Synthesis of 2-Oxindoles Sharing Vicinal All-Carbon Quaternary Stereocenters via Organocatalytic Aldol Reaction

Abstract

An organocatalytic enantioselective aldol reaction using paraformaldehyde as C1-unit has been developed for the synthesis of 2-oxindoles sharing vicinal all-carbon quaternary stereocenters. The methodology is eventually employed in the formal total synthesis of (+)-folicanthine (1b).

Pentanidium-Catalyzed Direct Assembly of Vicinal All-Carbon Quaternary Stereocenters through C(sp 3 )–C(sp 3 ) Bond Formation

“…However, stereoselective construction of all-carbon quaternary stereocenters remains a significant challenge in synthetic chemistry. 5,6 Amongst the limited number of strategies, for the formation of this highly congested moiety, double Heck coupling, 7,8 double Aldol reaction, 9 and double allylation 10 have been reported to be useful (Figure 1a). Separately, the use of multi-substituted alkenes in [3+2] annulation, 11,12 Diels-Alder [13][14][15] and other cycloadditions 16,17 is another common approach (Figure 1a).…”

Stereoselective synthesis and applications of spirocyclic oxindoles

“…280 In 2016, Bisai reported an enantioselective aldol reaction of dimeric oxindoles which resulted in ring opening of one of the oxindoles, and in doing so developed a highly enantioselective thiourea catalysed aldol reaction with formaldehyde. 281 The first process scale synthesis of TV-45070 (Fig. 9) employed a phase-transfer catalysed asymmetric alkylation using a Lygo phase transfer catalyst.…”

Recent Advances in Natural Products Synthesis Using Bifunctional Organocatalysts Bearing a Hydrogen‐Bonding Donor Moiety

“…The same group applied the organocatalytic aldol reaction for the synthesis of the dimeric HPI alkaloid (+)‐folicanthine ( 57 ) from symmetric bis‐oxindole 46 (Scheme ) . In this reaction, enantioselective aldol reaction of 46 and subsequent translactonization reaction proceeded simultaneously to generate spiro‐lactone 47 in 96% yield with 93% ee (d.r.=1 : 1).…”