Decarboxylation, enantioselective

Figure 10.47 Dynamic kinetic resolution ofThrA generated diastereomers by enantioselective decarboxylation (a).

Figure 7 Enantioselectivity of different types of decarboxylation reaction.

Also, decarboxylations of malonate-type compounds have been confirmed to proceed with retention of configuration. Indeed, malonyl-CoA decarboxylase from uropygial gland is enantioselective to the substrate as well as the product. Only... 

The tertiary structure of glutamate racemase has already been resolved and it has also been shown that a substrate analog glutamine binds between two cysteine residues. These data enabled us to predict that the new proton-donating amino acid residue should be introduced at position 74 instead of Gly for the inversion of enantioselectivity of the decarboxylation reaction. 

As can be seen from the above examples, the decarboxylation reaction can be said to generate carbanion-equivalent, which is capable of undergoing the enantioselective reactions not only with a proton but also with a carbon electrophile in an aqueous medium. In the future extension of this field, this characteristic point should be utilized for the design of the unique reactions. 

Nair and co-workers have demonstrated NHC-catalysed formation of spirocyclic diketones 173 from a,P-unsaturated aldehydes 174 and snbstitnted dibenzylidine-cyclopentanones 175. Where chalcones and dibenzylidene cyclohexanones give only cyclopentene products (as a result of P-lactone formation then decarboxylation), cyclopentanones 175 give only the spirocychc diketone prodncts 173 [73]. Of particular note is the formation of an all-carbon quaternary centre and the excellent level of diastereoselectivity observed in the reaction. An asymmetric variant of this reaction has been demonstrated by Bode using chiral imidazolium salt 176, obtaining the desymmetrised product with good diastereo- and enantioselectivity, though in modest yield (Scheme 12.38) [74],... 

Correspondingly, the catalytic 1,4-addition of dialkylzinc reagents to 3-nitro-coumarin 89 (Scheme 7.24), with a fixed trans orientation of the aryl and nitro groups, proceeds with excellent yields (90-99%), high diastereoselectivity (d.r. up to 20 1), and enantioselectivities of up to 92%. Hydrolysis of the lactone moiety in 90 was accompanied by decarboxylation, providing an asymmetric synthesis of 8-aryl-nitroalkane 91. 

Dicarbonyl donors bearing a thioester has been applied in the Mannich reaction to A -tosyl imines. Ricci presented an enantioselective decarboxylative addition of malonic half thioester 37 to imine 38. In the Mannich-type addition, catalyst 36 deprotonates the malonic acid thioester followed by decarboxylation to generate a stabilized thioacetate enolate. This stabilized anion reacts with facial selectivity to the imine due to steric-tuning from 36 [47] (Scheme 8). 

The enantioselective palladium-catalysed decarboxylative allylic alkylation has been highlighted.50... 

Chiral a-fhiom ketones (e.g. 75) bearing a gem-allyl function have been prepared by catalytic enantioselective decarboxylation of the racemic allyl ester (76), using a range of palladium(II) catalysts.297... 

The enantioselective reaction mechanism can be explained by considering the photochemical aspects and also the molecular arrangements (Scheme 36 and Fig. 7). Hydroacridine radical species 155 and 156, which satisfy both such conditions, should be preferably produced with their higher stability. Next, decarboxylation of 154 gives the diphenylmethyl radical 150. In the chiral crystal lattice of M-150 DPA, the molecular pairs of acridine and diphenyl acetic acid stack with... 

Disubstituted flavanones and chromanones are produced with good enantioselectivity from chalcones activated by an a-fert-butyl ester function through an intramolecular Michael addition catalysed by a chiral thiourea derivative. In situ decarboxylation enhances the ee and yields remain high <07JA3830>. A comprehensive study of the asymmetric cyclisation of 2 -hydroxychalcones to flavanones has refuted the ability of camphorsulfonic acid to achieve enantioselectivity but has shown that cinchona-based catalysts can be effective <07EJO5886>. 

Enantioselective aldol synthesis. The dioxolones formed from (S)- or (R)-l and aromatic aldehydes undergo a diastereoselective condensation with enol silyl ethers. Optically active aldols are obtained by removal of the chiral auxiliary by oxidative decarboxylation with PbfOAcfj. A typical example using the dioxolone (2) formed from (R)-1 and benzaldehyde is shown in equation (I). However, only moderate diastereoselectivity... 

Pyruvate decarboxylase catalyzes the nonoxidative decarboxylation of pyruvate to acetaldehyde and carbon dioxide. When an aldehyde is present with pyruvate, the enzyme promotes an acyloin condensation reaction. The mechanistic reason for this fortuitous reaction is well understood and involves the aldehyde outcompeting a proton for bond formation with a reactive thiamine pyrophosphate-bound intermediate (90,91). When acetaldehyde is present, the product formed is acetoin. Benzalde-hyde results in the production of phenylacetylcarbinol (Fig. 26). Both of these condensations are enantioselective, forming the R enantiomer preferentially in both cases. 

The first enantioselective formal total synthesis of paeonilactone A was reported by J.E. Backvall who used a palladium(ll)-catalyzed 1,4-oxylactonization of a conjugated diene as the key step. The lactonization precursor diene acid was obtained from an enantiopure dimethyl malonate derivative via sequential Krapcho decarboxylation and ester hydrolysis. 

---