Iminium hydrolysis

From a series of experiments in solutions of pD varying from 6.5 to 12.8 and six equivalents of XMe.b, the buildup and hydrolysis of the iminium cationic intermediate was studied in the rearrangement and hydrolysis of [33 C 1] . In neutral pD (pD 6.5-8), the rates of iminium hydrolysis are essentially constant, with water acting as the nucleophile. However, in more basic solution, a dependence on [OD ] is observed until approximately pD 11, at which point saturation is observed. The observed linear first-order dependence on hydroxide concentration from the pD rage of 9-10.5 supports the mechanistic model where the iminium cation is ejected from the assembly and then hydrolyzed in solution. The presence of saturation implies that, after pD 11, the rate of iminium dissociation from 1 becomes rate limiting because hydrolysis becomes faster than the re-encapsulation process. 

By using a three-component system of acetone, 4-nitrobenzaldehyde (2a) and p-anisidine (3), an electrophihc imine was formed, which reacted with the in situ formed proline-derived chiral enamine 4 to form the adduct 5. Subsequent iminium hydrolysis then led to the Mannich product 6 and regeneration of the organocatalyst. Hydrogen bonding interactions between the carboxylate of the enamine 4 and the... 

Acid-catalysed iminium hydrolysis gives the ketone product. 

Organo-SOMO catalysis has been successfully exploited to achieve the first asymmetric a-vinylation of aldehydes using vinyl trifluoroborate salts and the commercial Kim and MacMillan catalyst 191. " ° Vinyl potassium trifluoroborate salts participate in enantioselective and regioselec-tive carbon-carbon bond formation with the aldehyde-derived radical cation 192 to form a (3-borato-stabilized radical 193 (Scheme 25.90), which in the presence of a suitable oxidant will undergo rapid electron transfer to render the (3-cation (not shown). Subsequent Peterson elimination of the trifluoroborate group with tran.s-selectivity followed by iminium hydrolysis of 194 would then reveal an optically enriched R-( )-vinyl aldehyde (e.g., 195). 

The dye is initially linked to a ballasted thiazoUdine, which reacts with silver to form a silver iminium complex. The alkaline hydrolysis of that complex yields an alkali-mobile dye. Concomitantiy the silver ion is immobilized by reaction with the ballasted aminoethane thiol formed by cleavage of the thiazolidine ring. 

The tetrasubstituted isomer of the morpholine enamine of 2-methyl-cyclohexanone (20) because cf the diminished electronic overlap should be expected to exhibit lower degree of enamine-type reactivity toward electrophilic agents than the trisubstituted isomer. This was demonstrated to be the case when the treatment of the enamine with dilute acetic acid at room temperature resulted in the completely selective hydrolysis of the trisubstituted isomer within 5 min. The tetrasubstituted isomer was rather slow to react and was 96% hydrolyzed after 22 hr (77). The slowness might also be due to the intermediacy of quaternary iminium ion 23, which suffers from a severe. 4< strain 7,7a) between the equatorial C-2 methyl group and the methylene group adjacent to the nitrogen atom, 23 being formed by the stereoelectronically controlled axial protonation of 20. 

The alkylation of dienamines has not been studied extensively. Thus the dienamine (44) is reported (43,44) to alkylate at Cj with methyl iodide to give the iminium salt (45), which on hydrolysis gives the alkylated a,)3-unsatur-ated ketone (46). Similar dienamines prepared from A -2-oko steroids. On the other hand, are reported to undergo only N alkylation (45). 

More recently the acylation of aldehyde enamines has been reinvestigated (75) and shown to proceed normally when the enamine is added to the acid chloride. The morpholine enamine of isobutyraldehyde (98), on being added to an ether solution of acetyl chloride, afforded the iminium salt (99), from which the ketoaldehyde (100) was obtained in 66% yield by hydrolysis (75). 

The reaction of other nucleophiles such as amines 123,124), hydroxyl-amines, various carbanions, and hydroxide 120) have been tried but not examined in detail. Hydrolysis of iminium salts is covered elsewhere 123). 

The reaction of iminium salts such as 66 with salts of trichloroacetic acid has been shown to yield amides such as 84 on hydrolysis 126). It was suggested that the reaction proceeds by addition of dichlorocarbene to give an aziridinium intermediate (85), which was opened by trichloroacetate followed by hydrolysis to give the observed products 126). The observed products from the reaction can be accounted for by formation of CCI3,... 

Cleavage of the chiral auxiliary is effected in a three-step procedure commencing with quatemization of the nitrogen with methyl fluorosulfonate, methyl trlfluoromethanesulfonate, or trimethyloxonium tetrafluoroborate. Reduction of the corresponding iminium salt 19 with NaBH4 and acidic hydrolysis of the resulting product affords substituted aldehyde 5 without epimerization of either stereocenter. 

Hydrolysis of 3-[(2,6-dimethoxy-4-pyrimidinyl)hydroxymethyl]perhydro-pyrido[l,2-c]pyrimidin-l-iminium salts 174-177 in boiling cone. HCl afforded the appropriate 3-[(2-hydroxy-6-oxo-l,6-dihydropyrimidin-4-yl) hydroxymethyl] derivative (98TL7021, 00JA5017). 

In all the reactions described so far a chiral Lewis acid has been employed to promote the Diels-Alder reaction, but recently a completely different methodology for the asymmetric Diels-Alder reaction has been published. MacMillan and coworkers reported that the chiral secondary amine 40 catalyzes the Diels-Alder reaction between a,/ -unsaturated aldehydes and a variety of dienes [59]. The reaction mechanism is shown in Scheme 1.73. An a,/ -unsaturated aldehyde reacts with the chiral amine 40 to give an iminium ion that is sufficiently activated to engage a diene reaction partner. Diels-Alder reaction leads to a new iminium ion, which upon hydrolysis af-... 

The electrophile 4 adds to the aromatic ring to give a cationic intermediate 5. Loss of a proton from 5 and concomitant rearomatization completes the substitution step. Subsequent hydrolysis of the iminium species 2 yields the formylated aromatic product 3. Instead of the highly toxic hydrogen cyanide, zinc cyanide can be used. The hydrogen cyanide is then generated in situ upon reaction with the hydrogen chloride. The zinc chloride, which is thereby formed, then acts as Lewis acid catalyst. 

Iminium ions (2) would be expected to undergo hydrolysis quite readily, since there is a contributing form with a positive charge on the carbon. Indeed, they react with water at room temperature." Acid-catalyzed hydrolysis of enamines (the last step of the Stork reaction, 12-18) involves conversion to iminium ions " ... 

The reactivity of dipyrrolylmethane 236 has similarly been exploited in its reaction with 4-dimethylamino-l,l,l-trifluoro-3-buten-2-one 239 and trifluoromethanesulfonic anhydride to generate the iminium ion 240 followed by hydrolysis to give the fluorinated product 241 in 56% yield (Scheme 16) <2003CHE776>. 

---