Organocatalytic, Asymmetric Total Synthesis of (−)‐Haliclonin A

Abstract

The first total synthesis of the alkaloid (-)-haliclonin A is reported. The asymmetric synthesis relied on a novel organocatalytic asymmetric conjugate addition of nitromethane with 3-alkenyl cyclohex-2-enone to set the stereochemistry of the all-carbon quaternary stereogenic center. The synthesis also features a Pd-promoted cyclization to form the 3-azabicyclo[3,3,1]nonane core, a SmI2 -mediated intermolecular reductive coupling of enone with aldehyde to form the requisite secondary chiral alcohol, ring-closing alkene and alkyne metathesis reactions to build the two aza-macrocyclic ring systems, and an unprecedented direct transformation of enol into enone.

Marine natural products

“…[539][540][541][542] Aurantoside G 543 has been synthesised, 544 while a synthesis of haliclonin A, 545 consistent with the written description of the conguration of the molecule but opposite to that drawn (incorrectly) in the original publication, has been reported. 546 Renieramycin T 547 has been made, 548,549 while the absolute congurations of isowondonins A 1008 and B 1009, 550 isolated from Poecillastra wondoensis, were established following their syntheses. 551 Other rst total syntheses of hyrtinadine B, 552,553 dictyodendrin H and I, 554,555 crambescin A and C, 556,557 clavatadine C, 558,559 cyclosmenospongine, 560,561 strongylophorine 1, 2, 3, 562 8, 563 and 9, 564,565 arenaran A and B, 566,567 polyrhaphin D, 568,569 hamigeran D, 570 579 as has the side-chain conguration of clathsterol 1012.…”

Molybdenum Alkylidyne Complexes with Tripodal Silanolate Ligands: The Next Generation of Alkyne Metathesis Catalysts

“…[4][5][6] This auspicious profile is manifest, inter alia, in the high-yielding formation of numerous polyfunctionalized targets;t he examples shown in Figure 1a re representative. [7][8][9][10][11][12][13][14] Even protic groups were found to be compatible in favorable cases,although important limitations still remain: [15] the polarization of the operative [Mo CR] unit, which is inherently nucleophilic and basic at carbon, constitutes apotential Achilles heel of any Schrock alkylidyne in ap rotic environment. [16,17] Moreover,s ubstrates able to entail ligand exchange will eventually bring productive alkyne metathesis to ahold since catalyst 1 and congeners draw their excellent performance from a( largely) intact siloxide ligand sphere.Inconsideration thereof,itmay not come as asurprise that the attempted metathesis reaction of as ubstrate as simple as 8 containing an unhindered primary alcohol basically met with failure (Scheme 1).…”

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

“…A challenging issue in the synthesis of (−)‐haliclonin A ( 27 ) is the asymmetric construction of the all‐carbon quaternary stereocenter at C6 (Scheme ). Huang and co‐workers examined enantioselective conjugate addition of nitromethane to enone 15 in the presence of amine‐thiourea bifunctional organocatalyst 14 (20 mol%), obtaining the conjugate addition product 16 in 80% yield with 97% ee . In this reaction, nitromethane, a nucleophile, was used as the solvent (Scheme ).…”