Tw oenantioselective total syntheses of the nortriterpenoid natural product rubriflordilactone Aa re described, which use palladium-or cobalt-catalyzed cyclizations to form the CDE rings,a nd converge on al ate-stage synthetic intermediate.T hese key processes are set up through the convergent coupling of ac ommon diyne component with appropriate AB-ring aldehydes,astrategy that sets the stage for the synthetic exploration of other members of this family of natural products.

Taking advantage of a 6π electrocyclization-aromatization strategy, we accomplished the first and asymmetric total synthesis of rubriflordilactone B, a heptacyclic Schisandraceae bisnortriterpenoid featuring a tetrasubstituted arene moiety. The left-hand fragment was accessed through a chiral-pool-based route, and linked to the right-hand fragment by a Sonogashira coupling. The cis geometry of the electrocyclization substrates was established by hydrogenation or hydrosilylation of the alkyne. An electrocyclization-aromatization sequence finally built the multisubstituted arene. The hydrosilylation approach was of significant advantage in terms of reaction scale, reproducibility, and intermediate stability. The structure of synthetic rubriflordilactone B was validated by X-ray crystallographic analysis, and found to be consistent with that reported for the authentic natural product based on an independent X-ray crystallographic analysis. However, obvious differences in the NMR spectra of the synthetic and authentic samples suggest that the authentic samples subjected to X-ray crystallography and NMR spectroscopy were two different compounds.

A practical method is developed for the cleavage of catechol monomethyl ethers and o-carbonylphenyl methyl ethers using aluminum chloride and sodium iodide in acetonitrile. Acid scavengers such as 1,3-diisopropylcarbodiimide and CaO are used to prevent acid-labile functional groups from sidereactions. This method is efficient for the deprotection of various o-hydroxyphenyl methyl ethers such as acetovanillone, eugenol, guaiacol, vanillin, isovanillin and ortho-vanillin. The AlCl 3 -NaI system is less efficient than AlI 3 for the cleavage of other typical aryl alkyl ethers without a neighboring hydroxyl or carbonyl group, or for the removal of bulkier alkyl groups from catechol monoalkyl ethers. This procedure represents a convenient approach for the preparation of catechols. 2 3 4 5 6 7 8

Three-component coupling reactions of sulfonylimidates, silyl glyoxylates and N-tert-butanesulfinyl aldimines efficiently provide cyclic N-sulfonylamidines containing free endocyclic N-H. The formation of two C-C bonds (contiguous stereogenic carbons), one O-Si bond, and one C-N bond, together with the cleavage of the chiral auxiliary (tert-butanesulfinyl group), occurs with excellent chemoselectivity, diastereoselectivity, and enantioselectivity in this one-pot cascade transformation.

Using eugenol and vanillin as model substrates, a practical method is developed for the cleavage o-hydroxyphenyl alkyl ethers. Aluminum oxide iodide (O=AlI), generated in situ from aluminum triiodide and dimethyl sulfoxide, is the reactive ether cleaving species. The method is applicable to catechol monoalkyl ethers as well as normal phenyl alkyl ethers for the removal of methyl, ethyl, isopropyl, and benzyl groups. A variety of functional groups such as alkenyl, allyl, amide, cyano, formyl, keto, nitro, and halogen are well tolerated under the optimum conditions. Partial hydrodebromination was observed during the demethylation of 4-bromoguaiacol, and was resolved using excess DMSO as an acid scavenger. This convenient and efficient procedure would be a practical tool for the preparation of catechols.

Studies have shown that a proper acid scavenger is a requisite to prevent acid‐labile functional groups from deterioration during aluminum triiodide‐mediated cleavage of o‐hydroxyphenyl alkyl ethers. In this work, the acid scavenging effect of inexpensive and bench stable inorganic bases and metal oxides were evaluated using eugenol as a model substrate. Among the bases and oxides screened, KOtBu, Na2CO3, CaO, CuO and ZnO were found effective. The method is compatible with a variety of functional groups, and was applied successfully in cleaving catechol monoethers such as guaiacol, vanillin, isovanillin, vanillonitrile, isovanillonitrile, acetovanillone, nonivamide, ethylvanillin and o‐isopropoxyphenol. The corresponding catechols were obtained in excellent yields. The oxophilicity of aluminum triiodide is not markedly suppressed by these inorganic acid scavengers, making the aluminum triiodide‐acid scavenger method effective in cleaving general phenyl methyl ethers such as m‐guaiacol, 4‐allylanisole, veratraldehyde and methyl eugenol without the anchimeric assistance of an o‐hydroxyl group.

An efficient and flexible route for the synthesis of α-tertiary (α,α-dibranched) α-silylamines via sequential reactions of sulfonylimidates using readily available phenyldimethylsilyllithium and Grignard reagents is described. The procedure allows successive formation of C-Si/C-C bonds in a single flask.

Rubriflordilactone B (1) is a schinortriterpenoid isolated by Sun and colleagues, which possesses a tetrasubstituted benzene moiety and eight stereocenters. The previous synthesis of 1 by Li and co-workers uncovered the existence of its naturally occurring stereoisomer “pseudorubriflordilactone B”. Here we report a collaborative study by the two groups that elucidates the structure of pseudorubriflordilactone B to be 16,17-bis-epi-rubriflordilactone B (26). Chemical synthesis served as an important tool in the structure determination. Taking advantage of a modular synthetic route, we systematically “mutated” the configurations of C-23, C-22, C-20, and C-16/C-17 located at the right-hand domain of 1, and thus prepared its 15 stereoisomers for spectrum comparison. The 1H NMR spectra of synthetic 26 in deuterated chloroform and pyridine were identical to those of authentic pseudorubriflordilactone B, respectively. This synthetic sample displayed anti-HIV activity (EC50 = 0.288 μM) in vitro.