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Directed ortho -lithiation (DoL) has been developed as an effective method for the ortho -substitution of BINOL-phosphoric acid and BINOL- N -triflylphosphoramide (BINOL-P-acids). It can be employed in the rapid assembly of either mono- or disubstituted BINOL-P-acids, including unsymmetrical disubstitution through iterative DoL. Most significantly, DoL has proven to be highly effective in the diastereoselective desymmetrization of pseudo- C 2 - symmetric BINOL- N -triflylphosphoramide, affording a chiral P-group.

The total synthesis of viridiofungins A ( 1 ) and B ( 2 ) via β-lactone 3 in 13 steps is reported. Key steps included an HF-mediated rearrangement of cyclobutene diester 9 to form a bicyclic lactone 6 , an olefin cross metathesis between disubstituted alkene 3 and alkene 4 in which isomerization was suppressed, and a novel β-lactone ring opening to form the amide. Deprotection then gave either viridiofungin A ( 1 ) or B ( 2 ) in high yield.

The stereoselective 12-step total synthesis of the reassigned structure for citrafungin A ( 1a ) via cyclobutene diester 10 is described. Key steps involved a formal [2 + 2]-cycloaddition, oxa-Michael/cyclobutanone ring-opening cascade to secure the alkyl citrate core, and asymmetric vinylzinc addition to form the C6 stereocenter. In addition, no oxidative adjustments are required to secure the citrate oxidation level.

An efficient and step-economic new approach to alkyl citrate natural products from a cyclobutene diester is presented. The key sequence involves a formal [2 + 2]-cycloaddition of a silylketene acetal with dimethylacetylene dicarboxylate to provide the cyclobutene diester 14 with 4.5:1 stereoselectivity. Exposure of diester 14 in acidic methanol effected a hydrolysis, intramolecular oxy-Michael reaction, and cyclobutanone methanolysis cascade to give the triester 15. Iodination and elimination then afforded a key alkyl citrate alkene intermediate, which was converted into the natural products (-)-CJ-13,982 (1), (-)-CJ-13,981 (2), and (-)-L-731,120 (3) via a cross-metathesis and subsequent reduction.

The synthesis of the C1-C18 fragment of the myxobacteria metabolite rhizopodin is described. Initial attempts at installing the E,E-diene via cross coupling with an oxazole fragment gave poor results. An alternative approach, in which the diene was formed prior and the oxazole introduced by an acylation/O,N-shift protocol, gave the C1-C18 fragment 2 of rhizopodin (1).

An efficient, formal enantioselective synthesis of (+)- and (-)-pauciflorol F has been achieved using a recently introduced oxazolidinone controlled torquoselective Nazarov reaction. The absolute stereochemistry of pauciflorol F and its biosynthetic precursors has been unambiguously confirmed using X-ray crystallography.

The first total synthesis of mycocyclosin, a diketopiperazine natural product isolated from M. tuberculosis, is described. While direct oxidative coupling of tyrosine phenolic groups was unsuccessful, construction of the highly strained bicyclic framework was successfully accomplished through an intramolecular Miyaura-Suzuki cross-coupling to generate the biaryl linkage.

Petasis reactions of substituted styrenylboronic acids and glyoxylic acid, employing tert-butylsulfinamide as the 'amine' component, proceed with high stereoselectivity to produce β,γ-dehydrohomoarylalanine derivatives. Subsequent asymmetric dihydroxylation under neutral conditions gives the corresponding protected β,γ-dihydroxyhomoarylalanines with up to 15:1 dr. The method has been exploited in the efficient, stereoselective synthesis of protected β,γ-dihydroxyhomotyrosine, a component of the antifungal cyclic peptide echinocandin B.

A nonstabilized azomethine ylide reacts with a wide range of substituted isatoic anhydrides to afford novel 1,3-benzodiazepin-5-one derivatives, which are generally isolated in high yield. The transformations involve 1,3-dipolar cycloaddition reactions of the ylide with the anhydrides to give transient, and in a representative case spectroscopically observable, oxazolidine intermediates that undergo ring-opening-decarboxylation-ring-closing reaction cascades to yield the 1,3-benzodiazepin-5-one products.

[reaction: see text] A short total synthesis of the putative structure of the marine natural product tridachiahydropyrone as a single enantiomer is described. Novel steps include a cuprate addition and cyclization to form a cyclohexanone ring and formation of the bicyclic pyrone with P(2)O(5) on Celite. The spectroscopic data obtained for compound 1 do not match those reported for tridachiahydropyrone; therefore, revision of the assigned natural product structure is warranted.

[reaction: see text] A novel approach to the formation of the unusual pyrone-containing ring systems as found in polypropionate metabolites from the Tridachia family of marine molluscs has been developed. This approach includes an intramolecular cyclization of a beta-keto acid onto a cyclohexenone ring to afford a fused, bicyclic pyrone.

Low-temperature crystal structures of three pyrrolediones (3-5) and a furandione (9) were obtained and compared to structurally related compounds that cannot undergo decarbonylation. Systematic trends in bond lengths and angles are consistent with distortions along the reaction coordinate, in accord with the structure correlation principle of Dunitz. Since the pyrroledione and furandione rings in 3-5 and 9 are planar, these ground-state geometries prefigure the calculated planar, pseudopericyclic transition states.

The beta-silyl tropylium cation 9 has been successfully generated in the presence of the noncoordinating counterion tetrakis(pentafluorophenyl)borate in benzene and toluene. The (13)C and (29)Si NMR spectra of 9 demonstrate that the beta-silicon substituent interacts strongly with the aromatic pi-system of the cation by hyperconjugation. The crystal structure of 9 shows structural effects consistent with this interaction. [structure--see text]

The formal total synthesis of the myxobacteria metabolite (-)-apicularen A (1) is described. The key step involved a novel acid-mediated transannular conjugate addition of the C13 hydroxyl into the alpha,beta-unsaturated ketone in either of the macrolactones 5a or 5b to provide the same trans-pyranone 4. Conversion of 4 into the known apicularen intermediate diol 3 completed the formal synthesis. [reaction: see text]

[structure: see text] The total synthesis of the proposed structure for spirofungin B (2) is described. The data for the synthetic material did not compare with that for the natural product leading to the conclusion that the structure 2 assigned for spirofungin B is incorrect. Analysis of the NMR data reported for spirofungins A and B as well as related spiroketals allowed for the reassignment of the stereochemistry of spirofungin B to be that corresponding to 15-epi-spirofungin A (27).