Leticia Quintero

Highly diastereoselective alkylation, acylation and aldol condensation of cis- and trans-(N-acyloyl)hexahydrobenzoxazolidin-2-ones

Abstract The potential of hexahydrobenzoxazolidinones 1a – d as chiral auxiliaries was explored. N -Acylation of 1a – d , 2a – d and 3a – d was followed by methylation and benzylation via the corresponding sodium enolates generated by treatment with NaHMDS. Diastereoselectivities of 98% or higher were observed. The absolute configuration of the newly created stereogenic center was established by chemical correlation with 2-benzyl-1-propanol. The stereochemical results are congruent with addition to the electrophile from the less hindered face of a ( Z )-configured enolate, the sodium cation being coordinated by both carbonyl oxygens of the substrate. cis - and trans - N -Propionyl derivatives 2a – d were treated with Bu 2 BOTf/Et 3 N to give dialkylboron enolates 6a – d , which were then reacted with acetaldehyde and benzaldehyde. 1 H and 13 C NMR analyses showed the formation of a single diastereomeric aldol addition product, whose relative configuration was ascertained as syn from the measurement of the 3 J H(2′)/H(3′) coupling constants, and whose absolute configuration was determined by X-ray crystallographic analysis. The results are rationalized in terms of a Zimmerman–Traxler transition state, with a ( Z )-configured enolate where boron is coordinated to the aldehyde carbonyl rather than the oxazolidinone carbonyl. Substrate 2a was also reacted with acyl chlorides via the sodium enolate (NaHMDS). The effect of reaction conditions on O - versus C -acylation, as well as the influence of solvent and additives on diastereoselectivity, are discussed.

Diastereoselective synthesis of 1,2-O-isopropylidene-1,6-dioxaspiro[4,4]nonane applying the methodology of generation of radical cations under non-oxidizing conditions

Abstract We report the stereoselective synthesis of an optically pure spiroketal via an intramolecular tandem hydrogen abstraction reaction promoted by an alkoxy radical. Expanding the use of alkene radical cation under non-oxidizing conditions in the synthetic scenario.

(S)-4-Isopropyl-5,5-dimethyl-1,3-oxazolidinethione as chiral auxiliary for the intramolecular sulfur transfer in α,β-unsaturated N-acylimides, promoted by NbCl5

Abstract The 1,3-oxazolidinethione 4 has been synthesized from ( S )-valine and used in the intramolecular sulfur transfer in its N -enoyl derivatives in the presence of NbCl 5 as catalyst, which, moreover, works as an indicator of the course of the reaction. The adducts have subsequently been transformed into the corresponding β-mercapto esters by action of Sm(OTf) 3 in methanol.

Application of phosphorylated reagents derived from N,N′-di-[(S)-α-phenylethyl]-cyclohexane-1,2-diamines in the determination of the enantiomeric purity of chiral alcohols

Abstract The synthesis of two new N -[( S )-α-phenylethyl] substituted P -chloro-1,3-diazaphospholidines derived from C 2 -symmetric trans -1,2-diaminocyclohexanes, and their application as chiral derivatizing agents in the determination of enantiomeric purities of chiral alcohols by means of 31 P NMR spectroscopy is described.

Preparation of enantiomerically pure cis- and trans-N-(propionyl)hexahydrobenzoxazolidin-2-ones

Abstract A high-yield, five-step synthesis of novel enantiomerically pure cis - and trans - N -(propionyl)-hexahydrobenzoxazolidin-2-ones 5a-d from cyclohexene oxide and ( S )- α -methylbenzylamine is described. The highly diastereoselective benzylation of 5b is also described.

Synthesis of enantiomerically pure 2-amino alcohols from amino acids mediated by sulfoxides

Abstract Enantiomerically pure (R1,S2)- and (S1,S2)-2-amino alcohols can be easily synthesized by stereodivergent reduction of α′-(N-Boc)amino β-keto sulfoxides (easily synthesized from readily available N-Boc amino ester hydrochlorides) with DIBAH (de 82–92%) and DIBAH/ZnBr2 (de 80%), followed by hydrogenolysis of the C–S bond of the resulting hydroxy sulfoxides and final hydrolysis of the N-Boc protecting group.

The Stabilizing Role of the Intramolecular C-H···O Hydrogen Bond in Cyclic Amides Derived From α-Methylbenzylamine.

A series of five-, six-, seven-, and eight-membered lactams containing the chiral auxiliary α-methylbenzylamine were structurally analyzed and further studied by DFT calculations with the purpose to examine with detail the previously detected intramolecular C-H···O hydrogen-bonding interaction formed between the hydrogen atom of the α-methylbenzylamine and the carbonyl group of the cyclic amide. The main objective was to establish whether its presence does have a tangible relevance in their spatial arrangement in solution and in the solid state or is a simple and not stabilizing interaction.

Conformational analysis of cyclic phosphates derived from 5-C′ substituted 1,2-O-isopropylidene-α-d-xylofuranose derivatives

Abstract Twelve 2-phenoxy-2-oxo-1,3,2-dioxaphosphorinanes fused with a 1,2-O-isopropylidene-α- d -xylofuranose moiety in cis orientation and substituted at the C′5 position were prepared in two steps from commercially available diacetone-α- d -glucose. Their conformations, and configurations were determined by 1H and 31P NMR and X-ray crystallographic techniques. Both, chair–twisted–chair and chair–boat equilibria were observed in solution. We observed that the strong anisotropic shielding effect of the benzene ring in the phenoxy group generates an upfield shift of the H1 hydrogen atom, when the cyclic phosphates adopt a boat conformation. This is due to a relative cis-orientation of the P-phenoxy group and the H1 proton of the 1,2-O-isopropylidene-α- d -xylofuranose moiety. Therefore, the configuration of the phosphorus center (SP or RP) can be determined by 1H NMR spectroscopy. Interestingly, the crystal structure of one of the cyclic phosphates exhibits two independent molecules in the asymmetric unit, one with a chair and the other one with a boat conformation.

Synthesis of 6-allyl and 6-heteroarylindoles by palladium catalyzed Stille cross-coupling reaction

Several 6-allyl and 6-heteroarylindoles have been synthesized in high yield by means of palladium catalyzed cross-coupling reactions between tributyltin derivatives and 6-haloindoles to give useful intermediates for the synthesis of analogues of biologically active natural products.

Direct Chemical Method for Preparing 2,3-Epoxyamides Using Sodium Chlorite

A direct method for preparing 2,3-epoxyamides from tertiary allylamines via a tandem C-H oxidation/double bond epoxidation using sodium chlorite is reported. Apparently, the reaction course consists of two steps: (i) allylic oxidation of the starting allylamine to corresponding unsaturated allylamide with sodium chlorite followed by (ii) epoxidation of the allylamide to the 2,3-epoxyamide mediated by hypochlorite ion, which is formed in situ by reduction of sodium chlorite. The reaction conditions tolerate the presence of free hydroxyl groups and typical functional groups such as TBS, aryl, alkyl, allyl, acetyl, and benzyl groups; however, when an activated aromatic ring (e.g., sesamol) is present in the substrate, the use of a scavenger is necessary.