Cembrene synthesis

Cembrene synthesis (5,473). The complete report of the synthesis of cem-brene by coupling of two terminal allylic bromides is available... 

The method for forming cycloolefins from bis-allylic halides and nickel carbonyl was first reported by Corey and coworkers [135] and has been appli to the synthesis of several macrocycUc natural products [136]. The 14-membered diter-pene cembrene (225) was synthesized by Dauben et al. [136b], for example. As... 

The closure of the macrocyclic ring by means of an intramolecular 8 2 reaction is a straightforward approach, and sulfur-stabilized carbanion alkylation has been successfully applied in the synthesis of 14-membered cembranoids. The synthesis of nephthenol (40) and cembrene A (59) is an example of this methodology. In Li and Yue s report, the total synthesis of ( )-sarcophytol M (17) was achieved from ger-aniol (137) through 12 steps and in 8.9% overall yield with an intramolecular nucleophilic addition of a sulfur-stabilized carbanion to a ketone as a key step. This example is the first of the closure of a macrocyclic ring with the intramolecular nucleophihc addition of a sulfur-stabilized carbanion to a ketone (Scheme 6-7). 

The closure of the macrocyclic ring by means of an intramolecular Sn2 reaction is a straightforward approach. For example, an intramolecular nucleophilic addition of sulfur-stabilized carbanion to epoxide was used in the synthesis of nephthenol (40) and cembrene A (59) from trani.tran -geranylhanlool (144) (Scheme 6-10). ... 

The first enantioselective total synthesis of l -(—)-cembrene A (59) and / -( )-nephthenol (40) were achieved by employing an intramolecular nucleophilic addition of sulfur-stabilized carbanion to asymmetric epoxide as the key step, starting from L-serine (Scheme 6-13). ... 

Yue et al. reported on the total synthesis of / -(—)-cembrene A by using the mod-ihed Wittig reaction and titanium-induced intramolecular carbonyl coupling as key steps the overall yield is 29% starting from -geranylacetone (164) and R-(+)-limonene (168) (Scheme 6-15). ... 

Li et al. reported on the total synthesis of cembrene C from geraniol (137) or trans, frani-famesol (91) by using the titantium-induced intramolecular coupling of the dicarbonyl precursor keto enal 176 as the key macrocyclization step (Scheme 6-17). 

Stereoselective construction of the epoxide functionality in the macrocyclic cembrene skeleton comprises a challenging task for total synthesis. We report herein the completion of the total syntheses of the above cembranoxides in detail. 

Starting from the chiral pool (/f-(+)-hmonene), the total synthesis of natural (-f)-3,4-epoxycembrene A (56) has been achieved by Liu et al. with the low-valent titanium-mediated intramolecular pinacol couphng of the corresponding sec-keto aldehyde precursor 171 (Scheme 6-25). A more general and efficient enantioselective synthesis of (+)-3,4-epoxy-cembrene A (56) with a chiral pool protocol and Sharpless asymmetric epoxidation for the introduction of three chiral centers has also been reported by the same authors in 2001 (Scheme 6-26). ... 

Characteristic to some important cembrane diterpenoids, such as isocembrene, cembrene, cembrene C, and sarcophytol A, is a 1,3-diene unit in the macrocyclic skeleton. In continuation of our ongoing project on the total synthesis of cembrane-type diterpenoids, we intended to explore a novel macrocyclization method to... 

Thus, an efficient and convergent total synthesis of ( )-isocembrene has been accomplished in seven steps from the known geranylacetone through an intramolecular Stille cross-coupling reaction. The strategy is of great potential for the divergent synthesis of complex cembrane-type diterpenoids such as cembrene-C and sarcophytols. 

The availability of the triene (108) prompted the preparation of all m-cembrene A (110) which was achieved by standard methods. Thus, five of the eight possible 3,7,11,15-cembratetraenes have been prepared. Of these, the 3 ,7 ,11 ,15- and the 3Z,7 ,11 , 15-isomers have been found as natural products and prepared by synthesis. The 3 ,7Z,11 ,15-, 3 ,7 ,11Z,15- and the 3Z,7Z,1 lZ,15-isomers have been synthesized only (16). 

The ring-forming step in a reported synthesis of cembrene was the nickel tetra-carbonyl-catalysed cyclization of acetoxy-dibromide (37 = H, = OAc) to the... 

Wender has applied his macroexpansion methodology to the synthesis of cembrene A in optically active form, starting with (+)-0 0... 

Tietze has also applied his method for the synthesis of natural products [83], Recently, he has prepared precursors for the synthesis of polyoxygenated cembrene 60 [84] and (/ )-(+)-orizaterpenyl benzoate 64 [85] by using the auxiliaries 58 and 62, respectively, under trifluoromethane-sulfonic acid catalysis (Scheme 12.17). 

The intramolecular coupling reaction has allowed the synthesis of cembrene (CXV), a 14-membered diterpene (Dauben et al., 1974). 

Kodama, M., Shimada, K., and ltd, S. (1977) Synthesis of macrocyclic terpenoids by intramolecular cydization. 111. Model reactions for the synthesis of cembrene and thimbergol derivatives. Tetrahedron Lett., 18, 2763-2764. 

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