Ynamines protonation

Thus, ynaminoketones with 1,2-diaminobenzene form benzodiazepines with retention of the dialkylamino group. The reaction occurs as a nucleophilic addition in the absence of catalysts. With Q, /3-acetylenic ketones 1,2-diaminobenzene reacts in the same manner, but under proton-catalyzed conditions (72LA24). At the same time, ynamines and enynamines furnish with 1,2-diaminobenzene substituted benzimidazoles as aresultof double attack at the acetylene bond(83ZOR926 84ZOR1648). 

A key step in the synthesis in Scheme 13.11 was a cycloaddition between an electron-rich ynamine and the electron-poor enone. The cyclobutane ring was then opened in a process that corresponds to retrosynthetic step 10-IIa 10-IIIa in Scheme 13.10. The crucial step for stereochemical control occurs in Step B. The stereoselectivity of this step results from preferential protonation of the enamine from the less hindered side of the bicyclic intermediate. 

The different behaviour of bis(AT,N-diethylamino)propene and AT,A(-dimorpholinopropene towards methyl vinyl ketone is of interest. The latter yields some 4/f-pyran (153) identical with that obtained from the ynamine. However, the former compound gives only the Stork adduct (154) by proton transfer. The elimination of the amine moiety from the dihydropyran (152) is easier from the less basic enamine (Scheme 22). 

These compounds have proven to be the most versatile building blocks for construction of other ynamines mainly through protonation, alkylation and acylation. Such reactions are called aminoethynylation 131). More recent development involves the use of stable stannyl ynamines. Lithio ynamines 44 are prepared in situ and alkylation is achieved by adding the corresponding alkyl halide or tosylate. The D3-ynamine 45 was prepared via the latter method (80) 132). Two selected examples (81, 82) where the acetylene chain carries a latent functionality follow 133,134). 

A small amount (up to one equivalent) of HMPT is necessary in order to accelerate the alkylation step. Sec.-butyl bromide gives 38 % of the expected ynamine together with 25 % butene and 22 % of diethylaminoacetylene. Expectedly, t-butyl bromide undergoes only elimination and it serves as a convenient proton source to liberate N-ethynyl-methylaniline 106 Primary substrates react smoothly, however, even in complex cases and with this in mind, the scope of this reaction is almost unlimited. One more example illustrates this technique (83),35). 

Ynamines are obtained by thiol elimination from ketene 5, A -acetals (1-aIkylthio-l-dialkylaminoalkenes) in 40-50% yields on treatment with LiNEt, at 20 °C or with NaNHo in boiling piperidine, or by leading them over solid NaNH.j at 150-165 °C. In the first two procedures the formed ynamines are fractionally distilled from the reaction mixture (equation 83) . When elimination is effected with KNHj in HMPT, aqueous work-up leads to the hydration of the ynamine. Therefore, 1,2-dibromo-ethane is added to the reaction mixture. It functions as a proton donor for the... 

The rate-determining step always corresponds to protonation or deprotonation of a carbon atom, while equilibration of oxygen acids with their conjugate bases is established rapidly. This fact can be used to determine the acidity constants of enols, ynols and ynamines by flash photolysis, Kf, either kinetically, from downward bends in the pH rate profiles indicating a pre-equilibrium, or from the changes of the transient absorption in solutions of different pH (spectrographic titration). Such studies have provided some remarkable benchmark numbers, such as the acidity constant of phenylynol (pKf < 2.1),476 phenylynamine (pKf < 18.0)477 and its pentafluoro derivative (pKf = 10.3),478 and of the carbon acid 2,4-cyclohexadienone, pKf = —2.9 475 The enolization constant of 2,4-cyclohexadienone is pKE = 12.7. 

The first stereoselective synthesis of ( )-dihydroantirhine (86) employs a neat device for stereochemical control, and proceeds in a remarkable overall yield of 40% from the lactam (87). Addition of the ynamine (88) to (87) involves preferentially a transition state in which ring d has a flattened half-chair, rather than a half-boat, conformation, which results in the formation of the intermediate (89). Proton addition to (89) during acid hydrolysis to the lactam-acid (90) occurs predominantly on the more accessible exo face the stereochemistry of (90), and thus of ( )-dihydroantirhine (86), is thereby assured (Scheme 11). ... 

To a flask containing 2.0 gm (0.01 mole) of cupric acetate in 25 ml (0.38 mole) of dimethylamine in 100 ml of benzene at 5°C are added dropwise simultaneously a solution of 5.1 gm (0.05 mole) of phenyl-acetylene in 100 ml of benzene over 30 min and a stream of oxygen (1.0 ft /hr). The oxygen stream is added for 30 min more after the phenylacetylene addition has been completed. The copper ions are precipitated by adding 100 ml of ice water. The organic layer is separated, dried, and concentrated under reduced pressure. A gas chromatograph of the crude (column 10 ft x in. 410 gum rubber) showed two peaks A, iV-dimethylamino-2-phenylacetylene and 1,4-diphenylbutadiyne. The ynamine was obtained in 40% yield as determined by reaction of the crude mixture with dilute hydrochloric acid and isolating the resultant A, iV-dimethyl- aminophenylacetylene. The ynamine has characteristic IR absorption bands at 2205 and 2235 cm and NMR absorption bands at S 7.14 (4.0 protons) and 2.73 (6.05 protons). 

Chiang, Y, Grant, A. S., Kresge, A. J. and Paine, S. W., Flash Photolytic Generation of Primary, Secondary and Tertiary Ynamines in Aqueous Solution and Study of Their Carbon-Protonation Reactions in That Medium, /. Am. Chem. Soc., 118,4366, 1996. 

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