Unintended Formation of a 26-Membered Cycle in the Course of a Novel Approach to Myricanol, a Strained [7,0]-Metacyclophane

Abstract

A convergent approach for the synthesis of (±)-myricanol, a strained diarylheptanoid isolated from Myricacae, was undertaken using a Suzuki–Miyaura coupling followed by a ring-closing metathesis (RCM). Herein, we report the unintentional formation of a 26-membered macrocycle as RCM product resulting from a head-to-tail dimerization of the seco-precursor, even in relay ring-closing metathesis (RRCM) conditions.

Access to 12-Membered Cyclic ortho,meta-Diarylheptanoids: Total Synthesis of Actinidione via Isomyricanone

“…3b 6) starting from (7) and (8). (18) To a roundbottomed flask was added 7 (1.5 equiv., 1.91 g, 4.71 mmol) and 8 (1 equiv., 1.27 g, 3.21 mmol). Then, H 2 O (10 mL) and dioxane (40 mL) were added, followed by tetrakis(triphenylphosphine)palladium(0) (11 mol%, 414 mg, 0.358 mmol) and dry K 2 CO 3 (5 equiv., 2.22 g, 16.06 mmol).…”

“…This implies that the ring strain is fully released in an ortho,meta-diarylheptanoid compared to a meta,meta-diarylheptanoid. 18 Subsequently, an hydrogenation was achieved in order to saturate the heptylene chain and to deprotect the benzyl groups, giving prominence to pressure to ensure reproducibility. Finally, isomyricanone 3, the 12-membered key intermediate was furnished in 12 steps with an overall yield of 33%.…”

New synthesized polyoxygenated diarylheptanoids suppress lipopolysaccharide-induced neuroinflammation

“…The requisite allylphenols 1a and 1b were accessed in two steps from commercially available 2,3dimethoxyphenol [13]. Coupling partners 2a, b and 3 were readily prepared from commercial methyl 3-(4-benzyloxyphenyl)propanoate [14,15]. With the key fragments 1a, 1b, 2a, 2b and 3 in hands, we attempted cross metathesis (CM) reactions as depicted in Scheme 1 [14,19,20].…”

“…Taking into consideration the biological importance of linear diarylheptanoids in general, and myricanol and curcumin in particular, we planned a straightforward access to a series of linear diarylheptanoid derivatives using the cross-metathesis reaction on readily available precursors 1a,b, 2a,b and 3 [13][14][15]. Terminal olefins 1-3 [14] were easily prepared and used to give access to new linear diarylheptanoids and to the cyclic one, myricanol.…”

Cluster Preface: Special Edition Dedicated to ISySyCat2019

“…Starting with Massé and co-workers (University of Strasbourg/University of Basilicata, Italy) who presented their work on the application of a sequential Suzuki-Miyauraring-closing metathesis for the synthesis of the strained [7,0]-metacyclophane, myricanol (we learn that in fact it was unintentional!). 3 Coelho and co-workers (University of Campinas, Brazil) contributed an article on the application of the aza-Morita-Baylis-Hillman reaction with vinyl-oxadiazoles to give a new class of heterocycle. 4 Garrido and coworkers (University of Salamanca, Spain) reported on the synthesis of chiral 2,3,6-trisubstituted piperidines via chiral lithium amide addition (pioneered by Steve Davies) to Baylis-Hillman adducts.…”