Decarboxylative approach

Threshold CID can be used to measure the energy required for decarboxylation, in order to determine the enthalpy of formation of R, which can be used to calculate the gas-phase acidity. While nominally straight-forward, the decarboxylation approach is limited to systems that have a bound anion, R, and requires an instrument with the capability of carrying out energy-resolved CID. However, it does have an advantage of being a regiospecific approach. 

An exhaustive series of reports by Grigg et al. (28) outlined two basic methods for the generation of azomethine ylides proceeding via either a 1,2-prototropic shift, or by a decarboxylative approach (29). The decarboxylative route to azomethine ylides can be exemplified by the condensation of benzaldehyde with the cyclic amino acid tetrahydroisoquinoline (108) (30), in DMF at 120 °C, to generate the intermediate awfi-dipole 109, which underwent subsequent cycloaddition with N-methyl maleimide to furnish a 1 1 endo/exo mixture of adducts 110 (R = Ph), in 82% yield (Scheme 3.30). 

In an extensive study into the application of the decarboxylative approach to azomethine ylides, Giigg reported the construction of numerous, complex polycyclic systems via an intramolecular protocol. Thiazolidine-4-carboxylic acid (263) was shown to react with 264 in refluxing toluene to furnish a 2 1 mixture of 265 and 266 in 63% yield (81). The reaction is assumed to occur via condensation of the aldehyde and amino acid to generate the imine 267, followed by cyclization to 268. Subsequent thermal decarboxylation of the ester generates either a syn dipole leading to 265 from an exo transition state, or an anti dipole and endo transition state generating adduct 266 (Scheme 3.90). 

Similar products could be generated via azomethine yhdes derived by a formal 1,2-H shift from the precusor imine, rather than by the decarboxylative approach outlined above (82,83). For example (83), condensation of aldehyde 272 with the requisite amino ester 273 led to the intermediate ylide, which dehvered adducts 274 and 275 in a 1.2 1 ratio in 75% yield. Grigg has once again applied this protocol to the synthesis of a wide range of complex molecular frameworks (276... 

The decarboxylative approach to the ylide formation generated cycloaddition products derived from cycloaddition of the ylide to the carbonyl moiety of the molecule, as opposed to the alkene as seen in previous examples. Kanemasa has reconciled this observation by consideration of the postulated transition state model of the reaction. It was assumed that the steric repulsion of the terminal olehnic substituent and the ylide would favor transition state 309 (Fig. 3.19). Additionally, nonstabilized azomethine ylides have a higher energy HOMO than stabilized ylides, and would therefore prefer the LUMO of the carbonyl than the lower lying alkene LUMO. Formation of fused hve-membered rings would also be kinetically favored over construction of six-membered ring (Scheme 3.103). 

A decarboxylative approach to cross-coupling was explored with pico-linic acids (Scheme 38) (13T5732).The advantages of this approach are the stable and inexpensive starting materials when compared to organometallics and boronic acids. Under optimized conditions, a number of aryl bromides were coupled with picolinic acid. Lower yields were seen when the aryl bromides had electron-withdrawing groups (NO2 or CN).The yields were also moderate to poor when picolinic acid was coupled with 1- or 2-bro-monaphthalene or 2-bromopyridine. 2-Quinolinic acid coupled with bro-mobenzene in moderate yield. 

SCHEME 440 Decarboxylative approach to the synthesis of a-aminophosphine oxides [91]. 

Are there decarboxylative approaches to the synthesis of alkylphosphine oxides that start from propiolic acids ... 

---