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Asymmetric synthesis of the pentacyclic alkaloid (-)-cephalotaxine was accomplished via palladium-catalyzed enantioselective Tsuji allylation for construction of the aza-containing tetrasubstituted stereogenic center (95% yield, 93% ee). The allyl enol carbonate precursor was prepared from Hanaoka's ketone intermediate, which was formed by a novel formic acid promoted ring-expansion reaction.

We report a protocol for efficient stereoselective installation of the chiral oxygen-containing tetrasubstituted tertiary carbon stereocenter of the side chain of cephalotaxus esters by means of highly diastereoselective Mukaiyama aldol reactions between α-keto esters (2) and a (Z)-α-chloro ketene silyl acetal. This protocol permitted synthesis of cephalotaxus esters including six natural products in good to excellent yields (up to 94%) with high diastereoselectivities (dr up to 97:3) and could be performed on a multigram scale.

A concise total synthesis of (±)-cephalotaxine (1) has been achieved from dioxolanone derivative 15 via a transannulation strategy. The key transformation is a facile reductive oxy-Nazarov cyclization as illustrated above, involving presumably a tethered 1,2-oxidopentadienyl cation species 7a or 7b, which represents a new variant of the oxy-Nazarov cyclization and constitutes an effective, regio- and stereospecific 5-hydroxy cyclopentenone annulation protocol under mild hydride reduction conditions.

An efficient and highly stereoselective synthesis of functionalized trisubstituted E-olefins from cyclopropyl carbinol derivatives via a Julia-type olefination mediated by an intriguing Lewis acidic system consisting of CeCl3·7H2O and NaI in refluxing acetonitrile is reported. This facile olefination allows for the iterative incorporation of methylcyclopropyl ketone as a C5 prenylation synthon in the synthesis of acyclic terpenoids, as demonstrated in the facile synthesis of plaunotol 6E-isomer 12, a biologically significant diterpene diol, and naturally occurring diterpene 17.

[reaction: see text] An unusual cyclopropanation of 9-bromocamphor derivatives 1 to a 7-spiro-cyclopropyl camphor derivative 3 was effected by the action of potassium tert-butoxide (or sodium hydride) in warm DMSO. The exo-hydroxy group and a non-hydrogen endo-substituent at C(2) have proven to be essential structural elements, and the solvent DMSO has proven to be the sole effective reaction medium. Tricyclic compound 3 undergoes a facile tandem Wagner-Meerwein rearrangement-cyclopropyl ring-opening under mild acidic conditions, leading to norbornenyl derivative 12 and subsequent Meinwald rearrangement of bicyclic epoxide 13 to a formal C(1)-C(7) bond cleavage product 14.

A novel facile synthesis of substituted and functionalized allylsilane has been developed. This essentially one-pot procedure involves (1) (dimethylphenylsilyl)methyl cerium chloride addition to cyclopropyl ketone and (2) MgI(2) etherate-mediated Julia homoallylic transposition of the corresponding cyclopropyl carbinol. The bifunctional homoiodo allylsilanes, readily accessible by this method, would be useful and versatile synthons in organic synthesis. [reaction: see text]

Mukaiyama-type aldol coupling of typical silyl enolates 2-4 with aryl or vinyl aldehydes and acetals was realized in the presence of 1-5 mol % of MgI(2) etherate (1) in a mild, efficient, and highly chemoselective manner. Iodide counterion, weakly coordinating peripheral ethereal ligands (Et(2)O) of Mg(II), and a noncoordinating reaction media (i.e. CH(2)Cl(2)) are among the critical factors for the unique reactivity of this catalytic system. [reaction: see text]

A facile total synthesis of hainanensine (1), a structurally unique Cephalotaxus alkaloid, via an effective acid-mediated rearrangement/Friedel-Crafts annulation cascade (7a/7b --8a/8b), is described.

Regioselective and stereospecific intramolecular alkylative arylation of unsaturated oxabicyclic diol 6, mediated by Lewis acid or strong protic acid to give the tetracyclic products 7a and 7b, as shown above, represents the first example of an electrophilic (cationic in character) ring-opening-cyclization of oxabicyclic alkene. This constitutes the key cyclization step for a long-standing and potentially useful diene approach for the synthesis of estrone and analogous steroid structures. [structure: see text]

[structure: see text] A novel method for the stereocontrolled construction of the eudesmane ring system based on a cationic cyclization is presented, and the approach is exemplified in a short and efficient total synthesis of (+/-)-balanitol (2).

[reaction: see text] An efficient and highly stereoselective synthesis of functionalized trisubstituted E-olefins from cyclopropyl carbinol derivatives via a Julia-type olefination mediated by an intriguing Lewis acidic system consisting of CeCl(3).7H(2)O and NaI in refluxing acetonitrile is reported. This facile olefination allows for the iterative incorporation of methylcyclopropyl ketone as a C(5) prenylation synthon in the synthesis of acyclic terpenoids, as demonstrated in the facile synthesis of plaunotol 6E-isomer 12, a biologically significant diterpene diol, and naturally occurring diterpene 17.

[reaction: see text] A novel approach for the stereocontrolled synthesis of eudesmanolides was developed based on a quasi-biomimetic strategy starting from a functionalized oxabicyclic template, as shown above, by which the first total syntheses of gallicadiol (6) and isogallicadiol (7) were achieved. The key elements of the synthesis include: (1) a facile and stereospecific synthesis of a functionalized epoxy aldehyde intermediate; (2) a mild Lewis acid-mediated stereoselective ene cyclization; and (3) a stereocontrolled gamma-lactonization.

[reaction: see text] Total synthesis of cephalotaxine (CET), the parent member of a class of structurally unique antileukemia Cephalotaxus alkaloids, was accomplished on the basis of a conceptually novel strategy featuring transannular reductive skeletal rearrangements as the key transformations for the construction of the pentacyclic ring skeleton of CET. The synthetic potential of the designated Clemmensen-Clemo-Prelog-Leonard reductive rearrangement was demonstrated for the first time in a facile synthesis of the benzazepine subunit of CET. A novel endocyclic enamine (cyclopentenone) annulation was discovered and rationalized as an unusual azo-Nazarov-type cyclization.