Carbene catalyzed umpolung of α,β-enals: a reactivity study of diamino dienols vs. azolium enolates, and the characterization of advanced reaction intermediates

NMR/X-ray evidence is provided for hitherto postulated reactivity patterns of homoenolate vs. azolium enolate intermediates in NHC-catalyzed umpolung of enals.


Reaction of the 2,2-diamino dienol 1 with an equimolar amount of ethyl E-3benzoylacrylate (3b-Et)
In a glovebox, an NMR tube was charged with 12 mg (31 µmol, 1.0 equiv) of SiPr in [D 8 ] THF and sealed with a septum. 1.0 Equiv of E-cinnamic aldehyde (4.1 mg, 3.9 µl) was added with a syringe, followed by measuring 1 H NMR, showing the signals of 1 (see figure S39). Then 1.0 equiv of ethyl-E-3-benzoylacrylate 3b-Et (6.27 mg, 5.6 µl) was added with a syringe and the reaction was followed by NMR. The reaction was completed within 10 min, affording the Michael addition product 4b-Et (see figure S51-S60 for 1D and 2D NMR).

Reaction of the 2,2-diamino dienol 1 with an equimolar amount of E-chalcone (3c)
In a glovebox, an NMR tube was charged with 15 mg (38 µmol, 1.0 equiv) of SiPr in [D 8 ] THF and sealed with a septum. 1.0 Equiv of E-cinnamic aldehyde (5.08 mg, 4.8 µl) was added with a syringe, followed by measuring 1 H NMR, showing the signals of 1 (see figure S39).
Then 1.0 equiv of E-chalcone 3c (8.0 mg, 38 µmol) was added and the reaction was followed by NMR. After 12 h, 80% of E-chalcone was consumed, affording the Michael addition product 4c (see figure S61-S70 for 1D and 2D NMR).

Reaction of the 2,2-diamino dienol 1 with an equimolar amount of methyl E-3benzoylacrylate (3b-Me)
In a glovebox, an NMR tube was charged with 16 mg (41 µmol, 1.0 equiv) of SiPr in [D 8 ] THF and sealed with a septum. 1.0 Equiv of E-cinnamic aldehyde (5.4 mg, 5.2 µl) was added with a syringe, followed by measuring 1 H NMR, showing the signals of 1 (see figure S39).
1.0 Equiv of methyl-E-3-benzoylacrylate 3b-Me (7.8 mg, 41 µmol) was added, and the reaction was followed by NMR. The reaction was completed within 10 min, affording the Michael addition product 4b-Me (see figure S71-80 for 1D and 2D NMR).

NMR studies of cyclopentene formation from the Michael addition products
The Michael addition products 4b-Et and 4c were prepared in an NMR tube according to the previously described procedure (see page S8, S9). These NMR tubes were heated in an oil bath to 80 °C, and the course of the reaction was followed by NMR spectroscopy. The formation of the cyclopentenes 5b-Et (see figure S1-S2 for characteristic signals of 5b-Et) and 5c (see figure S3-S4 for characteristic signals of 5c) were observed.
The identity of the 5b-Et and 5c was proven by independent synthesis (see page S19-S20).  1.0 Equiv of benzaldehyde (4.1 mg, 3.9 µl) was added and this NMR tube was heated in an oil bath to 70 °C, and the course of the reaction was followed by NMR spectroscopy. The formation of 7 was observed (see figure S5-S6 for characteristic signals of 7) along with the regenerated SIPr, which then reacts with benzaldehyde affording the diamino enol 8 (OH is indicative peak in the case of diamino enol 8).
The identity of the 7 was proven by independent synthesis (page S20).  E-chalcone (8.0 mg, 38 µmol, 1.0 eq.) was added and the course of the reaction was followed by NMR spectroscopy. The formation of 12a (see figure S7-S11 for characteristic signals of 12a) was observed.
The identity of the 12a was proven by independent synthesis (see page S21).
The identity of the 12b was proven by independent synthesis (see page S22). 9 Independent synthesis of cyclopentene products