Heterocycle-annulated NHCs

Figure 1.9 Benzannulated and heterocycle-annulated NHCs (Np = neopentyl Am = amyl).

To vary the electronic properties of the carbene carbon atom a number of carbo- and heterocycle-annulated NHCs were prepared and studied. Single pyrido-annulated NHCs (93-96) as well as the doubly pyrido-annulated carbene 97 were obtained by deprotonation of the corresponding azolium salts. NHCs such as the quinone-annulated carbene 98/ the naphtho-annu-lated carbene 99 and related polycyclic compounds have also been obtained from more extended ring systems. 

A wide range of a,p-unsaturated aldehydes, including 3-alkyl derivatives, undergo /V-heterocyclic carbene (NHC)-catalyzed annulations with A -sulfonyl ketimines under mild conditions to provide bicyclo[3.2.0]lactams 194 with outstanding dia-stereo- and enantioselectivity (Scheme 70) [101]. This concise route to p-lactams... 

Ye and co-workers [30] ingeniously replaced the enals by bromoenals and used a M-heterocyclic carbene (NHC) as chiral organocatalyst for the formation of the corresponding dihydropyranones in a formal enantioselective [3-1-3] annulation reaction (Scheme 16.14). Similarly, Scheldt s group [31] reported the synthesis of optically active bi- or tricyclic dihydropyranones by an NHC-catalyzed domino intramolecular Michael/acylation sequence. 

Scheme 7.103 NHC-catal3 ed asymmetric annulation of 2-bromoenals with heterocyclic C—H acids reported by Biju.

NHC-catalyzed divergent annulation of enals with heterocyclic enones was developed to produce benzo[I ]furan-containing 8-lactones or spiro-heterocycles in a highly diastereo- and enantioselective fashion... 

Recently, the Glorius group developed the NHC-catalysed formal [3 -I- 2] annulation of enals with aza-aurones or aurone to provide valuable enantioenriched substituted spiro-heterocycles 64. Several different classes of enals proved suitable for the reaction, and the desired products were... 

In 2010, Scheldt and coworkers reported cooperative N-heterocyclic car-bene/Lewis acid catalysis for highly stereoselective annulation reactions. This cooperative catalysis process integrating titanium(iv) and triazolium-derived NHCs allowed the synthesis of ds-cyclopentenes 69 with a broad substrate scope and high enantioselectivity (Scheme 20.33). 

The first example of group 4 complexes comprising an annulated derivative with a pendant NHC group was reported in 2006 by Downing and Danopoulos (Scheme 14.20) [14,68]. The titanium (III) complex 37 was obtained by reaction of the Ti(IV) bis-amido precursor TiQ2(NMc2)2 with the corresponding potassium fluorenyl NHC salt and proceeded with Ti(IV) to Ti(III) reduction. Dimethyl-functionalized N-heterocyclic carbene complexes of Ti(IV), Ti(III), and Zr(IV) were also prepared by salt metathesis reactions, and the bidentate coordination mode was confirmed by various X-ray diffraction studies (complexes 38) [69]. 

DFT studies showed that annulation of imidazol-2-ylidenes generally destabilizes the NHC. This becomes also apparent when analogies between benzannulated N-heterocyclic carbenes and saturated imidazolin-2-ylidenes 86 (see Figure 1.8) are considered. Both types of NHC dimerize rapidly if the nitrogen atoms of the heterocycle are substituted with sterically less demanding substituents. No such dimerization is observed with imidazol-2-ylidenes 78, which possess an unsaturated heterocycle like the benzimidazol-2-ylidenes. 

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