Cyclooctane synthesis

An illustrative example of the potency of the second-generation Ru catalyst C is found in Paquette s highly efficient total synthesis of the natural products teubrevin G (122) and teubrevin H (123), which feature a cyclooctane core fused and spiroannulated to smaller oxygen-containing rings [76]. In the retrosyn-thetic analysis, the viability of an RCM step for annulation of a cyclooctenone ring to the furan played a central role. 

Intramolecular cycloadditions of a,p-unsaturated lactones to alkenes have been used as key step in the synthesis of a precursor of the terpene reserpine 480) (4.68) and of fused cyclooctanes (4.69) 481 ... 

Synthesis, Stereochemistry and Transformations of Cyclopentane-, Cyclohexane-, Cycloheptane-, and Cyclooctane-Fused 1,3-Oxazines, 1,3-Thiazines, and Pyrimidines... 

The final chapter in Volume 69 is concerned with the synthesis, stereochemistry, and transformation of cyclopentane-, cyclohexane-, cyclohep-tane-, and cyclooctane-fused 1,3-oxazines, 1,3-thiazines, and pyrimidines and is authored by Professors Ferenc Ftilop, Gabor Bernath, and Kalevi Pihlaja from the Universities of Szeged in Hungary and Turku in Finland. This is a field which has shown rapid development over the last dozen years because of the increased availability of spectroscopic and other analytical methods allowing definition of the precise steric chemistry of these compounds. 

The reaction of 1,2-dicarbonyl compounds with amidrazones, semicarbazide, thiosemicarbazide and aminoguanidine has also been used for the synthesis of condensed 1,2,4-triazines. Cyclohexane-, cycloheptane- and cyclooctane-1,2-diones (489) with amidrazones (453) afford the cycloalkatriazines (490) (78HC(33)189, p.66l). 

Cycloadditiom. This reaction provides an enantioselective synthesis of a cyclooctane-containing terpenoid (5). The optically active precursor (3) was obtained by reduction of the r-alkyl alkynyl ketone 1 with lithium aluminum hydride... 

Asteriscanolide (65) is a cyclooctane sesquiterpene lactone that has been synthesised by a number of groups who have employed a variety of different strategies. In 2001, Krafft and co-workers developed a strategy that utilised the intermolecular PK reaction as a key step in its synthesis (63- 64 - Scheme 23).71... 

Because of the excellent performance of the new catalysts, many research groups use ringclosing metathesis as the key step in natural product synthesis [12]-[18]. Scheme 6 shows some examples. Via ring-closing metathesis of the olefin 37 to the hydroazulene 38, Blechert et al. [12] succeeded in synthesizing a cyclic system which is part of many sesquiterpenes. Cyclooctane derivatives, whose synthesis is the main problem in taxol synthesis, can be obtained in good yields (39 40), as demonstrated by Grubbs et al. [ 13]. 

Section 1.13.5 Miscellaneous reactions. Takeshita and coworkers reported the remarkable use of intramolecular ene reactions to form cycloheptanes and cyclooctanes. Pyrolysis of (216) in toluene at 200 C gives 97% of the cycloheptane (215). Reaction of (216) with SnCU in THF gives 85% of cyclooctane (217), which is an intermediate in the synthesis of cycloaraneosene. 

The nickel-mediated [4 -i- 4] cycloaddition strategy has also provided a concise and stereocontroUed route into the sequiterpene lactone (+)-asteiiscanolide (128). The basic features of this approach are outlined in Scheme 17. The critical [4 + 4] cycloaddition st occurred under standard conditions to give the key intermediate in 67% yield. Clearly, the intramolecular version of the nickel-catalyzed diene cy-clodimerization has been established as a powerful and highly-selective protocol for the synthesis of cyclooctane ring systems and should find extensive qjplication to natural product synthesis. 

Another common strategy for construction of fused cyclooctanones is to first build a fused cyclobutanone by [2 + 2] cycloaddition of a vinylketene to a cycloalkene. Equation (58) illustrates this approach with Paquette s synthesis of the tricyclic skeleton of the ophiobolins. Cyclobutanone (108) is assembled by addition of a vinylketene to cyclopentadiene. Cyclopentenyllithium then adds to the less-hindered face of (108), and the lithium alkoxide undergoes a spontaneous anionic oxy-Cope rearrangement to afford the central cyclooctane ring. 

Cyclooctyne (75) can be prepared according to the usual rhethods of synthesis of acetylenic compounds. For instance, oxidation of the bishydrazone of cyclooctane-1,2-dione (74) " " or debromination of 1,2-dibromocyclooctene (76) with magnesium or the photolysis of the anion of I-tosyIamino-1,2,3-triazole derivative (77) gave cyclooctyne (75). 

Problem 9.22 Outline a synthesis of the following alicyclic compounds from acyclic compounds, (a) 1,1-Dimethylcyclopropane (b) (c) Cyclooctane... 

Intramolecular [ 2 + 2] photoadditions in sulphur-containing systems have been employed in studies directed towards the total synthesis of dicyclopenta[a,d]cyclooctane terpenoids and in the conversion of the tetrathiadiene (145) into the propellane (146), a process in which the ease of reaction is... 

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