Carbene annulation reaction

The chromium carbene annulation reaction proceeds rapidly in the presence of ultrasound to give good yields of quinone product on oxidative work-up. For example, ultrasound mediated... 

A combination of a Diels-Alder and a Fisher carbene-cyclopentannulation is described as the last example in this subgroup. Thus, Barluenga and coworkers used a [4+2] cycloaddition of 2-amino-l,3-butadienes 4-115 with a Fischer alkoxy-arylalky-nylcarbene complex 4-116 this is followed by a cyclopenta-annulation reaction with the aromatic ring in 4-116 to give 4-117 (Scheme 4.25) [36]. An extension of this domino process is the reaction of 4-118 with 2equiv. of the alkynyl carbene 4-119 containing an additional C-C-double bond (Table 4.2) [37]. The final product 4-120, which was obtained in high yield, is formed by a second [4+2] cycloaddition of the primarily obtained cyclopenta-annulated intermediate. 

The major direction taken with Fischer carbenes, however, has been annulation reactions (e.g., Eqs. 11-13) rather than cyclopropanation and insertion. Here, the dissociation of carbon monoxide initiates the sequence of events that lead to product (e.g., Eq. 42). °° Alternatively, an unsaturated unit conjugated with the carbene... 

Dotz, K. H., Tomuschat, P. Annulation reactions of chromium carbene complexes scope, selectivity and recent developments. Chem. Soc. Rev. 1999, 28, 187-198. 

Scheme 3-5 Cyclopentene annulations via a tandem Michael addition-carbene insertion reaction [51].

In 2012, Alexakis and co orkers disclosed the first stereoselective annulation reaction between ynals and a-cyano-l,4-diketones which is mediated by a catalytic amount of a triazolium salt precatalyst and a weak carboxylate base. This transformation proceeds smoothly under mild reaction conditions and generates three contiguous stereogenic centers, one of which is a quaternary acetal carbon, and affords privileged bicyclic scaffolds in 61-90% yields with up to 20 1 diastereomeric preference. A mechanistic rationalization for the NHC-catalyzed annulation of a-cyano-l,4-diketones with ynals is proposed as the following. Initially, the free carbene condenses with a molecule of ynal to form the key d,p-unsaturated acylazolium intermediate followed by a direct nucleophilic conjugate addition of 1,4-diketone. Subsequent intramolecular H-migration and an irreversible lactonization furnish the observed bicyclic product and liberate free carbene for the next catalytic cycle (Scheme 7.98). 

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. 

The same authors have also used this chiral IV-heterocyclic carbene catalyst in combination with Ti(Oz-Pr)4 to promote a highly diastereo- and enantioselective annulation reaction between a,p-unsaturated aldehydes and enones, which provided the corresponding chiral substituted ds-cyclo-pentenes in good yields and remarkable diastereo- and enantioselectivities of 90% de and 98 to 99% ee, respectively, as shown in Scheme 7.14. ... 

Scheme 7.14 Annulation reaction catalysed by chiral JV-heterocyclic carbene catalysis and titanium catalysis.

Treatment of M(C0)5[C(0Me)(CsCPh)] (M = Cr, W) with CpH modifies the carbene by Diels-Alder type addition of the alkyne across CpH. " Carbenes Cr(CO)5(carbene) react with 1-alkynols to form hydroquinone and/or vinyl lactone derivatives via vinyl ketene intermediates. Annulation reactions of Cr carbene complexes with 3-carbomethoxy-5-hexynoate and CO form part of a new regiospecific route relevant to the synthesis of... 

The selectivity for two-alkyne annulation can be increased by involving an intramolecular tethering of the carbene complex to both alkynes. This was accomplished by the synthesis of aryl-diynecarbene complexes 115 and 116 from the triynylcarbene complexes 113 and 114, respectively, and Danishefsky s diene in a Diels-Alder reaction [70a]. The diene adds chemoselectively to the triple bond next to the electrophilic carbene carbon. The thermally induced two-alkyne annulation of the complexes 115 and 116 was performed in benzene and yielded the steroid ring systems 117 and 118 (Scheme 51). This tandem Diels-Alder/two-alkyne annulation, which could also be applied in a one-pot procedure, offers new strategies for steroid synthesis in the class O—>ABCD. 

Merlic developed a new variation of the thermally induced benzannulation reaction. The dienylcarbene complex 132 was reacted with isonitrile to give an orf/zo-alkoxyaniline derivative 135 [76] (Scheme 56). This annulation product is regiocomplementary to those reported from photochemical reaction of chromium dienyl(amino)carbene complexes. The metathesis of the isocyanide with the dienylcarbene complex 132 generates a chromium-complexed di-enylketenimine intermediate 133 which undergoes electrocyclisation. Final tau-tomerisation and demetalation afford the orf/zo-alkoxyaniline 135. 

Reaction of the imine moiety of 278 with excess ethyl diazoacetate in the presence of Cu(acac)2 led to the cyclopentane-annulated product 279 the structure of which was confirmed by an X-ray analysis 262. It is assumed that 279 results from reaction between a carbene dimer (diethyl fumarate) and an intermediate N-ylide or the... 

The reactivity of cage-annulated carbene (53) was found to depend markedly on the method of its formation." Pyrolysis of the corresponding tosylhydrazone sodium salt gave products of intramolecular CH insertion or H-abstraction. Photolysis of a diazirine precursor gave only azine products by reaction of the carbene with the precursor or diazo compound. Treatment of the m-dibromoalkane with BuLi gave products due to intermolecular insertion of the carbene into CH bonds of the solvent. 

In 1986, we found that alkynyl-A3-iodanes serve as good Michael acceptors toward soft nucleophiles, because of the highly electron-deficient nature of the /3-acetylenic carbon atom. This conjugate addition of nucleophiles constitutes a key step of a highly versatile cyclopentene annulation of alkynyl-A3-iodanes via the tandem Michael-carbene insertion (MCI) reaction [Eq. (103)] [185]. 

Cyclopentenes are commonly formed in the reaction of the appropriate alkynyliodonium salts with enolate anions. Various alkynyliodonium tetrafluo-roborates interact with / -dicarbonyl enolates to give products of cyclopentene annulation in 50-90% yield [121]. Several examples of such annulations are shown in Scheme 59. The carbene cyclization can also occur when the long alkyl... 

The cyclopentene annulations can also occur in the reactions of alkynyliodo-nium salts with nitrogen- and sulfur nucleophiles (Scheme 61). Specifically, azi-docyclopentene 155 is formed upon treatment of octynyliodonium tosylate 154 with sodium azide in dichloromethane [123]. The reaction of alkynyliodonium salt 156 with sodium toluenesulfinate results in the formation of substituted indene 157 via alkylidene carbene aromatic C-H bond insertion [124]. 

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