Fused Five-membered Rings

Fused Five-membered Rings.—Structures based on the linear fusion of three five-membered rings are easily synthesized by intramolecular photocyclizations of dicyclopent-l-enylmethanes [viz. (75)], followed by in situ addition of methanol to the presumed intermediate bicyclo[2,l,0]pentanes (76) the general method has been applied in a synthesis of the hirsutane carbon skeleton (77) found in hirsutic acid and related natural sesquiterpenoids. 

The bicyclo[3,3,0]octenol (78) is produced by a transannular cyclization of cyclo-octa-1,5-diene induced by thallium(lll) trifluoroacetate, and Joulain and Rouessac have found that the fused 5,5-system (80) is produced when the bis-alcohol (79) is treated with perchloric acid in nitropropane.  

Yamada, A. Shibata, K. Iguchi, and H. Sanjoh, Tetrahedron Letters, 1977, 2407. D. Joulain and F. Rouessac, Tetrahedron Letters, 1977, 3585. 

Fused Five-membered Rings. - As in the preparation of cyclopentanes, radical ring closures are playing an increasingly useful role in the synthesis of fused five-membered rings for instance, a further 

Three highly useful fused five-membered ring synthetic building blocks are bicyclo[3.3.0]oct-1-ene-3-one, bicyclo[3.3.0]octane-3, 

Tandem reactions are currently very popular as seen in the section on radical cyclizations, and two more examples have been described. Firstly, the combination of Claisen 

Base treatment and Michael addition to the a,8-unsaturated ester of (42) to form a hydrindanone has been reported as a key step in a synthesis of racemic fawcettimine,6 and a novel base induced 

Two related pieces of work giving rise to functionalized cyclopentanes have appeared, involving the intramolecular reaction 

Fused Five-membered Rings.- Radical cyclizations continue to give ready access to fused cyclopentanoids. For example the stereo-controlled formation of (37) allows a radical-induced ring closure to the cyclopentanol (38) in a process which has been described as 

The previously described tandem radical cycllzation strategy has 

The Pauson-Khand reaction is currently undergoing a renaissance 

One way of achieving the synthesis of annulated cyclopentanes is via the intramolecular cycllzation of a variety of silicon and tin derivatives. For instance the enol ether (47) has been shown to 

A new process leading to some potentially useful dienes involves 

Fused Five-membered Rings.—A number of biologically important terpenoids show structures based on the fusion of two or three five-membered rings, e.g. hirsutic acid, pentenolactone, coriolin, capnellane, and retigeranic acid, and efforts directed towards total synthesis of these structural types have burgeoned in the past few years. 

The tricyclic hydrocarbon hirsutene (94), isolated recently from Coriolus consors, is a probable precursor for coriolin (95), found in C. consors, and also for hirsutic acid (96), isolated from Stereum hirsutum. In a biogenetically patterned synthesis of hirsutene, Ohfume et al. have shown that treatment of the tricyclic hydrocarbon (92) with a catalytic amount of toluene-p-sulphonic acid leads to the endo-isomer (93), in 95% yield, which by manipulation of the double bond can be 

Ketone (111) in the hitherto unknown cw,5 y ,cw-tricyclo[6,3,0,0 ]undecane series has been prepared, using acid-catalysed cyclization of 1,1-dicyclopentenyl ketone (110) as a key stage.  

A full report has been published on the chemistry of the highly functionalized bicyclo[3.2.0]heptene (90), reaction of which with diazoethane gives a mixture ica. 7 3) of the useful ring-expanded products (91) and (92). A synthesis of another potential precursor (93) of polycyclopentanoids has also been reported.  

In another full report, details are given of the preparation of (95a) by an intramolecular Wadsworth-Emmons reaction of the phosphonate (94) this method constitutes a key step in a synthesis of 6a-carbaprostaglandin 12. A related Wittig reaction using a phosphonium salt derived from a chiral phosphine has been used to obtain (96) in high optical purity. Bicyclo-A -octenone 

Another example of the acid-catalysed intramolecular cyclization of diazoketones cf. refs. 58, 92, 93) is a high-yielding preparation of polycyclic enones (101) from diazoketones (100). Further reports have appeared on the preparation of fused cyclopentanones by condensations between acetonedicar-boxylate and a-diketones yields are higher if the substituents on the latter substrates are small. An alternative approach to polycyclopentanoids, consisting of successive additions of propargyl alcohol anions to cyclopentanones followed by double dehydrative cyclization and hydrogenation, has been used to prepare the potential dodecahedrane precursor (102) cf ref. 63). The cage compound (103), obtained from 1,4-naphthoquinones and cyclopentadiene, produces the polycyclopentanoid (104) under acyloin condensation conditions.  

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Whereas the condensation of o-iodonitrobenzene with copper acetylides is accompanied by cyclization into isatogens, neither 4-iodo-3-nitro- nor 5-iodo-4-nitro-l,3-dimethylpyrazole gives cyclized products in conditions of acetylide synthesis. Moreover, nitropyrazolylphenylacetylene, as compared with o-nitrotolane, does not undergo thermal, catalytic, or photochemical isomerization to give the fused five-membered rings. 

B. Compounds with Two Fused Five-Membered Rings. 279... 

This result should be compared to the cydization of the more advanced intermediate 49 (4 1 mixture of isomers at the acetal position Scheme 9.25), which afforded the bicyclic oxepane 50 as the sole product in excellent yield. It was suggested that this result was due to the presence of a trans-fused five-membered ring, which restricts the rotation around the C7-C8 bond and thus promotes the 7-endo cydization. 

The 1,3-cyclopentanediyl (62) motif has been further expanded into a bicycUc module containing two fused five-membered rings. The 2,2-disubstituted... 

For his synthesis of the anti-tumour compound diketo-coriolin, Danishefsky needed (9) with its two fused five-membered rings, Enone disconnection suggests two possible precursors. 

The number of methods available for the synthesis of bicyclic systems containing two fused five-membered rings with one bridgehead nitrogen can be summarized in a few general reactions dehydrative ring closure, oxidative Schiff base cyclization, and base-induced closure (Scheme 3). One-pot reactions involving precursor synthesis followed by cyclization are also known. 

A number of other ring systems have been prepared by intramolecular bis-annulation procedures. Pyrrolothiadiazolines 174 were prepared by condensation between hydrazides and compound 173 (Equation 14) <1998JPR676>. The thermally induced intra-intermolecular criss-cross cycloaddition of azine 175 in the presence of phenyl isocyanate leads to heterocyclic compound 176 containing three fused five-membered rings (Equation 15) <2002TL6431>. 

REACTIVITY OF BENZOHETEROPINES WITH FUSED FIVE-MEMBERED RINGS... 

Heteropines with fused five-membered rings are structural blocks of valuable natural products and their synthetic analogs. Latonduines 424 A (R = H) and B (R = COOH) (Eigure 9), two new alkaloids with pyrrolo-pyridoazepinone heterocyclic skeletons, have been isolated from the Indonesian marine sponge... 

Benzoheteropine Rings with Two Heteroatoms on the Heteropine ring Systems with More than Two Atoms on the Heteropine Ring and Miscellaneous Ring Systems Reactivity of Benzoheteropines with Fused Five-Membered Rings... 

Properties of Benzoheteropines with Fused Five-Membered Rings Important Compounds and Applications References... 

D3)-Trishomocubane (451) is a saturated pentacyclic cage compound who carbon skeleton is made up of fused five-membered rings. The mola ule, which is intrinsically chiral, possesses the rare point group symmetry and is consequently of interest as a test system for chiroptic theories. Whereas racemic 451 has been known for more than a decade the enantiomers have recently b x me available and... 

Synthesis of the Fused Five-Membered Ring [1,2,5]Thiadiazolo[3,4-d]pyrimidine 699... 

When 1,2,5-thia- and selena-diazolo[3,4- pyrimidine-5,7-dione W-oxides are treated with sodium hypochlorite, the respective S or Se atom is replaced by O to give 1,2,5-oxadiazoles, as shown in Scheme 82 (precise yields not given) <2000CHE1359>. A more vigorous oxidation leads to ring-opening of the fused five-membered ring (see Section 10.13.5.4). 

This section provides a critical evaluation of synthetic methods available for the preparation of the most common compounds. Most heterocyclic systems included in this review are made by only one of the following protocols synthesis of the fused srx-membered ring (Section 10.13.9.1), synthesis of the fused five-membered ring (Section... 

Tricyclic Systems Central Carbocyclic Ring with Fused Five-membered Rings... 

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