Chiral Synthesis of Erythrina Alkaloids. I Total Synthesis of (+)-Erysotrine via Asymmetric Diels-Alder Reaction under High Pressure.

Phosphite‐Catalyzed C−H Allylation of Azaarenes via an Enantioselective [2,3]‐Aza‐Wittig Rearrangement

“…We report herein the first enantioselective CÀHallylation of azaarenes via ac onceptually novel chiral phosphitepromoted [2,3]-aza-Wittig rearrangement ( Figure 1c). Our interest in enantioselective CÀHf unctionalization of imines embedded in azaarenes prompted us to explore the possibility of umpolung reactivity.…”

“…Abstract: Ap hosphite-mediated [2,3]-aza-Wittig rearrangement has been developed for the regio-and enantioselective allylic alkylation of six-membered heteroaromatic compounds (azaarenes). The nucleophilic phosphite adducts of N-allyl salts undergo as tereoselective base-mediated aza-Wittig rearrangement and dissociation of the chiral phosphite for overall C À Hf unctionalization of azaarenes.T his method provides efficient access to tertiary and quaternary chiral centers in isoquinoline,q uinoline,a nd pyridine systems,t olerating ab road variety of substituents on both the allyl part and azaarenes.C atalysis with chiral phosphites is also demonstrated with synthetically useful yields and enantioselectivities.…”

“…[1] Consequently, great advances have been made in their enantioselective synthesis. [2] Fore xample,m ethods have been developed that commence from acyclicp recursors or prefunctionalized azaarene halides and organometallic reagents. [2,3] Recently, elegant protocols for the direct CÀHa lkylation from feedstock azaarenes have also been reported.…”

“…[2] Fore xample,m ethods have been developed that commence from acyclicp recursors or prefunctionalized azaarene halides and organometallic reagents. [2,3] Recently, elegant protocols for the direct CÀHa lkylation from feedstock azaarenes have also been reported. [4][5][6] Unfortunately, an enantioselective CÀHallylation of azaarenes has remained elusive,d espite the potential utility of the synthetically versatile chiral allylated azaarene products for further functionalization (Figure 1b).…”

Heck Cyclization Strategy for Preparation of Erythrinan Alkaloids: Asymmetric Synthesis of Unnatural (−)-Erysotramidine fromL-Tartaric Acid

“…The first asymmetric synthesis of both alkaloids from (S)-3,4-dimethoxyphenylalanine methyl ester was reported by Tsuda two decades ago. 5 Another synthetic approach was announced by Simpkins et al 4e They accomplished a 13-step synthesis of (+)-erysotramidine (93% ee) using a chiral base imide desymmetrization, N-acyliminium addition, and radical cyclization as the key steps. The most recent formal synthesis of the discussed alkaloid was reported by Tietze et al 4i A crucial step of their elegant synthesis was a domino process: condensation of enantiopure keto ester with 3,4-dimethoxyphenethylamine, which led to spirocyclic silane with a complete erythrinan skeleton.…”