Formaldehyde anion equivalent

Addition of lithio alkene 636, a formaldehyde-anion equivalent ( CHO), to 808 at low temperature gives adduct 813 with a diastereomeric excess of 92%. Lithium—bromine exchange, desilation, ketalization, and ozonolysis furnishes aldehyde 814 (> 98% de). The last stereocenter is introduced by aldol condensation with R-HYTRA, thus giving 815 as a 91 9 mixture of isomers. Lactonization to 816 followed by reduction with disiamylborane gives 817, which is separated from the accompanying minor isomer by column chromatography. 

Azomethinium salts are very versatile intermediates since they present an extremely electrophilic carbon for nucleophilic attack. High yields of these salts can be obtained in one step from a-amino acids via their tert-dcsmno derivatives Ethyl N-Benzylidene-glycinate has been used for the synthesis of a-amino acids and as an acyl carbanion equivalent A new reactive formaldehyde anion equivalent is lithium methylthioformaldine, (4,5-dihydro-5-methyl-l,3,5-dithiazin-2-yllithium A convenient synthesis of 2-alkyl- and 2-aryl-l,3-benzo-dithioles, which are precursors of acyl carbanion equivalents, has recently been published . 

In 2008, the same group employed chiral dicarboxylic acid (R)-5 (5 mol%, R = 4- Bu-2,6-Me2-CgHj) as the catalyst in the asymmetric addition of aldehyde N,N-dialkylhydrazones 81 to aromatic iV-Boc-imines 11 in the presence of 4 A molecular sieves to provide a-amino hydrazones 176, valuable precursors of a-amino ketones, in good yields with excellent enantioselectivities (35-89%, 84-99% ee) (Scheme 74) [93], Aldehyde hydrazones are known as a class of acyl anion equivalents due to their aza-enamine structure. Their application in the field of asymmetric catalysis has been limited to the use of formaldehyde hydrazones (Scheme 30). Remarkably, the dicarboxylic acid-catalyzed method applied not only to formaldehyde hydrazone 81a (R = H) but also allowed for the use of various aryl-aldehyde hydrazones 81b (R = Ar) under shghtly modified conditions. Prior to this... 

J.-M. Lassaletta and R. FemSndez, Michael addition of formaldehyde dimethyl-hydrazone to nitroolefins. A new formyl anion equivalent, Tetrahedron Lett. 33 3691 (1992). 

Thiamine-catalyzed transformations are reversible, thus TV,/V-dialkyl hydrazones were selected as alternative acyl anion equivalents that were reported to react with electrophiles without acidic activation.41 One especially reactive example, formaldehyde hydrazone resin 13, was constructed from polymer-supported hydrazines and was employed in the first polymer-supported, uncatalyzed acyl anion additions (Fig. 8).38 As test substrates, nitroalkenes (as Michael acceptors) and activated aldehydes were selected. Reactivity of these acyl anion equivalents depended critically not only on the nature of the starting hydrazine, but also on the protocol for hydrazine formation. 

Formaldehyde f-butyl hydrazone, H2C=N-NH-Bu has been used as a formyl anion equivalent it reacts with isatins to give functionalized 3-hydroxy-2-oxindoles. 

CH2—The anions of 2-substituted-l,3-benzodithioles (34) are readily prepared and are useful acyl carbanion equivalents. N,iV-Diethylamino-acetonitrile anion, EtaNCHCN, has been used as a latent formaldehyde anion. Acetals of /8-diphenylphosphinoyl-ketones (35) (available by five different routes) act as equivalents of homoenolate anions [CH(R )CH(R )COR ] on... 

An innovative development in the use of Enders chiral hydrazines involves reaction of the formaldehyde hydrazone 87 as a chiral formyl anion equivalent (Scheme 12.13) [93, 94]. Hydrazone 87 adds to nitroolefms to afford the corresponding adducts with excellent diastereoselectivity. Addition of 87 to nitroolefm 88, for example, proceeded to furnish 89 in 93 % yield and dr >99 1. The resulting adduct could subsequently be converted into aldehyde 91 (> 98 % ee) by ozonolytic cleavage or into nitrile [95] 92 (> 99 % ee) under mild oxidative conditions by treatment with magnesium monoperoxyphthalate (90) [94]. 

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