C o n f i r m a t i o n o f t h e S t r u c t u r e o f V e n t i l o q u i n o n e J t h r o u g h S y n t h e s iAbstract: An unambiguous route has been developed for the synthesis of rac ventiloquinones J and E as well as their diastereoisomers, rac isoventiloquinones J and E by using a mercury(II) mediated ring closure as a key step. Some time ago Thomson et al. 1 reported the isolation and structural elucidation of eleven new ventiloquinones found in the root bark of Ventilago maderaspatana and V. calyculata. This work, which focused on the (1R,3S)-1,3-dimethylnaphtho[2,3-c]-pyran-5,10-and -6,9-quinones supported and expanded earlier isolations in which Thomson et al. 2 focused on isofuranonaphthoquinones. Subsequent to these investigations, Thomson et al. 3 described the isolation of ventiloquinones L, M, N and O from V. goughii, while ventiloquinones G, L and M were reported to be isolated from the root bark of Fijian V. vitiensis. 4 Although the Thomson group were able to assign structures to most of the ventiloquinones isolated, they were unable to unambiguously assign the structure of ventiloquinone J as either 1 or 2. 1 This paper describes a protocol for the unambiguous synthesis of ventiloquinone J to confirm its structure as 1. (Figure 1).
Figure 1For various reasons we were interested in the synthesis of the 6,9-rather than the corresponding isomeric 5,10-quinones. Some early successful syntheses of ventilagone 3 and ventiloquinone H, 4 were accomplished by Brassard et al. 5 via an elegant Diels-Alder methodology. Following on this, Giles et al. 6 described their syntheses of ventiloquinones E, 5 and G, 6 and the regioisomer of ventiloquinone J, viz., 2. This latter finding clearly suggested that by default, the correct structure of ventiloquinone J is 1. Cameron et al. 7 subsequently described a synthesis of ventilagone 3, the last step of which involved the introduction of the C8 methyl group via a radical C-methylation protocol. In a further extention of their earlier work, Brassard et al. 8 described the syntheses of ventiloquinones C, D, E and G. In the same year the Cameron group also reported on the synthesis of ventiloquinone E, 5 but using a new strategy. 9 These ventiloquinones all possess the 1R,3S absolute stereochemistry for these cis-1,3-dimethylnaphthopyrans.Our approach to this first synthesis of ventiloquinone J was based on the premise that we would be able to chemoselectively differentiate between groups attached to the C5-and C10-oxygen atoms of the naphthopyran nucleus by the judicious choice of protecting groups placed on these oxygens. The group at the C10-oxygen had to additionally enable sufficient (1R,3S)-1,3-dimethylnaphthopyran to form during the mercury(II) mediated ring closure reaction (vide infra).Consequently, naphthalene 7 6 was pyrolyzed at 160 °C under nitrogen and the subsequent phenolic product derived by the Claisen rearrangement was not isolated but immediately methylated with 5 molar equivalents of K 2 CO 3 and MeI in boiling acetone to afford naphthalene ...
