Asymmetric phosphonylation

Other homochiral cyclic diol ligands such as (S,S)-148 for titanium alkoxide have also been tested for catalyzing phosphonylation of aldehydes, but it has been found that these diols are a poor choice of ligand for asymmetric phosphonylation.163 For most of the aldehydes studied (substituted benzaldehydes, a,/ -unsaturated aldehydes, and cyclohexanecarboxaldehyde), only moderate enantioselectivity was obtained (Scheme 2-62). 

Hydroxyalkyl Acids. The first reliable synthesis of 1-hydroxyalkylphos-phonates (241) in high enantiomeric excess has been achieved via titanium alkoxide-catalysed asymmetric phosphonylation of aldehydes then acetylation and enzyme-catalysed kinetic resolution of the acetates (Scheme 63). ... 

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... 

An asymmetric synthesis of phosphonylated thiazolines has been described. The phosphonodithioacetate 46 was aminated with a chiral amino alcohol 47 to give the phosphonylated thioamide 48 in good yield. This was then cyclised using a Mitsunobu procedure to give the chiral thiazoline phosphonate 49 in good yields under mild conditions. Homer-Wadsworth-Emmons reaction of these phosphonylated thiazolines gave chiral vinylic thiazolines 50 <00S1143>. 

Reviews have featured epoxidation, cyclopropanation, aziridination, olefination, and rearrangement reactions of asymmetric ylides 66 non-phosphorus stabilized carbanions in alkene synthesis 67 phosphorus ylides and related compounds 68 the Wittig reaction 69,70 and [2,3]-Wittig rearrangement of a-phosphonylated sulfonium and ammonium ylides.71 Reactions of carbanions with electrophilic reagents, including alkylation and Wittig-Homer olefination reactions, have been discussed with reference to Hammett per correlations.72... 

Notable were highly enantioselective additions of N-phosphonyl imines with dialkyl zinc or hydroxyketones and a one-pot reaction of alkynylzirconocenes with alkynyl phosphazenes and zinc carbenoids to give single isomer cyclopropylphosphonamides. The importance of enantioselective and dynamic kinetic asymmetric transformations is illustrated in many publications. Other interesting reports cover the use of phosphoramidates for the synthesis of allylic amines as well as the first example of C-P cleavage of a-aminophosphono acids using periodate. 

An efficient synthesis of new chiral phosphonylated thiazolines (332), readily accessible from phosphonodithioacetate and commercial chiral aminoalcohols via intermediate (333), has been described. (Scheme 88). These thiazolinephos-phonates (332) were then involved in H-W-E reactions to give asymmetric vinylic thiazolines. ... 

Scheme 80). The reactions exhibit high diastereoselectivity, probably due to a 10-membered trans-decalyl-like transition state, and with chiral allyl phosphonyl anions of type (50) even good asymmetric induction could be accomplished. ... 

In contrast to the rearrangement of phosphonamidates, the results obtained with phos-phonamides are poor. The rearrangement of chiral versions of different phosphonamide structural classes, e.g., 9,11,13, 15, and 18, show a high internal induction, but sluggish asymmetric induction. Models feature a planar carbanion and chelation between the phosphonyl and the ether-type oxygen, with insufficient differentiation for asymmetric induction provided by the tV-ligands634. 

Considerable work has been published on stoichiometric asymmetric routes to a-functionalised phosphonate esters. One of the most commonly exploited methods is the phosphonylation of a chiral aldehyde or imine by a phospho-rus(ni) ester (Scheme lb) or a by a hydrogen phosphonate (Scheme la). Thus, a team from Bristol-Myers Squibb reported the base-mediated addition of dimethyl H-phosphonate (DMHP) to a chiral aldehyde (Scheme 2) as a key step in their synthesis of renin inhibitors [6j. Subsequently, work from the Hoechst AG laboratories in Frankfurt used a related approach to the building of HIV protease inhibitor frameworks (Scheme 3) [9]. 

Some of the metal-based catalysts used in the asymmetric hydrophosphonylation of aldehydes (see Section 6.4) can also be applied to the phosphonylation of imines. For instance, Shibasaki s heterobimetallic BINOL complexes work well for the catalytic asymmetric hydrophosphonylation of imines. In this case lanthanum-potassium-BINOL complexes (6.138) have been found to provide the highest enantioselectivities for the hydrophosphonylation of acyclic imines (6.139). The hydrophosphonylation of cyclic imines using heterobimetallic lanthanoid complexes has been reported. Ytterbium and samarium complexes in combination with cyclic phosphites have shown the best results in the cases investigated so far. For example, 3-thiazoline (6.140) is converted into the phosphonate (6.141) with 99% ee using ytterbium complex (6.142) and dimethyl phosphite (6.108). The aluminium(salalen) complex (6.110) developed by Katsuki and coworkers also functions as an effective catalyst for the hydrophosphonylation of both aromatic and aliphatic aldimines providing the resulting a-aminophosphonate with 81-91% ee. ... 

Derivatives of carbohydrates that have been used to complex with rhodium catalysts to promote asymmetric hydrogenation include the phosphorus derivatives (6) and (7)/ and (8) (12) synthesized by esterification of the hydroxy-compounds with the appropriate phosphonyl chloride. Treatment of 7r-allyl-palladium chloride with the phosphite ester (13) gave a complex that was an enantioselective catalyst for hydrogenation of unsaturated acids and esters. ... 

In the catalytic enantioselective Strecker reaction, chiral aluminium complexes, especially aluminium-salen-based catalysts and aluminium-binaphthol-based catalysts have been widely used, and great achievements have been obtained. In 2010, the Li group reported a highly enantioselective Strecker reaction of achiral IV-phosphonyl imines by using primary free L-phenglycine 42 as the catalyst and diethylaluminium cyanide as the nucleophile. This work also presented the novel use of nonvolatile and inexpensive diethylaluminium cyanide in asymmetric catalysis (Scheme 19.51). ... 

It has been also found that chiral phosphine oxides (5)-BINAPO catalyzed silicon tetrachloride-mediated, enantioselective phosphonylation of aldehydes with trialkyl phosphites, led to formation of optically active a-hydroxyphosphonates with low to moderate enantioselectivities (ee 22-52%)7 This reaction constituted the first example of asymmetric Abra-mov-type phosphonylation of aldehydes with trialkyl phosphites catalyzed by chiral Lewis bases. 

Recently, Katsukiand coworkers reported that chiral Al(salen) complex (74) served as the catalyst for catalytic asymmetric hydrophosphonation of aldehydes with dimethylphosphite (Scheme 6.56) [71]. It was determined by X-ray crystallographic analysis that AI[(R,R)-saIene]CI (74) is a monomeric cis-P aluminum species. On the basis of the X-ray structure of complex (74), intramolecular phosphonylation mechanism was proposed. 

After Kobayashi spioneering study on theabiUty of (S)-2,2 -bis(diphenylphosphanyl)-1,1 -binaphthyl dioxide (9, BINAPO) as a promoter of the enantioselective allylation of a-hydrazono esters with allyltrichlorosilanes [27], Nakajima reported the first catalytic system for the allylation of aldehydes, in which the use of N,N-diisopropylethylamine and tetrabutylammonium iodide was essential for accelerating the catalytic cycle (Scheme 7.16) [28], For this allylation, y-functionahzed nucleophiles such as cis-y-bromoallyltrichlorosilane could be employed as addressed by Maikov and Kodovsky [29], In addition, 9 could be apphed to the asymmetric ring opening of meso-epoxides with SiCh, as expected from the scope of the chiral bipyridine N,N -dioxide catalysis [30], and could also catalyze the SiCfi-mediated, enanhoselective phosphonylation of aldehydes with trialkyl phosphites [31],... 

In our work, tridentate Schilf base ligands LI reacted in situ with Et2AlBr to form catalyst Call (Scheme 6.8) which was used to catalyze asymmetric hydro-phosphonylation of aldehydes and ketones. In order to improve the enantioselec-tivity of this reaction, the steric effects of ligands LI on enantioselectivity were examined. Different groups including i-Pr, i-Bu, Ph, benzyl or adamanlyl as R or were respectively introduced into ligands H which were further used to prepare corresponding catalysts Al(III) complexes Catl. As an example, these Al(III)... 

Kaur P, Wever W, Rajale T, Li G. Asymmetric hydrophos-phylation of chiral V-phosphonyl imines provides an efficient approach to chiral a-amino phosphonates. Chem. Biol. Drug Dev. 2010 76 314-319. 

A series of ot-amino-l,3-dithianes (56) containing a triamidephosphate moiety have been synthesised via the asymmetric Umpolung reaction of 2-lithio-l,3-dithianes (55) with chiral A-phosphonyl imines (54) in good chemical yields (up to 82%) and good to excellent diastereoselectivities (>99 1) (Scheme 12). ... 

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