Polyene Cyclisations

Of particular interest and of industrial relevance are the attempts to make Ceta/oA and Ambrox accessible using biomimetic approaches. 

0Cabredva oil is obtained by steam distillation from the tropical Brazilian wood Myrocarpus fastigiatus. (Cabreuva is the name of a district in Brazil, near Sao Paulo.)The main constituent of the oil is the sesquiterpene nerolidol. 

The central starting material for the preparation of homofarnesic acid and homofarnesol is (+)-( )-nerolidol, which can be obtained from Cabreuva oil by fractional distillation. 

Racemic ( )-nerolidol is obtained, equally easily, from linalool using dike-tene or methyl acetoacetate by a Carroll reaction and treatment with vinylmag-nesium chloride. Alternatively, linalool can be treated with diketene or isopro-penyl methyl ether (Saucy-Marbet reaction) instead of the Grignard reaction, the intermediate undergoes an addition of acetylene, followed by a Lindlar hydrogenation. [244] 

The conversion of nerolidol into homofarnesylic acid, either via the corresponding bromide, its substitution by cyanide and hydrolysis, or by direct carbonyl-ation, [245] produces a mixture of (3 /2,7 )-isomers. 

---

A novel sodium ion templated polyene cyclisation reaction has been proposed for the biosynthesis of tetronasin, based on biomimetic studies [91]. This... 

Carbon monoxide Ketone synthesis using cyanide ion Reactions with a-halo-carbonyl compounds Polyene Cyclisations Looking Forwards... 

Recent developments include asymmetric polyene cyclisations but also include new ways to initiate cyclisations. Iron tricarbonyl stabilises pentadienyl cations and its complexes with dienes are chiral. Addition of the achiral lithium derivative 268 to the chiral complex 269 gives the polyene precursor 270 that cyclises with Lewis acid to give a single diastereoisomer of the bicyclic compound43 271. 

An asymmetric polyene cyclisation (asymmetric tandem Heck) has been reported in the synthesis of the pentacyclic polyketide (-l-)-xestoquinone. ... 

Very detailed mechanistic studies on polyene cyclisation have been pursued by Roger Snowden at Firmenich. [254] Cyclisation of the tricyclic system is initiated by terminal protonation, and anti-addition to the double bonds of the nascent six-membered rings occm-s from their chair conformations. Whether or not the cyclisation proceeds in a concerted manner, according to the Stork-Eschenmoser hypothesis, cannot be resolved from the experimental data. A stepwise process, in which the bond indicated in red is formed first, is equally conceivable. The following ring closure giving or 9b-epi-Ambrox is... 

The unquestionably most elegant total synthesis of Ambro is achieved by an enantioselective polyene cyclisation. For this reaction, Hisashi Yamamoto used an enantiomericaUy pure Lewis acid / Bronsted acid from 0-(o-fluoro-... 

The enantioselective polyene cyclisation of squalene to the pentacydic hopene and hopanol ranks as one of the most complicated biochemical reactions. In a single step, nine stereogenic centres are formed. Hopene is one of 512 (2 ) possible stereoisomers. 

Polyene cyclisation in squalene-hopene cyclase. (D aspartic acid, F Phenylalanine, H Histidine,... 

Polyene cyclisations of homofarnesol and homofarnesylic acid constitute especially elegant total syntheses. 

Q Bloch had to flee as a Jew from the Nazi regime in 1936 via Switzerland to the USA. At Columbia University in New York, he was able to show together with David Rittenberg in 1942, using isotopically labelled acetate, that this was a precursor for the cholesterol synthesis in animals. The polyene cyclisation of the triterpene squalene produces lanosterol, which is degraded to cholesterol, the central intermediate of all human steroids. [350]... 

A pioneering step in synthetic poiyene cyciisation for the preparation of steroids was the synthesis of racemic progesterone in a few stages and with excel-ient yields by Wiiiiam S. Johnson (1913-1995) in 1971. [8] The first diastereo-selective polyene cyciisation, starting from an enantio-merically pure epoxide, originates from Elias J. Corey cf. section 3.7.5 - Polyene cyclisations). [9]... 

Mechanistical details of polyene cyclisation B. A. Hess, L. Smentek, Angew. 

A spectacular application of chiral acetals is in the biomimetic polyene cyclisation to give the steroid skeleton (106) made famous by Johnson. jjere no fewer than seven new stereogenic centres are created in one step. 

Braddock DC, Marklew JS, Thomas AJF. Enantiospecific bromonium ion generation and intramolecular capture a model system for asymmetric bromonium ion-induced polyene cyclisations. Chem. Common. 2011 47(32) 9051-9053. 

---