Asymmetric Total Synthesis of Rollicosin

Abstract

[structure: see text] The first total synthesis of rollicosin, a member of a rare subgroup of Annonaceous acetogenins containing two terminal gamma-lactones, is reported. The approach features a highly regio- and stereoselective tandem ring-closing/cross-metathesis reaction for construction of the east-wing lactone and incorporation of the alkyl spacer. Establishment of the C4 stereocenter and addition of the west-wing lactone were achieved by Sharpless asymmetric dihydroxylation and enolate alkylation.

Synthesis of Dihydrofurans and Dihydropyrans with Unsaturated Side Chains Based on Ring Size‐Selective Ring‐Closing Metathesis

“…This would be particularly attractive from the synthetic point of view, as 1 is easily available in multi-gram quantities from d-mannitol, [20,21] while its enantiomer ent-1 can be synthesized from R,R-dimethyl tartrate. [22] Both 1 and ent-1 have previously been used as building blocks for the synthesis of metathesis precursors: for instance, Quinn et al reported the total synthesis of the five-membered ring lactones muricatacin [23] and rollicosin [24] from 1, while Michaelis and Blechert recently published a synthesis of the sixmembered ring lactone phomopsolide C from ent-1. [22] Burke et al exploited the C 2 -symmetry of dienediol 1 in the total synthesis of several natural products, such as brevicomin, [25] sialic acids, [26] and densely functionalized spiroacetals.…”

Palladium‐Catalyzed O‐Allylation of α‐Hydroxy Carbonyl Compounds

“…Optical purities were determined by HPLC using a HP-LC-1050 system equipped with a Daicel Chiralcel OD column. The following compounds were prepared according to procedures described in the literature: 10c, [45] 10d, [47] 10e, [46] 10g, [49] 10h, [56] 10i, [3] 10j, [57] Pd 2 (dba) 3 · CHCl 3 , [58] [Pd(h 3 -C 3 H 5 )Cl] 2 , [59] and [Pd(PPh 3 ) 4 ]. [58] Screening Experiments for Different Pd-Precatalysts…”

“…Spectroscopic data are identical to those reported in the literature. [3] (3R,4R)-3-Allyloxy-4-(tert-butyldimethylsilanyloxy)-1,5-hexadiene (11j): Obtained from 10j [57] (228 mg, 1 mmol) as a colorless liquid; yield: 200 mg (74%).…”

“…After 15 min of stirring, a solution of 10j [57] (1.80 g, 7.9 mmol) in DCM (5 mL), followed by a solution of tert-butyl hydroperoxide in toluene (2.85 M, 14.2 mmol, 5.0 mL) was added. The reaction mixture was then stored in a freezer at À 30 8C for 15 days, after which another 10.0 mL of tert-butyl hydroperoxide in toluene (2.85 M, 28.4 mmol) were added.…”

“…Alternatively, to a solution of 10j [57] (460 mg, 2.0 mmol) in toluene (10 mL) was added vanadyl acetylacetonate (11 mg, 2 mol %) and tert-butyl hydroperoxide (0.45 mL, 5.5 M in decane, 2.5 mmol). After heating the mixture to reflux for 3 hours, additional tert-butyl hydroperoxide (0.2 mL, 5.5 M in decane, 1.1 mmol) was added and heating was continued for 0.5 hours.…”