOMURA, K.; EBIHARA, M.; MATSUI, M.; J. Org. Chem. 73 (2008) 12, 4694-4697; Dep. Mater. Sci. Technol., Fac. Eng., Gifu Univ., Yanagido, Gifu 501-11, Japan; Eng.) -Jannicke 42-191

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

“…The aza nucleophile could be the benzyl amine (intermolecular reaction) or the benzyl amide resulting from the transamidation of Weinreb amide 16 (intramolecular reaction). 17 According to the stereochemical outcome of the reaction, regardless the nucleophile, addition to the trifluoromethyl ketone would happen via the Felkin-Anh transition state TS-2, 18,19 as shown in Having developed a short and highly efficient synthesis of enantiopure atrifluoromethylated N,O-acetals having a cis-diol motif, we envisaged to use this reaction sequence to prepare original N-acyliminium ions precursors allowing to study diastereoselective Pictet-Spengler cyclization. The required starting N,O-acetals 5a-g were easily prepared by reacting the hydrated ketone 3 with 2 equiv of variously substituted phenethylamines or the 1-methyltryptamine at reflux of toluene (Table 3).…”

“…Diastereomeric ratios (dr) were determined by 19 F NMR. HRMS were recorded on an ESI-Q-TOF mass spectrometer using an electrospray source in positive mode.…”

“…A solution of hydrated ketone 3 and amine (2 equiv) was heated at reflux of toluene with a heating mantle. After completion of the reaction (monitored by 19 F NMR), the solution was cooled to rt and concentrated under reduced pressure.…”

“…Unfortunately, treatment of the O-acetyl N,O-acetal 6g containing an N-methylindole ring under this strong acidic conditions led only to a very complex mixture from which Pictet-Spengler products could not be identified.The major diastereomers 7a and 7f obtained for the Pictet-Spengler cyclization of 6a and 6f were unambiguously established by X-ray crystallography to have the S configuration for the newly formed stereogenic center. Similar trends in the19 F chemical shifts observed for the major diastereomer 7a-f (s, -73.6-74.1 ppm) and for the minor diastereomer epi-7a-f (br s, 25 -66.1-67.0 ppm) of all Pictet-Spengler products allowed the assignment of the same stereochemistry. Pictet-Spengler cyclization of O-Acetyl N,O-Acetals 6a-f with Triflic Acid in HFIP.…”

“…, entries1- 2). No traces of the bis-trifluoromethylated derivative were detected in the19 F NMR spectrum of the crude reaction mixture. All usual ammonium fluorides in THF gave a complex mixture of fluorinated compounds (Table1, entry 3).…”