Configurational stability of N-protected .alpha.-amino aldehydes

Abstract

A three-step synthesis of JV-(9-(9-phenylfluorenyl))-L-alaninal (5) from alanine is described. Exposure to silica or nonnucleophilic base causes no detectable racemization of this -amino aldehyde. The 9-(9-phenylfluorenyl) N-protecting group also maintains the configurational integrity of -amino aldehyde 5 during C-C bond-forming reactions, providing enantiomerically pure products from Wittig reaction, aldol condensation, and addition of Grignard reagent.The synthetic applications of optically active N-protected examino aldehydes have increased dramatically with the rising interest in the synthesis of polyfunctional amino acids,1 peptide analogues,1

Synthesis of Chiral (Indol‐2‐yl)methanamines and Insight into the Stereochemistry Protecting Effects of the 9‐Phenyl‐9‐fluorenyl Protecting Group

“…The other main reaction component was found to be 9-phenylfluorene, indicating that elimination of an aromatic 9-phenylfluorenyl anion took place preferentially over deprotonation/inversion/reprotonation of the stereogenic center on the aldehyde. [22] The lack of detailed information regarding the molecular mechanics calculations, [37] or any publications further addressing the subject, prompted us to perform the first thorough investigation of the mechanism behind the stereoprotecting effects of the Pf group, by computational conformational analysis, supported by X-ray crystal structures and NMR analysis.…”

“…[21,22] The exact mechanism behind this stereochemical protecting effect has however not yet been elucidated and no thorough mechanistic investigations have yet to be undertaken. Therefore, within the framework of this work, we also aim to offer insight into the stereochemical protecting effects of the Pf-protecting group.…”

“…The crude product was purified by trituration from MeOH to give 18c: yield 75 % (630 mg) over two steps; R f 0. 22 (S)-1-(1H-Indol-2-yl)ethanamine (22a): Compound 18a (400 mg, 1 mmol, 100 mol-%) was dissolved in MeOH (8 mL) and the resulting solution was degassed with argon. Pd/C (45 mg, 0.05 mmol, 10 wt.-%, 5 mol-%) was added and hydrogen (1 atm, balloon) was introduced and the reaction was stirred for 18 h at room temp.…”

Chirospecific Synthesis of D-erythro- and L-threo-Sphinganines from Sugars

“…We chose the 9-phenyl-9-fluorenyl (Pf) group for protection of the amine since the protecting group has been shown to inhibit deprotonation at the α-position of an α-amino ester. 9 For regioselective hydrolysis of the terminal O-isopropylidene group in diisopropylidene 3 under acidic condition, Dowex 50W-X8 was treated to 3 in 90% methanol to give the diol 4 in 95% yield. The diol 4 was oxidized in the presence of NaIO 4 ; this was followed by NaBH 4 reduction of the resulting aldehyde, which led to the formation of alcohol 5 in quantitative yield.…”

“…9,24.2,24.5,27.5,30.9,31.0,31.1,31.2,31.2,31.2,33.5,34.6,58.8,59.8,and 71.0;MS m/z: 284,270,252 (M + ); Anal. calcd.…”