Allenoates addition

At almost the same time. Miller et al. published a communication on pyridylalanine (Pal)-peptide 45 catalyzed enantioselective allenoate additions to A-acylimines 46 with moderate to good yields with high enantioselectivities (Scheme 1.21)." ... 

The product of the previous reaction provides a Baylis-Hillman type product via an intermolecular addition of an allenoate to an epoxide. The first example of a true Morita-Baylis-Hillman reaction of an epoxide has recently been reported <06CC2977>. Treatment of enone 34 with Me3P provides a good yield of the epoxide-opened product 35. The reaction must be carried out at low concentrations in order to avoid the generation of a variety of side products. When the terminal end of the epoxide is substituted (e.g. 34) the exo-mode of cyclization is the only product observed. When the terminal end of the epoxide is unsubstituted (e.g. 36), the endo-mode of cyclization predominates providing 37. 

Morpholine, pyrrolidine and sodium azide can also be also used as nucleophiles in the synthesis of 3-substitututed A3-cephems 515 via the conjugate addition of the 2,3-allenoate moiety in 513 [233]. 

Zhang et al. developed the enantioselective chiral phosphine-catalyzed addition of 2,3-allenoates with carbon-centered nucleophiles and electron-deficient olefins leading to efficient enantioselective C-C bond formation [248, 249]. 

Conjugate additions of thiols to a 2,3-allenoate proceed easily [236b, 249, 250],... 

The addition reaction of HBr to 2,3-allenoic acids afforded 2-bromo-2-propenoic acid [251],... 

Enantiopure quinolizidinones and indolizidinones were obtained by Ma and Zhu in an intramolecular conjugate addition of the secondary amine of 293 to the alkynoate ester to provide the intermediate allenoate 294, which was subsequently trapped in a condensation reaction to afford 295 (Scheme 19.53) [62], In some instances, intermediate 296 was isolated, which could also be converted to 295. This quinolizidinone intermediate was then converted in a concise manner to lasubine II (297). 

Michael-aldol reaction as an alternative to the Morita-Baylis-Hillman reaction 14 recent results in conjugate addition of nitroalkanes to electron-poor alkenes 15 asymmetric cyclopropanation of chiral (l-phosphoryl)vinyl sulfoxides 16 synthetic methodology using tertiary phosphines as nucleophilic catalysts in combination with allenoates or 2-alkynoates 17 recent advances in the transition metal-catalysed asymmetric hydrosilylation of ketones, imines, and electrophilic C=C bonds 18 Michael additions catalysed by transition metals and lanthanide species 19 recent progress in asymmetric organocatalysis, including the aldol reaction, Mannich reaction, Michael addition, cycloadditions, allylation, epoxidation, and phase-transfer catalysis 20 and nucleophilic phosphine organocatalysis.21... 

This section aims to complete the picture on the studies summarized in CHEC-II(1996) on the synthesis of classical cephalosporins, describing the main cephalosporin methodologies developed during the last decade. In CHEC-II(1996), an approach was presented for the formation of the cephalosporin framework bearing various heteroatom and carbon substituents at the C-3 position, which relies on a sequential addition/cyclization of allenoate 70, derived from penicillin G. 

More recently, the synthesis of 3-norcephalosporin 72 has been performed successfully by reaction of either allenoate 70 or 3,4-disubstituted 2-butenoates 73a and 73b with copper(i) chloride and tributyltin hydride in NMP <1996GG2705, 1999J(P1 )3463>. Conversion of the allenoate 70 into 72 took place through Michael addition of copper(l) hydride to the central carbon of the allene moiety of 70 and subsequent ring closure of adduct 71. The sequential reaction could be performed successfully by treatment of 70 with copper) 0 chloride and tributyltin hydride in NMP at room temperature, affording 72 in 79% yield without any detectable amount of the A2-isomer (Scheme 16). 

Ynoates in the presence of Me2CuLi LiI show syn-addition of the cuprate followed by a rapid isomerization of a lithium allenolate to the Z-substituted alkene. " Removing Lil can decelerate E- to Z-aUcene isomerization, and the allenoate can be trapped by TMSCl if present in the reaction mixture. 

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... 

Carbon-carbon bond formation by using metal enolates as synthons in organic chemistry and the protonation, alkylation, arylation, and vinylation of enolates have been reviewed. " The stereoselective carbon-carbon formation of bond through Mannich reaction has been detailed according to the type of Mannich base produced. Phosphine-catalysed asymmetric additions of malonate esters to y-substituted allenoates and aUenamides have been reported. ... 

Theoretical, NMR, kinetic, and mechanistic investigations of the reaction between triphenylphosphine, dialkyl acetylenedicarboxylates, and phenols have been reported " Mechanistic studies have provided insight into the phosphine-catalysed asymmetric additions of malonate esters to y-substituted allenoates and allenamides ... 

The authors found that the addition of TMEDA before oxidation was necessary to increase both reproducibility and yields of this sequential process, presumably due to the inhibition of the oxidative dimerization [98], a side reaction known in the chemistry of organocopper compounds. Alkynes with electron-withdrawing groups directly bound to the sp carbon were also employed in the stereoselective carbocupration [99]. For example, the carbocupration of alkynoates 341 promoted by Lewis acids, such as trimethylsilyl triflate, leads to the isomeric TMS-allenoate compounds, which on hydrolysis or a Mukaiyama-type aldol reaction produce the corresponding di- and trisubstituted acrylates 342 (Scheme 10.116) [100]. 

MacMillan has developed a Lewis acid-catalyzed addition-rearrangement sequence which facilitates the conjugate addition of allylamine 408 to allenoate ester 409 to generate the zwitterionic intermediate for the Claisen rearrangement. The minimization of steric interactions between the ammonium species and the y-allenyl substituent led... 

The reaction starts with the nucleophilic addition of the carbene to the aldehyde followed by [3+2] cycloaddition with the allenoate to furnish spirodihydrofuran intermediates 19/111. In the presence of a base, opening of the imidazole ring and rearranganent of the exocyclic to endocyclic carbon-carbon double bond afford carbanions I10/I12. Finally, protonadon of these intermediates yields furans 20 and 21 (Schane 5.15). 

The phosphine-catalysed aza-Michael addition of tosylhydrazones ArCH=NNHTs to allenoates CH2=C=CHC02R can be tuned by the choice of the phosphine ... 

Spirophosphine (335) has been employed as a catalyst for the intra- and inter-molecular /-addition of nitrogen nucleophiles to alkynoates (336) and allenoates (338) to give enantioenriched pyrrolidines (337), indolines, and /-amino-a, -unsaturated carbonyl derivatives (339) with <95%... 

The synthesis of 3-alkenyl and 3-benzyl-A -cephems 145 through the allenoate has been reported [94]. The reaction involves the reductive 1,2-elimination of 3,4-disubstituted 2-butenoate 144 followed by the reductive addition of allyl and benzyl halides employing the Mn/NiGl2(bpy)/AlGl3/N-methyl-pyrrolidone (NMP) system (Scheme 3.43). 

Phosphine-Catalyzed Reactions Enantioselective [3+2] cycloaddition of allenes with enones leads to the synthesis of cyclopentenes, which can be further transformed to cyclopentanes (Scheme 6.4). The phosphine addition to allenoate generates an allylic carbanion, which undergoes addition to the enone in the a and the p positions followed by the phosphine elimination to afford 3 and 4, respeetively [6]. 

In addition, a C6 thiourea derivative of P-isocupreidine 25 has been prepared and shown to catalyze the Rauhut-Currier reaction between allenoates and maleimides with the formation of products in a high yield but only moderate ee (Scheme 6.30) [72]. 

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