Lithium diethyl phosphite

To complement the above information, a highly enantioselective synthesis of a-amino phosphonate diesters should be mentioned.164 Addition of lithium diethyl phosphite to a variety of chiral imines gives a-amino phosphonate with good to excellent diastereoselectivity (de ranges from 76% to over 98%). The stereoselective addition of the nucleophile can be governed by the preexisting chirality of the chiral auxiliaries (Scheme 2-63). 

Lefebvre and Evans found that lithium diethyl phosphite [(EtO)2POLi] adds to (Ss)-N-benzylidene-p-toIuenesulfinamide (126) to give (Ss,S)-128 in 85% yield and 84% de.77 The diastereomeric excess was improved to 93% de by using the sodium salt and to >97% with lithium diisopropyl phosphite. Transition state 127, involving si-face attack of the nucleophile, was proposed to account for the favored formation of 128. a-Aminobenzyl phosphonic acid 129 was obtained on hydrolysis of 128.78 Similar results were reported for the addition of diamido phosphite to 126.78... 

Enantiomerically pure substituted cyclohexanones, such as 9, react with lithium diethyl phosphite to give 5-(diethoxyphosphinyl)cyclohexanones 10 with complete diastereoselectivity 10 . 

Dialkyl l-lithio-l,l-difluoromethylphosphonates are usually generated in situ at low temperature from difluoromethylphosphonates in the presence of LDA or LiHMDS. Because of tlieir instability (rapid dissociation to give difluorocarbene and lithium diethyl phosphite) and poor nucleophilicity, 152,462. these highly deactivated carbanions require very powerful electrophiles in order to obtain satisfactory results. 

Another variation of the classic Darzens reaction is a one-pot synthesis of dietliyl 1-perfluoro-alkyl-1,2-epoxyalkylphosphonates using the nucleophilic attack of lithium diethyl phosphite on the carbonyl carbon of perfluorinated P-oxophosphonium salts (Scheme 4.8). The resulting intermediate can eliminate in two directions. When the oxygen anion in the least sterically hindered position (R = R = Me) attacks the neighboring carbon atom, diethyl 1-perfluoroalkyl-1,2-epoxyalkylphosphonates aie obtained in moderate yields (42-51%) after elimination of PhjP (anti fashion). The formation of a-(perfluoroalkyl)vinylphosphonates by attack at phosphorus (syn fashion) can be a competing reaction. The results indicate that the selectivity can be controlled to produce exclusively either epoxyphosphonates or vinylphosphonates. ... 

The preparation of diethyl 3,3-diethoxy-2-hydroxypropylphosphonate in 38% yield is possible through the addition of lithium diethyl phosphite to a mixture of D-glycidaldehyde diethyl acetal and BFgEtgO at -80°C in THF (Scheme 5.26)3 The relatively low yield may be explained by deactivation of the epoxide and the weakly nucleophilic character of the phosphite anion. Deprotection of the formyl group is accomplished under mild conditions with 0.1 M HCl at 40°C. ... 

This sequential Michael and Homer-Wadsworth-Emmons reactions has been developed with a large variety of charged nucleophiles such as Uthium carbanions of phenylethynyl, methyl[(meth-ylsulfoxyl)methyl]sullide and ethyl a-(methylthio)acetate5 ° or lithium diethyl phosphite to prepare functionalized dienes, trienes, and their analogues. 

An efficient, versatile protocol for the synthesis of highly enantioenriched a-aminophosphonate has been devised. The addition of lithium diethyl phosphite in THF at room temperature to imines prepared from methyl and methoxymethyl (MOM) ethers of (7 )-(-)-2-phenylglycinol and a wide variety of aldehydes has been explored. The reaction generates predominantly the (R,R) diastereomers whose hydrogenolysis produces a-aminophosphonates in good yields (Scheme 8.67). 

The addition of lithium diethyl phosphite to the imines (201) from (/ )-(—)- -amino-l-phenyl-2-methoxyethane gave mixtures of (202) and (203) in the ratios of >110 1 to 7 1, but mostly around 50 1. The sequence was completed by hydrogenolytic removal of the benzylic group, when the product (1-aminoalkyl)-phosphonic diesters had e.e.s of 96-99%. The diastereoisomeric ratios within (205), obtained from the chiral sulfoxides (204) and diethyl (lithiomethyl)phos-phonate, varied from 4.9 1 (R = PhCH=CH) to 9.2 1 (R = 2-thienyl), but the ratio also depended, to some extent, on the nature of the phosphonate alkyl group. ... 

Biacetyl reacts with a dialkyl hydrogenphosphonate in a manner identical with that observed in the first stage for glyoxal, and gives the esteis 239 A reaction between lithium diethyl phosphite and the 1,2-dioxocyclobutene 240 affords the hydroxy phosphonate... 

Yager KM, Taylor CM, Snuth AB. Asymmetric synthesis of a-aminophosphonates via diastereoselective addition of lithium diethyl phosphite to chelating imines. J. Am. Chem. Soc. 1994 116 9377-9378. 

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