Pentalene, synthesis

This type of asymmetric conjugate addition of allylic sulfinyl carbanions to cyclopen-tenones has been applied successfully to total synthesis of some natural products. For example, enantiomerically pure (+ )-hirsutene (29) is prepared (via 28) using as a key step conjugate addition of an allylic sulfinyl carbanion to 2-methyl-2-cyclopentenone (equation 28)65, and (+ )-pentalene (31) is prepared using as a key step kinetically controlled conjugate addition of racemic crotyl sulfinyl carbanion to enantiomerically pure cyclopentenone 30 (equation 29) this kinetic resolution of the crotyl sulfoxide is followed by several chemical transformations leading to (+ )-pentalene (31)68. 

Of the fundamental nonalternant hydrocarbons, only two prototypes were known about fifteen years ago azulene (XI, Fig. 5), the molecular structure of which was determined by Pfau and Plattner and fulvene (XIX) synthesized by Thiec and Wiemann. Early in the 1960 s many other interesting prototypes have come to be synthesized. Doering succeeded in synthesizing heptafulvene (XX) fulvalene (XXI) and heptafulvalene (XXIII). Prinzbach and Rosswog reported the synthesis of sesquifulvalene (XXII). Preparation of a condensed bicyclic nonalternant hydrocarbon, heptalene (VII), was reported by Dauben and Bertelli . On the other hand, its 5-membered analogue, pentalene (I), has remained, up to the present, unvanquished to many attempts made by synthetic chemists. Very recently, de Mayo and his associates have succeeded in synthesizing its closest derivative, 1-methylpentalene. It is added in this connection that dimethyl derivatives of condensed tricyclic nonaltemant hydrocarbons composed of 5- and 7-membered rings (XIV and XV), known as Hafner s hydrocarbons, were synthesized by Hafner and Schneider already in 1958. 

Sequential pyrrolidine and hydantoin ring-forming reactions via intramolecular [2+3] cycloaddition have been applied to the stereoselective solid-phase synthesis of conformationally constrained tricyclic triazacyclopenta [C]pentalene scaffold 43 < 1999JOC8342>. These novel compounds 43 share the structural complexity characteristic of certain alkaloid natural products, angular triquinanes. The retrosynthetic analysis is shown in Scheme 87. 

A synthesis of annulated oxadithiadiazapentalene 130 can be achieved by the cyclization of 1,3-dioximes with sulfur monochloride. Moderate yields were accompanied by a small amount of dioxathiadiazapentalene 131. Although yields of pentalenes 130 were from low to moderate, it still is the most convenient route to all known compounds of this class (1979BSF199, 1984USP4440564, 1985JPP62036388, 1985JCS(P2)1797 Scheme 65). 

Paquette, asymmetric synthesis of 15-nor-pentalene by Pericas and Moyano, and the synthesis of the D/E ring in pentacyclic steroid xestoergsterol as described by Krafft (Equation (43)). ... 

Intramolecular [2 + 2] photocycloadditions of 3-alkenylcyclopent-2-enones represent the key step in the total synthesis of various natural products, e.g. pentalenolactone 6-methyl ester19 and pentalenic acid,20 as well as in the preparation of strained fenestranes21 and laurenene.22 Similarly, the photoisomerization of 3-alkenylcyclohexcnoncs to tricyclo[6.3.0.01-6]undecanones are steps in the syntheses of tricyclic sesquiterpene isocomene23 and precursors to members of the acorane family.24... 

The effect of substituents at the a-carbon of the enone on the stereoselectivity was examined on compounds 270, with the stereogenic center located at the alkenyl side chain. Crimmins and DeLoach122 found that the stereoselectivity encountered upon irradiation of 270 depends on the degree of steric hindrance associated with the ester group linked to the double bond. The ratio of the two epimeric centers at the C-9 position varied from 13 1 (R = Me) to 17 1 (R = Et), then 20 1 (R = i-Pr). These results demonstrate that steric effects play an important role in controlling the stereofacial selectivity in these and related systems. Fragmentation of the photoproduced four-membered ring and simple transformations afforded synthesis of ( )-pentalene 274, (i)-pentalenic acid 275 and (i)-deoxypentalenic acid 276 (Scheme 59). 

Bis(pentalene) uranium complexes, preparation, 4, 221—222 Bis(pentamethylcyclopentadienyl)actinide(IV) compounds, synthesis and reactions, 4, 210 Bis(pentamethylcyclopentadienyl)actinide(V) compounds, synthesis and reactions, 4, 210 Bis(pentamethylcyclopentadienyl)actinide(VI) compounds, synthesis and reactions, 4, 210... 

Cyclopentadienyl rings, in chromocenes with heteroatom substitutions, 5, 330 with pentalene rings, 5, 331 with substitutions, 5, 329 Cyclopentadienyl ruthenocenes, synthesis, 6, 639 Cyclopentadienyl—silylamido complexes, with Zr(IV) and Hf(IV) and monodentate ligands, 4, 852 Cyclopentadienyl—silylamido dienes, with Zr(IV) and Hf(IV),... 

These 107i-systems are isoelectronic with the pentalene dianion and have been of some theoretical interest. 1,5-Diheteropentalene systems are very popular substrates for the investigation of inter- and intramolecular cycloaddition reactions due to their diene character. Such cycloaddition processes allow for a rapid entry into complex polyheterocyclic rings and makes these compounds potentially useful for natural product synthesis. 

Erhardt, J. M. Grover, E. R. Wuest, J. D. Transfer of hydrogen from orfhoamides. Synthesis, structure, and reactions of hexahydro-6bH-2a,4a,6a-triazacydopenta[cd pentalene and perhydro-3a,6a,9a-triazaphenalene. /. Am. Chem. Soc. 1980, 102, 6365-6369. 

K. Gloe, H. Granbaum, M. Wiist, et al., Macrocyclic and open-chain ligands with the redox switchable trithiadiaza-pentalene unit synthesis, structures... 

The question of aromaticity versus antiaromaticity and delocalized versus localized double bonds in pentalene (2) dates back to 1922, when Armit and Robinson compared it with naphthalene and postulated that the former might be similarly aromatic [32, 33]. While the first synthesis of a non-fused hexaphenylpentalene (38) [30] provided only some clues as to the non-aromatic reactivity of the pentalene skeleton, the tri-tert-butyl derivative 39, prepared and studied by Hafner et al. in great detail [31], gave a better insight. The ring-proton signals of this alkyl-substituted pentalene 39 are shifted upfield compared to those of fulvene (27) and other cyclic polyenes. This observation led to the conclusion that the pentalene derivative 39 should be an antiaromatic species. However, the results did not permit a distinction... 

Cook has developed in recent years a tandem PKR towards the synthesis of pentalenes, that is, linear [5.5.5.5] systems. Their first studies used suitable diendiynes 141-143 that gave the corresponding tetracyclic bis-cyclopentenones. These were described as precursors of dicyclopenta[a, d] (144) and [a, e] pentalenes (145). The same methodology allowed the synthesis of [5.6.6.5] systems (146) where the central decaline system was cis fused (Scheme 43) [150-152]. This group succeeded in tuning up efficient photochemical catalytic conditions for these reactions [153]. 

Scheme 45 The synthesis of a dicyclopenta[a,e]pentalene via molybdenum-mediated tandem allenic PKR...

The peculiarity of the pentalene molecule resides in its central bond which connects nonalternant atoms (a perturbed [8]annulene), its completely conjugated and alternating w bond periphery, and its apparent antiaromatic nature. The transannular bond conveys planarity to the structure without contributing to its stabilization. Consequently, pentalene is expected to be highly reactive since, in a sense, it has ground state properties customarily found in excited states. The many early attempts to synthesize pentalene have been reviewed224-226 and will not be considered per se here. Suffice it to say that the lability of minimally substituted pentalenes ultimately required the implementation of rather specific reaction conditions for their successful synthesis (vide infra). 

The dark blue crystalline l,3-bis(dimethylamino)pentalene (157) was the second derivative to yield to synthesis (Scheme 26).233-1 Upon condensation of sodium cyclopentadienide with the salt 153, there is obtained the fulvene 154 which can be cyclized with loss of dimethylamine when heated in xylene. Treatment of the resulting ketone (155) with dimethylammonium perchlorate afforded the salt 156 which was successfully deprotonated with isopropylmagnesium bromide. Interestingly, 155 could be reversibly converted to its blue-colored enolate without polymerization or decomposition. 

SP synthetic strategy to 3.83 The designed synthesis included as a final step the formation of an urea on 3.89 with simultaneous intramolecular cyclization on the carboxylic ester (Fig. 3.34) the use of an ester function to support the 3.89-like intermediate would have allowed the cyclative cleavage of the desired hexahydro-2,3a,7-triazacyclopenta[c]pentalene-l,3-dione. The use of classical PS resins was not prevented by any of the transformations needed to give 3.83. 

The concept of torquoselectivity is now accepted as an extension of the Woodward-Hoffman rules. It has been used as a guide for synthetic chemists to prepare the appropriate stereoisomer. Examples include Danishefsky s exploitation of the stereoselective ring opening of fran5 -l,2-disiloxybenzocyclobutenes 133 to prepare idarubicin, Paquette s use of the electrocyclization of 134 that ultimately leads to a very efficient synthesis of pentalene, and Murakami s ... 

Oxidation reactions of this nature are common in the literature. For example, selenium dioxide in refluxing etiumolic solution brought about the allylic oxidative rearrangement geranyl acetate, which was further functionalized in a synthesis of the norsesquiterpenoid gytinidal (equation 46). This trans formation was also used in a total synthesis of phytol. Similarly, an a, -unsaturated aldehyde was obtained undm similar conditions in studies of a synthesis of pentalenic acid derivatives (equation 47). ... 

The pentalane class of sesquiterpenoids has received substantial attention in the past year from the standpoints of structural elucidation, biosynthesis, and synthesis. Two new metabolites of this class are pentalenic acid (298) and pentalenolactone H (299). Both these compounds have a secondary hydroxyl function adjacent to the gem-dimethyl group and are thus potential precursors of pentalenolactone (300) in which one of these methyl groups has undergone a 1,2-migration. Cane and Rossi " have now identified a further metabolite of a Streptomyces strain which has been named pentalenolactone E (301) and is now... 

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