Synthetic studies towards complex diterpenoids. Part 18. Total synthesis of (±)-isopisiferin and the related compounds

Abstract

A simple convergent and general method has been developed for the synthesis of (f)-isopisiferin (1 c), a rearranged abietane diterpene, having a hexahydrodibenzo[a,d]cycloheptene ring system, and the related model systems (la) and (lb), through the respective enolisable tricyclic ketone mixtures (12c) and (13c), (12a) and (13a), and (12b) and (13b), obtained from the corresponding easily accessible 2-arylethyl-3,3-dimethylcyclohexanones (7c), (7a), and (7b). Demethylation of the styrenoid ethers (15b) and (15c) under acid conditions gave the tetracyclic dienones (17b) and (17c) through Ar,-5 cyclisation.The recent structural elucidation 'J of isopisiferin (lc), pisiferanol (2), and a number of related compounds, isolated from the seeds of Chamaecyparis pisifera (Cupressaceae), along with the earlier reported phenols, pisiferin (34) and barbatusol (3b),5 represent an interesting group of rearranged 9(1& 20)-abeo-abieta-8,11,13-triene diterpenoids. Recently, the total syntheses of ( + )-pisiferin (3a) and (+)-barbatus01 (3) ' have been reported. We present here the first total synthesis of (+)isopisiferin (lc) and the related model compounds (la) and (lb) by a simple and general convergent route.. .

Total Synthesis of (–)‐Isopisiferin: Confirmation of Absolute Configuration

“…to afford single enantiomer (-)-15 without contamination with any over-reduced products in 79 % yield over three steps from (-)-13. [13] Finally, upon deprotection with EtSNa, [14] as employed in the previous two arts, [6,7] (-)-15 was smoothly converted into target (-)-(1) in 62 % yield. The spectroscopic data ( 1 H NMR, IR, and HRMS) [15] and specific rotation of the synthetic molecule {[α] D 25 = -191.8 (c = 3.45, CHCl 3 )} were found to be in good agreement with those reported for natural product 1 {[α] D 25 = -193.1 (c = 2.56, CHCl 3 )}.…”

“…Thus, subsequent hydrogenation (H 2 , Pd/C, MeOH/ EtOAc = 1:9) occurred exclusively at the electron-rich exo double bond to furnish (-)-11 in 97 % yield, which in turn was subjected to basic hydrolysis to afford the corresponding carboxylic acid (-)-12 in virtually quantitative yield. With (-)-12 in hand (Scheme 3), and following the strategy of Ghatak, [6] the central seven-membered ring was constructed in a straightforward manner by intramolecular Friedel-Crafts acylation [10] to afford tricyclic ketone (-)-13 in 52 % yield. [11] For further chemical transformations, the keto carbonyl of (-)-13 was first reduced with NaBH 4 / CeCl 3 ·7H 2 O, known as Luche's conditions [12] by which 1,2-addition was highly anticipated to take place, leading to the desired allylic alcohol.…”

“…[6][7][8] Herein, we wish to present the first enantioselective synthesis of natural 1 in a simple and convergent route.…”

Bridged aromatic alkenes for the study of carbocation–π interaction

“…7-exo-Isopropenyl-6,7,8,9-tetrahydro-5H-5,9-methano-benzocycloheptene (9). According to a modification of a procedure by Deb et al, 47 (28). According to a procedure by Rudolph et al, 26 in a 100-mL roundbottomed flask was placed 7.9 g (0.056 mol) of 27, prepared by the method of Mich et al, 24 0.073 g (0.5 mol %) of methyltrioxorhenium, 0.55 mL (12 mol %) of pyridine and 40 mL of CH 2 Cl 2 .…”

“…Tricyclo[6.4.1.0 2,7 ]trideca-2(7),3,5-trien-13-ylidene-acetic acid ethyl ester (47). As in the preparation of 31, 2.67 g (66.7 mmol) of NaH (60% dispersion in mineral oil) and 11.9 mL (59.9 mmol) of triethylphosphonoacetate, plus 5.47 g (29.4 mmol) of 41 gave 5.61 g (75%) of 47 as a pale yellow oil.…”