A-Arylaziridines

A -Arylaziridines were synthesized in very good yield by palladium-catalyzed N-arylamination reactions utilizing BINAP or xantphos as suitable ligands and either CS2CO3 or NaO/-Bu as a base <07S243>. 

The dipole moments of aziridine (1) and 1//-azirine (3) were calculated to be 1.92-1.94 D and 2.29-2.31 D, respectively, using ab initio MO methods (87JPC6484, 88JST(165)99, 89JCC468). These studies also estimated the dipole moments of the planar transition states attained during pyramidal inversion to be 0.21 D and 0.56 D, respectively, for (1) and (3). The value for aziridine compares with the known experimental value of 1.89 D. The dipole moment of 2//-azirine has also been estimated by theoretical methods <84CHEC-I(7)47>. Dipole moment measurements have been used to determine the preferred conformation of A-arylaziridines <7UCS(B)2104>. 

MO methods have been used to calculate dipole moments of each of the three ring systems (73MI50403, B-70MI50400). Calculated values for aziridine are somewhat higher (2.09-2.40 D) than the known experimental value (1.89 D). Dipole moment studies on a few simple aziridines have led to the determination of the preferred conformation of N-arylaziridines in solution and in the vapor state (71JCS(C)2104, 66DOK(169)839). For the 1-azirine system, no values have been determined experimentally, but values of 2.40-2.56 D for 1-azirine and 2.50-2.51 D for 2-azirine have been calculated (73MI50403). 

This area of research has only recently attracted the attention of synthetic organic chemists, but there has been a flurry of impressive activity in the area. Simple (i. e., unstabilized) carbenes suffer from many of the problems of nitrenes (vide infra) and most reported synthetically useful procedures use carbenoids the majority of recent reports have focussed upon reactions between a-diazoesters and imines in the presence of a range of catalysts. In one of the earliest reports of enantioselective carbene-imine reactions, for instance, Jacobsen and Finney reported that ethyl diazoacetate reacts with N-arylaldimines in the presence of cop-per(i) hexafluorophosphate with mediocre stereoselectivity to give N-arylaziridine carboxylates. Though the diastereoselectivities of the reaction were often acceptable (usually >10 1, in favor of the cis isomers) the observed enantioselectivity was low (no more than 44% ee Scheme 4.27) [33],... 

P-Iodo azides can be reduced to aziridines with LiAlH,682 or converted to N-alkyl- or N-arylaziridines by treatment with an alkyl- or aryldichloroborane followed by a base.683 In... 

The asymmetric aziridination of a, P-unsaturated carboxylic acid derivatives is a direct route to optically active aza-cyclic a-amino acids, and this class of chiral aziridines can also be used as chiral building blocks for the preparation of other amino acids, P-lactams, and alkaloids. Prabhakar and coworkers carried out an asymmetric aziridination reaction of tert-butyl acrylate with O-pivaloyl-N-arylhydroxylamine 25 in the presence of cinchonine-derived chiral ammonium salt 2e under phase-transfer conditions, which furnished the corresponding chiral N-arylaziridine 26 with moderate enantioselectivity (Scheme 2.24) [46],... 

Biotransformation can serve as an alternative route towards enantiopure aziridines. (1R,25)-1 -Benzyl- and l-arylaziridine-2-carboxamides were obtained in enantiomerically pure form via kinetic resolution of their racemates by Rhodococcus rhodochrous IFO 15564 catalyzed hydrolysis <07OF521>. Rhodococcus erythropolis AJ270 was reported as an efficient whole cell catalyst for the synthesis of highly enantiopure 5,-l-arylaziridine-2-carboxamides and A-l-arylaziridine-2-carboxylic acids <07JOC2040>. Enantiopure 2-... 

Expansion of aziridines to -lactams. This rhodium complex catalyzes a regio-specific carbonylation of N-f-butyl-2-arylaziridines (1) to form lactams (2). The reaction fails if the alkyl group on nitrogen contains acidic hydrogens adjacent to nitrogen. 

More recently, Takeda et reported [Pd(SlPr)(cin)Cl)] (39) to be highly efficient in the regioselechve and stereospecific cross-coupling of enantiopure 2-arylaziridines with arylboronic acids. Using 4 mol% of the pre-catalyst, a variety of chiral 2-aryl-phenethylamine derivatives were produced under mild reaction conditions in high yield and with excellent enantioselectivity (up to 99% ee, Scheme 17). Electron neutral and electron deficient aziridines and sterically encumbered and/or funchonalized aryl boronic acids were all well tolerated under the developed conditions. 

With the same type of PT catalyst Aires-de-Sousa et al. [43] described recently an enantioselective synthesis of N-arylaziridines starting from W-acylarylhydrox-ylamines in a PT system of NaOH/toluene. High conversion needs highly concentrated NaOH (>33%) and yielded only up to 50% ee. Decreasing the NaOH... 

A method for the synthesis of cw-jV-arylaziridines involves sequential condensation of a substituted chloro p-tolyl sulfoxide and an aromatic imine, cyclization with Bu OK and desulfinylation with ethylmagnesium bromide (Scheme 20).48 Treatment of 1-chloroundecanyl p-tolyl sulfoxide with LDA (-40 C) followed by benzalaniline (89 Ar1 = Ar2 = Ph) affords the corresponding crystalline adduct (90) as a single diastereomer (94% yield). Cyclization provides the sulfinylaziridine (91) in 87% yield desulfinylation (-55 to -35 °C, 2 h) provides stereospecifically (retention) the m-aziridine (92) in 95% yield. Several related examples are provided in which products are obtained stereospecifically in similar yields. 

The benzylic position of 2-arylaziridines is readily lithiated. A-Substituted trans-2,3-diphenylaziridines afford diastereomers according to the solvent used (whether HMPA is present). More dramatic differences are observed in the case of aziridines bearing an oxazoline substituent at C-2. ... 

N-Tosyl-2-aryl-4-pentenylamines Lewis acid-catalyzed opening of ALtosyl-2-arylaziridines in the presence of allyltrimethylsilane gives a mixture of the pentenylamines and 4-aryl-2-trimethylsilylmethylpyrrolidines. A homogeneous product is obtained on treating such a mixture with TBAF. 

Mono- and disubstituted N-alkyl and N-arylaziridines are reported to undergo a photoinduced electron transfer [3+2] cycloaddition to dipolarophiles to produce five-membered heterocycles, and it is suggested that in this process the radical cation intermediate behaves differently from the corresponding classical azomethine ylide. Intramolecular [4+4] photocycloaddition of the dipyridyl-propane (73) followed by Li/NHa reduction is a useful route to the eleven-membered ring system (74), and on irradiation of benzene solutions of 2,3-dicyano-5,6-dimethylpyrazine in the presence of allylic silanes a [2+2] cyclisation is induced followed by rearrangement to give 2,8-diazatricyclo[3.2.1.0 ]oct-2-ene (75 R = H, Me). ... 

The products reported as obtained from (l-alkyl-3-arylaziridin-2-yl)-arylmethanone tosylhydrazones 271 <1996H(43)305> and semicarbazones 272 <1994NKK893>, respectively, by treatment with boron trifluoride etherate are not tetrahydro-l,2,3-triazines 269 and 270 but 2,3,4,5-tetrahydro-l,2,4-triazines 273 and 274 (Equation 119), as proven by a single crystal X-ray structural analysis for 273 (R = f-C6Hn, Ar = Ar = Ph)... 

The analogous additions of a-sulfinyl carbanions to imines have provided asymmetric access to fV-arylaziridines [81] and have been applied to natural product synthesis [82]. 

Murugan and coworkers developed a new procedure for asymmetric aziridination reactions to achieve excellent levels of enantioselectivity using a new type of catalysts 8v and 7l, derived from cinchonine and cinchonidine, respectively. Substituted Al-arylaziridine derivatives were synthesised enantioselectively from AI-acyl-N-atylhydro qrlamine and electron deficient olefins in the presence of their novel PTC catalysts (Scheme 16.40). °... 

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