Bidirectional Hiyama–Denmark Cross‐Coupling Reactions of Bissilyldeca‐1,3,5,7,9‐pentaenes for the Synthesis of Symmetrical and Non‐Symmetrical Carotenoids

Abstract

The construction of the carotenoid skeleton by Pd-catalyzed Csp 2 ÀCsp 2 cross-coupling reactions of symmetrical and non-symmetrical1 ,10-bissilyldeca-1,3,5,7,9-pentaenes andt he corresponding complementary alkenyl iodides has been developed. Reaction conditions for these bidirectionala nd orthogonal Hiyama-Denmark cross-coupling reactions of bisfunctionalized pentaenes are mild andt he carotenoid products preserve the stereochemical information of the corresponding oligoenep artners. The carotenoids synthesized in this manner include b,b-carotenea nd (3R,3'R)-zeaxanthin (symmetrical)a sw ell as 9-cis-b,b-carotene, 7,8-dihydro-b,b-carotenea nd b-cryptoxanthin (nonsymmetrical).Scheme3.To tal synthesis of symmetrical carotenoids (7, 8)byH iyama-Denmark cross-coupling of symmetrical pentaenylbissilane (5)and trienyliodides (1 and 22).

State-of-the-art methodological investigation of carotenoid activity and metabolism – from organic synthesis via metabolism to biological activity – exemplified by a novel retinoid signalling pathway

“…This is particularly true when used as tandem processes to more efficiently generate molecular complexity, thus highlighting the advantages of the Hiyama-Denmark cross-coupling reaction for stepwise polyene construction of highly unstable ciscarotenoids in general. 26,33 Materials. Silica gel column chromatography, CN-silica gel (40-63 µm particle size; loading 1.85 mmol g −1 ), visualization for analytical TLC, UV irradiation (254 nm) or staining with an ethanolic solution of phosphomolybdic acid.…”

“…The sequential Hiyama–Denmark cross-coupling reaction 25 of a non-symmetrical 1,10-bissilyldeca-1,3,5,7,9-pentaene (Fig. 3, 1 ) 26 with modulated reactivity and positional selectivity 27 was used for the synthesis of 9- cis -β,β-carotene ( 5 ), without isolation of the octaenylsilane intermediate ( 3 ).…”

Synthesis of Symmetrical and Nonsymmetrical Polyenes by Iterative and Bidirectional Palladium‐Catalyzed Cross‐Coupling Reactions

“…Representative symmetrical 1,10‐dimetalo‐1,3,5,7,9‐decapentaenes (Figure 4) have been prepared from precursor metalodienylphosphonates and metalodienals, [6b, 78] and more recently from silyltetraenynes [79] …”

“…Either symmetrical or non‐symmetrical carotenoids would result from the coupling of pentaenylbissilanes by two‐fold or position‐selective Hiyama–Denmark cross‐coupling reactions. Pentaenylbissilanes were alternatively prepared by the Horner–Wadsworth–Emmons condensation of silyldienal 216 and phosphonate 215 and by hydrosilylation of tetraenyne 219 previously made using the same condensation reaction starting from enynylphosphonate 217 [79] . In both cases, the incorporation of the silyl group in these building blocks relied on the regioselective cis ‐hydrosilylation reaction of the precursor enynes, as shown for silylated tetraenyne 219 (Scheme 24), which afforded the non‐symmetrical deca‐1,3,5,7,9‐pentaene‐(1,10‐diyl)bissilane of E geometry, upon treatment with HSiMe 2 (EtO) and Karstedt's catalyst [Pt(dvds)(P t Bu 3 )] (dvds=1,3‐divinyl‐1,1,3,3‐tetramethyldisiloxane) [12, 82] .…”

Development of a General Method for the Hiyama–Denmark Cross-Coupling of Tetrasubstituted Vinyl Silanes

“…Under these conditions, even with the use of electron-donating alkyl substitution on the aromatic ring, none of the desired product was observed (entry 2). Alkyl substituents, including benzyl, which had previously been shown to be effective in protodesilyation reactions and Hiyama–Denmark couplings of less substituted vinyl silanes, also lead to minimal product (entries 3–4). We also studied the reaction of 1-naphthyl substituted vinyl silane (entry 5), as protonation would likely be easier as a result of weakened aromaticity.…”