Vinyl aziridine

It is well known that aziridination with allylic ylides is difficult, due to the low reactivity of imines - relative to carbonyl compounds - towards ylide attack, although imines do react with highly reactive sulfur ylides such as Me2S+-CH2-. Dai and coworkers found aziridination with allylic ylides to be possible when the activated imines 22 were treated with allylic sulfonium salts 23 under phase-transfer conditions (Scheme 2.8) [15]. Although the stereoselectivities of the reaction were low, this was the first example of efficient preparation of vinylaziridines by an ylide route. Similar results were obtained with use of arsonium or telluronium salts [16]. The stereoselectivity of aziridination was improved by use of imines activated by a phosphinoyl group [17]. The same group also reported a catalytic sulfonium ylide-mediated aziridination to produce (2-phenylvinyl)aziridines, by treatment of arylsulfonylimines with cinnamyl bromide in the presence of solid K2C03 and catalytic dimethyl sulfide in MeCN [18]. Recently, the synthesis of 3-alkyl-2-vinyl-aziridines by extension of Dai s work was reported [19]. 

Note that the first example bears out the stereochemical prediction made earlier. Only the two isomers shown were formed. In the second example, migration can > continue around the ring. Migrations of this kind are called circumambulatory rearrangements. Such migrations are known for cyclopentadiene, pyrrole, and phosphole derivatives.[1,5] Hydrogen shifts are also known with vinyl aziridines." ... 

An indirect nucleophilic opening is depicted in Scheme 24. The functionalized vinyl aziridine 37 undergoes a Michael-initiated ring closure (MIRC) reaction upon treatment with suitable nucleophiles to give cyclopropanes with concomitant opening of the aziridine ring [34]. 

Various EADIs have been synthesized using different synthetic routes [30-34], One of the widely used methods of preparation of E-alkene peptide bond isosteres involving ring opening of vinyl aziridines by cuprates has recently been reviewed [35,36],... 

T.C. Henninger, P. Wipf, ( )-Alkene peptide bond isosteres by cuprate opening of vinyl aziridines. Methods Mol. Med. 23 (1999) 125-136. 

TrihydroxyheIiotridane-6,7-0-acetonide (351) was synthesized using the same method (67) (Scheme 9.67). When refluxed in benzene, the azide 348 afforded the diastereomeric vinyl aziridines 349 in 44% yield. On FVP of vinyl azrridine (349) followed by catalytic reduction and subsequent LiAUTj reduction of the ester group, trihydroxyheliotridane-6,7-0-acetonide (351) was formed in 34% yield. 

Sodium iodide catalyses a regioselective cycloaddition of cyclopropenes with (g) imines, to give c -vinylic aziridines.66... 

Vinyl aziridines have been prepared trans- and diastereo-selectively by reaction of N -/ - h u tv I sul 1 i n v limin e s with telluronium ylides.75... 

Nal catalyses the regioselective 1 + 2-cycloaddition of cyclopropenes with imines to yield cw-vinylic aziridines.205 The synthesis of a new series of mixed Rh(II)2... 

Similar developments were possible for the amines 28, which either formed dihydropyrroles 29 or vinyl aziridines 30 (Scheme 8) [25]. Here also the reaction heavily depends on the solvent, but no explanation has been provided so far. 

This nitrene-addition approach was used by Knight to synthesize vinyl aziridines from 1,3-dienes using PhI=NTs and a copper catalyst. The more electron-rich double bond is selectively transformed in most cases. When the electronic difference is negligible the regioselectivity is then determined by steric hindrance. A mixture of cis and tram isomers is usually obtained [95SL949],... 

Reaction of the quinone (12) with vinyl aziridine affords the dihydroazepinoquinone (14) in good yield <95TL4787>. The reaction proceeds via an aza-Claison rearrangement of the intermediate (13) followed by a sigmatropic rearrangement (Scheme 2). 

One straightforward route to the aziridine ring system is available through the ring closure of vicinal amino alcohols, an approach which has been used to prepare vinyl N-H aziridines. Thus, 4-amino-l-phenylhex-5-en-3-ol (111) was treated with sulfuryl chloride to provide the sulfamidate 112, which underwent clean thermolysis at 70 °C to form the vinyl aziridine 113 in 97% overall yield <02T5979>. 

Other useful nucleophiles for the ring opening of aziridines include bromide, as shown in the Amberlyst-15 catalyzed reaction of lithium bromide with vinyl aziridine 167 <02TL5867> and hydride, which can be delivered by lithium triethylborohydride. This is illustrated by the conversion of tosyl azabicyclo[3.1.0]hexene 169 to the corresponding protected cyclopentenyl amine (170) in 79% yield <02TL723>. 

The loss of CO, S, SO, SO2, SO3, and N2 by thermolysis or photolysis has been used to make three- and four-membered rings for example, the cyclic sulfamidate 94 undergoes clean thermolysis at 70 C to form the vinyl aziridine 95 in excellent yield <2002T5979, CHEC-III(1.01.6.5)79> and Wolff rearrangement of diazo compounds 96 gives -lactams 97 (Scheme 51) <1973J(P1)2024>. 

Imines can readily serve as aziridine precursors via an aza-Darzens or Darzens-like approach. Vinyl aziridines were synthesized in 57 to 77% yield by reacting ylides generated from substituted allyltetrahydrothiphenium salts with V-(dimethylsulfamoyl)phenyl imine <07SL2879>. Aziridines carrying two or three heteroaryl groups were synthesized on the basis of the Darzens reaction between imines and a-chloroalkyl heterocycles <07EJO5926>. 

A novel Pd-catalyzed asymmetric annulation was reported between 5-bromopyrrole-2-carboxylate esters and vinyl aziridines <07OL2357>. The resulting pyrrolopiperazinones such as 58 served as key intermediates in the enantioselective synthesis of longamide B and a number of other pyrrole alkaloids. 

The reaction of azides with 1,3-dienes affords vinyl aziridines (through nitrene or azide cycloaddition), which can be converted to dihydropyrroles. It is also possible that dihydropyrroles are directly produced from azidodienes. 

Coldham et al. <1995TL3557> and Somfai <1994CC2785, 1995TL1953> have independently investigated the ring expansion of vinyl aziridines to piperidines. Thus, Coldham et al. have prepared the unsaturated air-piperidines... 

A dynamic kinetic asymmetric transformation (DYKAT) of racemic vinyl aziridine 347 yielded the enantiopure imidazolidinone 348 (Scheme 90) <20050L823>. This transformation was the initial step in a total synthesis of (+)-pseudodistomin D. 

Cyclic and acyclic enol derivatives 480 can be asymmetrically aziridinated with (A -tosylimino)iodobenzene 481 using a chiral copper catalyst prepared in situ from [Cu(MeCN)4]PF6 and the optically active ligand 479. Collapse of the aminal (i.e., 482) leads to the formation of enantiomerically enriched Q-amino carbonyl compounds 483, although ee s to date are modest <2000EJ0557>. Similarly, dienes can be selectively aziridinated using the chiral Mn-salen complex 484 to give vinyl aziridines 486 in scalemic form (Scheme 124) <2000TL7089>. 

In a typical example for aziridine synthesis,, y-allyl tetrahydrothiophenium bromide 618 was smoothly deproto-nated with strong base to provide an ylide which adds to a variety of N-protected imines. For the iV-tosyl aldimine 619 derived from isovaleraldehyde, the corresponding vinyl aziridine 620 is formed in fair yield as a mixture of stereoisomers (Scheme 151) <2004TL1589>. 

Additions of nucleophiles to vinyl aziridines provide the issue of selectivity of 1,2 (Sn2) or 1,4 (Sn2 ) additions. During a very short efficient synthesis of pancratistatin, Hudlicky et al. chose to open a vinylaziridine 156 with an aromatic cuprate 157 <1996JA10752>. Formation of the trans-, Z adduct 158 was accomplished in 75% chemical yield (Equation 42). They found that the addition of simple lower order cuprates or Grignard reagents (aliphatic or aromatic) reacted to give the syn-, A addition, whereas higher-order cuprates gave the trans-, Z product. 

The reaction of simple cyclic vinyl aziridines with organozinc reagents typically provides the 1,4-addition product <2003TL8559>. Several binaphthyl phosphoramidate ligands were examined. In all cases, the /ra r-product 159a was the major product. When no catalyst was used a roughly 1 1 mixture of the trans. cis product was obtained. The use of the chiral phosphoramidate catalyst provided 159a with moderate % ee values (Equation 43). 

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