Diethyl methyl phosphonate, synthesis

Diethyl [(2-tetrahydropyranyloxy)methyl]phosphonate is useful in the Wlttig-Horner synthesis of enol ethers, which are intermediates in one-carbon homologations of carbonyl compounds. This procedure is an adaptation of a general method for making dialkyl hydroxymethylphosphonates. An 0-tetra-hydropyranyl derivative also has been made from dibutyl hydroxymethyl -phosphonate, and diethyl hydroxymethylphosphonate has been O-silylated with tert-butylchiorodimethylsilane and imidazole. Another useful congener in this series has been prepared by an Arbuzov reaction of methoxyethoxymethyl (HEM) chloride and triethyl phosphite. 

A general methodology for the construction of quaternary carbon atoms at the carbonyl carbon of ketones has been successfully exploited for the facile synthesis of ( )-lycoramine (299) (Scheme 30) (165). Thus, the O-allylated o-vanillin 322 was allowed to react with vinyl magnesium bromide followed by Jones oxidation, and the acid-catalyzed addition of benzyl IV-methylcarbamate to the intermediate a,(3-unsaturated ketone furnished 323. Wadsworth-Emmons olefination of 323 with the anion derived from diethyl[(benzylideneami-no)methyl]phosphonate (BAMP) provided the 2-azadiene 324. The subsequent regioselective addition of n-butyllithium to 324 delivered a metalloenamine that suffered alkylation with 2-(2-bromoethyl)-2-methyl-l,3-dioxolane to give, after acid-catalyzed hydrolysis of the imine and ketal moieties, the 8-keto aldehyde 325. Base-catalyzed cycloaldolization and dehydration of 325 then provided the 4,4-disubstituted cyclohexenone 326. The entire sequence of reactions involved in the conversion of 323 to 326 proceeded in very good overall yield and in one pot. 

BICYCLOPROPYLIDENE possesses unique reactivity toward a wide range of electrophiles and nucleophilic carbenes. (E)-I-DIMETH YLAMINO-3-tert-BUTYLDIMETHYL-SILOXY-1,3-BUTADIENE is a highly reactive diene for Diels-Alder reactions, as described in an accompanying procedure for the synthesis of 4-HYDROXYMETHYL-2-CYCLOHEXEN-1-ONE via the Diels-Alder reaction with methyl acrylate. Finally, this section concludes with the preparation of DIETHYL [(PHENYLSULFONYL)METHYL]PHOSPHONATE, a reagent that is very useful for synthesis of [Pg.285]

Lowen, G.T., and Almond, M.R.. A novel synthesis of phosphonates from diethyl (trichloro-methyl)phosphonate, J. Org. Chem.. 59, 4548, 1994. 

A synthesis of racemic fmoc-protected 4-phosphonomethylphenylalanine starts with the Arbuzov preparation of (257) (R = Me or Bu ) standard modifications to the aryl methyl group lead to the desired (258). Two procedures have been adopted for the preparation of the N-ivaoc or iV-boc derivatives of the difluoro derivative (259). In the first, triethyl phosphite and 4-(bromomethyl)benzoyl bromide and treatment of the resultant aroyl phosphonate with the DAST reagent yields (262) this reacts with the carbanion from (263) to give (264) hydrogenation of which (with PdCla) affords (260), then converted into its N-fmoc derivative and de-esterified with MeaSil. In the second procedure, triethyl phosphite and 4-iodobenzoyl chloride, followed by DAST reagent, yielded diethyl [difluoro(4-iodophenyl)methyl]phosphonate which was caused to react... 

An alternative route to the phosphonate moiety suitable for the synthesis of compounds (441) starts with diethyl [[2-(phenylseleno)ethoxy]methyl]phosphonate which, when acted on by NalO affords diethyl (vinyloxymethyl)phosphonate. The latter,... 

S. M. H. Khorassani, N. A. Torbati, A. Hosseinian, S. Garcla-Granda, L. Torre-Femindez, Heteroat. Chem. 2013, 24, 58—65. Synthesis and crystal structure study of diethyl aryl(benzo[d]thiazol-2-ylamino)methyl phosphonates. (u) C. B. Reddy, K. S. Kumar, M. A. Kumar, M. V. N. Reddy, B. S. Krishna, M. Naveen, M. K. Arunasree, C. S. Reddy, C. N. Raju, C. D. Reddy, Eur. J. Med Chem. 2012, 47, 553-559. PEG-SO3H catalyzed synthesis and cytotoxicity of a-aminophosphonates. 

The tetrahydropyranyl derivative of propaigyl alcohol, tetrahydro-2-(2-propynyloxy)-2/f-pyran, can be converted to methyl 4-hydroxy-2-butynoate in four steps. Diethyl [(2-tetrahydropyranyloxy)methyl]phosphonate is a convenient Wadsworth-Emmons reagent. Tetrahydropyranyl esters of a-bromo acids can be used in the Reformatsky reaction for the preparation of (3-hydroxy acids. Elimination of a tetrahydropy-ranyloxy moiety from butyne-l,4-diols with lithium hydride constitutes an efficient method for the synthesis of allenic alcohols. ... 

ASYMMETRIC SYNTHESIS OF DIETHYL (R)-(-)-(1 -AMINO-3-METHYL-BUTYL)-PHOSPHONATE... 

Sugars containing a carbon-phosphorus bond have been prepared by application of the Michaelis-Arbuzov reaction to bromodeoxy sugars. Thus, the reaction of 5-bromo-5-deoxy-l,2-0-isopropylidene-3-O-methyl-a-D-xylofuranose (131) with triethyl phosphite yields the corresponding diethyl phosphonate (132) compound 132 was employed for the synthesis of a sugar derivative having phosphorus as... 

Chattha, M.S., Synthesis and NMR spectrum of diethyl 3-buten-3-methyl-2-oxo-l-phosphonate, Chem. Ind. (London), 1031. 1976. 

Diethyl 3-cyano-2-butenylphosphonate4 - and 3-cyano-2-methyl-l-ethyl-2-propenyl-phosphonate appear as synthetically useful reagents in the synthesis of modified rctinals, whereas... 

Reduction of phenols [1, 252, after citation of ref. 3]. In achieving the synthesis of triptindane (11), Thompson obtained the methyl ether (8a) as an intermediate, demethylated it to (9), and effected deoxygenation to (11) by the method of Kenner and Williams consisting in reaction with diethyl phosphonate or mesyl chloride and reduction of the diethyl phosphate or the mesylate ester with sodium in liquid ammonia yields, first procedure 58% second procedure 36%. 

Many communications have concentrated on specific amino phosphonic acids or derivative types. Thus, esters of phosphonoaminoacetic add were obtained by the reactions between trialkyl (ethyl) phosphite and (218) and which are thought to proceed via the phosphorane (219). A sequence has been presented for the preparation of the mono- and di-benzyl esters of N-chz protected (a-aminoben-zyl)phosphonic acid. A synthesis of (aminomethylene)bisphosphonic acid from dibenzylamine, dibenzyl hydrogenphosphonate and triethyl orthoformate has been noted and the asymmetric hydrogenation of (220) in the presence of chiral phosphine catalysts yields samples of (221) with e.e.s of 63-96%. The pyrrolidine-based compound (222) has been prepared from methyl S)-N-methoxycarbonyl-4-oxo-2-pyrrolidinecarboxylate and iV-coupled 4-amino-butanal diethyl acetals were the starting materials in syntheses of the pyrrolidine-2-phosphonic add derivatives (223) in which Z represents the iV-protected amino add or peptide moiety. ... 

Two further reactions might be included here, since they involve modification at both carbon and sulphur. In the first reaction, dehydration of the sulphoxides 388 (R = Me or aryl R = H, Me, ethenyl or Ph) to the diethyl [(l-alkylthio)alk-l-enyl]phosphonates 389 is said to result following the action of trimethylsilyl trifluoromethanesulphonate The second reaction constitutes a new and improved synthesis of an ester of (mercap-tomethyl)phosphonic acid, and consists in the treatment of methyl (diisopropylphosphi-noyl)dithioformate with NaBH4. ... 

Diethyl pyrocarbonate has been used to convert uridine 2 - or 3 -phosphate into the 2, 3 -cyclic phosphate in high yield, and an adamantyl 2, 3 -cyclic phosphonate (421) was obtained when uridine reacted with I-adamantylphos-phonyl chloride. Phosphorylation of ribonucleosides with pyrophosphoryl chloride followed by hydrolysis in neutral solution afforded a simple synthesis of ribonucleoside 2, 3 -cyclic phosphate 5 -phosphates. Two phosphorylating agents mentioned earlier in this section can also yield 3, 5 -cyclic phosphates either by treatment of nucleoside 5 -(2-iV7V-dimethylamino-4-nitrophenyl phosphates) with acetic acid in pyridine (Scheme I4i) i, 83 qj. treatment of nucleoside 5 -(5 -methyl phosphorothioates) with iodine in pyridine. Another route to 3, 5 -cyclic phosphates involved cyclization of the nucleoside 5 -trichIoro-methylphosphonates (422) (obtained by the action of trichloromethylphosphonyl... 

Pasternak PV, Averkiev BB, Antipin MY, Peregudov AS, Chkanikov ND (2004) Synthesis and some heterocyclization reactions of new diethyl (l,l-difluoro-3,3-dicyano-2-ttifluoromethylaUyl)phosphonate and ethyl 3,3-dicyano-2-[(diethoxyphosphoryl)difluoro-methyl]acrylate. J Fluor Chem 125 1853-1868... 

Honda and coworkers began their synthesis of (—)-deoxynupharidine (1486) with the (i .)-pyroglutamate derivative 1504, which was converted in two steps into the known (4R)-methyl analog (+)-1505 (Scheme 193). Reduction of the lactam with lithium triethylborohy-dride gave an intermediate aminal, reaction of which with diethyl (JV-methoxy-JV-methylcarbamoylmethyl)phosphonate afforded the... 

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