Keto phosphonates

The reaction tolerates different N-protecting groups as well as a variety of substituted 3-keto-phosphonates. In all cases, the tetracyclic structures were obtained as single diastereomers, however with respect to the natural product with the undesired trans-junction between the rings A and B. 

A series of /3-keto phosphonates have been hydrogenated with the Ru-BINAP system to give various chiral /3-hydroxyl phosphonates (Equation (75)).286 An Ru-MeO-BIPHEP catalyst is also effective for this transformation.287 /3-Keto thiophosphonates can also be smoothly transformed into /3-hydroxyl thiophosphonates with high ee.287... 

An efficient dynamic kinetic resolution is observed when an a-bromo- or a-acetylamino-/3-keto phosphate is subjected to the hydrogenation with an Ru-BINAP catalyst under suitable conditions. With RuC12[(A)-BINAP](DMF) (0.18 mM) as the catalyst, a racemic a-bromo-/3-keto phosphonate is hydrogenated at 25 °G under... 

Enantioselective hydrogenation of / -keto phosphonates in the presence of an ( R)-BINAP-Ru complex under 1-4 atm H2 and at room temperature provides the (R)-yS-hydroxy phosphonates in up to 99% ee (Fig. 32.20) [69]. The sense of enantioface selection is the same as that observed in the reaction of / -keto carboxylic esters (see Fig. 32.14). A BDPP-Ru catalyst is also usable [70]. Similarly, / -keto thiophosphonates are hydrogenated with a MeO-BIPHEP-Ru catalyst with up to 94% optical yield [69 b]. 

A new strategy has been developed for the preparation of /3-keto-phosphonates... 

Ketones cannot generally be used as acceptors, at least not directly, due to unfavorable equilibrium between the aldol product and the starting ketones. However, highly reactive ketones [87, 88], such as isatin 2 [95] (Fig. 3) and a-keto phosphonates (e.g. 112) [110] can readily be used as acceptors. 

The zinc-mediated reaction tolerates a variety of functionality in the p-keto ester. In fact, the method described above has been applied successfully to p-keto amides and p-keto phosphonates, Unsubstituted p-keto esters, amides and phosphonates have been chain-extended in yields that ranged from 58% to 98% (Table I). The primary limitation to this method is the inefficiency with which a-substituted esters and amides undergo methylene insertion. The zinc carbenoid must be employed in at least a threefold excess h... 

Other electron-withdrawing groups are compatible with diazo transfer and cyclization, Both the / -keto sulfone 9 and the /J-keto phosphonate 11 have been cyclized using rhodium acetate catalysis4 8,49. The cyclized keto phosphonate 12 can be further reacted49 with formaldehyde to yield the a-alkylidene cyclopentanone 13. 

I.4.I.4. Keto Pkospkonates, Keto Sulfonates, and Methylsulfones Asymmetric hydrogenation of P-keto phosphonates by using a BINAP-Ru complex affords P-hydroxy phosphonates... 

Hydrogenation of a-acylamino or a-halogeno (3-keto phosphonates with a BINAP-Ru complex gives the corresponding syn alcohols selectively with >98% ee (Scheme 1.58) [243a,251]. The sense of enantio- and diastereoface discrimination is the same as that in the case of ot-substituted [3-keto carboxylic esters (see Table of Scheme 1.57). 

Keywords 1-hydroxyphosphonate, Cr03/alumina, microwave irradiation, a-keto phosphonate... 

Reactions of carbocyclic P-keto esters, sulfonium ylides and enamines with activated alkynes such as DMAD are known to result in formation of (n + 2) ring expanded products. In a study of the analogous reactions of carbocyclic p-keto phosphonates, it was found that in the cases of the simple cyclic P-keto phosphonates 1, ring expansion occurred to give 2 in reasonable yield. Extension of the method to the tetralone 3, however, led to formation of two products, the "expected" (n + 2) ring expansion product analogous to 2 (37%), and the lactone 4 (29%). 

Step 1 (3-keto phosphonates often are used for olefmation of ketones (Horner-Wadsworth-Emmons modification of the Wittig reaction). Steps 2 + 3 The cuprate-mediated 1,4-addition and subsequent Lemieux-Johnson oxidation of a vinyl group are excellent procedures for the introduction of the p-formyl group. 

A direct stereoselective addition of an activated imine to jS-keto phosphonates in the presence of a chiral copper(II) catalyst has been developed 83... 

Catalytic enantioselective fluorination using chiral Pd complexes (59) and (60) has been reported.166,167 This method has provided various fluorinated compounds, includ- ing /3-keto phosphonates, oxindoles, and phenylacetate derivatives, in a highly enantioselective manner (75-96% ee). 

To obtain more information on the nature of the quasiphosphonium intermediates involved in these systems we have studied the reactions gf sterically hindered neopentyl esters by means of 1P nmr spectroscopy. Trineopentyl phosphite and a-bromoacetophenone gave rise to a peak at +41 ppm due to the ketophosphonium intermediate 3 (R = Me.CCH, R = Ph X = Br ) within half an hour of mixingJthe reactants in acetone-dfi at 27 °C ( p nmr shifts are relative to 85% H-PO. down-field positive). Peaks due to the ketophospnonate 4 +19 ppm and the vinyl phosphate 7 (-7 ppm) were also observed (compound 4 and 7 have satisfactory elemental analysis and spectroscopic data ). The concentration of the intermediate reached a maximum after about two hours when it was precipitated from acetone solution by the addition of anhydrous ether to give white crystals of trineopentyloxy (phenacyl)phosphonium bromide, identified by elemental analysis and nmr spectroscopy ( XP 6+41, in CDCl ). When redissolved in acetone-dg, deuterochloroform, acetic acid, or acetic acid-acetone mixtures, the intermediate decomposed to yield keto-phosphonate 4 but none of the vinyl phosphate 6 (Perkow product). Nor was the course of reaction affected by the addition of chloride ion or of a-chloro-acetophenone in acetonitrile. 

The presence of an alkene in the seven-membered ring of (—)-reiswigin A provides an immediate disconnection point for this target. Kim and coworkers capitalised on this fact and retrosynthetically cleaved this ring to obtain keto-phosphonate 1 (Scheme 12.1).3 A further clearance and protection of the reactive functionality within 1 then led to cyclopentane 2. 

Treatment of acyl phosphates with allylindium reagents in the presence of acetic acid affords the corresponding a-hydroxy phosphonates in good yields under mild conditions (Equation (52)).240 (3-Keto phosphonates give the corresponding / -hydroxy phosphonates in good yields by indium-mediated allylations (Equation (53)).241... 

TL 29 1555, 6327 (1988) (both /J-keto esters) 31 5509 (1990) (y-keto esters) 35 3325, 4559 (1994) (both /J-keto esters) 36 2063 (a-chloro-/ -keto ester), 5769 (a-acetamido-/J-keto phosphonate)... 

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