Indanones aldol reaction

Keywords veratraldehyde, 4-phenylcyclohexanone, 1-indanone, aldol reaction, ,/i-unsaturated ketone... 

A novd example of a catalytic enantioselective domino process1201 is the inter-intramolecular nitro-aldol reaction described by Shibasaki et al which generates substituted indanones. As catalyst a praseodym-heterobimetallic complex with binaph-thol as chiral ligand is employed. Treatment of keto-aldehyde 41 with nitromethane in the presence of the catalyst 46 at -40 °C and successive warming to room temperature affords diredly the produd 42 in an overall yield of 41 % and 96 % ee after several recrystallizations (scheme 9). As intermediates the nitromethane adduct 43 and the hemiacetal 44 can be proposed. In a second aldol reaction 44 leads to 45 which isomerizes to the thermodynamically more stable epimer 42. 

The mechanism of the catalytic cycle is outlined in Scheme 1.37 [11]. It involves the formation of a reactive 16-electron tricarbonyliron species by coordination of allyl alcohol to pentacarbonyliron and sequential loss of two carbon monoxide ligands. Oxidative addition to a Jt-allyl hydride complex with iron in the oxidation state +2, followed by reductive elimination, affords an alkene-tricarbonyliron complex. As a result of the [1, 3]-hydride shift the allyl alcohol has been converted to an enol, which is released and the catalytically active tricarbonyliron species is regenerated. This example demonstrates that oxidation and reduction steps can be merged to a one-pot procedure by transferring them into oxidative addition and reductive elimination using the transition metal as a reversible switch. Recently, this reaction has been integrated into a tandem isomerization-aldolization reaction which was applied to the synthesis of indanones and indenones [81] and for the transformation of vinylic furanoses into cydopentenones [82]. 

D. The use of chiral oxazaborolidines as enantioselective catalysts for the reduction of prochiral ketones, imines, and oximes, the reduction of 2-pyranones to afford chiral biaryls, the addition of diethylzinc to aldehydes, the asymmetric hydroboration, the Diels-Alder reaction, and the aldol reaction has recently been reviewed.15b d The yield and enantioselectivity of reductions using stoichiometric or catalytic amounts of the oxazaborolidine-borane complex are equal to or greater than those obtained using the free oxazaborolidine.13 The above procedure demonstrates the catalytic use of the oxazaborolidine-borane complex for the enantioselective reduction of 1-indanone. The enantiomeric purity of the crude product is 97.8%. A... 

For the synthesis of tris-annulated benzene rings, the aldol trimerization of cyclic ketones has been known as a powerful tool since the 19 century. Why the reaction works so well with some ketones (e.g., indanone) but fails so miserably with others (e.g., tetralone), however, has never been adequately explained. This chapter outlines the development and scrutiny of a hypothesis that says formation of an a,/ -unsaturated (conjugated) dimer from a cyclic ketone is vital to the success of an aldol trimerization reaction for the synthesis of a tris-annulated benzene the reaction will fail with ketones that form only / ,y-unsaturated (unconjugated) dimers. This hypothesis unifies much experimental chemistry and is supported by theoretical calculations. 

Bengtson, A., Larhed, M. and Hallberg, A. (2002) Protected indanones by a Heck-aldol annu-lation reaction. J. Org. Chem., 67,5854-6. 

In many of the previous cases, palladium is the sole mediator of the reaction. Xiao and collaborators, however, found a catalytic two-bond-forming reaction that furnishes 1-indanones with the aid of a solvent [45]. The Heck-aldol-type cascade allows a great variety of aryl aldehydes/ketones in combination with an array of enol inputs (Scheme 14.24). The product contains the indan scaffold of the antibacterial pterosin C, which is also found in a diverse set of marketed drugs, for example, (-E)-indacrinone (hypertension) and donepezil (HIV protease inhibitor). 

An intramolecular version of this tandem reaction has been applied to the synthesis of indanones and indenones (Scheme 4-294). Accordingly, a sequence of pentacarbonyliron-catalyzed isomerization, aldolization, and dehydration can be exploited to transform vinyl sugars into substituted cyclopentenones (Scheme 4—295). The latter represent versatile intermediates for the synthesis of a variety of natural products. ... 

---