Tricyclic diol

The convention adopted for designation of the stereochemistry of the hydroxy groups in this and subsequent tricyclic diols is syn or anti with respect to the larger of the bridges across the molecular twofold or pseudo-twofold axis... 

In working towards the synthesis of nonracemic 3-deoxyschweinfurthin B (1-42), an analogue of the biological active schweinfurthin B, Wiemer and coworkers developed an acid-catalyzed cationic domino reaction to afford the tricyclic diol (f ,f ,i )-l-41 from 1-40 in moderate yield (Scheme 1.11) [11]. 

Pattenden and Teague have prepared tricyclic diol 684 which is epimeric to the naturally occurring A < -capnellene-8p,10a-diol (68S) Their strategy, which is summarized in Scheme LXXI, encompasses two critical cyclization steps. The first is the Lewis acid-catalyzed ring closure of enol acetate 686 and the second involves reductive closure of acetylenic ketone 687. It is of interest that the oxidation of 688 proved to be stereospecific. 

Complete details of the acid-catalysed rearrangement of humulene 1,2-epox-ide (249) have now been presented. With 1.8M-sulphuric acid in acetone at 0 °C for 30 min the sole product is the previously "known tricyclic diol (250). After an extended period this diol gives rise to five other identified products. 

During the total synthesis of (+)-ingenol by I. Kuwajima and co-workers, an advanced tricyclic diol intermediate was... 

Suffert et reported the first examples of palladium-catalyzed 4-exo-dig cyclization-anion capture processes (Scheme 5.6.3). In an ingenious sequence, which incorporates two separate electrocyclic steps, the vinyl starter species 10, in the presence of Pd(0) and iranx-vinyl distannane 11 in benzene at 90 °C for 30 min, affords 12, which on further heating undergoes disrotatory electrocyclization to the strained tricyclic diol 13 (Scheme 5.6.3). The electrocyclization process establishes the expected anti-stereochemistry of the 6-H and tri-n-butylstannyl group. Intermediate 13 undergoes elimination-... 

The adduct (276) from j9-pinene (241) and acrolein undergoes an acid-catalysed cyclisation giving 6-isopropyltetralin and the tricyclic diol (277), the latter being favoured at low acid concentrations. The enamines of pinocamphone (278) and verbanone (280) can be alkylated, and when methyl vinyl ketone is employed, the product is a tricyclic ketone [e.g. (279), from the pinocamphone]. ... 

Naya and Kotake, in an examination of Japanese hop oil, have isolated three humulane-type compounds, viz., humuladienone (161, R = Me), humulenone II (161,R = =CH2), and humulol (162), in addition to the tricyclic diol (163, R = OH), m.p. 207 °C. This diol has already been prepared in two different ways (a) Sutherland et treated humulene (164) with AT-bromosuccini-mide in aqueous acetone and converted the resultant bromohydrin (163, R = Br) to the diol (163, R = OH), m.p. 205—206 °C, by hydrolysis, (b) McKervey and Wright obtained the same diol, m.p. 201—203 °C, by acid-catalysed (20% sulphuric acid) rearrangement of humulene 1,2-epoxide (165), a known natural product. On the basis of these findings and the fact that both caryophyllene (166) and humulene can be derived from the above bromohydrin by two in vitro steps, McKervey and Wright postulated that humulene 1,2-epoxide may be involved in the biosynthesis of the tricyclic diol and caryophyllene. This postulate does not, however, readily accommodate the observed rotations of the relevant... 

A synthesis of [6]paracyclophane has been reported which involves flash pyrolysis of the lithium salt of tosylhydrazone (119). Authentic samples of diketones (120) have been prepared by lead tetra-acetate oxidation of the corresponding tricyclic diols. ... 

As for cyclic alcohols, bi- or tricyclic diols of different structures are excellent substrates and furnish excellent results in terms of stereosel tivity [263-267]. Scheme 62 presents a few selected examples of the successful asymmetrization of bi- and tricyclic substrates. 

Recently, Ogasawara and co-workers [54] disclosed an efficient synthesis of tiie enantiomerically pure tricyclic dienone 222 in both enantiomeric forms by employing lipase-mediated asymmetrization of the meso-synunetric precursor, and the novel palladium-mediated elimination reaction of the chiral monoacylated product. With this they show a new synthetic approach to A-ring synthon 189c (Scheme 13) [55]. Treatment of tricyclic diol 220, obtained from reduction of diketene 219, with two equivalents of vinyl acetate in acetonitrile in the presence of PSL furnished the monoacetate 221 in 79% yield after being stirred for 16 days at 28 C. The optically active acetate 221 was treated with ammonium formate in the presence of catalytic amounts of PdCl2(PPh3)2 to furnish the... 

An easy, silica gel-promoted 6-endo cyclization of y-epoxy alcohol 32 to pyran 33, followed by acid-catalyzed spiroketalization of the keto diol 34, afforded the common tricyclic spiroketal fragment 35 of lituarines A, B, and C (Scheme 8.8) [20b],... 

Finally, new tricyclic hexacoordinated phosphoranes with internal P-N coordination were synthesized by Swamy and coworkers by oxidative addition of cyclic phosphite precursors with quinones or with a combination of diols and (z-Pr)2NCl [57, 58]. Various ring sizes from five to eight membered were obtained showing the generality of the approach. A selection of compounds (47a-47e) is presented in Fig. 8. 

The key cyclization in Step B-2 was followed by a sequence of steps that effected a ring expansion via a carbene addition and cyclopropyl halide solvolysis. The products of Steps E and F are interesting in that the tricyclic structures are largely converted to tetracyclic derivatives by intramolecular aldol reactions. The extraneous bond was broken in Step G. First a diol was formed by NaBH4 reduction and this was converted via the lithium alkoxide to a monomesylate. The resulting (3-hydroxy mesylate is capable of a concerted fragmentation, which occurred on treatment with potassium f-butoxide. 

The same group also published a similar procedure using unsaturated bicyclic diols 7-124 to yield the tricyclic ene-acetals 7-125, using PhI(OAc)2 as oxidizing agent The products can be further transformed by treatment with Pb(OAc)4, and this led to the tricyclic bisacetat 7-126 in remarkably good yield (Scheme 7.33) [56]. 

The vicinal diol of the monoterpene series, (15,2S,3/ ,5S)-(+)-2,6,6-trimethylbicyclo [3.1.1]heptane-2,3-diol (1), was converted upon reaction with methyl dichloro-phosphite into a tricyclic phosphite 2 showing a 95 5 ratio of epimers differing at the phosphorus stereocentre (Scheme 1). Its complexes with Rh(I) and Pd(II) were found to have the structures (u-Cl)2[Rh(CO)L, and ris-CL,PdL2 respectively [16]. 

A unique tricyclic bisphospholane ligand, C5-Tricyclophos (34), has been described in a patent by Zhang [57]. Derived from resolved bicyclopentyl-2,2 -diol (originally used in the preparation of the chiral diphosphine, B1CP [58]), this li-... 

Diastereoselective reduction of the aldol 221/ can be achieved using AIH3 in toluene at —78°C. The corresponding ra-diol is preferentially formed. The diol can be protected with isopropylidene acetal to provide tricyclic compound 222. This can be converted to conformationally rigid C-l ketone 223 by deprotection of the PMB group and successive oxidation with PDC (Scheme 7-73). 

An equilibrium mixture of the cyclohexane- 1,3-dione (42) and its enol form (43) was irradiated in the presence of cyclopentene in MeOH to afford the intermediate (44), which was readily transformed to the tricyclic intermediate (45) and subsequently followed an retroaldolization sequence to give the cyclooctanedione (46) in 90 % yield. When refluxed with titanium trichloride and K metal in THF for 5 min., compound (46) gave the diol (47) 21K... 

The apparently latest total synthesis of a dolastane diterpene was published by Williams and coworkers in 1993 as a short communication (Fig. 16) [91]. (-)-Clavulara-l(15),17-dien-3,4-diol (129) was synthesized using a strategy that relied on the availability of the enantiomerically pure building block 162 from (+)-9,10-dibromocamphor (163) (Fig. 16). Cornerstones of the synthesis are a macrocyclization that afforded the 11-membered (A+B)C-ring (160) and a transannular cyclization that converted a bicyclic into a tricyclic ring system. Two of the seven chirality centres in the synthetic clavu-... 

Treatment of the /3-keto ester 220 with sodium ethoxide at elevated temperature triggered off an epoxide ring opening by / -elimination that was followed by the desired Knoevenagel condensation to afford the tricyclic product 206 (Scheme 34). The enone moiety in the intermediate 221 did not show a propensity for deprotonation and, therefore, the ketone carbonyl function of the enone moiety was available for a Knoevenagel condensation. The reduction of the p-keto ester (206) to the corresponding diol was the next objective. Treatment of the TES-protected -keto ester (TES-206) with DIBAH afforded the diastereomeric diols 222 and 223 in a moderate diastereoselec-tivity in favour of the undesired diastereomer 222. The diastereomers were separated and the undesired diastereomer 222 was epimerized to 223 by a sequence that consists of Mitsunobu inversion and benzoate ester reduction [98, 99]. 

The class of 3-silyl-substituted reagents provides, upon addition with aldehydes, allylic silanes that offer many options for further derivatization. Oxidative processes are described in previous sections (see the sections on Preparation of 1,2-Diols and 1,4-Diols). If the appropriate silicon substituents are chosen, formal [3+2] cycloadditions with aldehydes can be promoted under Lewis acid catalysis. For example, the mismatched addition of the Z-3-propyl-3-benzhydryldimethyl allylsilane 183 to an a-benzyloxy aldehyde proceeds with low diastereofacial selectivity in favor of product 184 however, after protection of the secondary alcohol, an efficient [3+2] annulation provides the polysubsubstituted furan 185 in good yield and acceptable stereoselectivity (Scheme 24). ° The latter is brought forward to a tricyclic unit found in the antitumor natural product angelmicin B. 

The clinical and commercial success of the antidepressant compound fluoxetine (Chapter 2 Prozac) engendered considerable work in other laboratories. A benzo-dioxan based compound that shows similar activity shares only a few stmctural features with the prototype. The benzodioxan nucleus (68-3) is formed by an alkylation reaction between the fluorocatechol (68-1) and the derivative (68-2) from meso, and hence achiral, butanetetrol. The benzyl protecting groups are then removed by hydrogenation over palladium, and the thus-obtained diol is converted to the fiii-toluene-sulfonate (68-4) by reaction with toluenesulfonyl chloride. Treatment of that intermediate with benzylamine leads to fiw-alkylation on the same nitrogen to form a pyrrolidine ring and thus the tricyclic compound (68-5). A second hydrogenolysis step then leads to fluparoxan (68-6) [70]. 

A variation of this route was applied to the preparation of a-methylenecyclo-pentane 179, an intermediate that was employed for the synthesis of prostaglandin PGF2o, (180) (Scheme 6.82). The acetonide-protected oxime-diol 175 [derived from propanal (174)] was treated with sodium hypochlorite without the addition of base. This led to the tricyclic adduct 176 with high stereoselectivity. One of the side chains was subsequently elaborated and the fully protected cyclopentano-isoxazo-line (177), when exposed to Raney Ni/boron trichloride, gave the 2-hydroxymethyl-cyclopentanone (178). This compound was dehydrated using mesyl chloride/ pyridine to furnish enone (179) (324). In another related synthesis of PGF2q, the p-side-chain (3-hydroxyoctenyl) was introduced prior to the cycloaddition (325). 

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