Aziridin-2-yl methanol

A series of enantiomericaUy pure aziridin-2-yl methanols (e.g., 53) have been used as organocatalysts in Diels-Alder reactions of cyclopentadiene and a, i-unsaturated aldehydes by Bonini, et al. Scheme 3.20 [33]. However, moderate ees were obtained. 

After the success of Macmillan s catalysts, other types of chiral amine were disclosed and applied in the FCA reaction as activators of a,(3-unsaturated aldehydes. Reports from a few groups have revealed that diaryIprolinol silyl ethers [11], camphor sulfonyl hydrazine [12], chiral aziridin-2-yl methanols [13], and A-isopropylated bipyrrolidine [14] were efficient catalysts in the enantioselective alkylations of 4,7-dihydroindoles, 1-naphthols, and indoles. NEt3, benzoic acid, or... 

Much work in the review period has concerned enantioselective substitution in five-membered heterocyclics. The enantioselective alkylation of some pyrroles by unsaturated 2-acylimidazoles catalysed by the bis(oxazolinyl)pyridine-scandium(in) triflate complex (31) has been reported.39 Compound (33) is formed in 98% yield and 94% ee from the 2-acylimidazole (32) and pyrrole at —40 °C. A series of enantiomer- ically pure aziridin-2-ylmethanols has been tested as catalysts in the alkylation of /V-mclhylpyrrolc and (V-methylindole by ,/l-unsalura(cd aldehydes.40 Enantiomeric excesses of up to 75% were observed for the alkylation of /V-mcthylpyrrole by ( >crotonaldehyde using (2.S ,3.S )-3-mclhylazirin-2-yl(diphenyl)methanol TFA salt as catalyst to form (34). 

Elimination followed by nucleophilic addition to a strained C-C double bond was the main reaction sequence observed when a 1 3 mixture of (2-bromo-5-methyltetracy-clo[3.2.0.0 . 0 ]hept-l-yl)methanol and (7-bromo-5-methyltetracyclo[3.2.0.0 .0 ]hept-l-yl)methanol was allowed to react with a large excess of lithium aziridide. The main product, identified as 2-(aziridin-l-yl)-5-methyltetracyclo[3.2.0.0 -. 0" ]hept-l-yl methanol (13) and isolated in 21% yield, most likely results from aziridide attack on the intermediate lithium 5-methyltetracyclo[3.2.0.0 .0" ]hept-2(7)-en-l-yl)methoxide at C2. ° The other main product, 3-(aziridin-l-yl)-l-methyl-4-oxatetracyclo[4.3.0.0 .0 ]nonane (14), which was isolated in 15% yield, conceivably originates from the same intermediate as outlined above. Acyclo-propene intermediate was probably also formed when l-chloro-5-methyl-exo-6-phenyl-3-oxabicyclo[3.1.0]hex-2-one reacted with lithium 2,2,6,6-tetramethylpiperidide (LTMP) and gave 5-methyl-e.vo-6-phenyl-l-(2,2,6,6-tetramethyl-l-piperidyl)-3-oxabicyclo[3.1.0]hex-2-one (15) in 66% yield. 

The reaction of 3-bromo-5-methoxy-17f[l,2,4]triazole (218) with l-benzyl-2-methoxycarbonyl-aziridine (219) in the presence of boron trifluoride diethylether complex leads to an unseparable mixture of the two isomeric alkylation products methyl 2-benzylamino-3-bromo-5-methoxy-l,2,4-triazol-l-yl)propionate (220) and methyl 2-benzylamino-3-(5-bromo-3-methoxy[l,2,4]triazol-l-yl)-propionate (221). Treatment of the unseparated mixture with hydrogen chloride in methanol affords methyl 4-benzyl-5,6-dihydro-2-methoxy-5-methoxy-carbonylimidazo[l, 2-6][l, 2,4]triazole (222 R = H) <92TA51>. Under identical reaction conditions the use of 2-(S)-methoxycarbonyl-l-(/ )-phenylethylaziridine (5,R-(219)) results in a reaction mixture from which the bicyclic product S,R (222) R = Me) is isolated (Scheme 18) <92TA5l>. 

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