Hydrophosphonylation asymmetric

Scheme 5-26 Titanium alkoxide-catalyzed asymmetric hydrophosphonylation of arylaldehydes...

Scheme 5-28 Asymmetric hydrophosphonylation of arylaldehy-des catalyzed by a heterobimetallic La/Li/BINOL catalyst (LLB)...

Scheme 5-29 LLB-catalyzed asymmetric hydrophosphonylation of cinnamaldehyde LLB = La/Li/BINOL...

An improved preparation of Shibasaki s LLB catalyst allowed higher asymmetric induction in the chemistry shown in Scheme 5-28. The new recipe involved mixing LaCl3 7H20 (1 equiv.), BINOL-dilithium salt (2.7 equiv.) and NaOt-Bu (0.3 equiv.) in THF at 50°C. This catalyst allowed asymmetric hydrophosphonylation of aldehydes in high yields and up to 95% ee (Scheme 5-33, Eq. 1), and gave better results for aliphatic aldehydes than a related aluminum catalyst (ALB, see Scheme 5-37 below). 

Scheme 5-36 La/Li/(diphenylBINOL)-catalyzed asymmetric hydrophosphonylation of aldehydes...

Scheme 5-42 Zinc-catalyzed asymmetric hydrophosphonylation of benzaldehyde...

Shibasaki reported the first catalytic asymmetric hydrophosphonylation of imines in 1995 (Scheme 5-45) using heterobimetallic LLB-type catalysts. 

Scheme 5-46 Proposed mechanism for LPB-catalyzed asymmetric hydrophosphonylation ofimines...

Scheme 5-47 Asymmetric hydrophosphonylation of a cyclic imine catalyzed by heterobimetallic rare earth/alkali metal/BI-NOL complexes or by chiral titanium alkoxide complexes...

In comparison to related P(III) chemistry, metal-catalyzed additions of P-H bonds in P(V) compounds to unsaturated substrates have been studied in more detail, and several synthetically useful processes have been developed. In particular, the use of heterobimetallic BINOL-based catalysts allows asymmetric hydrophosphonylation of aldehydes and imines in high yield and enantiomeric excess. 

Groeger, H., Saida, Y., Arai, S., Martens, J., Sasai, H., and Shibasaki, M., First catalytic asymmetric hydrophosphonylation of cyclic imines highly efficient enantioselective approach to a 4-thiazolidinylphosphonate via chiral titanium and lanthanoid catalysts,Tetrahedron Lett., 37, 9291, 1996. 

Akiyama et al. disclosed an asymmetric hydrophosphonylation in 2005 (Scheme 32) [55], Addition of diisopropyl phosphite (85a) to A-arylated aldimines 86 in the presence of BINOL phosphate (R)-M (10 mol%, R = 3,5-(CF3)j-C Hj) afforded a-amino phosphonates 87 in good yields (72-97%). The enantioselectivities were satisfactory (81-90% ee) in the case of imines derived from a,(3-unsaturated aldehydes and moderate (52-77% ee) for aromatic substrates. 

Scheme 6.48 Product range of the asymmetric hydrophosphonylation of N-benzylated aldimines promoted by thiourea derivative 47.

The asymmetric catalytic hydrophosphonylation is an attractive approach for the synthesis of optically active a-amino phosphonates [84]. The first example of this type of reaction was reported by the Shibasaki group in 1995 using heterobimetal-lie lanthanoid catalysts for the hydrophosphonylation of acyclic imines [85a]. This concept has been extended to the asymmetric synthesis of cyclic a-amino phosphonates [85b—d]. Very recently, the Jacobsen group developed the first organocatalytic asymmetric hydrophosphonylation of imines [86], In the presence of 10 mol% of thiourea-type organocatalyst 71, the reaction proceeds under formation of a-amino phosphonates 72 in high yield (up to 93%) and with enantioselectivity of up to 99% ee [86], A selected example is shown in Scheme 5.42. Di-o-nitrobenzyl phosphite 70 turned out to be the preferred nucleophile. 

Asymmetric catalytic addition of dialkylphosphites to a C=0 double bond is a powerful method, and probably the most general and widely applied, for formation of optically active a-hydroxy phosphonates [258], The basic principle of this reaction is shown in Scheme 6.108. Several types of catalyst have been found to be useful. The transition-metal-catalyzed asymmetric hydrophosphonylation using chiral titanium or lanthanoid complexes was developed by several groups [259, 260], The most efficient type of chiral catalyst so far is a heterobimetallic complex consisting... 

I. Catalytic, asymmetric hydrophosphonylation of imines promoted by the lanthanoid-potassium-BINOL catalyst (LnPB)... 

The second part of the chapter deals with several kinds of asymmetric reactions catalyzed by unique heterobimetallic complexes. These reagents are lanthanoid-alkali metal hybrids which form BINOL derivative complexes (LnMB, where Ln = lanthanoid, M = alkali metal, and B = BINOL derivative). These complexes efficiently promote asymmetric aldol-type reactions as well as asymmetric hydrophosphonylations of aldehydes (catalyzed by LnLB, where L = lithium), asymmetric Michael reactions (catalyzed by LnSB, where S = sodium), and asymmetric hydrophosphonylations of imines (catalyzed by LnPB, where P = potassium) to give the corresponding desired products in up to 98% ee. Spectroscopic analysis and computer simulations of these asymmetric reactions have revealed the synergistic cooperation of the two different metals in the complexes. These complexes are believed to function as both Brpnsted bases and as Lewis acids may prove to be applicable to a variety of new asymmetric catalytic reactions.1,2... 

Figure 34. A proposed catalytic cycle for asymmetric hydrophosphonylation.

The proposed mechanism for this catalytic asymmetric hydrophosphonylation is shown in Figure 35. The first step of this reaction is the deprotonation of dimethyl phosphite by LPB to generate potassium dimethyl phosphite. This potassium phosphite immediately coordinates to a lanthanoid to give I due to the strong oxophilicity of lanthanoid metals. The complex I then reacts (in the stereochemistry-determining step) with an imine to give the potassium salt of the a-aminophosphonate. A proton-exchange reaction affords the product... 

Scheme 10. LnPB-catalyzed asymmetric hydrophosphonylation of imines.

A number of phosphonate and phosphinate derivatives where the phosphorus atom is directly bonded to non-aromatic cyclic systems have been reported. The synthesis and reactions of a number of compounds with the general structure 103 have been reported. Enantiomerically pure cyclopropanephosphonic acids which are constrained analogues of the GABA antagonist phaclophen, have been prepared by stereocontrolled Michael addition of a-anions derived from chiral chloromethylphosphonamides 104 to a,P-unsaturated esters followed by in situ cyclisation. Other asymmetric syntheses include those of (/ )- and (S)-piper-idin-2-ylphosphonic acid (105) via the addition to trialkyl phosphites to iminium salt equivalents and 4-thiazolidinylphosphonate 106 by catalytic asymmetric hydrophosphonylation of 3-thiazoline. In the latter case both titanium and lanthanoid (which give much better e.e. values) chiral catalysts are used. 

---