Efficient Asymmetric Synthesis of P-Chiral Phosphine Oxides via Properly Designed and Activated Benzoxazaphosphinine-2-oxide Agents

Abstract

A general, efficient, and highly diastereoselective method for the synthesis of structurally and sterically diverse P-chiral phosphine oxides was developed. The method relies on sequential nucleophilic substitution on the versatile chiral phosphinyl transfer agent 1,3,2-benzoxazaphosphinine-2-oxide, which features enhanced and differentiated P-N and P-O bond reactivity toward nucleophiles. The reactivities of both bonds are fine-tuned to allow cleavage to occur even with sterically hindered nucleophiles under mild conditions.

The synthesis of heteroleptic phosphines

“…(However, an excellent body of research has been done and is continuing on this subject. [25][26][27] In contrast to homoleptic and asymmetric phosphines, heteroleptic phosphines are both synthetically accessible and tailorable. Furthermore, heteroleptic phosphines make excellent polydentate phosphines and can also be chiral (e.g., (+)-DIOP, Figure 2).…”

Turning Regioselectivity into Stereoselectivity: Efficient Dual Resolution of P‐Stereogenic Phosphine Oxides through Bifurcation of the Reaction Pathway of a Common Intermediate

“…[1] As asymmetric synthesis has matured, methods for this highly desirable goal have been developed only slowly, but have become an emerging topic in synthetic methodology. [8] 2) Use of (À)-menthol as an inexpensive template: Introduced by Mislow and co-workers, [9] it has been used in a number of ways to synthesize both enantiomers of Pstereogenic compounds, commonly by classical diastereomer separation and subsequent separate manipulations of both isomers. [6] Some progress towards dual stereoselection has been achieved and two distinct types of approach towards this ideal scenario for P-stereogenic compounds may be discerned: 1) Inversion of the order of attachment of two groups at a phosphorus atom that already bears a chiral auxiliary, for example, ephedrine, [7] which recently culminated in the development of a very effective route based on 1-phenylethylamine by Han and co-workers.…”

Pd-catalyzed enantioselective C–H arylation of phosphinamides with boronic acids for the synthesis of P-stereogenic compounds

“…The most commonly used methods for the preparation of Pstereogenic molecules have mainly relied on resolution, [24][25][26] chiral-auxiliary-aided asymmetric synthesis, [27][28][29][30][31][32][33][34] and asymmetric lithiation-trapping reactions. [35][36][37][38] Other alternative methods include the NHC-catalyzed desymmetrization of bisphenolic phosphinates, 39 the metal-catalyzed asymmetric cross-coupling of phosphines or phosphine oxides, [40][41][42][43][44][45] hydrophosphination of olefins, 46 addition reactions of phosphorus nucleophiles, 47,48 and olefin metathesis of divinyl phosphinates.…”