P-LACTONES, decarboxylation

Recently, the Biju group demonstrated a highly enantioselective NHC-eatalyzed synthesis of functionalized cyclopentenes via o,p-unsaturated acyl azolium intermediates. This organo cascade reaetion of modified enals with malonic ester derivatives having a y-benzoyl group involves the Michael/ intramolecular aldol/p-lactonization/decarboxylation sequence to deliver functionalized cyclopentenes in good yields and excellent ee values (up to 85% yield and >99% ee) (Scheme 7.105). 

Decarboxylation of p-lactones (see 17-27) may be regarded as a degenerate example of this reaction. Unsymmetrical diacyl peroxides RCO—OO—COR lose two molecules of CO2 when photolyzed in the solid state to give the product RR. Electrolysis was also used, but yields were lower. This is an alternative to the Kolbe reaction (11-37). See also 17-29 and 17-40. 

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],... 

Decarboxylation of p-lactones to olefins,4 6 stereoselective reactions of p-lactones with a variety of electrophiles,6 9 and the regioselective fission of p-lactones by many different nucleophiles10 12 make these highly reactive compounds versatile intermediates for organic syntheses.13 Although several methods exist for the preparation of p-lactones, most p-lactones are now synthesized by [2+2] cycloaddition... 

Upon fonnation of intermediate LI, conjugate addition to a chalcone and subsequent proton transfer is proposed to lead to enolate LIII (Scheme 37). An intramolecular aldol addition provides activated carboxylate LIV in which alkoxide acylation regenerates the catalyst and delivers p-lactone LVI which, upon decarboxylation, gives rise to a trisubstituted cyclopentene. 

Intramolecular [2 + 2]cycloadditions benzofurans. On dehydrochlorination with triethylamine in refluxing C6H6, these acid chlorides are converted into (o-acylphenoxy)ketenes, which undergo a [2 + 2]cycloaddition reaction to form p-lactones, which are converted to benzofurans by spontaneous decarboxylation in 53-82% yield.1... 

Not much is currently known concerning diastereoselective addition of metal enolates to ketones 48,108), but selectivities are expected to be lower. In case of titanium enolates, several examples have been studied 77). The reaction shown in Equation 67 involves an ester-enolate21 and proceeds strictly in a 1,2 manner with 90% diastereoselectivity. The observation is significant because similar reactions with aldehydes are essentially stereo-random77). Also, the lithium analog of 203 affords a 1 1 mixture of diastereomers. Diastereoface-selectivity in Equation 67 is not an exception, because 203 adds to acetophenone and pinacolone to afford 85 15 and >76 24 diastereomer mixtures, respectively 77). Although stereochemical assignments have not been made in all cases, the acetophenone adduct was converted stereospecifically into the p-lactone which was decarboxylated to yield an 85 15 mixture of Z- and E-2-phenyi-2-butene 77). 

Dehydrative decarboxylation. The convc sion of p-hydroxy carboxylic acids to alkenes by reaction with a DMF dialkyl acetal iirvolves an r/n/Z-elimination, and thus is complementary to the known. yv/i-elimination of these hydroxy acids via a P-lactone (5, 22 9, 504). These reactions were used to obtain both the (E)- and the (Z)-l-alkoxy-l,3-... 

Decarboxylation of p-Hydroxy Carboxyhc Acids and of p-Lactones Carboxy-hydroxy-elimination... 

The reaction has also been accomplished under extremely mild conditions (a few seconds at 0°C) with PPh3 and diethyl azodicarboxylate EtOOC-N=N-COOEt. " In a related procedure, p-lactones undergo thermal decarboxylation to give alkenes in high yields. The reaction has been shown to be a stereospecific syn-eUmination. There is evidence that this reaction also involves a zwitterionic intermediate. ... 

Decarboxylation of p-lactones described above may be considered a degenerate reaction of this type. Another example is the loss of CO from certain ketones ... 

Aldol reactions. A route to y-arylidenebutenolides involves reaction of the lithiated butenolide with aromatic aldehydes followed by dehydration. p-Lactones are formed by reaction of enolates with S-aryl cyclopropanethioate. Since these lactones undergo decarboxylation at slightly above 100 , cyclopropylidenation of carbonyl compounds is achieved."... 

The thermal decarboxylation of a P-lactone has been widely used for preparation of an olefin. See [51, 52]. Recent examples of the thermal decarboxylation of P-lactones are described in [53-57], 301efins have been prepared by elimination reactions, in which oxazolidinone functioned as a leaving group. See [59-61],... 

Matrix photolysis of 2i/-pyran-2-one at 8 K leads to electrocyclic ring opening of the bond O/C-2 and formation of the aldoketene 8 which, by addition of CH3OH, can be intercepted as ester 10. Photolysis at higher temperatures or in ether leads to electrocyclization of the 1,3-diene system and formation of the p-lactone 9 which, by addition of CH3OH, yields the enol ether 12. Further photolysis of the P-lactone 9 causes decarboxylation resulting in cyclobutadiene 11 and its products, e.g. the dimer 14 (CHAPMAN) [12] ... 

Scheme 18 Proposed decarboxylation mechanism of 46 via the four-membered ring intermediate C (P-lactone)...

In 2006, Nair disclosed the synthesis of ( )-tra s-l,3,4-trisubstituted cyclopentenes resulting from the addition of enals to chalcones catalysed by an achiral carbene." " Mechanistically, the addition of the generated homo-enol to enones to give adduct II, followed by intramolecular acylation to afford cyclopentane-fused p-lactone IV. The final cyclopentene 67 was formed by the in situ decarboxylation of the p-lactones (Scheme 20.32). The enantioselective variant of the process to access ds-cyclopentenes was reported by Bode et al. in 2007. ... 

Irradiation of 4,6-dimethyl-a-pyrone immobilized in a guanidinium-sulfonate-calixarene gives rise to a 4,6-dimethyl-Dewar-p-lactone, a carboxyl zwitterion and 1,3-dimethylcyclobutadiene, both in the solid crystalline state and in aqueous solution. Diarylmethyl carbocations have been generated within the cavities of non-protic zeolites (LiY, NaY, KY, RbY, CsY, and NaX) via laser-mediated decarboxylation of diarylacetic acids. 

P-Lactones.—Studies continue on the synthesis and reactions of /3-lactones derived from acid dianions and carbonyl compounds. The decarboxylation of these compounds to sterically hindered olefins, and the steric control of the process by acid catalysis has been described (Scheme 60). ° In the latter case, increasing the acidity of the reaction medium changes the stereochemistry from retention (>98%) to inversion (>98%) of configuration. 

JM5-disubstituted cyclopentenes, rather than the expected cyclopentanones, in good yield and as single stereoisomers. Key to this process was the spontaneous decarboxylation of p-lactone 41 to give the observed cyclopentene products. 

Nair and coworkers showed in 2006 that Michael acceptors (112) can also act as electrophiles for achiral imidazolium-derived homoenolates, although the expected cyclopentanone products were not obtained [96]. Instead, dx-substituted cyclopentenes 114 resulting from a proton transfer, aldol, P-lactone formation, and decarboxylation sequence were isolated (Scheme 18.20). 

The NHC-generated azolium enolate can also react in a Mannich [lid], Michael [108], or aldol fashion [86], such as in the desymmetrization of 1,3-diketones to access enantiomerically-enriched cyclopentenes following decarboxylation of the P-lactone product [109]. Scheldt and coworkers took advantage of this reaction in the total synthesis of bakkenolides 1, J, and S (Scheme 18.26) [110]. 

Scheldt and coworkers also reported an enantioselective desymmetrization reaction of 1,3-diketones 62 in the presence of triazolium salt 61. This new process combines an intramolecular aldol reaction followed by a decarboxylation process of P-lactone intermediates, giving chiral cyclopentenes 63 in moderate yields and with high ees. Notably, with aliphatic diketones 64 or 66, p-lactone products 65 or 67, respectively, were obtained (Scheme 36.17) [23]. 

DMF dineopentyl acetal has been used as a reagent for dehydrative decarboxylation in order to avoid the possibility of competing 0-alkylation of the carboxyl group. This conversion of P-hydroxy carboxylic acids to alkenes by reaction with a DMF acetal involves an anti elimination, and it is thus complementary to the syn elimination of these hydroxy acids via the p-lactone. These reactions have been used to obtain both )- and (Z)-1 -alkoxy-1,3-butadienes (eq 6). For additional examples of alkenes obtained from p-hydroxy acids with DMF acetals, see Scheeren et al. ... 

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