P-TsOH

The 3-alkyi-1,3-butadiene-2-carboxylate (2-vinylacrylate) 850 is obtained in a high yield by the carbonylation of the 2-alkyl-2,3-butadienyl carbonate 849 under mild conditions (room temperature, atm)[522]. The corresponding acids are obtained in moderate yields by the carbonylation of 2,3-alkadienyl alcohols under severe conditions (100 °C, 20 atm) using a cationic Pd catalyst and p-TsOH[523],... 

Alkyldithio carbamates are prepared from the acid chloride (Et N, EtOAc, 0°) and amino acid, either free or as the O-silyl derivatives (70-88% yield). The N- i-propyldithio) carbamate has been used in the protection of proline during peptide synthesis. Alkyldithio carbamates can be cleaved with thiols, NaOH, Ph P/TsOH. They are stable to acid. Cleavage rates are a function of the size of the alkyl group as illustrated in the table below. 

Many acids other than sulfuric acid have been used for the challenging cyclodehydration step. It is important to note that when the concentration of sulfuric acid is below 70%, hydrolysis of the imine or enamine occurs. As previously mentioned, HCl/AcOH, ZnCla, PPA, POCI3, and lactic acid have been successfully applied to promote the cyclization. Chloroacetic acid was found to perform similar to lactic acid. Concentrated HCl, p-TsOH, and have proven beneficial in generating linear... 

We have previously discussed that keto-aldehydes react with anilines first at the aldehyde carbon to form the aldimine. Subsequent condensation with another aniline formed a bis-imine or enamino-imine. The aniline of the ketimine normally cyclizes on the aldimine (24 —> 26). Conversely, cyclization of the aldimine could be forced with minimal aniline migration to the ketimine using PPA (30 —> 31). The use of unsymmetrical ketones has not been thoroughly explored a few examples are cited below. One-pot enamine formation and cyclization occurred when aniline 48 was reacted with dione 49 in the presence of catalytic p-TsOH and heat. Imine formation occurred at the less-hindered ketone, and cyclization with attack on the reactive carbonyl was preferred. ... 

When [Fe(CN)2(CO)3H] 57a is treated with excess p-TsOH the complex is completely consumed and evolution of H2 and an equimolar amount of CO... 

Depending on the reaction conditions, the major products were different (1) formation of 26 in the presence of catalytic amount of p-TsOH in THF, (2) formation of... 

However, pMBCl 42 has a thermal stability issue and is expensive (Aldrich price 25 g for 69.90 the largest bottle). On the other hand, pMBOH 43 is stable and economically viable (Aldrich price 500 g for 84.90 the largest bottle). It was found that mono-N-alkylation of 36 proceeded well by slow addition (over 3 h) of 43 to a solution of 36 in acetonitrile in the presence of a catalytic amount of acid (p-TsOH) at 70 °C, as shown in Scheme 1.16. Slow addition of alcohol 43 minimized the self-condensation of 43 to form symmetrical ether 44, which was an equally effective alkylating agent. The product 41 was then directly crystallized from the reaction mixture by addition of water and was isolated in 90% yield and in >99% purity. A toluene solution of 41 can be used for the next reaction without isolation but the yield and optical purity of the asymmetric addition product were more robust if isolated 41 was used. In general, the more complex the reaction, the purer the starting materials the better. 

Scheme 21. Preparation of cyanoethyltropinone (200). Reagents i, piperidine, C6H6, p-TsOH, reflux, 20 hr, H20 separation ii, CH2=CHCN, dioxane, reflux, 20 hr iii, H20, HC1.

Scheme 25. Oxidation of oxyberberine (58) with lead tetraacetate. Reagents a, Pb(OAc)4, CH2C12 b, LAH c, NaBH4 d, Pb(OAc)4> CHC13 e, p-TsOH, MeOH, or EtOH.

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