Access to Enantiomerically Enriched cis-2,3-Disubstituted Azetidines via Diastereoselective Hydrozirconation

Abstract

An asymmetric variant of the hydrozirconation reaction has been established starting from Boc-protected chiral allylic amines. The resulting diastereoselectively formed N-functionalized organozirconiums can be considered as promising chirons. In this case, they have been transformed into enantiomerically enriched cis-2,3-disubstituted azetidines through a iodination/cyclization sequence.

Asymmetric Carbamoyl Anion Additions to Chiral N-Phosphonyl Imines via the GAP Chemistry Process and Stereoselectivity Enrichments

“…For the reverse-GAP enhancement, pure enriched products can be precipitated from the diethyl ether solution via addition of petroleum ether, to remove any nondiastereomeric impurities, which tend to stay in the ether solution during GAP ether washing. In order to isolate the α-amino amides, the auxiliary can be cleaved from the products under mild conditions, using a 5:1 mixture of methanol:1.0 N HCl (aq) at room temperature over 1 h, followed by Boc protection, affording 6c , which is a known compound 28 (Scheme 2 ).…”

“…These 1 H NMR data match those found in the literature. 28 ■ ASSOCIATED CONTENT * S Supporting Information 1 H, 13 C, and 31 P NMR spectra of all compounds, as well as data for the X-ray crystal structure of 5c (CCDC 1022082) and the accompanying CIF file are included. This material is available free of charge via the Internet at http://pubs.acs.org.…”

Recent Developments and Synthetic Applications of Nucleophilic Zirconocene Complexes from Schwartz's Reagent

“…One year later, Szymoniak's research group expanded the reaction scope to the preparation of cis ‐2,3‐disubstituted azetidines through a similar diastereoselective hydrozirconation/iodination/cyclization reaction sequence (Scheme ) . These products are versatile building blocks, bearing a challenging to prepare four‐membered ring, with potential application in both total synthesis and in the design of new organocatalysts.…”

Recent advances in synthetic facets of immensely reactive azetidines

“…The synthetic approach involved the treatment of 37 with Schwartz reagent to yield the hydro- A range of substituents were explored leading to diastereoselective access of cis-2,3-disubstituted azetidine 42 in as depicted in Scheme 11. 15 However the lack of diastereoselectivity was observed in case of 42d and 42e (R 1 ¼ i-Pr, Ph and R 2 ¼ Me) could be attributed due to steric hinderance created by the bulky substituents. When (R 1 ¼ allylamine, R 2 ¼ Ph) dehydrozirconation turned out to be more favorable pathway and the reaction did not lead to iodonation/cyclisation product (Scheme 11).…”

“…The synthetic potential of 3-bromo-substituted azetidines was further explored by its reaction with different nucleophiles resulting in the formation of C-3-substituted azetidines as depicted in Scheme 9. 14 Szymoniak et al 15 have recently explored the stereoselective synthesis of cis-2,3-disubstituted azetidines through diastereoselective hydrozirconation. The synthetic approach involved the treatment of 37 with Schwartz reagent to yield the hydro- A range of substituents were explored leading to diastereoselective access of cis-2,3-disubstituted azetidine 42 in as depicted in Scheme 11.…”