2-allenyl malonate

Allenic halides can also react with monosubstituted malonates to afford 2-(l, 2 -allenyl)malonates 128 and 131. With an unsubstituted malonate the migration of the C=C bond was observed to form 1,3-dienes 129 and 130 [65]. 

The palladium-catalyzed reaction of iodobenzene and an allenyl malonate provided vinylcyclopropane in a highly regioselective manner (Scheme 16.7) [11, 12]. A jT-allylpalladium complex, generated by the addition of PhPdl to a 2-allenyl malonate, can be trapped by an internal malonate anion to afford a vinylcyclopropyl derivative. The site selectivity in this cyclization is dependent on the nature of the entering RX groups, catalytic systems involving phosphine ligands, solvents and bases. 

Backvall et al. studied Pd(II)-catalyzed cyclization between the allene moiety and the alkene moiety in 2-allylic-2-(r,2 -allenyl)malonates 93,95, and 97 in the presence of two equivalents of benzoquinone in THF (Scheme 45) [30]. The reactions of 95 and 97 leading to cyclopentene-containing fused bicyclic products showed an excellent cis stereoselectivity, probably due to the formation of the cyclopentene ring. 

Ma et al. described the palladium(0)-eatalyzed three-component tandem double-addition-cyclization reaction of 2-(2,3-allenyl)malonate 218, Phi, and A-Ts-imine 219 for the stereoselective synthesis of 2,5-m-pyrrolidine 220... 

Four cationic palladium intermediates in the Pd(0)-catalysed three-component cascade double addition-cyclization of organic halides, 2-(2,3-allenyl)malonates, and imines have been characterized by the high-resolution ESI-FTMS technology.84... 

Scheme 12. Proposed mechanism for the formation of cis-pyrolidine derivatives from imine, iodobenzene and 2-(2,3-allenyl)malonate by ESI(+)-FrMS, m/z values are given for observed cationic intermediates.

Yamamoto et al. developed the Pd-catalyzed [3+2] cycloaddition reaction of 2-(2, 3 -allenyl)malonates 109 with electron-deficient olefins bearing two geminal electron-withdrawing groups 111 (Scheme 51). The reaction proceeded via the oxidative addition of the C-H bond at the 2 position of the starting... 

Backvall has reported the gold(III)-catalyzed cycloisomerization of allene-substituted malonic esters to form p,Y-unsaturated 6-lactones [115]. For example, treatment of allenyl malonate derivative 76 with a catalytic 1 3 mixture of AUCI3 and AgSbF in acetic acid at 70 °C led to isolation of 8-lactone 77 in 99% yield (Eq. (12.41)). The transformation was restricted to substrates that contained a terminally disubstituted allenyl moiety and presumably occurs via nucleophilic attack of the carbonyl oxygen atom on a gold-complexed allene followed by acetate-mediated demethylation and protodeauration. 

All the key intermediates were detected by ESI-FTICRMS over time, such as those ions of m/z 707.1,891.2 and 1150.3 (Figure 4.2). After these intermediate ions were further characterized by sustained off-resonance irradiation collision-induced dissociation (SORI-CID), one mechanism was proposed as shown in Scheme 4.3. The mechanism involving the carbopalladation with 2-(2,3-allenyl)malonate yielding the 7t-allyl palladium intermediate (Scheme 4.3) was confirmed. 

Figure4.2 ESI( + )-MS for a solution ofthe sample taken from the reaction mixture of 2-(2,3-allenyl)malonate, iodobenzene, imine, Pd(PPh3)4, and K2CO3 in THF stirred at85°C in a nitrogen atmosphere at the reaction time of 40 min.

In another study of palladiumotalyzed reactions involving allenes [38], Guo et al. described a three-component tandem double addition-cyclization reaction of allenyl malonates, aryl halides and imines to give pyrroUdine derivatives [42] (Scheme 7.22). Apart from the methodological synthetic study, the authors conducted a mechanistic study of the process using the ESI-MS technique [43]. The particular reaction studied is shown in Scheme 7.22. 

Finally, the synthesis of allenyl ketones is also possible by carbonylation if carbonates 103 are treated with C-H acidic compounds 104 such as /3-diketones or derivatives of malonic ester to yield products of type 105 [143],... 

The reaction of 1,2-allenyl sulfoxides with sodium malonate also afforded 2-[bis (methoxycarbonyl)methyl]-2-alkenyl sulfoxides 177, which upon further transformation would provide an efficient access to butenolide derivatives 180 [90, 91]. 

Type III reactions proceed by attack of a nucleophile at the central sp carbon of the allenyl system of the complexes 5. Reactions of soft carbon nucleophiles derived from active methylene compounds, such as /i-kcto esters or malonates, and oxygen nucleophiles belong to this type. The attack of the nucleophile generates the intermediates 9, which are regarded as the palladium-carbene complexes 10. The intermediates 9 pick up a proton from the active methylene compound and n-allylpalladium complexes 11 are formed, which undergo further reaction with the nucleophile, as expected, and hence the alkenes 12 are formed by the introduction of two nucleophiles. 

In the case of steroidal propargylic alcohols the first rearrangement produced a mixture of allenyl sulfoxides, epimeric at the sulfur atom, which reacted with an added nucleophile to produce substituted allylic sulfoxides. Rearrangement of the sulfoxide resulted in the exclusive formation of a-hydroxy derivatives. This reaction sequence has been applied in a synthesis of hydrocortisone acetate74 (Nu = OCH3) from androstene-3,17-dione and in a transformation of mesantrol75 (Nu = malonate) to a spirolactone. 

Altenbach used the Michael addition of sodium methyl malonate to allene (206) for a dia-stereoselective spiroannulation to a steroid (equation 72). Or, in imaginative work by Okamura, allenyl sulfoxides were transformed into enantiomerically pure hydrocarbons by pericyclic reactions like electrocyclic ring closure (equation 73) or intramolecular cycloaddition (equation 74). Note that the starting materials (propargylic alcohols) are readily accessible as single enantiomers. 

Dimethyl malonate derivatives containing an allenyl sulfone substituent at the y- or 3-position undergo endo-mode ring closure to give cyclopentene or cyclohexene derivatives upon treatment with 1.5 equiv of t-BuOK in t-BuOH at rt. The intermediate unsaturated cycloadducts undergo demethoxycarbonylation and double bond isomerization under the reaction conditions (eq 53). Other active methine compounds behave similarly. A threefold excess of i-BuOK is more effective than certain amine bases for the conversion of phenylsulfonyl methyl derivatives of aromatic or heteroaromatic compounds into the corresponding dithio esters upon reaction with an excess of elemental sulfur. ... 

In general, Pd-catalyzed reaction of propargyl compounds provides synthetically valuable allenyl compounds through addition, transmetallation, or oxypalladation of allenylpalla-dium intermediates. Exceptionally, soft carbon nucleophiles such as malonate and methyl acetoacetate attack the sp carbon of allenylpalladium intermediates to afford allylic compounds and furan derivatives. 

Dearomatization of r -benzylpalladium complexes represents an electronically reversed variation on the reactions described earlier. Initial examples utilized allyl and allenyl stan-nanes as nucleophilic components in combination with benzyl halides and invoked mechanisms involving aryl-alkyl Pd(II) intermediates [84]. Subsequently, direct addition of stabilized nucleophiles (e.g., malonate anions) to q -naphthylpalladium complexes has been achieved [85]. 

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