Organocatalytic Enantioselective Synthesis of P‐Stereogenic Chiral Oxazaphospholidines

Abstract

The enantioselective synthesis of P‐stereogenic chiral organophosphines under organocatalysis is a challenging research field, and reports that use this approach are rare. Herein, we have developed the enantioselective synthesis of P‐stereogenic chiral oxazaphospholidines by using a bicyclic thiazole as the organocatalyst in the P–N and P–O bond‐forming reaction. The P‐chiral products were prepared in high yields with moderate enantioselectivities. The base that was used in this process had a significant influence on the enantioselectivity of the reaction and in some cases led to the opposite configuration of the P‐chiral center.

A Powerful P−N Connection: Preparative Approaches, Reactivity, and Applications of P‐Stereogenic Aminophosphines

“…Due to the possibility of diastereomeric separation methods, this approach is often more reliable in terms of stereoselectivity than novel techniques such as the challenging organocatalyzed synthesis of single enantiomers. For example, in 2016, the preparation of P ‐stereogenic oxazaphospholidines catalyzed by tertiary amines only gave moderate enantioselectivities, possibly due to unwanted side reactions [24] . P ‐stereogenic compounds with P−N bonds are often prepared as chalcogenides or boranes and are either used directly as they are or are deprotected prior to use depending on the intended synthetic purpose.…”

“…For example, in 2016, the preparation of P-stereogenic oxazaphospholidines catalyzed by tertiary amines only gave moderate enantioselectivities, possibly due to unwanted side reactions. [24] P-stereogenic compounds with PÀ N bonds are often prepared as chalcogenides or boranes and are either used directly as they are or are deprotected prior to use depending on the intended synthetic purpose. Some examples for commonly used chiral auxiliaries are shown in Figure 1.…”

Copper-Catalyzed Oxidative Alkylation (Methylation) of Phosphonamides and Phosphinamides Using Dicumyl Peroxide

“…Phosphonamides and phosphinamides, which represent typical amino-fused organophosphorus compounds, have gained increasing interest due to not only the unique structures but also the distinguished properties in pharmaceutical applications and material science . As well, the chiral P-centered modules have been successfully designed for enantioselective synthesis . Apart from this, they have been considered as pivotal intermediates for formations of heterocycles such as benzazaphosphole-1-oxides and phosphaisoquinolin-1-oxides, which were biologically active molecules.…”

TBHP/NH4I-Mediated Direct N–H Phosphorylation of Imines and Imidates

“…Organophosphorus compounds containing P–N bonds have been widely applied in biological chemistry and modern organic synthesis . For instance, cyclic phosphoramidates exhibit strong inhibitory activity against matrix metalloproteinase .…”

“…For instance, cyclic phosphoramidates exhibit strong inhibitory activity against matrix metalloproteinase . Chiral phosphoramidates have been used as organocatalysts for a variety of asymmetric reactions with excellent results . Hence, it has been of great synthetic interest to develop efficient methods for the construction of P–N bonds.…”