Pauson-Khand reaction, hetero

Mukai, C., Yoshida, T., Sorimachi, M., Odani, A. (2006) Co2(CO)8-Catalyzed Intramolecular Hetero-Pauson-Khand Reaction of Alkynecarbodiimide Synthesis of ( )-Physostigmine. Organic Letters, 8, 83-86. 

Hetero Pauson-Khand reactions with an aldehyde or ketone component have been shown to afford synthetically versatile y-butyrolactones. Buchwald [50] and Crowe [51] independently showed that aliphatic enones and enals react with CO under Cp2Ti(PMe3)2 mediation (Scheme 11). CO insertion and thermal (or oxidative) decomposition gave diastereomerically pure bicyclic y-butyrolactones and stable Cp2Ti(CO)2. Imines did not react under the reaction conditions. 

Scheme 11 Titanium-mediated hetero Pauson-Khand reaction...

Scheme 12 Ruthenium-catalyzed hetero Pauson-Khand reactions with alkynes and al-lenes...

One approach to tetrahydropyridinones is the Lewis acid mediated hetero-Diels-Alder reaction of electron-rich dienes with polystyrene-bound imines (Entries 3 and 4, Table 15.23). The Ugi reaction of 5-oxo carboxylic acids and primary amines with support-bound isonitriles has been used to prepare piperidinones on insoluble supports (Entry 5, Table 15.23). Entry 6 in Table 15.23 is an example of the preparation of a 4-piperidinone by amine-induced 3-elimination of a resin-bound sulfinate followed by Michael addition of the amine to the newly generated divinyl ketone. The intramolecular Pauson-Khand reaction of propargyl(3-butenyl)amines, which yields cyclopenta[c]pyridin-6-ones, is depicted in Table 12.4. 

There is only one example of a catalytic Pauson-Khand reaction in an ionic liquid1471 although the reaction has also been conducted in ionic liquids using stoichiometric amounts of Co2(CO)8/481 In the catalysed reaction 10 mol% of Co2(CO)8 was used in [C4Ciim][PF6] under 10 bar of CO. Under these conditions, diethylallyl malonates could be obtained in 90-99% yield within 90 minutes at 80°C, as shown in Scheme 9.14. However, with hetero-bridged enynes, as well as in the reaction between norbomene and phenylacetylene, only poor to moderate yields were achieved. A slight increase in activity was observed with the analogous tetrafluoroborate ionic liquid. 

Hetero-Pauson-Khand Reactions Synthesis of y-Butyrolactones... 

Buchwald and his group have also synthesized y-butyrolactones successfully by a metallocene mediated cyclization of enones (and ynones) with carbon monoxide in a formal [2-r2-rl]-ad-dition, and have thus achieved the first hetero-Pauson-Khand reaction [31]. The reactions can be conducted in high yields with either stoichio-metrical or catalytical amounts of [Cp2Ti(PMe,)2] as the example in Scheme 9 shows. 

Scheme 9. An example of a hetero-Pauson-Khand reaction according to Buchwald.

Recently, catalytic hetero-[2 + 2 + 1]-cycloaddition of a carbon—carbon multiple bond, a carbon—heteroatom bond, and carbon monoxide, the so-called hetero-Pauson—Khand reaction, has been used frequently for the synthesis of functionalized y-butyro-lactones and y-butyrolactams 381 (Scheme 120). 

The catalytic intramolecular hetero-Pauson—Khand reaction has been extensively studied by several groups.184 Kablaoui et al. reported the titanocene-catalyzed hetero-Pauson—Khand reaction of the 2-ally lphenyl ketones 382.184ab In the presence of Cp2Ti-(PMe3)2 and trimethylphosphine, the reaction of 382 with carbon monoxide gave the polycyclic lactones 383 in high yields (Scheme 121). 

Mandal et al. recently demonstrated that the asymmetric intramolecular hetero-Pauson—Khand reaction of the enals and enones 384 in the presence of the chiral titanocene catalyst 386 gave the chiral y-butyrolactones 385 with high ee values and in high chemical yields (Scheme 122).185... 

Kang et al. reported that the ruthenium-catalyzed intramolecular hetero-Pauson—Khand reaction of the allenyl aldehydes and ketones 387 gave the a-meth-ylene-y-butyrolactones 388 (Scheme 123).186... 

Complementary to the hetero-Pauson-Khand reaction (see Section 2.2.6), [2 + 2] cydoaddition of ketenes and aldehydes provides rapid access to P-lactones from relatively simple starting materials. Cationic [Pd(dppb)(CH3CN)2]Bp4 was selected as the optimal catalyst (Scheme 2.64) (122,123]. A tandem allylic rearrangement/ring expansion sequence was also developed that provides elaboration of P-lactones to 3,6-dihydro-2H-pyran-2-ones in a one-pot process (Scheme 2.65) [123]. 

J. Adrio, J.C. Carretero, Butenohde synthesis by molybdenum-mediated hetero-pauson-khand reaction of alkynyl aldehydes, J. Am. Chem. Soc. 129 (2007) 778-779. 

This hetero-Pauson-Khand reaction is a complete diastereoselective synthesis of y-butyrolactones from the condensation of an alkene, a carbonyl moiety and CO. In a single process, two carbon-carbon bonds and two rings are constructed. The catalytic variant of this procedure has been also established on conjugated aromatic ketones (Scheme 12.44) [64]. 

Cycloadditions of an Alkyne, a Carbonyl Functionality, and CO Hetero-Pauson-Khand-Type Reaction... 

Imhof, W., Anders, E., Gobel, A., Gorls, H. Atheoretical study on the complete catalytic c cle of the hetero-Pauson-Khand-type [2+2+1] cycloaddition reaction of ketimines, carbon monoxide and ethylene catalyzed by iron carbonyl complexes. Chem.— Eur. J. 2003, 9,1166-1181. 

The greater part of this chapter is concerned with the Diels-Alder and hetero-Diels-Alder reaction. The asymmetric version of both of these reactions can be catalysed with metal-based Lewis acids and also organocatalysts. The catalytic asymmetric 1,3-dipolar cycloaddition of nitrones and azomethine ylides is also discussed. Again, most success in this area has been achieved using metal-based Lewis acids and the use of organocatalysts is begiiming to be explored. This chapter concludes with a brief account of recent research into the asymmetric [2+2]-cycloaddition, catalysed by enantiomerically pure Lewis acids and amine bases, and also the Pauson-Khand [2- -2- -l] cycloaddition mediated by titanium, rhodium and iridium complexes. 

Heterocycloaddition with CO can also provide facile access to lactones. The intramolecular hetero-Pauson-Khand [2 + 2 + 1] cycloaddition of aldehydes or ketones generates bicyclic lactones from acyclic precursors. Catalytic reactions employing Ti [59, 60] and Ru [61, 62] via radical and ionic mechanisms, respectively, have been reported. An enantioselective variant has also been achieved with a C2-symmetric titanocene derivative (Scheme 2.24) [60]. 

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