Efficient Synthesis of Diospyrol via Suzuki-Miyaura and Modified in situ Cross-Coupling

Abstract

Tetramethoxydiospyrol was synthesized via Suzuki-Miyaura cross-coupling of the two key intermediates, halonaphthalene and naphthaleneboronic acid derivatives, which were derived from the same naphthol. Moreover, the product could be conveniently obtained by a one-pot modified in situ Suzuki coupling. The naphthol was synthesized via the cyclization of ortho-allylbenzamide intermediate.

Key words

biaryls - Suzuki-Miyaura cross-coupling - metalation - diospyrol

References

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11

The bromination and iodination of naphthol 6 also gave para halogenated products (Scheme 5). Compounds 7a and 7b were further methylated without purification.

16

1,8-Dimethoxy-3-methylnaphthalene [17] obtained as dehalogenation adduct from half-Suzuki cross-coupling was a white solid; mp 89-90 °C (MeOH). ¹H NMR (200 MHz, CDCl₃): δ = 2.47 (s, 3 H, CH₃), 3.98 (s, 6 H, 2 OCH₃), 6.69 (d, J = 1.0 Hz, 1 H), 6.78 (dd, J = 6.2, 8.4 Hz, 1 H), 7.19 (br s, 1 H), 7.35 (m, 2 H). ¹³C NMR (50 MHz, CDCl₃): δ = 21.7, 56.2, 56.3, 105.2, 108.2, 115.6, 120.0, 120.2, 126.4, 136.1, 137.5, 156.8, 157.0. MS (EI, 70 eV): m/z (%) = 128 (71), 129 (99), 159 (58), 201 (100) 202 (50, [M⁺]).