Clarification of the mechanism of rearrangement of enol silyl ether epoxides

Total Synthesis of the Antiviral Natural Product Houttuynoid B

“…The synthesis of the second building block 6 a (Scheme ) started from the inexpensive commercially available natural product chrysin ( 13 ), which after double O ‐benzylation was degraded by retro‐aldol reaction to the resulting acetophenone derivative ( 14 ) as described by Caldwell et al . α‐Oxidation under Rubottom conditions then furnished the hydroxylated product 15 . It is worth noting that, despite the modest yield, this method opened a reliable and practical access to 15 on a multigram scale.…”

“…Subsequent Pinnick oxidation [14] of the aldehyde functiong ave the carboxylic acid 5a.T op repare for the planned ester formation (see Scheme 2), this buildingb lock was further converted into the HOBT-activated ester 12, [15] which provedt ob ee asy to handle and was stable for months without significant decomposition. [16] The synthesis of the second building block 6a (Scheme 4) started from the inexpensive commerciallya vailablen atural product chrysin (13), whicha fter double O-benzylation was degraded by retro-aldol reaction to the resulting acetophenone derivative( 14)a sd escribed by Caldwell et al [17] a-Oxidation under Rubottom conditions [17,18] then furnished the hydroxylated product 15.I ti sw orth noting that, despitet he modest yield, this methodo penedareliable and practical access to 15 on am ultigram scale. Lastly,t he installation of a b-galactose moiety wasa ccomplished in good yield by reacting am ixture of the alcohol 15 with peracetylated b-galactose in the presence of BF 3 -etherate as aL ewis acid at room temperature.…”

A Stereoselective Route to Guanacastepene A through a Surprising Epoxidation This work was supported by the National Institutes of Health (CA-28824). S.L. is a US Army breast cancer research program postdoctoral fellow (DAMD-17-99-1-9373). G.B.D. is an NIH postdoctoral fellow (1 F32 NS11150-01). D.S.T. is a Damon Runyon Cancer Research Foundation postdoctoral fellow (DRG-1641). We thank Dr. George Sukenick and Sylvi Rusli (NMR Core Facility, CA-02848) for mass spectral analyses.

“…As before, the diagnostic coupling constants demonstrated that acetoxylation had occurred syn to the isopropyl and methyl substituents. As the rearrangement associated with the Rubottom protocol can be safely assumed to occur by retention,18 we must conclude that epoxidation had again occurred from the β face. The assignment of the stereochemistry of 17 was confirmed by its ultimate transformation into guanacastepene A (Scheme ).…”

Unified Approach to the Chemoselective α-Functionalization of Amides with Heteroatom Nucleophiles

“…1,2 Because of the inherent electronegativity of most heteroatoms listed in the preceding sentence (O, N, and halogens), their derivatives are also typically nucleophilic in nature. Introducing such a species into the α-position of a carbonyl therefore formally requires an oxidation event, either in the reaction itself 3,4 or in the generation of highly reactive electrophilic heteroatom reagents. 5−7 Although this can result in poor functional group tolerance under the reaction conditions, it more significantly means that a truly unified approach has failed to materialize, with specific reagents required for each element (Figure 1a).…”

“…Indeed, the recognition of the synthetic value of nucleophilic enolates, available by treatment of a carbonyl precursor with a strong base, has rendered them the reactants of choice for C–C, C–O, C–N, C–S, and C–halogen bond formation at the α-position of a carbonyl moiety for more than half a century. , Because of the inherent electronegativity of most heteroatoms listed in the preceding sentence (O, N, and halogens), their derivatives are also typically nucleophilic in nature. Introducing such a species into the α-position of a carbonyl therefore formally requires an oxidation event, either in the reaction itself , or in the generation of highly reactive electrophilic heteroatom reagents. − Although this can result in poor functional group tolerance under the reaction conditions, it more significantly means that a truly unified approach has failed to materialize, with specific reagents required for each element (Figure a).…”