Formal C – H Amination of Cyclopropenes

alkene feedstocks can be transformed to a nitrogen-containing molecules, invites vibrant academic and industrial interests. Due to the relatively weaker allylic/bisallylic C–H bonds, their selective functionalization to C–N bonds is possible with either electrophilic nitrogen sources or nitrogen nucleophiles 15 in combination with electrophilic metal catalysts. In this context, we were intrigued by the C–H amination of cyclopropenes (1 → 2 or 3) because, in its nature, the C(3)–H bond in cyclopropene 1 is bisallylic, therefore, its reactivity should mirror that of typical bisallylic C–H bonds. 20

context, we were intrigued by the C-H amination of cyclopropenes (1 → 2 or 3) because, in its nature, the C(3)-H bond in cyclopropene 1 is bisallylic, therefore, its reactivity should mirror that of typical bisallylic C-H bonds.

Scheme 1 Allylic C-H amination
Cyclopropenes have high chemical reactivity: 4 the unsubstituted parent cyclopropene undergoes dimerization and polymerization even at -25 °C.5a Substituted cyclopropenes are more stable, yet they dimerize at higher temperature.5b-5e A radical 5b and an Alder-ene mechanism 5a were proposed, and comprehensive quantum mechanical studies by Dowd and Houk 6 provided good mechanistic pictures into these processes.Despite the broad theoretical and mechanistic interests in dimerizations of cyclopropenes, 7 only sporadic ene reactions with other enophiles were reported. 8o gauge the cross ene reactivity of cyclopropenes, citronellal-derived silyl cyclopropene 1a 9 was treated with diisopropyl azodicarboxylate (DIAD, 1.1 equiv) in CDCl 3 at 45 o C (entry 1 in Table 1).After 40 hours two products were isolated, which were identified as 2a and 3a.Surprisingly, the major product 2a was not the expected ene product but a C-H amination product, although the minor compound 3a was indeed derived from the expected ene reaction.The high  For a specified period of time at rt followed by silica gel treatment. 11emoselectivity for the cyclopropene moiety over the trisubstituted alkene is noteworthy. 10ith this encouraging result, we further examined the reaction scope of various cyclopropenes (Table 1).Similar to 50 1a, other cyclopropenes containing an additional alkene substituent (1b-h) provided 2b-h and 3b-h in good yields (entries 2-8).However, the ratio of 2:3 varies significantly ranging from 12:1 to 2.3:1 depending on the nature of the alkyl group at C2. Cyclopropenes 1i and 1j containing bulky 55 saturated adamantylmethyl and hydrocinnamyl substituents behaved similarly, providing product mixtures of 2i/2j and 3i/3j, respectively (entries 9 and 10).The high selectivity for 1i (7:1) compared to that of 1j (1.5:1) is most likely due to the steric effect of the substituents.Cyclopropenes that contain an ether linkage (1k-1o) provided products 2k-2o and 3k-3o in high yields but with low (entries 11-15).Especially, these ether-containing substrates showed a different selectivity trend probably due to the inductive effect of the oxygen atoms, even culminating in a reversed 1:3 ratio of C-H amination product 2o and ene product 3o (entry 15).
Once a general trend of the ene reaction is established, we probed the mechanism of the C-H amination yielding 2.
Toward this end, the reaction of 1a and diisopropyl azodicarboxylate (DIAD, 1.0 equiv) was monitored by NMR spectroscopy in CDCl 3 at 45 °C (Scheme 2).While 1a gradually decreased, two new products grew in a roughly 6:1 ratio.As the reaction proceeded, the minor compound constantly grew but the major turned into another compound.After 40 hours, two products were isolated, and they were identified as 2a and 3a.In this monitoring, we were able to identify that the initially formed compound was a regioisomeric ene product I-2a, which then rearranged to 2a.

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On the other hand, the other minor regioisomer 3a did not rearrange to 2a even at an elevated temperature, thus it was accumulated.The relatively facile rearrangement of I-2a to the final product 2 via an allylic transposition of the C-N bond 12 is assumed to be mainly the consequence of the steric 25 pressure of the trimethylsilyl group.

Scheme 2. [1,3]-transposition of Alder-ene products
To further confirm the identity of the intermediates and products 2 and 3, the ene reaction products derived from 1j 30 were desilylated with tetrabutylammonium fluoride (Scheme 3).It is interesting to note that I-2j is resistant to desilylation but the regioisomer 3j was readily desilylated, giving 5j.However, the isolated I-2j rearranged to 2j at 45 °C, which was then treated with TBAF to provide 4j.Upon desilylation of 2j, the C3-H at 3.8 ppm remained same but a new vinyl proton signal appeared at 6.7 ppm, a characteristic chemical shift of the vinyl proton on the alkyl-substituted double bond of cyclopropene.On the other hand, 3j displaying a vinyl proton signal at 7.7 ppm, a characteristic signal for the proton 40 on the silyl-substituted double bond of cyclopropene, provided a new compound upon desilylation, which now shows two identical vinyl protons at 7.3 ppm, the characteristic chemical shift of 3,3-disubstituted cyclopropene.From the NMR signal assignment, we deduced the structures of I-2j, 2j and 3j as assigned (see supporting information for details).shows a signal at 7.8 ppm.From these data, the structures of these compounds could be assigned unambiguously as 2p and 60 3p, respectively.This 13 C-label-based structural assignment for 1p is consistent with that of the chemical derivatization through desilylation of 2j and 3j derived from 1j.In addition, the reaction profile showed that the intensity of 3p remained constant after 1p disappeared completely, which clearly  The ene reaction of 6b containing a C3-substituent but devoid of silyl substituent at C1 (Eq 4 in Scheme 5), and 6c containing no substituent at C1 and C3 were also examined (Eq 5).As expected, 6b provided only 7b in 95% yield without 8b, and the reaction was much faster than that of trisubstituted cyclopropene 6a.The lack of forming C3-H amination products 8b is most likely due to a high barrier for the rearrangement of 7b.Similarly, C2-monosubstituted cyclopropene 6c afforded regioisomer 4j without forming 5j.In case of 4j, we surmised that there should be a degenerate allylic transposition (Eq 5).To examine this possibility, the reaction of a deuterium-labeled 6c-d was monitored with 1 H NMR spectroscopy (Eq 6).At ambient temperature in CDCl 3 , 6c-d underwent a rapid ene reaction to form 7c-d, confirmed by the C3-vinyl proton signal at 6.8 ppm but lacking C1 proton signal at 3.7 ppm.It was found 20 that 7c-d remained unchanged even at 80 °C, which indicates that 7c-d never rearranged to isotopomer 7c'-d.With this observation, we conclude that the allyic transpositions of 7b, 4j and 7c-d derived from nonsilylated cyclopropenes have much higher activation barrier than those derived from silyl cyclopropenes.
In conclusion, we have disclosed a novel C-H amination of silylcyclopropenes.This amination involves a rapid Alder-ene reaction followed by an allylic transposition of the quaternary hydrazodicarboxylate intermediate from the carbon bearing 30 the trimethylsilyl group.DFT calculation-based mechanistic studies on this C-H amination of cyclopropenes will be reported in due course.

Notes and references
a Department of Chemisty, Univeristy of Illinois at Chicago, Chicago,

Table of Contents
A novel C(sp 3 )−H amination of silylated cyclopropenes via a regioselective ene reaction with azodicarboxylate followed by its site-selective allylic transposition is described.
Unless otherwise indicated, reactions were performed with 0.5 mmol of cyclopropenes in 1 mL CDCl 3 at 45 o C for the indicated time.[b] Based on the crude NMR.[c] Isolated yields.[d] With DEAD at rt. [e] 45 Scheme 3. Mechanistic study via desilylationAdditional proof for the formation of intermediates and 50

65 indicatesFigure 1 .
Figure 1.Reaction profile of a 13 C-labeled cyclopropene Next, we examined the C-H amination of 6a that contains an extra alkyl substituent at C3 (Scheme 4).A mixture of C3-70

Table 1 .
C-H amination of silyl cyclopropenes a