Asymmetric Pictet–Spengler Reactions Employing N,N‐Phthaloyl Amino Acids as Chiral Auxiliary Groups

Abstract

Both aromatic and aliphatic Schiff bases 1 can be cyclized asymmetrically in the presence of titanium alkoxides if N,N‐phthaloyl‐protected amino acids are employed as chiral auxiliaries. The desired heterocycles 3, which are suitable for alkaloid syntheses, are formed with diastereomer ratios of up to 99%. R  nPr, iPr; R1  Me, Et, iPr, Ph, Ar; R2  Me, iPr, tBu.

Total Synthesis of Enantiopure Phalarine via a Stereospecific Pictet−Spengler Reaction: Traceless Transfer of Chirality from l-Tryptophan

“…Given the information provided above, it did not seem very likely that we could defeat the potentiality for retro-Mannich-induced loss of enantiointegrity at the quaternary β-carbon in the spiroindolenine en route to phalarine (see Scheme 3). Happily, an interesting alternative solution presented itself 25,31–33. A structure such as 31 would be generated in the tryptophane ester series and this would subsequently be converted to a pre-phalarine product ( 32 , Scheme 6).…”

Pharmacological Importance of Optically Active Tetrahydro-β-carbolines and Synthetic Approaches to Create the C1 Stereocenter

“…However, simple benzyl- or naphthyl-derived chiral groups provide only moderate diastereoselectivity and only 30%–80% de [38,39]. Yet, good diastereoselectivities have been obtained using N,N -phthaloylamino acids (Scheme 9) [40]. In this example the pre-formed imine 18 is protected with a phthaloylamino acid derivative and the N -protected THβC 19 is formed diastereoselectively.…”

Synthesis of new Amides based on N-Phthaloyl-α-Amino Acids

“…Nphthaloyl-(S)-aminoacyl chlorides with alkyl and aryl side chains [19][20][21] serve as a favorable agent for enantiomer separation of heterocyclic amines. Mannich [22] and Pictet-Spengler reactions [23] have been shown to form product enantiomers with a large relative difference between them when administered sterically using N,N-phthaloyl-tret-leucinylchloride. Also, nonracemate chiral reducing agent based on N, Nphthaloylamine acids have been used effectively in the enantioselective reduction of prochiral cyclic imins to obtain important alkaloid derivatives [24].…”