Scope and limitations in sulfur ylide mediated catalytic asymmetric aziridination of imines: use of phenyldiazomethane, diazoesters and diazoacetamides†

Abstract

Imine aziridination using diazo-compounds and catalytic quantities of metal salts and sulfides has been investigated. A range of imines derived from benzaldehyde bearing electron-withdrawing groups (N-Ts,CCl 3 ) were prepared and tested in the aziridination process using Me 2 S and phenyldiazomethane. High yields were obtained with all imines but diastereoselectivity varied considerably (3 : 1->10 : 1). A range of N-SES imines were tested with stoichiometric amounts of sulfides and high yields were obtained with both aromatic and aliphatic imines. These imines were subsequently tested with stoichiometric and sub-stoichiometric loadings of enantiomerically pure 1,3-oxathiane 3 with Rh 2 (OAc) 4 and with Cu(acac) 2 . Good yields and high enantioselectivities (89-95%) were observed with Rh 2 (OAc) 4 , although a small reduction in enantiomeric excess was observed with Cu(acac) 2 (85-95%) especially when sub-stoichiometric amounts of sulfide were employed. The same sulfide was also tested with a range of electron-withdrawing groups on the imine nitrogen and in all cases good yields and high enantioselectivities were maintained. Improved diastereoselectivity was observed with carbamate groups.The aziridination process was extended to include diazoester and diazoacetamides with a range of N-Ts imines, and again good yields were obtained although diastereoselectivity varied according to the diazo-compound employed. Although the 1,3-oxathiane 3 could not be employed with these more stable diazo-compounds, (R,R)-2,5-dimethylthiolane 5 was found to be a suitable chiral catalyst and gave moderate enantio-and diastereoselectivities. Rationales for the origin of the diastereoselectivity and enantioselectivity are provided. Scheme 1 Atkinson's aziridination. Scheme 2 Darzens-type addition of a bromoacyl sultam. Reagents and conditions: (i) RCH᎐ ᎐ NP(O)Ph 2 , LiHMDS, THF, Ϫ78 ЊC, 47-87% yield.

Tuning Electronic and Steric Effects: Highly Enantioselective [4+1] Pyrroline Annulation of Sulfur Ylides with α,β‐Unsaturated Imines

“…[11] To our knowledge, almost all previous endeavors with unstable or semistabilized ylides have suffered from the kinetic preference to form aziridines or cyclopropanes (Scheme 2 a). [12,13] Therefore the [4+1] annulation between sulfur ylides and a,b-unsaturated imines to synthesize pyrrolines remains a stimulating challenge.…”

Asymmetric Syntheses with Aziridinecarboxylate and Aziridinephosphonate Building Blocks

“…A number of chiral ligands have been developed and studied for this purpose [46][47][48][49][50][51][52][53][54]: some examples include bis(oxazoline) 39 (Scheme 3.13) [46,47], biphenylimine 40 [48,49], and binaphthylimine 41 [50]. Treatment of 42 with PhI=NTs in the presence of CuClO 4 and ligand 41, for example, gave 43 in 91 % yield and 97 % ee [50].…”

“…An asymmetric version of this reaction using chiral nonracemic catalysts has been described [53,[56][57][58]. As an example, catalytic aziridination of imine 44 (Scheme 3.14) with ethyl diazoacetate in the presence of 10 % catalyst generated Scheme 3.13 Scheme 3.14 from triphenylborate and ligand 45 afforded aziridine-2-carboxylate 46 in 80 % yield [57].…”

Recent Advances in Catalytic Asymmetric Addition to Imines and Related C=N Systems

“…The same group also described the use of ethyl diazoacetate as carbene source [329]. Although the reactivity of the corresponding ester-stabilized chiral sulfur ylide derived from 132a was low, switching to the C 2 -symmetric chiral tetrahydrothiophene 132b showed good reactivity with a range of N-tosylimines.…”