Allenoate activations

Besides chiral amines, also phosphines, sulfides, A(-heterocyclic carbenes (NHCs), phosphoramides, and form-amides have been impressively utilized as chiral Lewis base catalysts in numerous case studies [14, 88]. Chiral phosphines have been mainly used for BayUs-Hillman-type reactions and allenoate activations in this context [88, 94]. 

The metal-catalyzed conversion of 2,3-allenoates to A -butenolides has proven to be superior to the acid-catalyzed cyclization of the corresponding carboxylic acids. The reaction of the esters can be effected by Au(m) catalysts in improved yields <2005TL7431>, and furan-2(5//)-ones functionalized in the 4-position can be prepared by iodo- or seleno-lactonization in moderate to good yields (Scheme 33) <2006T4444, 2005EJO3942>. The cycloisomerization of optically active 2,3-allE itoic acids, on the other hand, can proceed with complete conservation of stereochemical information when copper(i) chloride is used as a catalyst <2006S3711>. 

The high affinity of allenoic esters to phosphines enables catalytic activation of the y-carhon to engage in nucleophilic addition. Thus with MesP the condensation of methyl... 

Backvall et al. demonstrated the Pd(II)-catalyzed cyclizations of 4,5- or 5,6-allenoic acids 45,3,4- or 4,5-allenols 47, and 4,5-allenyltoluenesulfonamides 49 with LiBr (Scheme 25). The reaction was initiated with bromopalladation of the allene moiety affording a 2-bromo-substituted 71-allylic palladium intermediate, which underwent intramolecular nucleophilic substitution to afford the heterocyclic products and Pd(0) (pathway 1, Scheme 1). The in situ generated Pd(0) was oxidized to the catalytically active Pd(II) species by its reaction with benzoquinone [18]. 

Pd(OAc)2 can catalyze the reaction of 2,3-allenoic acids with non-allylic alkenyl bromides with a terminal C=C bond leading to P-alkenyl butenolides 61 and 62 (Scheme 29). The reaction proceeded via oxypalladation-carbopal-ladation, repeated P-dehydropalladation/hydropalladation-dehalopalladation, in which Pd(II) is the catalytically active species [21]. 

From optically active 2,3-allenoic acids the corresponding optically active butenolides can be prepared in high yields and ee values. In this reaction excess... 

More recently, allenes, acetylenes and activated dienes have been added as olefin equivalents, leading to products of more eomplex skeletons. Though the first report on allenic compounds involved in a MBH reaction dates back to the DABCO-catalyzed and butyllithium-promoted aldol condensation of allenic ester with aldehydes reported by Tsuboi et there are very few reports of MBH reactions involving allenoates because they easily undergo cycloaddition reactions under different Lewis bases. For instance, five-membered pyrrolidine... 

Whereas these transformations require stoichiometric gold compounds, catalytic amounts of both gold and palladium are sufficient for the cycloisomerization of allyl allenoates to allyl-substituted butenolides. Blum and co-workers reported this tandem C-O/C-C bond formation, which is initiated by activation of the distal allenic double bond with PhaPAuOTf (Scheme 4-107). This induces cyclization to an allyl oxonium intermediate, which undergoes deallylation in the presence of Pd2dba3. Nucleophilic attack of the resulting a-vinylgold intermediate at the ti-allylpalladium species and reductive elimination furnish the allylated butenolide and regenerate both catalysts. 

The tertiary phosphine catalyzed [3+2] cycloadditions of allenoates 98 and electron-deficient olefins 99 was first discovered by Zhang and Lu [61] in 1995. Only two years later, the first enantioselective organocatalytic version of this reaction was reported by Chen and co-workers [62]. They showed that chiral phosphabicyclo[2.2.1]heptanes 100 catalyzes this reaction to give synthetically interesting optically active cyclopaitene derivatives 102 (Scheme 6.23). The mechanism for this reaction was later investigated... 

The triphenylphosphene-catalysed formal 3 + 2-cycloaddition of allenoates with trifluoromethylketones produced dihydrofurans in good yields and with excellent regio-selectivities. " The SnC -promoted 3 + 2-cycloaddition reaction between activated donor-acceptor cyclopropyl ketones and nitriles produced 1-pyrrolines as single cis-diastereoisomers in moderate to good yields. (g)... 

A review of formal aza-Diels-Alder reactions of imines with e-rich dienes and enones, in the presence of Lewis acids/Brpnsted acids/organocatalysts, has been presented. Bifunctional A-acyl aminophosphine catalysts (75) are effective asymmetric organocatalysts in the hetero-4- -2-cycloaddition of a-substituted allenoates with tosylaldimines to produce optically active tetrahydropyridines. The Brpnsted acid-catalysed aza-Diels-Alder reactions of cyclopentadiene with iminoacetates possessing two chiral auxiliaries yielded 2-azabicyclo[2.2.1]hept-5-ene cycloadducts with high exo-selectivities. ... 

The nickel-iminophosphine-catalysed 4- -2-cycloaddition of enones with allenes formed highly substituted dihydropyrans. The enantioselective amine-catalysed 4-I-2-cycloaddition of allenoates with oxo-dienes produced polysubstituted dihydropyrans in high yields and with high enantioselectivities. Novel enam-ine/metal Lewis acid bifunctional catalysis has been used in the asymmetric inverse-electron-demand hetero-Diels—Alder reactions of cyclic ketones with Q ,j9-unsaturated a-ketoesters. The 4- -2-cycloaddition of acylketenes (80) with 2-unsubstituted and 2-monosubstituted 3-aryl-2//-azirines (81) produced 1 1 (82) or 2 1 (83) adducts, being derivatives of 5-oxa-l-azabicyclo[4.1.0]hept-3-ene or 5,7-dioxa-l-azabicyclo[4.4.1]undeca-3,8-diene. The formation of the monoadducts proceeds via a stepwise non-pericyclic mechanism (Scheme 25). A-heterocyclic carbene-catalysed 4- -2-cycloaddition of ketenes with 1-azadienes yielded optically active 3,4-dihydropyrimidin-2-ones (93% ee) ... 

J. Li, Y. Liu, C. Li, X. Jia, Adv. Synth. Catal. 2011, 353, 913-917. Silver hexafluoroantimonate-catalyzed three-component [2-I-2-I-1] cycloadditions of allenoates, dual activated olefins, and isocyanides. 

The phosphine-catalyzed [4-1-2] annulation of allenoates with activated olefins 427 affords the annulation products 428 or 429 depending on the phosphine catalyst being used... 

The [3+2] annulation reaction of a-substituted allenoates with ester-activated a,p-unsaturated imines in the presence of MePPh2 leads to the synthesis of highly functionalized cyclopentenes bearing an all-carbon quaternary center (Scheme 6.8) [10],... 

A phosphane-catalyzed [4 - -1] annulation between nitroalkenes and Morita-Baylis-Hillman carbonates was performed by He and co-workers. " The authors claimed the in situ formation of an allylic phosphorus ylide as an active intermediate. Allenoates and enones were able to form cyclopentenes via two cycloaddition reactions they underwent a [3 -F 2] or a [2 -F 4] process in the presence of catalytic phosphines or amines, respectively (Scheme 15). To explain such a different reactivity, Huang, Lankau and Yu, carried out M06-2X/6-31- -G calculations to study the role of ylide intermediates. ... 

Yu et al. then proved that 2,3-allenoates 59 were good dipolarophiles to azomethine ylides in phosphoric acid-catalyzed 1,3-dipolar cycloaddition. The bisphos-phoric acid 47 was again the optimal catalyst that afforded up to 97% ee for the 3-methylenepynolidine products 60 (Scheme 2.17) [28a]. The construction of a C—C double bond on the pyrrolidine ring increases the synthetic potential of cycloaddition products. They also developed a kinetic resolution of racemic 2,3-allenoates via this bisphosphoric acid-catalyzed 1,3-dipolar cycloaddition, which afforded the optically active 2,3-allenoates 61 and 3-methylenepyrrolidine derivatives 60 in high yields and enantioselectivities (Schane 2.17) [28b]. 

Based on the bicyclic structure of the octahydro-1,6-naphthyridin-4-one 92, a chemical library was prepared by employing a solid-phase synthesis technique and evaluated by an EC activation assay that measured the production of macrophage inflammatory protein 1 beta (MIPljS), a marker of EC activation by IFNy. Reaction conditions were first established by using SynPhase lanterns as solid supports. Allenoate 93 was subjected to a phosphine-catalyzed [4 + 2] annulation reaction with A-tosylbenzaldimine 94. 

Dinitrogen-fused heterocycles have been formed in high yield by thermal 3-1-2-cycloadditions of two types of azomethine imines with allenoates. Rhodium-catalysed formal 3 -l- 2-cycloadditions of racemic butadiene monoxide with imines in the presence of a chiral sulfur-alkene hybrid ligand have furnished spirooxindole oxazolidines and 1,3-oxazolidines stereoselectively. ° Formation of 1,2-disubstimted benzimidazoles on reaction of o-phenylenediamine with aldehydes is promoted by fluorous alcohols that enable initial bisimine formation through electrophilic activation of the aldehyde. 

DFT study of interception of the allenyl enolate intermediate of Meyer-Schuster rearrangement using aldehydes and imines has shown that the active form of the vanadium catalyst bears two triphenyl siloxy ligands and that vanadium enolate is directly involved in the C-C bond formation." DFT calculations have elucidated the mechanisms and diastereoselectivities of phosphine-catalysed [4-1-2] annulations between allenoates and ketones or aldimines (Scheme 44). 

An extensive review of the synthesis of a wide variety of five-membered heterocyclic compounds, via the formal 3-1-2-cycloaddition reactions of aziridines with alkenes, alkynes, nitriles, carbonyl groups, and heterocumulenes, has been presented." Supercritical CO2 has been used as the solvent in the formal 3-1-2-cycloaddition reactions of A-benzyl- and A-cyclohexyl-2-benzoyl-3-phenylaziridines with allenoates to yield pyrrole derivatives." The Lewis acid-catalysed intramolecular formal 3-1-2-cycloaddition reactions of 2-methyleneaziridines with tethered alkenes or alkynes (23) yielded cw-octahydrocyclopenta[c]pyrroles (24) after reductive workup. The reaction mechanism proceeds in a stepwise manner via a 2-aminoallyl cation (Scheme The Cu(I)/DTBM-Segphos-catalysed 1,3-dipolar cycloaddition reactions of a-silylimines and activated alkenes yielded highly enriched 5-unsubstituted a-quaternary proline cycloadducts with excellent diastereo- and enantio-selectivities (73-99% The... 

A-Acyl aminophosphines catalysed the 4 -i- 2-cycloaddition of a-substituted allenoates with dual-activated olefins at -18 °C with up to 97% ee. A key step in the reaction is the formation of a zwitterion between the catalyst and the allenoates. ... 

---