3- aziridine pyrrolidine

Schwarz, H. Bohlmann, F. Mass Spectrometric Investigation of Amides. II. Electron-Impact Induced Fragm tation of (Phenylacetyl)Aziridine, -Pyrrolidine, and -Pip dine. Tetrahedron Lett. 1973, 38, 3703-3706. 

Application of allenic compounds tandem cyclizations, particularly, in ring opening of ethynylaziridines with participation of organocopper compounds, Pd-catalyzed stereoselective cyclization of allenes leading to aziridines, pyrrolidines, and benzoindoles 05YZ899. 

Enantiopure sulfinamides in asymmetric synthesis of aziridines, pyrrolidine phosphonates, and natural bioactive heterocycles 05AA93. 

Diethylenetriamine Ethanolamine Triethanolamine, Tri-isopropanolamine -Diethylamino ethanol Aziridine Pyrrolidine N-Methylpyrrolidone Piperidine, N-Methyl-,... 

Azomethine ylides (Section 4.03.6.1.1) have been generated from a wide variety of aziridines using both thermal and photochemical methods. With carbon-carbon unsaturated dipolarophiles, pyrrolines or pyrrolidines are obtained. With hetero double bonds, however, ring systems of interest to this discussion result. 

Photoelectron spectroscopic studies show that the first ionization potential (lone pair electrons) for cyclic amines falls in the order aziridine (9.85 eV) > azetidine (9.04) > pyrrolidine (8.77) >piperidine (8.64), reflecting a decrease in lone pair 5-character in the series. This correlates well with the relative vapour phase basicities determined by ion cyclotron resonance, but not with basicity in aqueous solution, where azetidine (p/iTa 11.29) appears more basic than pyrrolidine (11.27) or piperidine (11.22). Clearly, solvation effects influence basicity (74JA288). 

In aqueous solution, azetidine (p/sTa 11.29) is slightly more basic than pyrrolidine and larger-ring cyclic amines and appreciably more basic than aziridine. It forms an addition compound (m.p. - 9 to -6 °C) with trimethylboron which is more stable than that formed by pyrrolidine (50JA2926, 64HC(l9-2)885). Azetidinium salts are well known (Section 5.09.2.2.7). 

Reduction of iV-(3-bromopropyl) imines gives a bromo-amine in situ, which cyclizes to the aziridine. Five-membered ring amines (pyrrolidines) can be prepared from alkenyl amines via treatment with N-chlorosuccinimide (NCS) and then BusSnH. " Internal addition of amine to allylic acetates, catalyzed by Pd(PPh3)4, leads to cyclic products via a Sn2 reaction. Acyclic amines can be prepared by a closely related reaction using palladium catalysts. Three-membered cyclic amines (aziridines)... 

The 1,3-dipolar reagent can in some cases be generated by the in situ opening of a suitable three-membered ring system. For example, aziridines can add to activated double bonds to give pyrrolidines, for example," ... 

Scheme 22 Stereoselective synthesis of 2-(l-aminoalkyl)aziridines and 2-(l-aminoalkyl) pyrrolidines...

P-Lactams have been used as a synthon for the preparation of a vast array of compounds. It has been reported that the reduction of 4-(haloalkyl)azetidin-2-ones with LiAlhL is a powerful method for the synthesis of stereodefined aziridines and azetidines <06OL1101>. However, reduction of 4-(haloalkyl)azetidin-2-ones with chloroalane afforded 2-(haloalkyl)azetidines, which were rearranged to 3,4-cw-disubstituted pyrrolidines and piperidines 32 <060L1105>. During these rearrangements, bicyclic azetidinium intermediates were formed which were ring opened by halides. The synthesis of a peptide-... 

Similar to the fullerene modifications using either glycine/formaldehyde derivatives or oxazolidinone compounds, Maggini and Scorrano (1993) found that aziridines could yield similar pyrrolidine derivatives. Heating aziridine compounds in toluene was found to result in ring... 

Figure 15.7 The reaction of aziridine derivatives with fullerenes also can give pyrrolidine derivatives useful for...

The 1,3-dipolar cycloaddition reactions to unsaturated carbon-carbon bonds have been known for quite some time and have become an important part of strategies for organic synthesis of many compounds (Smith and March, 2007). The 1,3-dipolar compounds that participate in this reaction include many of those that can be drawn having charged resonance hybrid structures, such as azides, diazoalkanes, nitriles, azomethine ylides, and aziridines, among others. The heterocyclic ring structures formed as the result of this reaction typically are triazoline, triazole, or pyrrolidine derivatives. In all cases, the product is a 5-membered heterocycle that contains components of both reactants and occurs with a reduction in the total bond unsaturation. In addition, this type of cycloaddition reaction can be done using carbon-carbon double bonds or triple bonds (alkynes). 

Che and co-workers developed a catalytic r-selective aziridination of aromatic /V-arylirnincs with ethyl diazoacetate catalyzed by a ruthenium(ll) porphyrin complex (Scheme 75).364 The corresponding pyrrolidines were isolated as minor byproducts. 

Cyclic analogs of DMT and DET, i.e, 43 and 44, respectively, have been synthesized the aziridine 43 appears to possess activity as a CNS depressant (171), while the pyrrolidine 44 displays some behavioral activity. Compound 44 was active in Hall s open-field test but was less active than DET (38) (23). In attempts to measure hyperthermic activity, 44 was found to be rather toxic in rabbits (111). Oddly enough, no cyclic analog has ever shown activity/potency comparable to its acyclic counterpart. Thus, based only on scant animal data, cyclization of the lower dialkyl homologs apparently does not lead to marked behavioral activity. 

When the reaction is conducted in the presence of added fumarate, the yield of pyrrolidine (130) increases at the expense of the aziridine. Jacobsen suggests that the aziridines and pyrrolidines arise from a common intermediate, azo-methine ylide (132), Scheme 6, which may also be partly responsible for the poor levels of asymmetric induction in this reaction. Electrocyclic ring closure of the azo-methine while still within the coordination sphere of the metal (131) may provide aziridine with some induction, while decomplexation (132) will lead to the formation of racemic aziridine and pyrrolidine. 

The ORD curves and ECD spectra of a number of chiral methyl-substituted cyclic amines, aziridine, azetidine, pyrrolidine and piperidine, and their A-mcthyl, A-halo and A-cyano derivatives, and of (5 )-l-azabicyclo[3.1.0]hexane [(5 )-115] were measured96. 

They transformed L-serine in seven steps to the iV-2-(trimethylsilyl)ethyl-sulfonyl(SES)-protected aziridine 104. The latter reacted with the lithio-an-ion of ( )-3-phenyl-l-(phenylsulfonyl)-2-propene (105) to a diastereomeric mixture of the sulfones 106 (Scheme 27). This mixture was treated with TBAF, yielding the pyrrolidine 107 as a single diastereoisomer with 2,3-frans-2,5-czs-configuration previously observed for 5-endo-trig cyclizations of this type. In three additional steps the pyrrolidine 107 was transformed to (+)-preussin (2), with 5% yield overall and in twelve steps altogether. 

Better reagents than lithium aluminum hydride alone are its alkoxy derivatives, especially di- and triethoxyaluminohydrides prepared in situ from lithium aluminum hydride and ethanol in ethereal solutions. The best of all, lithium triethoxyaluminohydride, gave higher yields than its trimethoxy and tris(/er/-butoxy) analogs. When an equimolar quantity of this reagent was added to an ethereal solution of a tertiary amide derived from dimethylamine, diethylamine, W-methylaniline, piperidine, pyrrolidine, aziridine or pyrrole, and the mixture was allowed to react at 0° for 1-1.5 hours aldehydes were isolated in 46-92% yields [95,1107], The reaction proved unsuccessful for the preparation of crotonaldehyde and cinnamaldehyde from the corresponding dimethyl amides [95]. 

Lewis acid-promoted [3+2] cycloadditions of aziridines and epoxides proceeding via carbon-carbon bond cleavage of three-membered ring heterocycles are demonstrated for the first time. This proposal details plans for extending these initial results into a general synthetic method for the enantioselective synthesis of structurally diverse pyrrolidine- and tetrahydrofuran-containing organic compounds. Expected outcomes of the proposed work will include... 

Pyrrolidine derivatives such as 206 have been synthesized by the addition of the corresponding azomethine ylide generated by the thermal ring opening of the aziridine 205 (or similar aziridines) as shown in Scheme 4.33 [204, 210-212],... 

Similarly, Takano et al. (79) reported the intramolecular, asymmetric cycloaddition of ylides derived from thermal decomposition of aziridines 255 with the stereoselectivity rationalized by the formation of a postulated nine-membered transition state 256 in which the benzyloxymethyl group was forced into an equatorial disposition. The resultant pyrrolidine 257 contained three new stereo-genic centers, each imposed with high control (Scheme 3.87). 

C in 88% yield, the pyrrolidine analogue [300, R, R = ( 112)3] had to be heated for 1-2 days in polar solvents. The corresponding acyclic diazoamide (300, R = R = H) possessed a half-life of >10 days at ambient temperamre. The intramolecular aziridination reaction, however, could be readily achieved under catalysis using Rh2(OAc)4. 

Chiral aziridines having the chiral moiety attached to the nitrogen atom have also been applied for diastereoselective formation of optically active pyrrolidine derivatives. In the first example, aziridines were used as precursors for azomethine ylides (90-95). Photolysis of the aziridine 57 produced the azomethine ylide 58, which was found to add smoothly to methyl acrylate (Scheme 12.20) (91,93-95). The 1,3-dipolar cycloaddition proceeded with little or no de, but this was not surprising, as the chiral center in 58 is somewhat remote from the reacting centers... 

NRR = NH2, NHCy, NMe2, NEt2, aziridin-l-yl, azetidin-l-yl, pyrrolidin-l-yl, piperidin-l-yl Y = alkyl, Ph, 2-futyl, 2-thienyl... 

Chlor-2-hexensaure-ethylester reagiert mit Aziridin ohne Solvens zu l-(2-Chlor-ethyl)-2-(ethoxycarbonylmethylj-pyrrolidin, vermutlich uber eine Spiro-Zwischenstufe2. 

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