Catalytic and thermal hydrocarbonation of methyleneaziridines

Reaction of the methyleneaziridine 1 with carbon pronucleophiles ( 2 , H-CR 3 ) proceeds smoothly in the presence of a palladium catalyst affording the corresponding hydrocarbonation products 5 in good to high yields. In the absence of palladium catalysts, the reaction of 1a with 2a at 120 °C afforded the ring opened product 9 in good yield


Introduction
2-Methyleneaziridines are small-ring compounds containing a nitrogen atom, which have high ring strain.It is known that the ring opening of methyleneaziridines with Grignard reagents (or organolithium compounds), 1a-d acid chlorides, 1e-f and HCl 1g occurs through N-C3 bond cleavage (eq 1), while ring opening with HOPh proceeds through N-C2 bond cleavage 1h (eq 2).Accordingly, the normal reaction of 2-methyleneaziridines with nucleophiles produces ringopened derivatives.Recently we reported that the reaction of the methyleneaziridines 1 with carbon pronucleophiles 2 proceeds smoothly in the presence of a palladium catalyst to give, in good-to high yields, the ring products 5 (eq 3). 2 Formally, this is a hydrocarbonation reaction of the double bond of 1 with carbon pronucleophiles.In this paper, we report the detailed study of the palladium-catalyzed hydrocarbonation of methyleneaziridines together with an attempt at asymmetric hydrocarbonation using chiral phosphine ligands.
c the diastereomeric ratio of 5g.

Scheme 1
The reaction with deuterated methylmalononitrile (2a-d, 90% D) substantiated the proposed mechanism.The reaction of 1a with 2a-d under the same reaction conditions as above gave 5a-d in 82% yield, in which the deuterium content was 76% (eq 6).Interestingly, the thermal reaction of 1a with 2a without any palladium catalyst in THF at 120 °C for 4 days gave the vinylic amine 9 in 73% yield (eq 7).These ring opening reactions of the methyleneaziridine most probably occurred by the nucleophilic addition of the carbanion derived from 2a to the C-3 position of the protonated methyleneaziridine, 10. 1 It is now clear that the palladium catalyzed and thermal reactions of 2a with 1a take totally different reaction courses; the Lewis acidic Pd(II)-nitrogen interaction (7) leads to 5a while the Brønsted acid H +nitrogen interaction (10) gives 9.The addition of carbon pronucleophiles to activated alkenes catalyzed by transition metals, that is the Michael addition, is known. 5Recently, we and other groups reported the palladium catalyzed addition of carbon pronucleophiles 2 to unactivated olefins such as allenes, 6 enynes, 7 methylenecyclopropanes, 8 and 1,3-dienes. 9The driving force for these reactions originates in the formation of stable π-allylpalladium complexes.The present hydrocarbonation reaction does not proceed through the formation of a π-allylpalladium intermediate, but most probably proceeds via a chelation effect of the nitrogen atom of the aziridine moiety.

Conclusions
We have developed the direct hydrocarbonation of methyleneaziridines 9 using carbon pronucleophiles in the presence of a palladium catalyst.The palladium-catalyzed reaction provides geminally disubstituted functionalized aziridines, while traditional reactions give ringopening products upon treatment with nucleophiles.

General procedure for the addition of the active methyne 1 to methyleneaziridines 4
To a solution of Pd(PPh 3 ) 4 (28.9 mg, 0.025 mmol), triphenylphosphine oxide (13.9 mg, 0.05 mmol) and active methyne 1 (0.5 mmol) in THF (1 mL) was added methyleneaziridine 4 (0.75 mmol) under Ar atmosphere in pressure vial.After heating at 120 °C for 4-15 hours, the reaction mixture was filtered through a short Florisil column using ethyl acetate as an eluent.Separation by passing through a Florisil column using n-hexane-ethyl acetate as eluent.The stereochemistry of 5j was determined by NOE experiment as shown in Figure 1.We could not measure an NOE experiment for the minor diastereoisomer of 5k because of overlap of the peaks.The ORTEP drawing of the major diastereomer of 5k is shown in Figure 3.

Figure 3 .
Figure 3. ORTEP drawing of the major isomer of 5k.

Table 1 .
Palladium catalyzed hydrocarbonation of 1 with 2 a

Table 2 .
Asymmetric hydrocarbonation of 1a with 2a a