Asymmetric Organocatalysis Revisited: Taming Hydrindanes with Jørgensen–Hayashi Catalyst

Abstract

The organocatalytic Michael reaction of easily available 1-cyclopentene-1-carbaldehyde and 1,3-dicarbonyl compounds led to cyclopentanecarbaldehydes on a gram scale with low catalyst loading (2 mol%) and high enantioselectivity. The synthetic potential of 4-acylhexahydroindenones from intramolecular aldol condensation was demonstrated by Diels–Alder reaction to a tetracyclic derivative with seven stereogenic centers. The diastereofacial preference of the tetracyclic product was confirmed by DFT calculations. The described reaction sequence is characterized by few redox-economic steps and high degree of molecular complexity.

Boron‐Based Enantiomerism

“…The complexation of boronic acids with chiral ligands was frequently accomplished by means of tridentade N,O,O‐ligands that are derived from various α‐amino acids: boronates 12 [14] from L‐isoleucine and 18 [18] from D ‐tert‐leucine. D ‐phenylglycine served us as the chiral source of ( R )‐2‐amino‐1,1,2‐triphenyl ethanol that was incorporated into the core unit of the amine‐complex 14 , [16] whereas the backbone of boronate 15 [17] and borinate 19 [20a] was provided by L ‐proline and pseudoephedrine, respectively. The imine‐complex 13 , [15] however, is based upon ( R )‐2‐amino‐1,2,2‐triphenyl ethanol, available from D ‐mandelic acid.…”

Chasing Polycyclic Natural Products: 5/6/5‐ or 5/6/6‐Carbotricyclic Scaffold Construction via Stereodivergent Diels‐Alder Reaction of Chiral Hydrindanes and Their Boron Complexes

“…Initially we focused on the optimization of the Diels-Alder (DA) reaction of indanone 3 with cyclopentadiene 4a as our preliminary experiment proceeded in a moderate yield of 35 % due to incomplete conversion of indanone 3a (Table 1, entry 1). [47] Again, trifluoromethanesulfonic acid (TfOH, 0.2 eq.) in toluene was the reagent of choice.…”

“…Furthermore, hydrindanes were employed as precursors of lycopladine A [40] and other anellated polycyclic natural products [41–43] or analogues [44–46] . In addition to the reported methodologies, we have established an alternative approach towards the hydrindane scaffold [47] . According to our previous report, 4‐substituted tetrahydroindanones 3a – c were prepared via a two‐step sequence consisting of an organocatalytic asymmetric 1,4‐addition on cyclopentene‐1‐carbaldehyde and subsequent aldol condensation.…”

Synthesis of Highly Functionalized Hydrindanes via Sequential Organocatalytic Michael/Mukaiyama Aldol Addition and Telescoped Hydrozirconation/Cross-Coupling as Key Steps: En Route to the AB System of Clifednamides

“…Selected examples are amaminol A ( 1 ) or members of the class of macrocyclic tetramic acid lactams such as maltophilin ( 2 ), ikarugamycin ( 3 ), and clifednamides A–J ( 4a – j ) , (Scheme ). Therefore, a large variety of synthetic approaches have been developed to generate the hydrindane unit. , Organocatalytic Michael additions of 1,3-dicarbonyls to enals provide an efficient tool for C–C bond formation with simultaneous installation of stereogenic centers and enlargement of structural diversity. , Several groups , including our own efforts have successfully employed organocatalytic Michael additions for the synthesis of functionalized hydrindanes. However, the combination of Michael addition with Mukaiyama aldol reaction to further extend the molecular complexity of hydrindanes and their precursors has been much less explored ,, despite the broad applications of Mukaiyama aldol and vinylogous Mukaiyama aldol reactions in target-oriented synthesis …”

“…Motivated by our recently reported hydrindane synthesis via organocatalytic Michael addition in the presence of the Jørgensen–Hayashi catalyst and the subsequent aldol reaction, we anticipated that a combination of both approaches, i.e., installation of the stereogenic center at C-4 by organocatalytic Michael addition, followed by Mukaiyama aldol condensation and formation of the six-membered ring via intramolecular Diels–Alder reaction, should lead to the functionalized hydrindanes 8 suitable for further elaboration to clifednamide derivatives 4 . In the current manuscript, we report on the successful realization of this strategy, thereby significantly reducing the number of steps and improving the overall yield of hydrindane 8b .…”