Hydrophosphonylation derivatives

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.

A BINOL-derived phosphoric acid derivative has been used as a catalyst in the enantioselective synthesis of a-amino phosphonates via hydrophosphonylation of imines with diisopropyl phosphite.82... 

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... 

Akiyama T, Morita H, Itoh J, Fuchibe K (2005a) Chiral Brpnsted acid catalyzed enantioselective hydrophosphonylation of imines asymmetric synthesis of alpha-amino phosphonates. Qrg Lett 7 2583-2585 Akiyama T, Saitoh Y, Morita H, Fuchibe K (2005b) Enantioselective Mannich-type reaction catalyzed by a chiral Bronsted acid derived from TADDOL. Adv Synth Catal 347 1523-1526... 

Introduction. Ti-TADDOLates are a,a,a, a -tetraaryl-2,2-disubstituted l,3-dioxolane-4,5-dimethanolatotitanium derivatives. The most common substituents are R, R = Me/Me and Ph/Me, Ar=Ph and 2-naphthyl, X, Y = C1/C1, t-PrO/Cl, Cp/Cl, and i-PrO/i-PtO. The corresponding TADDOLs (2) are available in both enantiomeric forms from tartrate esters which are acetalized (R R CO) and allowed to react with aryl Grignard reagents. The reactions performed in the presence of Ti-TADDOLates or with Ti-TADDOLate derivatives include nucleophilic additions to aldehydes - - and nitroalkenes of alkyl, aryl, and allylic - groups aldol additions hydrophosphonylations and cyanohydrin reactions of aldehydes inter- and intramolecular Diels-Alder additions ... 

The first highly diastereoselective hydrophosphonylation of heterocyclic imines, 3-thiazolines (330) by a chiral phosphorus reagent BINOL, has been performed. The relative configuration of BINOL and the newly formed stereogenic centre in the a-amino phosphonic acid derivatives (331) have been elucidated by X-ray analysis. 

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. 

Standard conditions for these reactions were chosen on the basis of preliminary test reactions from which several generalizations were derived (a) reactions occur more rapidly in MeOH than EtOH and with triethyl phosphite than with trimethyl phosphite (b) where the solvent alcohol is not identical with the alcohol from which the P(III) ester is derived, partial ester exchange results in a mixed P(V) ester and (c) reactions in phenol are cleaner and result in higher yields with only minor or no contamination by products from ester exchange. It has been demonstrated that when phenol is used as the proton source, crotonaldehyde undergoes hydrophosphonylation, even at 0°C, to selectively furnish the phosphonate as its diphenyl acetal. The yield of phosphonylated crotonaldehyde diphenyl acetal in phenol at lOO C was 82% against 59% of diethyl acetal in refluxing EtOH for the same time. ... 

Other titanium complexes derived from tartaric acid have been used as chiral catalysts. The complexes generated from diol 2.50 and TiCl2(0/-Pr)2 are used as catalysts in asymmetric ene-reactions [778, 816], and in Diels-Alder [778, 780] or [2+2] cycloadditions of ketene thioacetals and unsaturated sulfides [778, 817], The best enantiomeric excesses are observed with 2.50 (R = Me, R = Ph) [778, 817] or 2.50 (R = R = Et, Ar = 3,5-Me2CgH3) [45], These catalysts are also efficient in hydrophosphonylation [818] and in asymmetric hydrocyanation of aldehydes with Me3SiCN [778], These titanium complexes may be used in catalytic amounts provided that the reactions are run in the presence of molecular sieves [559,816],... 

A number of Bronsted acidic organocatalysts have been applied to the asymmetric hydrophosphonylation of aldimines. Thiourea catalysts related to (6.130) catalyse the asymmetric hydrophosphonylation of a range of aliphatic and aromatic aldimines with high ee and BINOL-derived phosphoric acid derivatives similar in structure to (6.131) are effective catalysts in the asymmetric phosphonylation of cinnamaldehyde-derived aldimines. Asymmetric hydrophosphonylation of aromatic aldimines can also be achieved with high ee using cheap, commercially... 

The hydrophosphonylation reaction of aldimines (173) with phosphites (174) has furnished a-amino phosphonates (175) with high enantioselectivities by means of the chiral phosphoric acid (125) derived from R) BINOL (Scheme 47). ... 

The asymmetric hydrophosphonylation reaction of aldimines (207) with dialkyl phosphites (206) has been reported using catalytical amounts of the phosphoric acid (125), derived from (7 )-BINOL to afford (l )-amino phos-phonates (208) in good to high enantioselectivities (up to 90% cc) (Scheme 58). ... 

Scheme 15.4 Hydrophosphonylation of isatine derivatives catalysed hy squaramide.

It worth to mention that despite the importance of the Kabachnik-Fields reaction, stereoselective versions for the synthesis of enantioenriched a-aminophosphonates are scarce [212, 213], and only few enantioselective examples have been published to date (for reviews on enantioselective catalytic direct hydrophosphonylations of imines, see Refs. [162a-c]). Organocatalytic examples use well-known chiral binol-derived phosphoric acid organocatalysts (Fig. 12.6,80 and 81) [214], and regarding metal catalysis, chiral scandium(III)-A,A -dioxide and... 

TABLE 28.7 Hydrophosphonylation of Benzaldehyde, Acetophenone, and Related Derivatives with Diethylphosphite Catalyzed hy Homoleptic and Heteroleptic Ae Complexes [33] ... 

In 2009, Feng et al. reported the asymmetric hydrophosphonylation of a-keto esters catalysed for the first time by cinchona-derived thiourea organocatalysts. Thus, a series of aromatic and heteroaromatic a-keto esters reacted with dimethyl phosphite to afford the corresponding a-hydroxy phosphonates in high yields and enantioselectivities of up to 91% ee (Scheme 2.53). 

Hydrophosphonylations of a-keto esters catalysed by dnchona-derived... 

A -Phosphinoyl and A -thiophosphinoyl ketimines, Ph-C(Me)=N-P(=X)Ph2 (X = O and S), have been hydrophosphonylated in high yield and ee using a copper(I) catalyst liganded with a chiral diphosphino ethane. In the case of the sulfur substrates, facile differentiated removal of the t/imphosphinoyl group affords a-amino phosphonic acid derivatives, Ph- C(Me)(NH2)-P(=0)(0Et)2, that is, phosphonic acid analogues of enantio-enriched a,a-disubstituted a-amino acids. The reaction also accommodates alkyl, cycloalkyl and alkenyl substituents in place of the phenyl. 

Kee and coworkers reported that Al(salen) (73a) and Al(salan) (67b) complexes catalyze hydrophosphonylation of benzaldehyde derivatives [70]. Enantioselectivi-ties were modest in the reactions catalyzed by each catalyst. Interestingly, compared to Al(salen) complex (73a), Al(salan) complex (67) results in better enantioselectiv-ity (Scheme 6.55). The structure of (67b) in solution was identified as a dimeric hydroxyl-bridged structure with the twisted ligand geometry. In addition, Jacobsen s Al(salen)Cl (67a), which is well known as an excellent asymmetric catalyst for hydrocyanation of aromatic imines, was not an effective catalyst for this reaction [62]. 

Pettersen D, Marcolini M, Bemardi L, Fini F, Herrera RP, Sgarzani V, Ricci A. Direct access to enantiomerically enriched a-aminophosphonic acid derivatives by organoca-talytic asymmetric hydrophosphonylation of imines. J. Org. Chem. 2006 71 6269-6272. 

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