Reduction aziridines

Asymmetric variants of imine reduction have also been developed towards enantiopure aziridines. Reduction of chiral /V-tert-butanesulfinyl a-halo imines afforded enantiopure aziridines in good to excellent yields <07JOC3211>. Enantioselective catalytic reduction of a-chloroimines utilizing metal-free L-valine-derived formamide 45 followed by base-mediated ring closure provided aziridines with preserved enantiopurity <07AG(I)3722>. 

An interesting variation of the aza-Corey-Chaykovsky reaction provides a pathway to difluoromethyl-substituted aziridines. Reduction of trifluoromethylimine 143 with magnesium in the presence of chlorotrimethylsilane gave the enamine 144. Treated with dimethyloxosulfonium methylide in DMSO, 144 hrst underwent desilylation and tautomerization to produce imine 145, which then afforded aziridine 146 via the aza-Corey-Chaykovsky reaction in 92% yield. 

Ar. ketals and thioketals, ar. and aliphatic epoxides, and ar. aziridines can be rapidly and conveniently reduced by alkali metals in liq. NHg. - E A soln. of 5 equivalents Na in liq. NHg added to a soln. of benzophenone ethylene ketal in ether, and the product isolated after 3 hrs. diphenylmethane. Y 94%. F. e., also alcohols from oxido comps., and amines from aziridines, as well as an anomalous aziridine reduction, s. E. M. Kaiser et al., J. Org. Chem. 36, 330 (1971). 

In some cases, the /3-haloamine undergoes spontaneous cyclization to the aziridine <70TL1125>. Most of these routes, however, require either reductive or base-induced cyclization to the aziridine. Access to a vast number of aziridines and 1-azirines has been... 

Aziridine, cis-7V-t-butyl-3-ethynyl-2-vinyl-rearrangement, 7, 540 Aziridine, 2-chlorocarbonyl-ring expansion, 7, 42 Aziridine, 2-chloromethyl-synthesis, 7, 42 Aziridine, Mcyanodiphenyl-irradiation, 7, 61 Aziridine, dihalo-reduction, 7, 74 thermolysis, 7, 73... 

Iodine azide, on the other hand, forms pure adducts with A -, A - and A -steroids by a mechanism analogous to that proposed for iodine isocyanate additions. Reduction of such adducts can lead to aziridines. However, most reducing agents effect elimination of the elements of iodine azide from the /mwj -diaxial adducts of the A - and A -olefins rather than reduction of the azide function to the iodo amine. Thus, this sequence appears to be of little value for the synthesis of A-, B- or C-ring aziridines. It is worthy to note that based on experience with nonsteroidal systems the application of electrophilic reducing agents such as diborane or lithium aluminum hydride-aluminum chloride may yet prove effective for the desired reduction. Lithium aluminum hydride accomplishes aziridine formation from the A -adducts, Le., 16 -azido-17a-iodoandrostanes (97) in a one-step reaction. The scope of this addition has been considerably enhanced by the recent... 

The properties of chlorine azide resemble those of bromine azide. Pon-sold has taken advantage of the stronger carbon-chlorine bond, i.e., the resistance to elimination, in the chloro azide adducts and thus synthesized several steroidal aziridines. 5a-Chloro-6 -azidocholestan-3 -ol (101) can be converted into 5, 6 -iminocholestan-3l -ol (102) in almost quantitative yield with lithium aluminum hydride. It is noteworthy that this aziridine cannot be synthesized by the more general mesyloxyazide route. Addition of chlorine azide to testosterone followed by acetylation gives both a cis- and a trans-2iddMct from which 4/S-chloro-17/S-hydroxy-5a-azidoandrostan-3-one acetate (104) is obtained by fractional crystallization. In this case, sodium borohydride is used for the stereoselective reduction of the 3-ketone... 

The azidohydrins obtained by azide ion opening of epoxides, except for those possessing a tertiary hydroxy group, can be readily converted to azido mesylates on treatment with pyridine/methanesulfonyl chloride. Reduction and subsequent aziridine formation results upon reaction with hydrazine/ Raney nickel, lithium aluminum hydride, or sodium borohydride/cobalt(II)... 

A number of nonfused steroidal aziridines have been synthesized. The reduction of the azirine (118) over a platinum catalyst yields the spiro aziridine (119). Several aziridine derivatives of the type (120) have been... 

Amino alcohols are also good substrates for aziridination under Mitsunobu conditions. The rfs-1,4-amino alcohols 48, obtained by reductive cleavage of the nitrogen-oxygen bonds of the hetero Diels-Alder adducts 47, underwent syn-SN2 -type displacement on treatment with PPh3 and DEAD to give cyclic vinylaziridines 49 (Scheme 2.15) [27]. 

Unsaturated oximes are attractive substrates for aziridine synthesis. Treatment of oxime 77 with Red-Al yielded vinylaziridines 78, 79, and 80, in various ratios depending on the E/Z ratio of the starting oxime 77 (Scheme 2.22) [38]. This reaction should proceed through abstraction of HA, Hb, or He in the intermediate 81, followed by hydride reduction of the resulting 2H-azirines 82-84. 

The first of the nudeophilic ring-opening reactions of vinylaziridines discussed in this section is diborane reduction, developed by Laurent and coworkers in 1976 (Scheme 2.24). Treatment of N-unsubstituted vinylaziridines 89 with B2H6 gives allyl amines 92 by SN2 reduction via cyclic intermediates 90 [40]. In contrast, treatment with 9-BBN gives 2-(hydroxyethyl)aziridines 93 after oxidative workup (Scheme 2.25) [41]. 

A general method for the synthesis of N-unsubstituted aziridine-2-carboxylates involves a triphenylphosphine-mediated reductive cyclization of hydroxy azido esters [17-22]. A recent example involves the treatment of [1-hydroxy-a-azido ester 15 (Scheme 3.6) with PPh3 to give aziridine 16 in 90% yield [19]. a-Hydroxy- 3-azido esters undergo similar reactions to give aziridine-2-carboxylates [20-22],... 

Reduction of azirine-2-phosphonates 99 (Scheme 3.32) with NaBH4 in ethanol exclusively gave ris-aziridine-2-phosphonates 100 in 81-82 % yield [86, 87]. A Diels-Alder reaction between azirine-2-phosphonate 101 and trans-piperylene 102... 

Reductive aziridine ring-opening with sodium cyanoborohydride has been described [74, 91]. In the presence of a catalytic amount of TsOH, compound 111 (Scheme 3.37) gave 112 in 68% yield on treatment with sodium cyanoborohydride [74, 91]. 

The chemistry of metalated aziridines is far less developed than the chemistry of metalated epoxides, although from what is known [lb], it is obvious that their chemistry is similar. Like metalated epoxides, metalated aziridines can act as classical nucleophiles with a variety of electrophiles to give more highly substituted aziridines (Scheme 5.56, Path A). A small amount is known about how they can act as electrophiles with strong nucleophiles to undergo reductive alkylation (Path B), and undergo C-H insertion reactions (Path C). 

O Brien et al. provided the first examples of olefin formation by reductive alkylation of aziridines [97]. Treatment of aziridine 267 with s-BuLi gave olefin 270 in 76% yield (Scheme 5.68). For the formation of olefin 270 they suggest a reaction pathway that proceeds in a manner analogous to that proposed for epoxides [36] namely, nucleophilic attack of s-BuLi on lithiated aziridine 268 to form dilithiated species 269, which eliminates Li2NTs (TsNH2 was observed as a product of this reaction) to yield olefin 270. 

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)... 

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