A Synthetic Route to Chiral Dihydrobenzothiazines through Ring Opening of Activated Aziridines with 2‐Halothiophenols/Copper‐Powder‐Mediated C−N Cyclization

A simple protocol for the synthesis of dihydrobenzothiazines through regio‐ and stereoselective S_N2‐type ring opening of N‐tosylaziridines with sulfur nucleophiles followed by copper‐powder‐mediated intramolecular C?N cyclization in excellent yields (up to 95 %) with high diastereo‐ and enantioselectivity (up to >99 %) is reported.     

Experimental and theoretical investigations for the regio and stereoselective transformation of trans 1,2,3-trisubstituted aziridines into trans oxazolidin-2-ones

The regio and stereoselective transformation of trans 1,2,3-trisubstituted aziridines into trans oxazolidin-2-ones takes place in good yield. However, the cis configuration at C2 and C3 in monocyclic aziridines is a limiting factor for this transformation. Ab initio calculations show that while the ring-opening process assisted by iodide is regioselective, the subsequent ring-closure is responsible for the retention of the configuration at the trans oxazolidin-2-one. The larger energy found for the ring-closure process for the cis aziridines accounts for the non-formation of the cis oxazolidin-2-ones.     

Nitrogen dynamics and reactivity of chiral aziridines: generation of configurationally stable aziridinyllithium compounds

Diastereomeric oxazolinylaziridines (R,R)-9 and (R,S)-9 have been regioselectively lithiated at the α-position with respect to the oxazolinyl ring. The resulting aziridinyllithium compounds proved to be chemically and configurationally stable under the experimental conditions used, thus furnishing, upon trapping with electrophiles, chiral 2,2-disubstituted aziridines, in contrast to the corresponding α-lithiated oxazolinyloxiranes that have been reported to be chemically stable but configurationally unstable. This peculiar behavior of the nitrogen-bearing heterocycle has been rationalized on the basis of DFT calculations and the observed dynamics of the aziridine nitrogen atom. The DFT analysis allowed the disclosure of a solvent-dependent differing stability of diastereomeric lithiated aziridines (R,R)-9-Li and (R,S)-9-Li, suggesting η(3)-coordinated oxazolinylaziridinyllithium compounds as likely intermediates. Such intermediates could be the result of a dynamically controlled lithiation that relies on the preliminary formation of a complex between the lithiating agent and the oxazolinyl ring. According to this model, the competing complexation of the lithiating agent by the lone pair of electrons on the aziridine nitrogen would cause addition to the oxazoline C=N bond, thus ending up with the formation of oxazolidines, which are precursors of useful chiral ketoaziridines. The proposed model has been also supported by estimating the nitrogen inversion barrier by dynamic NMR spectroscopic experiments.     

Regio- and stereoselective glycosylation of 2-(o-dihydroxyborylbenzyl) thioglucoside and unprotected methyl glycosides

A highly regio- and stereoselective glycosylation of a boronic acid-containing thioglucoside and unprotected methyl glycosides is described. A boronic acid moiety was installed at the ortho-position of the 2-O-benzyl group of a thioglucosyl donor. This provides transient partial protection for the unprotected glycosyl acceptor upon condensation and concomitantly prearranged the acceptor with respect to the donor for the ensuing intramolecular glycosylation.     

Syntheses and Fully Diastereospecific Photochromic Reactions of Thiophenophan‐1‐enes with Chiral Bridges

Thiophenophan‐1‐enes with chiral polyether bridges were prepared and their diastereospecific photochromic reactions were studied. The coupling reaction of substituted dithienylethenes and various chiral synthons afforded thiophenophan‐1‐enes, namely, bridged dithienylethenes, as single enantiomers without optical resolution, thus indicating that these reactions occurred diastereoselectively. Upon UV irradiation, each optically active thiophenophan‐1‐ene isomerized to the corresponding enantiomer of the closed form and returned to the initial enantiomer of the open form upon visible irradiation. Because thiophenophan‐1‐enes never isomerized to other diastereomers even at a high temperature, they underwent diastereospecific photochromic reactions. Large changes were observed in the measurement of the optical rotations of the solutions of thiophenophan‐1‐enes at 588 nm according to their photochromic reactions. As there was no absorption at this wavelength for both isomers of each thiophenophan‐1‐enes, the nondestructive readout of the photochromic reaction could be carried out by using these chiral thiophenophan‐1‐enes.     

Stereospecific and Stereodivergent Construction of Tertiary and Quaternary Carbon Centers through Switchable Directed/Nondirected Allylic Substitution

This study introduces the ortho‐diphenylphosphanylbenzoate (o‐DPPB)/o‐DPPB oxide system as a switchable directing/nondirecting leaving group in a copper‐mediated allylic substitution with Grignard and organozinc reagents. With this system, the regioselective, stereospecific, and stereodivergent construction of quaternary as well as tertiary carbon centers is possible in a reliable and predictable fashion. Starting from one substrate enantiomer, both optical antipodes of the substitution products are readily available. Hence, this methodology features reversed polarity in comparison to established enolate alkylation chemistry and may be an interesting alternative, particularly for the construction of quaternary stereogenic carbon centers.     

Highly Regio‐ and Enantioselective Synthesis of γ,δ‐Unsaturated Amido Esters by Catalytic Hydrogenation of Conjugated Enamides

An efficient and highly regio‐ and enantioselective catalytic asymmetric hydrogenation of α,γ‐dienamido esters to γ,δ‐unsaturated amido esters has been achieved using Rh/TangPhos as the catalyst. A series of γ,δ‐unsaturated amido acids were furnished in excellent yields with up to 99 % ee. This effective methodology was applied in the asymmetric synthesis of key intermediate of Ramipril, an ACE inhibitor.     

Stereoselective Dithiophosphorylation of Cinchona Alkaloids: Easy Approach to Prospective Chiral Ligands and Organocatalysts

Abstract

The 9-mesylates of Cinchona alkaloids reacted with HSP(S)(OEt)₂ in benzene at 50°C to give the corresponding O,O-diethyl-dithiophosphates of the alkaloids with complete inversion of configuration at the 9-C stereogenic centers (3 examples, 42–45% yields). Also O-ethyl-dithiophosphoric acid derivative of 9-epi-quinine was obtained. The configuration of the stereogenic centers were established using homo- and hetero-NOE NMR techniques and comparing the experimental and calculated (GIAO/DFT) spectra. The dithiophosphates of alkaloids were tested as chiral ligands in the Pd-catalyzed allylic alkylation of dimethyl malonate with rac-1,3-diphenylprop-2-enyl acetate and in the Cu-catalyzed asymmetric Henry reaction and gave the respective product with up to 51% ee. Quinine O,O-diethyl-phosphorodithioate was also tested as a novel potential chiral solvating agent for amino acids (N-Boc-phenylglycine) in ³¹P and ¹H NMR spectroscopy.

[Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental files: Additional figures]     

Catalytic Asymmetric Crotylation of Aldehydes: Application in Total Synthesis of (−)‐Elisabethadione

A new, highly efficient Lewis base catalyst for a practical enantio‐ and diastereoselective crotylation of unsaturated aldehydes with E‐ and Z‐crotyltrichlorosilanes has been developed. The method was employed as a key step in a novel asymmetric synthesis of bioactive serrulatane diterpene (?)‐elisabethadione. Other strategic reactions for setting up the stereogenic centers included anionic oxy‐Cope rearrangement and cationic cyclization. The synthetic route relies on simple, high yielding reactions and avoids use of protecting groups or chiral auxiliaries.