Stereochemistry Pauson-Khand reaction

Their retro synthetic study was based around the Pauson-Khand cyclization (6), which couples an alkene, an alkyne, and a carbon monoxide source (typically dicobalt octacarbonyl) to give a cyclopentenone ring (Fig. 3.5, top). This reaction has been widely used for synthetic purposes, and some excellent reviews (7,8) have covered its principal features and the recent improvements to its experimental conditions. This reaction, in its intramolecular version, is ideal for the assembly of the l//-[2]pyrindi-none scaffold in two distinct versions, differing in the stereochemistry of the ring junction (Fig. 3.5, bottom). Hence, the readily available unsaturated amino acid derivatives 3.1a,b undergo intramolecular Pauson-Khand reaction to produce the two unsamrated scaffolds 3.2a,b. 

The third compound was made by a Pauson-Khand reaction using the same starting material = the first. The only difference between these two target molecules is the position of the double bor. In the Nazarov reaction, it goes into the thermodynamically most favourable position but in 1-Pauson-Khand reaction it goes where the alkyne was. So we simply react the cyclic ether wci acetylene cobalt carbonyl complex. The cis stereochemistry is inevitable. 

Production of the tetrasubstituted cyclopentenone (15a, 15b)) involves condensing the protected vinyl ether (16) with (12) via a Pauson-Khand reaction. Studies on the Pauson-Khand reaction , 1 have shown that upon condensing an unsymmetrical alkene with an unsymmetrical alkyne in the presence of a cohalt carbonyl compound give rise to mixtures of diastereomers (Fig 1) with the bulkier substituents of the alkene and alkyne being a to the carbonyl of the cyclopentenone. However, the stereochemistry a to the... 

The Pauson-Khand reaction was first applied to the synthesis of several model compounds, e.g., the piperidine derivative 438, as illustrated in Scheme 4.43. The dotted fines show the atoms that are to be connected in the reaction. The desired bicycfic structure was indeed obtained. Of significance was the stereochemistry of the reaction product, where the aza bridge and the proton on C-2 are trans-oiiented as found in the alkaloid. 

Alkyne- Co2(CO)6) complexes for application in the Pauson-JChand cyclopentenone synthesis have been prepared in simple and convenient fashion by reduction of cobalt bromide by zinc in the presence of alkynes under carbon monoxide. An intramolecular Pauson-Khand reaction has been used 172 to incorporate the proper stereochemistry at the C/D/E rings of Xestobergsterol D. The use of Co2(CO)6l-alkyne complexes as stable intermediates for the construction of the core structures of the anti-tumor enediyne agents esperamicin, calicbeamicin, dynemicin and neocarzinostatin has been reviewe(H73,... 

Several routes to cycloalkanes have been developed (Fig. 4). Bolton [29] described the synthesis of azabicyclo[4.3, 0]nonen-8-ones using an intramolecular Pauson-Khand cycliza-tion. The relative stereochemistry was controlled in this cyclization step which proceeded in good yield regardless of whether the nitrogen atom bore an allyl (shown) or propargyl (not shown) substituent. The ene reaction was employed in a route to trans-substituted cyclopentane and cyclohexanes [30], Reductive cleavage from the resin with LiBFL, provided the diol or, alternatively, cleavage with Ti(OEt)4 produced the diester. 

Once the strategy was selected, the validation of the relevant cyclization in solution and the determination of its stereochemical outcome and yield were carried out. The synthetic scheme is reported in Fig. 3.6. The commercially available allyl (3.3) and propargylglycines (3.7) were sequentially tosylated and alkylated with propargyl and allyl bromide, respectively, to give 3.5 and 3.9. The intramolecular Pauson-Khand cyclization produced the two isomers 3.6 and 3.10, with different stereochemistries, in a stereospecific reaction (the chiral allylglycine produced 3.6 as a single enantiomer. 

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