2-Lithioacetals

A biarylpropionic acid derivative containing a furan ring as a prominent feature has antiinflammatory activity. The patented synthesis involves a straightforward organometal1ic addition of ethyl lithioacetate to aldehyde 12 followed by saponification... 

Chain extension.1 An alternative lo the malonic ester synthesis involves ttlkylnliim of r-bmyl lithioacetate, Yields arc improved by preparation of the enolate With l.il( A (4, 306) ui 78. Alkylaliun proceeds in highesl yields at -78 to -35"... 

A less common approach to the synthesis of phosphinates is the reaction of electrophilic phosphonates with carbon nucleophiles such as Grignard reagents or lithium enolates. For example, the phosphinic acid analogue 71 of the amino acid statine was synthesized by displacement of tert-butyl lithioacetate on a 5-phenyl phosphonothioate 70 (Scheme 23)d104l The racemic diastereomers of the 5-phenyl phosphonothioate were obtained in pure form, and the displacement of the phenylsulfanyl moiety was found to be stereospecific, although the stereocenter at phosphorus would later be lost on hydrolysis of the ester. A similar displacement reaction has been described using the p h osp h on och I ori d ate.1711... 

Michael intramolecular alkylation. The reaction of f-butyl lithioacetate (1) with ethyl 6-iodo-2-hexenoate 2 in the presence of potassium t-butoxide in THF at - 78° results in a single trans-1,2-disubstituted cyclopentane (3). Reaction of 2 with f-butyl lithiopropionate (4) under the same conditions results mainly in syn-5, but when HMPT is also present anti-5 is mainly formed. Similar stereoselectivity is observed in reaction of 1 and 4 with ethyl 6-iodo-2-heptenoate in formation of... 

Few examples exist for the conjugate addition of ester enolates to a,(3-unsaturated esters typically the incipient enolate undergoes decomposition and secondary reactions. The first examples, described by Schlessinger,144 are the addition of /-butyl lithioacetate and /-butyl a-lithio-a-(methylthio)propionate to butenolide (176 Scheme 69). Similarly, Normant reported that cyclopropanes are obtained from a-ha-loesters (177) and ethyl acrylate or acrylonitrile.145... 

Carbon nucleophiles of type (iii) add to the arene ligand and do not rearrange examples include the very reactive anions, such as 2-lithio-2-methyl-l,3-dithiane, and the less sterically encumbered anions, such as lithio acetonitrile and /-butyl lithioacetate. In these cases, the anion adds to an unsubstituted position (mainly ortho or meta to Cl, as in 22) and does not rearrange. Then iodine quenching, even after a long period at 25 °C, gives almost exclusively the products from formal substitution for hydrogen, as from (22) in Scheme 8. 

The major limitation on the reactivity of cycloheptadienyliron complexes is the fact that treatment with hard enolates, such as methyl lithioacetate results in deprotonation to give, e.g. the V-triene complex (89). This appears to be less of a problem in the corresponding cyclohexadienyl systems. 

The tricarbonyliron-coordinated cyclohexadienylium salts are readily available on a large scale by azadiene-catalyzed complexation of the corresponding cyclo-hexadienes with pentacarbonyliron [23] and subsequent hydride abstraction using trityl tetrafluoroborate [24]. Alkylation of methyl lithioacetate with the iron complex... 

Fukuyama and Yung (81TL3759) used adduct 69 as a key starting material for the synthesis of methyl ( )-3-(3-cyana-6-oxabicyclo[3.I.0]hex-2-en-5-yl)-2-propenoate (81). The reaction of cycloadduct 69 with methyl lithioacetate gave unsaturated ester 77. Reduction in acidic media of the conjugated double... 

Chiral allylation of imines by an allylstannane is promoted by a bis-Ji-allylpalladium complex based on the pinane skeleton, while using triallylborane to supply the allyl group a polymer-supported arenesulfonaminoisobomeol can provide a proper environment. The chirality of alkenyl sulfoxides imposes the approach of methyl lithioacetate, and therefore it enables the generation of optically active P-amino acids. ... 

Stirring the dithioacetals (30.8) with t-butyl lithioacetate and LDA at -78°C and then with t-butyl acetate gives a high yield of the pyran-2-one. 

Much less is known about aldol additions to chiral aldehydes that have heteroatoms other than oxygen at the a-stereocenter. In connection with a synthesis of statine analogs, a-amino aldehyde (176) was allowed to react with ethyl lithioacetate to obtain (177) and (178) in a ratio of 60 40 (equation 114). 

P,y-Unsaturated esters. Ruden and Gaffney have prepared j3,7-unsaturated esters by a method based on the facile elimination of trimethylsUanol from 3-hydroxysilanes. Thus reaction of trimethylsilylacetone (1) with f-butyl lithioacetate (2) gives the hydroxy ester (3), which is converted into (4) by treatment with acid. 

IV), and nitriles (V) by reaction with f-butyl lithioacetate, (5, 371), lithio N,N-dimethylacetamide, and lithio acetonitrile, respectively, followed by elimination of trimethylsilanol (Peterson reaction). 

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