Propargylation malonates

Thermal propargyl rearrangement-Claisen rearrangement of propargyl vinyl ethers and Cope-type rearrangements of propargyl malonates [93]. 

Evans used a single catalyst for an allylation-PKR sequence that only required changing the reaction temperature for each step. Thus, they synthesized cyclopentenone 101 from allylic acetate 99 and diethyl propargyl-malonate salt in the presence of [RhClCO(dppp)]2 with high yield. When formation of intermediate 100 was complete they just heated the reaction to 80 °C to get 101 (Scheme 29) [126]. 

Scheme 30 Tandem action of chiral Pd(II) and Co/C catalyst for the asymmetric synthesis of cydopentenones from propargyl malonate and allylic acetates...

Ionic liquids ([BMIM][PF6]) are suitable media for the Co2(CO)8-catalyzed intramolecular and intermolecular Pauson-Khand aimulation, provided that the reaction is carried out under a CO pressure of 10 bar [299]. Two diethyl allyl propargyl malonates were quantitatively converted into the relevant cydopentenones, whereas heteroatom tethered enynes gave lower yields in their cydocarbonjiation products. An example is shown in Scheme 5.2-138. The reaction also works with the direct addition of ethyldiazoacetate to imines in [BMIM][BF4] and [BMIMjfPFe] [300]. 

One pot synthesis of tricyclic enone 158 is possible via domino Pd-catalyzed allylation and Co-catalyzed Pauson-Khand reaction. Allylation of the propargylic malonate 156 with 3-acetoxycyclopentene under CO pressure afforded the fused tricyelic compovmd 158 via 157 in 73 % yield. Bimetallic catalyst PCNS (Pd and Co nanoparticles immobilized on silica) was used as a catalyst [55]. 

Continuing the organocobalt theme, two groups have reported using the Pauson-Khand reaction with carbohydrate templates to construct bis-annulated pyranosides. Propargylic ether substrates such as 148 and 150 provided the isomeric tricyclic systems 149 and 151, while the propargyl malonate substrates 152 and 154, cyclized to the isomeric tricyclic systems 153 and 155 (Scheme 38). ... 

Moderate the nitrogen flow, remove the septum, and put Pd2(dba)3 CHCl3 (158 mg, 0.153 mmol), dppe (0.243 g, 0.61 mmol), and dimethyl propargyl malonate (1.24 g, 7.32 mmol) into the Schlenk tube. 

When the reaction conditions were applied to allylic carbonate 8, the palladium-mediated cyclization occurred to form the 11-membered ketone 9 in 86% yield (eq 30). When the palladiun-catalyzed allylation of propargyl malonate 10 in the presence of BSA was combined with the rhodium-catalyzed Pauson-Khand t)fpe reaction, the tandem action of the two catalysts gave an excellent yield (92%) of bicyclopentenone 11 in one-pot (eq 31). ... 

No reaction of soft carbon nucleophiles takes place with propargylic acet-ates[37], but soft carbon nucleophiles, such as / -keto esters and malonates, react with propargylic carbonates under neutral conditions using dppe as a ligand. The carbon nucleophile attacks the central carbon of the cr-allenylpal-ladium complex 81 to form the rr-allylpalladium complex 82, which reacts further with the carbon nucleophile to give the alkene 83. Thus two molecules of the a-monosubstituted /3-keto ester 84, which has one active proton, are... 

Chiral allenyltitanium reagents, prepared from propargylic phosphates as outlined, react with alkylidene malonates to afford 1,4-adducts with excellent anti dia-stereoselectivity (Table 9.26) [42]. The addition is presumed to take place through an open antiperiplanar transition state (Scheme 9.12). 

The simplest 1,3-dicarbonyl precursor for the synthesis of 4//-pyrans is malonic dialdehyde. Because of its instability128 it must be generated in situ by hydration of propargyl aldehyde62,127 or 3-chloroacrolein,129,130 or by hydrolysis of 3-ethoxy-l,l,3-triethoxypropane.127 It underwent62,127,131 cycli-zation with a simple aldehyde, giving 3,5-diformyl-4//-pyrans 85a-d (40 to 90°7o). Lower yields were achieved in the preparation of 85e,f. 

In a similar manner, Lu and Liu have more recently utilized the hetero-Michael addition of lithium propargylic alkoxides to alkylidene malonates in a synthesis of stereodefined allylidene tetrahydrofurans, based on the use of allylic chloride as coupling partner [98]. In this case, the cydization reaction is initiated by a catalytic amount of palladium salt [Pd(OAc)2] rather than by an organopalladium species as mentioned above. 

An equimolar mixture of 3,4,5-trimethoxy phenyl iodide 157, lithium propargyl alkoxide 158, and diethyl ethoxymethylene malonate 159 was stirred at room temperature in the presence of a palladium catalyst. Then, to the resulting intermediate 161 potassium t-butoxide was added, and the ensuing base-promoted decarboxylative aromatization afforded tetrahydrofuran MCR adduct 162 in good yield. The ester was first reduced and the furan ring was hydrogenated with Raney nickel to furnish a diastereomeric mixture of products 163 in high yield. Further synthetic manipulations then provided a known precursor to the natural product. 

Type III reaction proceeds by an attack of a nucleophile at the central sp carbon of the allenylpalladium. Soft carbon nucleophiles such as / -keto esters and malonates react with propargylic carbonates under neutral conditions using DPPE as a ligand [35], The 2,3-disubstituted propenes 151 and 152 are obtained by the reaction of 2-propynyl carbonate (145) with two moles of malonate under neutral conditions in... 

In addition to softer neutral nucleophiles, harder anionic nucleophiles also alkylate the r/3-allcnyl/propargyl central carbon. The rhenium 7 3-2-butynyl complex reacts with malonate and lithium ferZ-butylacetylide to give rhenacyclo-butene complexes (Scheme 31) <1998JA722>. The reaction of sodium amide with an r/ -allenylplatinum complex similarly yields the platinacyclobutene complex, which does not further equilibrate (Equation 60) <1998JOM39>. 

A metal-catalyzed tandem 1,4-addition/cyclization of propargyl alcohols with Michael acceptors such as alkylidene-malonates has been developed. In the presence of catalytic amounts of zinc triflate and triethylamine, various 2-alkylidene-l,3-dicarbonyl compounds react with propargyl alcohols to give 3- or 4-methylenetetrahydrofurans in excellent yields (Equation 96) <20040L2015>. 

These -propargyl rhenium complexes undergo kinetic addition of nucleophiles at the central C atom to produce rhenacyclobutenes. The nucleophiles range from PR3 to malonate, acetylides, pyridines, and water. The derivatives of the addition of pyridines, however, are unstable and undergo further rearrangements to allene or acetylene complexes. Protonation of the metaUacyclobutenes produces u -allyl complexes. 

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. 

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