Dancing Silanols: Stereospecific Rearrangements of Silanol Epoxides into Silanoxy-Tetrahydrofurans and Silanoxy-Tetrahydropyrans.

We have developed highly stereospecific rearrangements of silanol epoxides into 1'-silanoxy-tetrahydrofurans and 1'-silanoxy-tetrahydropyrans. Upon treatment with Ph3CBF4 and NaHCO3 in CH2Cl2, di-substituted trans-epoxide silanols rearrange into products with an erythro configuration; di-substituted cis-epoxide silanols give products with a threo configuration. We have used these reactions as key steps in the syntheses of (±)-solerone and (±)-muricatacin.

Ring Opening of Aziridines by Pendant Sulfamates Allows for Regioselective and Stereospecific Preparation of Vicinal Diamines.

The ring opening of aziridines by pendant sulfamates is a viable strategy for the rapid preparation of vicinal diamines. Our reaction is compatible with both disubstituted cis- and trans-aziridines; unsubstituted, N-alkyl, and N-aryl sulfamates engage effectively. In all cases examined, the cyclization reaction is perfectly regioselective and stereospecific. Once activated, the product oxathiazinane heterocycles can be ring opened with a diverse range of nucleophiles.

Ring-Opening Reactions of Phosphoramidate Heterocycles.

We present protocols for the conversion of phosphoramidate heterocycles into 1,3-chloroamines and 1,3-aminoalcohols. For the formation of chloroamines, our optimized protocol involves heating the phosphoramidate starting material with 4 equivalents of HCl in a dioxane/toluene solvent mixture. The substituents on the phosphoramidate starting material have a profound influence on product formation. Phosphoramidates with a variety of aza-heterocyclic substituents engage, but those containing a 5-chloro-8-quinolinol arm are most competent for 1,3-chloroamine formation. Furthermore, only the phosphoramidate cis diastereomers allow for 1,3-chloroamine formation. X-ray crystallography studies coupled with DFT analysis provide a basis for the stark difference in reactivity between the cis and trans diastereomers. Amino-alcohol products form by heating phosphoramidate heterocycles with aqueous HF in toluene. Here, there is no diastereomeric preference or a requirement for an aza-heterocyclic arm. Based on a substrate survey, both reactions tolerate a broad range of substitution patterns and functional groups. This work establishes that phosphoramidates are competent synthons for interesting amine products and further increases the prominence of tethered aza-Wacker technology.

Highly Regio- and Diastereoselective Tethered Aza-Wacker Cyclizations of Alkenyl Phosphoramidates.

We present highly diastereoselective tethered aza-Wacker cyclization reactions of alkenyl phosphoramidates. "Arming" the phosphoramidate tether with 5-chloro-8-quinolinol was essential to achieving >20:1 diastereoselectivity in these reactions. The substrate scope with respect to alkenyl alcohols and phosphoramidate tether was extensively explored. The scalability of the oxidative cyclization was demonstrated, and the product cyclophosphoramidates were shown to be valuable synthons, including for tether removal. With chiral alkenyl precursors, enantiopure cyclic phosphoramidates were formed.

How important are the intermolecular hydrogen bonding interactions in methanol solvent for interpreting the chiroptical properties?

Two crispine A analogs and tetrahydrofuro[2,3-b]furan-3,3a(6aH)-diol, endowed with hydroxyl groups that can participate in intramolecular hydrogen bonding, have been synthesized and experimental vibrational circular dichroism (VCD) spectra and optical rotatory dispersion (ORD) data have been measured in CD3OD/CH3OH solvents. The absolute configurations (ACs) of these compounds have been determined using their synthetic schemes, supplemented wherever possible with X-ray diffraction data. The ACs are also analyzed with quantum chemical (QC) calculations of VCD and ORD utilizing implicit solvation as well as explicit solvation models, with the later employing classical molecular dynamics (MD) simulations. It is found that VCD calculations with implicit solvation model are adequate for determining the ACs, despite propensity of studied compounds for intermolecular hydrogen bonding between solute and solvent molecules. This observation is important because time-consuming MD simulations may not be necessary in the type of situations studied here. Additionally, it is found that the QC predicted VCD spectra provided enough diastereomer discrimination for determining the correct AC of studied compounds independently. The same observation did not apply to ORD.

Salient features of the aza-Wacker cyclization reaction.

The intramolecular aza-Wacker reaction has unparalleled potential for the site-selective amination of olefins, but it is perhaps underappreciated relative to other alkene oxidations. The first part of this review makes the distinction between classical and tethered aza-Wacker cyclization reactions and summarizes examples of the latter. The second portion focuses on developments in asymmetric aza-Wacker cyclization technology. The final part of the review summarizes applications of all classes of aza-Wacker cyclization reactions to natural product assembly.