Pyrrolidine, /V-

Ishiguro and Sugawara (1884) had a few more amines than those listed in the Schmeltz-Hoffmann compilation because they included as aliphatic amines several cyclic amines and their alkyl derivatives, such as pyrrolidine and piperidine. However, this need not be considered a discrepancy. Examination of the structures of A-ethylethanamine (dieth-ylamine) (IV) vs. pyrrolidine (V) or A-(l-methylethyl)-2-propanamine (VI] vs. 2,5-dimethylpyrrolidine VII reveals the structural similarities (Figure XH-2). 

S,5S)-2,5-Di(naphthalen-2-yl)pyrrolidine (V) (25, 55)-2,5-Di (naphthalen-2-yl)-2,5-dihydro-liS-pyrrole 7 (0.142g, 0.442 mmol, 1 equiv) (or the corresponding HBr salt) was dissolved in CH2CI2 (10 mL) at room temperature, an oxygen atmosphere was applied (balloon), and the reaction mixture was stirred extremely... 

In 1931 Winterfeld and Kneuer, as a result of their observation that jS-lupinane can be obtained from lupanine, and the formation of 2-methyl-pyrrolidine by the oxidation of sparteine, combined these two features in a partial formula (II) for lupanine, which could be developed in various ways depending on the mode of attachment of the methylpyrrolidine residue. In view, however, of Ing s demonstration of the relationship of anagyrine, CJ5H20ON2, to Z-lupanine, CJ5H24ON2, and d-sparteine, C15H28N2, it was elearly neeessary to consider formul for lupanine derivable from the two alternati-ves, which Ing had proposed for anagyrine and which are shown below as (III) and (IV) with the formul for lupanine derived from them (V) by Ing and (VI) by Clemo and Raper. Sparteine would be represented by (V) or (VI) with the change CO CH2. 

The increase in the proportion of the tetrasubstituted isomer in the cases of the morpholine and piperidine enamines of 2-methylcyelohexanone has been ascribed to both steric and electronic factors. The authors propose that the overlap of the electron pair on the nitrogen atom and the v electrons of the double bond is much more important in the case of the pyrrolidine enamines and much less with the others. Support for this postulate was provided by the NMR spectra of these enamines, wherein the chemical shifts of the vinylic protons of the pyrrolidine enamines were at a higher field than those of the corresponding morpholine and piperidine enamines by 20-27 Hz. The greater amount of overlap or electron delocalization, in the case of pyrrolidine enamine, is in accord with the postulate of Brown et al. (7- ) that the double bond exo to the five-membered ring is more favored than the double bond exo to the six-membered ring. 

Use of the valine derived (4S )-3-acetyl-4-isopropyl-1,3-oxazolidine (8)92, the C2-symmetric reagents (2.5,55)-l-acetyl-2,5-bissubstituted pyrrolidine 994, or the doubly deprotonated acetyl urea /V-acetyl- V..V -bis[(.S)-l-phcnylethyl]urea (10), also does not lead to sufficient induced stereoselectivity combined with acceptable chemical yield. When the acetyl urea enolate is reacted with aliphatic and aromatic aldehydes, the diastereomeric adducts (ratios ranging from 1 1 to 3 1) may be separated by column chromatography to give ultimately both enantiomers of the 3-hydroxy acids in 99% ee110. 

Finally, it should be mentioned that the allylation of 2,4-disubstituted pyrrolidine derivatives proceeds with reasonable diastereosclectivity for the trans-compound 2,4-rra .v-l, but with low selectivity for the m-isomer 2,4-m-l131. 

V-( 1,3-Pen tadienyl)pyrrolidine-l-carboxamide, 59, 8 (PENTAFLUOROPHENYL)ACETO-NITRILE, 57, 80... 

Direct injection of 0.3 g/ml solutions of amines indicated that the morpholine contained 240 yg/kg of NMOR and the pyrrolidine contained 550 yg/kg of NPYR (Table V). 

P 54] A 50 gl volume of a 0.3 M solution of cyclohexanone in anhydrous methanol with about 1 mg of DCC is placed in one reservoir of a micro-mixing tee chip reactor [11] 50 gl of a 0.3 M solution of pyrrolidine is added to the other reservoir and anhydrous methanol is filled in the third, the collection reservoir. Voltages ranging from 300 to 1000 V are applied for a period of 40 min to transport the reaction species. The reaction is carried out at room temperature. 

One example of this type of reaction is the photolytically initiated decomposition of (V-chloroamines in acidic solution, which is known as the Hofmann-Loeffler-Freytag reaction 11 The initial products are 8-chloroamines, but these are usually converted to pyrrolidines by intramolecular nucleophilic substitution. 

Isomerization of the epoxide (IV) with pyrrolidine was carried out as described by Sih (8) and consistently gave yields of 35-60% rather than the 73% reported. Changes in experimental conditions including longer reaction times at lower temperatures, use of freshly distilled pyrrolidine, use of NaOH dried pyrrolidine, and use of distilled epoxide (IV) had little effect on the yield. The only variation that improved the yield was to allow the reaction to proceed at ambient temperature for a longer period of time than the recommended 3 hours. Allowing the reaction to proceed for 40 hours provided a maximum 67.5% yield. Other bases such as sodium carbonate, tri ethyl amine, diethylamine l,5-diazabicyclo[4.3.0]non-5-ene(DBN), and sodium methoxide all gave lower yields of distilled product than pyrrolidine. It is important to use the hydroxyaldehyde (V) as soon as possible since it is a very unstable material. 

Domination of the S-diastereomers for the dioxovanadium(V) Schiff base complexes being derivatives of aromatic orf/zo-hydroxyaldehydes or ketones and (S)-(+)-2-(aminomethyl)-pyrrolidine [35] was shown and the molar ratio of the diastereomers was determined by means of integration of the H signals.85... 

Diastereomerically pure (2W,5.V)-l,3-diaza-2-(2-methylphenyl)-3-phenyl-2-phosphabicyclo[3.3.0]octane (.S )-202] was formed in the thermal reaction of (S)-2-(anilinomethyl)pyrrolidines (197a) with o-TolP(NMe2)2 and isolated in 27% yield after recrystallization (Scheme 56) [87], Its cyclopalladation with palladium diacetate followed by anion metathesis gave dimer (5,5)-203 (Scheme 56) [87],... 

Reagent and conditions i, ethyl formate, MeONa, MeOH ii, sulfonylbenzene chloride, DMF iii, methylthioglycolate, MeONa, MeOH iv, dimethoxy THF, 4-chloropyridine hydrochloride, dioxane v, pyrrolidine vi, (a) POCI3, (b) 10% NaOH... 

Reagent and conditions i, diethyl chloromalonate, DMF ii, DBN, MeOH iii, AcOH, H2O iv, AcONa, diethyl aminomalonate HCI, MeOH/H20 v, MeONa, MeOH vi, 2,5-dimethoxyTHF, 4-chloropyridine hydrochloride, dioxane vii, pyrrolidine viii, (a)POCI3, (b) 10%NaOH... 

The three-component reaction between isatin 432a, a-aminoacids 433 (proline and thioproline) and dipolarophiles in methanol/water medium was carried out by heating at 90 °C to afford the pyrrolidine-2-spiro-3 -(2-oxindoles) 51. The first step of the reaction is the formation of oxazlidinones 448. Loss of carbon dioxide from oxazolidinone proceeds via a stereospecific 1,3-cycloreversion to produce the formation of oxazolidinones almost exclusively with /razw-stereoselectivity. This /f-azomethine ylide undergo 1,3-dipolar cycloaddition with dipolarophiles to yield the pyrrohdinc-2-r/ V -3-(2-oxindolcs) 51. (Scheme 101) <2004EJ0413>. 

Bayon and co-workers observed that constrained 1,2-diphosphines such as (3R,4R)-1-benzyl-3,4-/u.v(diphenylphosphino)pyrrolidine (deguphos) form dimeric complexes in addition to the expected monomeric complexes.255... 

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