Pyrroline trimer

Pyrrolines readily form trimers of type (227). The trimer dissociates in boiling THF to 1 -pyrroline trimerization is relatively slow at — 78°C and the monomer can be trapped by reaction with acylating reagents to give iV-acyl-2-pyrrolines, e.g. (228) with ClC02Me (8UOC4791). 

Salicylaldehyde and triethyl phosphite upon heating gave, instead of the expected diphosphonate (20), the rearranged phosphate-phosphonate (21). A new method to obtain 1-aminoalkylphosphinic acids (22) has been published it involves addition of bis(trimethylsilyl) phosphonite to Af-trityl imines, followed by hydrolysis. A similar reaction of bis(trimethylsilyl) phosphonite with 1-pyrroline trimer gave 2-pyrrolidinylphosphinic acid in 90% yield. Bis(trimethylsilyl) phosphonite with carbamoyl chlorides and triethylamine gave fair yields of the carbamoylphosphonites (23). ... 

Some homoiogues of L-2-amino-5-(/ -methoxyphenyl)pentanoic acid have been prepared. 1-Pyrroline trimer (280) reacts with monoethyl malonate to give the P-amino-acid (281) (Scheme 138) seven examples were studied and yields of between 47 and 61 % were obtained. ... 

An application of the RCM strategy features polycyclization reactions, wherein for instance the substrate 176 could be converted in good yield into the 3-pyrroline trimer 177 using the catalyst 178 (Equation 55) <1998JOC4291>. 

The simplest compounds, -pyrroline and -piperideine,donotexistin the monomeric form. Schdpf et al. (29S) described two geometric isomers of J -piperideine trimer and called them a- and -tripiperideines (182). An equilibrium exists between A -piperideine and both trimers which, therefore, react as typical aldehyde ammonia. The trimer rearranges at pH 9-10 in an almost quantitative yield to isotripiperideine (183) which, in turn, is in equilibrium with tetrahydroanabasine (184) and -piperideine. 

The dimer of 1-methyl- -pyrroline (39) was obtained by reduction of N-methylpyrrole with zinc and hydrochloric acid (132) and, together with the trimer, by mercuric acetate dehydrogenation of N-methylpyrrolidine (131). J -Pyrroline-N-oxides form dimers in a similar manner (302). Treatment of 1,2-dimethyl-zl -piperideine with formaldehyde, producing l-methyl-3-acetylpiperidine (603), serves as an example of a mixed aldol reaction (Scheme 18). 

Aryl-A3-iodane oxidation of amines to imines also involves a combination of ligand exchange and successive reductive -elimination. Oxidation of pyrrolidine with iodosylbenzene 18 affords quantitatively an equilibrium mixture of 1-pyrroline and its trimer [72]. When oxidation of piperidine with 18 (2 equiv) was carried out in water, 2-piperidone was produced [73]. In the latter reaction, a sequence of ligand exchange and reductive -elimination was repeated two times [Eq. (38)]. 

A 1-Pyrroline affords a trimer, tripyrroline.344 Compounds analogous to isotripiperideine or aldotripiperideine have not yet been prepared in... 

Generally, dehydrogenation prevailed in secondary amines when treated with one equivalent of IOB in dichloromethane in this way ACt-butylbenzylamine gave its imine (PhCH = NBu , 88%), whereas pyrrolidine was converted into a mixture of 1-pyrroline and its trimer. Hydrogen elimination followed Hofmann s rule, for example in the following transformation [41] ... 

Decarboxylation with concomitant dehydrogenation occurred in some cyclic amino acids. For example, (I)-proline was converted into a mixture of 1-pyrroline and its trimer. The methyl ester of (L)-proline was simply dehydrogenated to its /i-imine (69%). With two equivalents of IOB in chloroform (L)-proline was converted directly into 2-pyrrolidinone (70%). This transformation was less efficient for pipecolinic acid and ( )-pyrrolidinone-5-carboxylic acid [48]. 

Trimeres Pyrrolin fiihrt bei 85° zum Pyrrolidin-2-phosphonsaure-diester342 ... 

Oxidation with excess iodosylbenzene converts proline into 2-pyirolidinone in up to 70% yield. Use of only 1 equiv. of iodosylbenzene in this reaction gives 1-pyrroline, plus the corresponding trimer. 

Achiwa reported a short synthesis of pyrrolizidine derivatives by the cycloadditions using a nonstabilized azomethine ylide 23 (m = 1) (82CPB3167). When the trimer of 1-pyrroline is treated with a silylmethyl triflate, N-alkylation of the 1-pyrroline takes place. Then the resulting iminium salt is desilylated with fluoride ion in the presence of ethyl acrylate to give ethyl pyrrolizidine-l-carboxylate 295 as a mixture of stereoisomers (28%). After the epimerization of 295 with LDA, the ester moiety is reduced with lithium aluminum hydride in ether to provide (+ )-trachelanthamidine (296). A double bond can be introduced into 295 by a sequence of phenyl-selenylation at the 1-position, oxidation with hydrogen peroxide, and elimination of the selenyl moiety. The 1,2-dehydropyrrolizidine-l-carboxylate 297 is an excellent precursor of (+ )-supinidine (298) and (+)-isoretronecanol (299). Though in poor yield, 297 is directly available by the reaction of 23 with ethyl 3-chloropropenoate. 

Cyclic imines, such as 1-pyrroline (6) and A -piperidine (32), which are prone to trimerization, can be prepared from iV-halopyirolidine and iV-halopiperidine respectively and treated in situ with organoli-thium reagents to provide 2-alkylated and 2-aiylated pyrrolidines and piperidines in modest yield. Corey et al. treated substituted piperidine (17) generated in this fashion with iV-pentyllithium to establish die stereochemistry of the remote pentyl side chain of perhydrohistrionicotoxin (33), as condensation occurred from the more accessible re-face of the imine ir-system of (17). 

The trimer of 1-piperidine, best prepared by dehydrochlorination of N-chloropiperidine, has been known for some time. 1-Pyrroline also appears to exist largely as the trimer. Both undergo Mannich reactions with electron-rich heterocycles. Indole reacts with 1-piperidine in a citrate buffer to afford 3-(2-piperidyl)indole in 40-55% yield (equation 45). ° The iV-methylpiperidyl analog has also been... 

Generally speaking, piperideines and pyrrolines exist predominantly in the imine form and not in the tautomeric enamine form A -alkyl analogues have no alternative but to exist as enamines. These cyclic imines are resistant to hydrolytic fission of the C = N bond, in strong contrast with acyclic imines, but nonetheless they are very susceptible to nucleophilic addition at the azomethine carbon. An example of this is that both piperideine and pyrroline exist as trimers formed by the nucleophilic addition of nitrogen of one molecule to the azomethine carbon of a second molecule, etc. 

The trimer of 1-pyrroline reacts readily with bis(trimethylsilyl)phosphonite to yield 2-pyrrolidinylphosphinic acid (335), following the addition of aqueous methanol to the intermediate trimethylsilyl derivative (334) (Scheme 106) <94TL1103>. 

---