Silvia Cardani

Asymmetric synthesis of functionalized α -amino-β-hydroxy acids via chiral norephedrine-derived oxazolidines

Abstract Both anti and syn enantiomerically pure functionalized α -amino-β-hydroxy acids and derivatives were synthesized starting from norephedrine-derived oxazolidine (1). The key-steps of the synthesis were the nucleophilic epoxidation of (1) and the nucleophilic opening of epoxy acid (3) with ammonia, both reactions proved regio- and diastereospecific. High yield preparation of the target anti aldehyde (9) was accomplished using standard procedures. The complementary syn aldehyde (23) was obtained via alkaline isomerization of the cis oxazolidinone (13) to the trans one. The aldehyde function of (9) and (23) provides a useful handle for manipulation to more complex structures, allowing potential access to a range of optically pure α -amino-β-hydroxy acids. The formal total synthesis of the monocyclic β-lactam antibiotic “carumonam” was accomplished using the present methodology.

Norephedrine derived 2-methoxy oxazolidines as chiral formyl cation equivalents

Lewis acid catalyzed reaction of silylenolethers with 1 followed by a straightforward nondestructive removal of the chiral auxiliary affords the corresponding aldehydes in good e.e. Compound 1 represents the first effective chiral synthetic equivalent of formyl cation.

Stereoselective aldol condensations via alkenyloxy dialkoxyboranes: synthetic applications using thioesters

Abstract A detailed Investigation of the enolization of phenyl thiopropionate with ethylenechloroboronate (ECB) and diisopropylethylamine (DPEA) and the subsequent aldol condensations of these enolates was conducted. Alkenyloxy dialkoxyboranes derived from thioesters were found to be stereoconvergent: both Z and E enolates give syn aldol condensation products. The thioester additions to chiral aldehydes were studied. Internal selectivity (syn) was usually very high, while the relative stereoselectivity ranged from poor to good, depending on the specific aldehyde used. The aldol products were transformed to known compounds for correlation.

High diastereoselectivity in lewis acid mediated aldol condensations using thioester silyl ketene acetals.

Abstract BF3 OEt2 mediated aldol condensations of thioester silyl ketene acetals are stereoconvergent, and exhibit high internal (anti) and relative (Cram) diastereoselectivity.

Allylic stereocenter directed asymmetric conjugate addition of cuprates in the presence of trimethylchlorosilane. enantioselective synthesis of 2-alkyl-4-benzyioxybutanal and 2-alkyl-4-oxopentanal

Abstract Cuprate reagents in the presence of trimethylchlorosilane add with excellent Tr-face selectivity and yield to α,β-unsafcurated ketone and aldehyde bearing In γ-position a masked aldehyde represented by the C-2 of a norephedrine-derlved oxazolidine. The title compounds are obtained in high enantlomeric excess after removal of the chiral auxiliary and of the protective group.

Catalytic osmylation of electron poor allylic alcohols and ethers. : A syhthetic approach to branched chain sugars

Abstract The catalytic osmylation of electron-poor allylic ethers and alcohols was studied. In the case of γ-alkoxy E-enoates reaction selectivity was found to range from 2:1 to 8:1 in favor of the arabino (2,3-syn - 3,4-anti) product, regardless of the double bond substitution. Lower (if any) selectivity was found for the Z-isomers. On the contrary, 2-Mthylene-3-hydroxy esters were osmylated with virtually complete 2,3-syn selectivity.The factors affecting the stereochemical outcome of the reactions are discussed

Asymmetric synthesis of malic acid-type synthons VIA chiral norephedrine-derived oxazolidines

Abstract Polyoxygenated C4 synthons 5-7 are synthesized in enantiomerically pure form starting from ephedrine derived oxazolidines 2,4 and 13. The 1,4-benzylate addition to 2 and 4, the key step in the synthesis of 5 and 6, proceeds cleanly with almost complete diastereoface selection. The key steps in the synthesis of target 7 are the nucleophilic epoxidation of aldehyde 13 and the lithium dimethyl cuprate epoxide opening, both of which proceed with high regio and stereocontrol. This route compares favorably with synthesis from malic acid, in that both enantiomers of ephedrine are available cheaply and it provides three differentiated oxygenated positions directly.

Stereoselective synthesis of t-butyl 2-amino-2,5-dideoxy-L-lyxo-pentanoate: formal synthesis of L-daunosamine

Abstract Enantiomerically pure t-Butyl 2-amino-2,5-dideoxy- L - lyxo -pentanoate 4c is synthesized via the highly diastereoselective MgBr2 mediated addition of dibenzylamino acetate silylketene acetal 2 to O-benzyl lactic aldehyde 3. The synthesis of γ-lactone 5c, a known intermediate in the synthesis of L-daunosamine and L-vancosamine, is also described.

Stereoselective aldol condensations via enolboronates.

Abstract Enolboronates, new enolates directly accessible from carbonyl compounds, exhibit extraordinary high erythro diastereoselection both with aliphatic and aromatic aldehydes.

Titanium tetrachloride-mediated enantioselective synthesis of trans β-lactones

Abstract Pharmacologically interesting trans β-lactones 11 and 16 were synthesized using a titanium tetrachloride-mediated enantioselective aldol reaction as the key synthetic step (see Scheme 2 ).