Solvent‐Controlled Hydrogenation of 2’‐Hydroxychalcones: A Simple Solution to the Total Synthesis of Bussealins

Abstract

A solvent-controlled hydrogenation of 2'-hydroxychalcones to selectively obtain different hydrogenation products is herein reported. Thus, hydrogenation of 2'-hydroxychalcones using EtOH as solvent provided the corresponding 1,3-diarylpropanes in excellent yields. On the contrary, when the hydrogenation was performed in DCM, the corresponding dihydrochalcones were isolated. Switching the reaction solvent to n-BuOH/H 2 O (1:1), afforded 1,3-diarylpropanols from moderate to good yields. The methodology here reported offers a straightforward, simple and cost-effective method for the preparation of a wide variety of 2'hydroxy-1,3-diarylpropanes derivatives, and was also applied to the preparation of natural Bussealins C and D.

Transfer Hydrogenation of Flavanones and ortho‐Hydroxychalcones to 1,3‐Diarylpropanols Catalyzed by CNN Pincer Ruthenium Complexes

“…[3] Flavanones can be reduced at the C=O group affording flavan-4-ols (Scheme 1, left), whereas ortho-hydroxychalcones are hydrogenated to dihydrochalcones, 1,3-diarylpropanols and 1,3-diarylpropanes (Scheme 1, right), which are compounds of high biological relevance. [4] While the syntheses of flavan-4ols, [5] dihydrochalcones [6] and 1,3-diarylpropanes [7][8][9] have been widely described in the literature, the preparation of orthohydroxy 1,3-diarylpropanols has not been properly covered yet. Interestingly, compounds containing this motif have shown to display inhibitory properties in the transcription factor NF-kB, [10] anti-cholinesterase, [11] anti-inflammatory activity [12] and P-glycoprotein-inhibitory effects (GP-88) [13] (Figure 1).…”

“…[15] Recently, our research group published a stereodivergent methodology for the hydrogenation of 2'-hydroxychalcones to generate their reduction products, but the preparation to 1,3-diarylpropanols was no general and difficult to achieve due to overreduction problems. [7] The lack of general and efficient methods for the preparation of ortho-hydroxy 1,3-diarylpropanols, prompted us to develop an alternative procedure via catalytic reduction of flavanones and ortho-hydroxychalcones, which are accessible from natural sources or can be easily synthesized following diverse approaches, including aldol condensation between ortho-hydroxyacetophenones and benzaldehydes in basic media and further cyclation [16,17] and arylation of chromanones with arylboronic acids in the presence of a palladium catalyst. [18] Employment of well-defined homogeneous catalysts has been demonstrated crucial for achieving high selectivity in several organic transformations, [19] reducing the formation of by-products and waste.…”

Pd/C‐catalyzed one‐pot Suzuki‐Miyaura cross‐coupling/hydrogenation of pyridine derivatives

“…Most importantly, the mechanism of the hydrogenation is completely different than that of the cross‐coupling reaction, that is, the substrates can be hydrogenated on the Pd surface whereas the homogeneous catalytic cycle is triggered by leaching of Pd due to the oxidative addition of heteroaryl halides [11]. As such, a careful selection of H 2 O as the solvent was crucial to the efficiency of the hydrogenation step [7,12] when considering the necessity to promote reabsorption of Pd back onto the support and to restrict the catalyst poisoning activity of the released bromide ion on the metal surface [13].…”

Two‐Step Access toβ‐Substitutedo‐Hydroxyphenyl Ethyl Ketones from 4‐Chromanone and its Application in Preparation of a Silica‐Supported Cobalt(II) Salen Complex

“…O ‐hydroxyphenyl ethyl ketones are typically prepared by the Fries rearrangement of phenol ester albeit in some cases, with moderate regioselectivity (Scheme 1a) [5] . The condensation of o ‐acetylphenol with aromatic aldehyde followed by noble‐metal‐catalysed hydrogenation provided an alternative way to generate β ‐aryl o ‐hydroxyphenyl ethyl ketones (Scheme 1b) [6] . In addition the hydroacylation of salicylaldehyde with olefins, [7] oxidation of o ‐hydroxybenzyl alcohols, [8] electrophilic addition of o ‐hydroxybenzamide or its congeners with organometallic compounds, [9] hydration of o ‐ethynylphenols [10] (Scheme 1c) and C−H hydroxylation aryl alkyl ketone (Scheme 1d), [11] have also been used to synthesize some specific o ‐hydroxyphenyl ethyl ketones.…”