Aza-Darzens Asymmetric Synthesis of N-(p-Toluenesulfinyl)aziridine 2-Carboxylate Esters from Sulfinimines (N-Sulfinyl Imines)

Abstract

The one-step aza-Darzens reaction of sulfinimines 2 with lithium R-bromoenolates readily affords diversely substituted cis and trans N-sulfinylaziridine 2-carboxylate esters 3 and 7 in good yield and excellent diastereoselectivity. Higher yields, but lower de's, result when a mixture of the R-bromo ester and 2 are treated with base. The N-sulfinyl group is transformed, nearly quantitatively, without ring opening, into the N-tosyl activating group by oxidation with m-CPBA. Selective removal of the N-sulfinyl group in aziridines 3a and 3h with TFA/H 2 O affords 1H-aziridines 21 which are difficult to prepared by other means. However, C(3) activated azirines such as 3b undergo ringopening under these conditions. Alternatively, the N-sulfinyl group, even in C(3)-activated aziridines, was selectively and efficiently removed by treatment of the aziridine with 2 equiv of MeMgBr.

Synthesis and Rearrangement of 1,2,3‐Triheteroaryl(aryl)‐Substituted Aziridines

“…[1,2] Recently, a review on the ability of this small heterocycle to undergo ring-opening reactions with a wide variety of nucleophiles was reported. [3] The synthesis of amino acids, [4] azasugars, [5] chiral ligands, [6] natural products [7] and more generally, nitrogen-containing organic compounds are some of the main synthetic applications. Moreover, further potential applications are possible with aziridines containing heterocyclic substituents, which are capable of freeing masked carbonyl functionalities.…”

Asymmetric Synthesis of Epoxides and Aziridines from Aldehydes and Imines

“…Davis has employed the enantiopure sulfinimine N-(benzylidene)-p-toluenesulfinimine in reactions with a-halo ester enolates to obtain aziridine-2-carboxylates in good yields and with high diastereoselectivities (Scheme 1.28) [52]. The selectivities are consistent with a six-membered chair-like transition state 100, containing a four-membered metallocycle.…”

Asymmetric aziridination of N-tert-butanesulfinyl imines with phenyldiazomethane via sulfur ylides

“…Similar procedures were followed when other imines were used. 11,133.17,129.09,129.06,128.90,128.43,124.00,57.33,49.16,46.94,22.39;Anal. Calcd.…”

“…Found: C,67.81;H,6.66;N,9.21. 11,149.25,135.78,133.46,128.09,127.99,127.53,122.35,122.07,57.22,42.14,40.29,22.83;Anal. Calcd.…”

“…Examples include reactions of optically pure N-p-toluenesulfinyl imines with α-bromoenolates, 11 α-chloro-N-tert-butanesulfinyl imines with Grignard reagents,12 and N-tertbutanesulfinyl imines with various nucleophiles such as phosphonate anions, 13 allenylzinc reagents, 14 telluronium ylides, 15 and sulfur ylides. 5 However, to the best of our knowledge, asymmetric aziridine synthesis from the reaction of readily available chiral N-sulfinyl imines with diazo compounds has not been reported in the literature.…”