Direct Asymmetric Allylic Alkylation of Butenolides with Morita−Baylis−Hillman Carbonates

Abstract

The direct asymmetric allylic alkylation of beta,gamma-butenolides with MBH carbonates to access gamma,gamma-disubstituted butenolides containing adjacent quaternary and tertiary chiral centers has been presented in excellent stereoselectivities (86-96% ee, dr >95:5) and moderate to good yield (50-83%). Their synthetic utility has been well demonstrated by the facile construction of bicyclic lactones bearing 4-5 stereogenic centers.

Diastereodivergent organocatalytic asymmetric vinylogous Michael reactions

“…(Table 4, entries [18][19][20][21][22]. Also, when R 1 substituent was an ethyl group, the corresponding product was obtained in a moderate diastereoselectivity (1/9 d.r.)…”

“…These compounds contain quaternary stereogenic centres and are important motifs in biologically active natural compounds and medicinally important agents [13][14][15][16][17][18] . The organocatalytic asymmetric synthesis of g, g-disubstituted butenolide derivatives has attracted much attention in the past few years [19][20][21][22][23][24][25][26] . However, the key limitation encountered with the previous asymmetric vinylogous reactions using b, g-butenolides was that only one diastereoisomer was accessed, therefore making it relevant to this study.…”

Diastereodivergent and Enantioselective [4+2] Annulations of γ-Butenolides with Cyclic 1-Azadienes

“…UV light and I2 were used to visualize products. All chemicals including α-angelica lactone 2a were used without purification as commercially available unless otherwise noted, and the other butenolides were prepared according to the literatures [15]. α,β-Unsaturated imines 2 and 7 were prepared according to the literature procedures [16].…”

“…In contrast to abundant γ-regioselective OPEN ACCESS vinylogous addition reactions, to the best of our knowledge, no examples have been reported to utilize the γ-butenolides as the reactants towards tandem reactions in consideration of the potential reactivity of both γ-and β-positions [14]. Recently, our group reported a direct asymmetric allylic alkylation of γ-butenolides with MBH carbonates to access γ,γ-disubstituted butenolides that could allow sequential aza-Michael addition to deliver interesting bicyclic piperidine derivatives [15]. These results inspired us to explore domino or tandem Michael addition-aza-Michael addition to construct a variety of polycyclic skeletons.…”

“…Importantly, they exhibit high electrophilicity, and can perform as either 2π or 4π partners in Diels-Alder cycloaddition reactions with HOMO-activated enamine species. Therefore, the good reactivity of such 1-azadienes in cycloaddition reactions suggests that they could be applied as potential reactants in the [4+2] reaction with the in situ generated dienolates from the γ-butenolides, either in a concerted or stepwise manner [15]. Here, we would like to report the asymmetric assembly of 3-vinyl-1,2-benzoisothiazole-1,1-dioxides and γ-butenolides to furnish chiral tetracyclic molecules with high structural and functional complexity.…”