Lithium diphenylamide

Beecham P-lactamase iiihibitoi BRL 42715 [102209-75-6] (89, R = Na), C IlgN O SNa (105). Lithium diphenylamide, a weaker base, was used to generate the anion of (88) which on sequential treatment with l-methyl-l,2,3-ttia2ole-4-carbaldehyde and acetic anhydride gives a mixture of diastereomers of the bromoacetate (90). Reductive elimination then provided the (Z)-penem (89, R = d5 Q [ OC15 -p) as major product which on Lewis acid mediated deprotection gave BRL 42715 (89, R = Na). 

In contrast to LDA, LiHMDS favors the Z-enolate.14 Certain other bases show a preference for formation of the Z-enolate. For example, lithium 2,4,6-trichloroanilide, lithium diphenylamide, and lithium trimethylsilylanilide show nearly complete Z-selectivity with 2-methyl-3-pentanone.15... 

Other changes in deprotonation conditions can influence enolate composition. Relatively weakly basic lithium anilides, specifically lithium 2,4,6-trichloroanilide and lithium diphenylamide, give high Z E ratios.10 Lithio l,l,3,3-tetramethyl-l,3-diphenyldisilylamide is also reported to favor the Z-enolate.11 On the other hand, lithium IV-trimethylsilyl-wo-propylamide and lithium iV-trimethylsilyl-fert-butylamide give selectivity for the fi-enolate12 (see Scheme 1.1). 

Treatment of the yellow chloride 159 with lithium diphenylamide gave rise to a thermally stable red iron amide complex [PhB(CH2PiPr2)3]FeNPh2, which was characterized structurally <2004JA6252>. 

Recent studies have begun to explore the consequences of complexed lithium amide solution structures for reaction mechanisms and rates. Double-labeling (6Li and 15N) NMR experiments, allied to colligative measurements, show that lithium diphenylamide in THF/hydrocarbon solutions exists as a cyclic oligomer at low THF concentrations, probably a bi- or trisolvated dimer [Fig. 48, structure (I) or (II), respectively]... 

DePue, J. S. Collum, D. B. Structure and reactivity of lithium diphenylamide. Role of aggregates, mixed aggregates, monomers, and free ions on the rates and selectivities of N-alkyla-tion and E2 elimination. /. Am. Chem. Soc. 1988, 220, 5524-5533. 

Other pathways, with trimethylsilyl azide and the appropriate iodonium salts, involved the formation of 3-alkyl-1-azido-cyclopentenes (Table 9.3.) or Z-fi-azidoalkenyl iodonium salts [69], Several types of alkynyl iodonium salts afforded with lithium diphenylamide push-pull ynamines overcoming some inherent limitations of other methods. 

Mukaiyama developed a variety of catalytic carbon-carbon bond-forming reactions with the use of trimethylsilyl nucleophiles in the presence of simple lithium Lewis-base catalysts, such as lithium acetate, lithium pyrro-lidone, lithium succinimide, lithium benzamide, lithium diphenylamide, and lithium benzyloxide (Scheme 2.1). For example, the Mukaiyama aldol... 

Ph2NLi)3LiCl(tmeda)3], 78, can be viewed as an adduct of a homodimeric lithium diphenylamide and a 1 1 mixed dimer. Notable is the rare Y-shaped, nearly planar (sum of angles 356°) conformation around the chlorine atom. Interestingly, the molecule can be viewed as a crystallographic snapshot of the process of amido-lithium ladder structure fragmentation by solvation [76]. 

New challenges were then made to develop useful Lewis base-catalyzed aldol reactions of trimethylsilyl enolates, simple and the most popular silicon enolates. It has recently been found that aldol reactions of trimethylsilyl enolates with aldehydes proceed smoothly under the action of a catalytic amount of lithium diphenylamide or lithium 2-pyrrilidone in DMF or pyridine (Eq. (38)) [57]. This Lewis base-catalyzed aldol reaction of trimethylsilyl enolates [58] has an advantage over acid-catalyzed reactions in that aldol reaction of carbonyl compounds with highly-coordinative functional groups with Lewis acid catalysts are smoothly catalyzed by Lewis bases to afford the desired aldol adducts in high yields. 

The latter is added to the benzyne. The initially formed carbanion is transformed by proton transfer to lithium-A N-diphenylamide, which upon aqueous workup undergoes protonation to give diphenylamine. 

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