Diquinane synthesis

Diquinane synthesis. 2-( 4-.Alken> i diquinanes on oxidation with tris( 4-bromophi temperature. 

D.i.d. Diquinanes. The successful execution of AHRs for the formation of 6,6- and 6,5-ring systems from prochiral substrates clearly suggested an extension of the method to the formation of 5,5-systems, which form the backbone of a large number of natural products. The use of prochiral cyclopentadienyl systems, however, involves the generation of a rr-allylpalladium species, which must then be trapped with a suitable nucleophile. " The greater reactivity of the 1,3-diene substrate toward the silver salts used in the reactions and the propensity for undesirable side reactions such as Diels-Alder cycloadditions must also be borne in mind. The former problem, in fact, figures prominently in the first example of an AHR-based diquinane synthesis to be published (Scheme... 

An electron-enriched 1,3-diene moiety as in the substrate 381 can act as a nucleophile toward an activated alkyne moiety (Scheme 94). Iwasawa340 has reported an elegant synthesis of a diquinane framework 382, which is catalyzed by various metals and the rhenium(i) complex appears to be the best catalyst among the metal complexes examined. Minor product 384 presumably is formed through an insertion of a carbenoid species into the neighboring activated benzylic C-H bond. The same carbenoid species can undergo a 1,2-H shift to give the major product 383. 

The homoenolate conjugate addition has been used very recently by Paquette and Cheney [17] to synthesise the key diquinane intermediate 18 in their studies directed towards the total synthesis of trixikingolide (Scheme 5.13). 

From an exhaustive retrosynthetic analysis and from the experimental work performed by Curran [29] [32], it was clear that the synthesis of modhephene required an elaborate strategy. In the first place, the tandem radical cyclisation should be conducted individually rather than just in one step since it allows more flexibility. In the second place, Curran s observation that the precursor of modhephene (54) could be the olefmic exocyclic derivative 55 allows the application of a series of heuristic principles already familiar to us, which greatly simplifies the retrosynthetic analysis and leads to diquinane and, finally, through a second radical retroannulation to the very simple cyclopentanone derivative (Scheme 7.24). 

The first total synthesis of kelsoene was achieved by Mehta and Srinivas [7, 8]. The tricyclic scaffold was established by an intermolecular [2+2]-photocycloaddition of diquinane enone rac-6 and 1,2-dichloroethylene (7) as the key step (Scheme 2). As a consequence of the steric hindrance implemented... 

In the first total synthesis of kelsoene (rac-l) [7, 8], commercially available 1,5-cyclooctadiene (11) was chosen as the starting material (Scheme 3). Oxidative cyclization with a mixture of PdCl2 and Pb(OAc)4 in acetic acid led to the formation of a diquinane diacetate [13] that was saponified to give... 

In a succeeding publication, the same authors reported on an enantiose-lective approach to diquinane enones 6 and ent-6 by combining the above-described synthesis with an enzymatic kinetic resolution (Scheme 4) [12]. After lipase-catalyzed enantioselective transesterification of diol rac-12. 

In a study which was conducted simultaneously to the work in the Mehta group and which also aimed to prove the absolute configuration of natural kelsoene (1), Schulz et al. used a stereoselective approach starting from the enantiomerically pure chiral pool material (i )-pulegone 17 [9, 10] (see above). The final steps of their synthesis of the unnatural enantiomer of kelsoene (ent-l) were similar to the above-described first total synthesis of natural kelsoene (1) (Scheme 8). Taking into account the steric limitations of the system as communicated by Srinivas and Mehta, diquinane enone ent-6... 

A stereoselective synthesis of compounds possessing an oxepane ring fused to a diquinane or a bicyclo[4.2.0]octane moieties using photochemical reactions of a common precursor 115 (Scheme 51) is developed the latter compound is related to sterpurane, another class of bioactive sesquiterpenes <2003TL475>. 

The fadal diastereoselectivity of intermolecular cyclopentenone [2 + 2]-photocy-cloaddition reactions is predictable if the cyclopentenone or a cyclic alkene reaction partner is chiral. Addition occurs from the more accessible side, and good stereocontrol can be expected if the stereogenic center is located at the a-position to the double bond. In their total synthesis of ( )-kelsoene (11), Piers et al. [22] utilized cyclopentenone 9 in the [2 + 2]-photocycloaddition to ethylene (Scheme 6.5). The cyclobutane 10 was obtained as a single diastereoisomer. In a similar fashion, Mehta et al. have frequently employed the fact that an approach to diquinane-type cis-bicydo [3.3.0]octenones occurs from the more accessible convex face. Applications can be found in the syntheses of (+)-kelsoene [23], (—)-sulcatine G [24], and ( )-merri-lactone A [25]. 

Four basic structural arrangements as shown in Scheme 16 have so far proven to be of broad utility in synthesis a parent type (I), with a minimal but very variable set of functionalities, and three more target-oriented complexer units (II)-(IV). The bold lines in the formulae depicted emphasize the functionality pattern characteristic of each representative, constituting in sum a fully flexible and complementary set of possible synthetic modifications at the diquinane core. 

The Nazarov cyclization has been featured in a variety of synthetic endeavors involving both natural and unnatural products. In the area of polyquinane natural products ( )-hirsutene (88), ( )-mod-hephene (89), ( )-silphinene (90), ( )-A 2)-capnellene (91) and ( )-cedrene, have all been prepared (Scheme 37). The synthesis of (91) is noteworthy in the iterative use of the silicon-directed Nazarov cyclization. TIk divinyl ketones were constructed by the carbonylation-coupling of enol triflates (92) and (95) with the -silylvinylstannane (Scheme 38). llie diquinane (94), obtained from Nazarov cyclization of (93), was transformed into enol triflate (95) which was coupled with the -silylvinylstaimane as before. Silicon-directed Nazarov cyclization of (96) was highly diastereoselective to provide the cis,anti,cis isomer of (16). The synthesis was completed by routine manipulations. 

The classical (Grignard-like) mechanism for Barbier reactions involves the primary formation of an Sm-alkyl species via halogen abstraction and subsequent reduction of the alkyl radical formed after the first electron transfer. Be that as it may, the Barbier reaction can be used to construct complex polycyclic target molecules, e.g. the synthesis of tetraquinanes from diquinane precursors by two independent intramolecular cyclization steps (Scheme 24) [83]. 

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