General Route to 4a-Methylhydrofluorene Diterpenoids: Total Syntheses of (()-Taiwaniaquinones D and H, (()-Taiwaniaquinol B, (()-Dichroanal B, and (()-Dichroanone Mainak Banerjee, Ranjan Mukhopadhyay, Basudeb Achari, and Asish Kr. Banerjee* Medicinal Chemistry DiVision, Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Kolkata-700 032, India ashisbanerjee@iicb.res.in ReceiVed December 16, 2005 A general and convergent route for the synthesis of the 4a-methylhydrofluorene diterpenoids has been established through a common hexahydrofluorenone intermediate (10) obtained via Pd(0)-catalyzed reductive cyclization of a substituted 2-(2-bromobenzyl) methylene cyclohexane (13). The strategy has been successfully utilized for the synthesis of (()-taiwaniaquinones D (3) and H (5), (()-taiwaniaquinol B(1), (()-dichroanal B (7), and (()-dichroanone (8). Introduction Recently a large number of highly rearranged abietane-type diterpenoids possessing the uncommon 4a-methyl tetra- (or hexa-) hydrofluorene skeleton were isolated mainly from a common Taiwanese pine tree, Taiwania cryptomerioides. 1 These include taiwaniaquinols B (1) 1a and D (2), 1c and taiwaniaquino- nes D (3), 1b F(4), 1c and H (5) 1d (Figure 1). A few more structurally related diterpenoids such as dichroanals A (6) and B(7), and dichroanone (8) were isolated from SalVia dichroan- tha. 2 Another novel diterpenoid, standishinal (9), was obtained from Thuja standishii. 3 Though the bioactivities of this family of compounds are yet to be examined comprehensively, preliminary studies 1d revealed that taiwaniaquinone D (3) possesses antitumoral cytotoxic activity, and standishinal (9) has promising antitumor 4 and aromatase inhibitory 5 potential. The published results on their bioactivities and the unique structural pattern make them attractive synthetic targets. Reports on the syntheses of the basic 4a-methyl hydrofluorene skeleton are relatively few, 6-10 though a large volume of literature exists on the synthesis of the gibberellin group of diterpenoids possessing a bridged hydrofluorene nucleus. 11 In the course of our studies on the synthesis of rearranged polycyclic diter- penoids 12 we have recently disclosed 12a in a preliminary account the first total syntheses of dichroanal B (7) and dichroanone (1) (a) Lin, W.-H.; Fang, J.-M.; Cheng, Y.-S. Phytochemistry 1995, 40, 871-873. (b) Lin, W.-H.; Fang, J.-M.; Cheng, Y.-S. Phytochemistry 1996, 42, 1657-1663. (c) Chang, C.-I.; Chien, S.-C.; Lee, S.-M.; Kuo, Y.-H. Chem. Pharm. Bull. 2003, 51, 1420-1422. (d) Chang, C.-I.; Chang, J.-Y.; Kuo, C.-C.; Pan, W.-Y.; Kuo, Y.-H. Planta Med. 2005, 71, 72-76. (2) Kawazoe, K.; Yamamoto, M.; Takaishi, Y.; Honda, G.; Fujita, T.; Sezik, E.; Yesilada, E. Phytochemistry 1999, 50, 493-497. (3) Ohtsu, H.; Iwamoto, M.; Ohishi, H.; Matsunaga, S.; Tanaka, R. Tetrahedron Lett. 1999, 40, 6419-6422. (4) Iwamoto, M.; Ohtsu, H.; Tokuda, H.; Nishino, H.; Matsunaga, S.; Tanaka, R. Bioorg. Med. Chem. 2001, 9, 1911-1921. (5) (a) Minami, T.; Iwamoto, M.; Ohtsu, H.; Ohishi, H.; Tanaka, R.; Yoshitake, A. Planta Med. 2002, 68, 742-745. (b) Hanson, J. R. Nat. Prod. Rep. 2004, 21, 312-320. FIGURE 1. 4a-Methylhydrofluorene diterpenoids. 10.1021/jo052589w CCC: $33.50 © 2006 American Chemical Society J. Org. Chem. 2006, 71, 2787-2796 2787 Published on Web 03/10/2006