Synthesis and Characterisation of Monophosphines and Aminophosphines Bearing Chiral Phosphetane Units

Abstract

Enantiomerically pure monophosphines bearing phosphetane units have been prepared from primary phosphines and the cyclic sulfates of anti-1,3-diols. Various substituents have been introduced on both the phosphorus and the ring carbon atoms, thus showing the high flexibility of the synthetic approach. The same synthetic method has been applied to the preparation of P-N heterobidentate ligands bearing phosphetane and azetidine rings. The final products have been characterised by X-ray diffraction studies.Structural modularity is a key feature for chiral ligands in order to be broadly useful in enantioselective catalysis. Thus, whenever a new efficient synthon or concept for ligand design has been highlighted, the versatility of the corresponding synthetic approach must be checked in a systematic fashion to ensure optimisation of the properties of these ligands for any given purpose. This is the case for the chiral synthons I, namely the 2,4-disubstituted phosphetane moieties, which are easily accessible from enantiomerically pure 1,3-diol derivatives. They have already been used for the synthesis of diphosphine ligands, II, highly efficient in enantioselective ruthenium and rhodium catalysed hydrogenations. 1 The nature of the phosphetane-connecting scaffold in II modulates the catalyst efficiency and opens, for instance, specific application fields to the bis-phosphetanoferrocenes (X = 1,1'-ferrocenediyl) with respect to the bis-phosphetanobenzenes (X = 1,2-phenylene) or bis-phosphetanoethanes (X = 1,2-ethanediyl) (Figure 1).Within a single family of bis-phosphetanes II, the steric properties of the ligands have been finely tuned by variations of the R substituents, as the chiral anti-1,3-diols required for their synthesis are very easily available via asymmetric hydrogenation of the corresponding 1,3-diketones. 2 As application field for chiral phosphetanes, previous work considered mainly catalytic hydrogenations, which founded the choice of bidentate, C 2 -symmetric phosphines as target structures. However, phosphetane-based ligands could also be designed for a number of other catalytic applications and, therefore, new variations of the general structure I are highly desirable. In this context we present here the synthesis and characterisation of new monodentate phosphetanes as well as the first examples of P-N heterobidentate phosphetanes.Generally speaking, the successful use of bidentate ligands in many asymmetric catalytic reactions obscures the field of chiral monodentate phosphines. Nevertheless, recent literature data provide clear evidence for the specific catalytic applications of monodentate phosphorus ligands and point out the crucial need for efficient chiral phosphines of this family. 3 In this context, monodentate phosphetanes could be interesting tools as they are readily available from virtually any primary phosphine and a number of 1,3-diols, according to the synthetic approach shown in Scheme 1. Consequently, after our initial report on the synthesis of 1a (R' = Ph, R = Me) and 2 (R' = Mesityl...

Synthesis of Chiral Heterocyclic Phosphines for Application in Asymmetric Catalysis

“…For example, Marinetti et al prepared the potentially chelating azetidinomono(phosphetane) ligand 1 and the methoxy-phosphetane 2 [12].…”

The Development of Bidentate P,N Ligands for Asymmetric Catalysis

“…[31] These worked well in the allylic alkylation of 1,3-diphenylpropenyl acetate (15) giving enantiomeric excesses of 93% and 96%, respectively, Table 11, entries 1 and 2.…”

“…[31] A wide range of cyclic sulfates is available from 1,3-diketones which allows for facile variation of the ligands. Further accounts detailing the utilisation of these ligands in asymmetric catalysis are expected.…”

Synthesis and application of chiral monodentate phosphines in asymmetric hydrogenation

“…Marinetti et al adopted the synthetic strategy of DuPhos-ligands, via formation of cyclic sulfates, for the synthesis of monodentate phosphetanes 4 (Scheme 28) [66]. Three ligands out of the huge number of the ones potentially accessible were chosen for testing their abilities in asymmetric hydrogenation of N-acetyl dehydrophenylalanine.…”