Amidation generation

Treatment of the potentially electrophilic Z-xfi-unsaturated iron-acyl complexes, such as 1, with alkyllithium species or lithium amides generates extended enolate species such as 2 products arising from 1,2- or 1,4-addition to the enone functionality are rarely observed. Subsequent reaction of 2 with electrophiles results in regiocontrolled stereoselective alkylation at the a-position to provide j8,y-unsaturated products 3. The origin of this selective y-deproto-nation is suggested to be precoordination of the base to the acyl carbonyl oxygen (see structures A), followed by proton abstraction while the enone moiety exists in the s-cis conformation23536. 

The reaction of alkenes or dienes, mercuric salts, and either nitriles or amides generates (3-amidomer-curials, which can be easily reduced to the corresponding amides (equation 174). This reaction effects H—NHCOR addition to alkenes and dienes, and has been thoroughly reviewed recently.242... 

Based on the above work, a new, practical, chromatography-free method for the preparation of the orally active CCR5 antagonist 248 has been reported by Ito et al. <20050PD168>. Two one-pot sequences were used to prepare 246 from 244 via 245 (Scheme 32). A Suzuki-Miyaura reaction of 246 to give 247, followed by hydrolysis and an amidation, generated 248 in good overall yield in six steps. 

Sonnet (1984) developed another general method of synthesizing chiral methylalkanes, based on fractional crystallization of the mixture of diastereomeric amides generated from... 

A complementary access to alkoxy- and aminocarbene complexes ( Semmelhack-Hegedus route ) involves the addition of the pentacarbonylchromate dianion 18 (obtained from the reduction of hexacarbonylchromium with C8K) to carboxylic acid chlorides and amides [27] (Scheme 10). While alkylation of acyl chromate 19 leads to alkoxycarbene complexes 12, addition of chromate dianion 18 to carboxylic amides generates the tetrahedral intermediates 20, which are deoxygenated by trimethylsilyl chloride to give amino carbene complexes 14. 

Just as ketones and esters may be derivatized by the action of molecular oxygen on the corresponding enolates, the same is true of amides. Generation of the lithio enolate (clearly not as facile as the previous substrates) and quenching with oxygen produce the a-hydroperoxyamide, which after in situ reduction, (P(OEt)3), or reductive work-up, (NaHSOs), gives good yields of the required material. 

Treatment of the laterally lithiated amide generated from lactam 273 with LDA with /ra r-2-phenylsulfonyl-3-phenyloxaziridine 33 afforded hydroxyl product 274 in 85% yield as a single isomer <1999JOC8627>. Use of (+)-(camphorsulfonyl)oxaziridine 202 gave similar results. The /ra t-stereoselectivity is consistent with the earlier finding that the hydroxylation stereochemistry is controlled by nonbonded steric interactions in the transition state such that the oxygen of the oxaziridine is delivered from the sterically least hindered direction. Treatment of 275 with LDA followed by (+)-(camphorsulfonyl)oxaziridine 202 afforded hydroxyl product 276 in 47% yield and 60% ee <1997T8881>. 

The Gabriel method of making primary amines (Scheme 2.33) rests on the fact that the imide hydrogen of phthalimide is rendered acidic by the two carbonyl groups. It therefore forms a potassium salt, which is a powerful nucleophile and may be alkylated. Hydrolysis of the amide generates the primary amine. The cleavage of the phthalimide may be carried out with hydrazine (H NNHj). 

N-AlkylaniUmes. Treatment ofbromobenzene substituted in the meta position by electron-attracting groups [OCH3, Cl, N(CH,)2] with sodium amide generates a benzyne derivative which reacts with a primary aliphatic amine to give the corresponding... 

A similar treatment of stable keteneiminium triflate 72 with sodium bis(trimethylsilyl)amide generates azomethine ylide 73, together with a small amount of the demethylated product of 72. Ylide 73 undergoes readily dimerizes, leading to l,4-diethyl-2,5-bis[2,2-dimethyl-l-(t-butyl)propyridene]-piperazine when no dipolarophile is present. The trapping of ylide 73 with electron-deficient olefins is completely unsuccessful because these activated olefins cannot withstand such strongly basic conditions. The only dipolar-... 

Reaction in protic media of diphenylcyclopropenone with pyridinium A -amide, generated from Af-aminopyridinium iodide in the presence of triethylamine, afforded products 12-15 consistent with a mechanism involving addition of solvent to an iminoketene intermediate. ... 

Asymmetric deprotonation of a prochiral compound having a sufficiently acidic C-H bond can be performed by a lithium amide generated from an enantio-pure secondary amine or by an organolithium reagent in the presence of a chiral tertiary amine [557, 559]. A chiral mixed aggregate is usually formed [77, 81, 974], and the reaction of this intermediate with electrophiles (including proton sources) can lead to a predominant enantiomer. 

Zinc ester enolates may also be obtained by the addition of ZnX2 to lithium or sodium enolates as first described by Hauser and Puterbaugh (equation 6)P This approach has so far received little attention but similar reactions have been used to obtain zinc ketone enolates. In this regard, it should be noted that Heathcock and coworkers have shown that deprotonation reactions of ketones with zinc dialkylamide bases reach equilibrium at only about 50% conversion (equation 7). This result implies that attempts to prepare zinc enolates from solutions of amide-generated lithium enolates will be successful only when the lithium enolate is made amine-free. 

More recently, the same group [62] showed that hydrotalcite catalyzes the epoxidation of olefins with 30 % H2O2 in the presence of an amide, e. g. isobutyramide was most effective, in 1,2-dichloroethane at 70 °C. Addition of an anionic surfactant, e. g. sodium dodecyl sulfate, further enhanced the rate. With less reactive terminal olefins, e. g. 1-octene, a large excess of the amide (10 equiv.) was necessary to attain a high yield of epoxide. A mechanism was proposed (Eqs 7 and 8) which involved reaction of HO2, formed on the hydrotalcite surface, with the amide generating a peracid and NH3 ... 

It is worth noting that ammonium amides, generated in situ from a mixture of aminosilanes and ammonium fluorides, have recently been employed as bases for organocatalytic deprotonative C-H functionalization of heteroaromatics under mild conditions (Scheme 30) [71]. 

Also, ALES surfactant with 3-mole EO generates slightly wetter foam than either 1-mole EO or 2-mole EO sulfate. Shampoos and bubble baths formulated with ALES-3EO and Calamide alkanol-amides generate profuse foam, and the product has been characterized to be mild and gentle, and perform well under use conditions. 

Primary amines also serve as reagents for the double carbonylation to give a-keto amides or their Shiff bases, which are produced by further attack of the primary amines on the a-keto amides generated in the reaction (Eq. 3). ° a-Amino amide can be produced by Pd-catalyzed hydrogenation from the corresponding Shiff base (Eq. 4). ° ... 

The second role of the alcohol is to avoid the reversion of the final 1,4-cyclohexadiene into the intermediate IV by means of the strong base (metal amide) generated in the reaction medium. This base is protonated by the alcohol giving a less strong base, the alkoxide, unable to deprotonate the 1,4-diene and to isomerize it to the most stable 1,3-system. In the absence of an alcohol, the reaction works at higher temperature, and usually, an amine is employed instead of ammonia. 

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