Polyenes stereoselectivity

If alkyl groups are attached to the ylide carbon atom, cis-olefins are formed at low temperatures with stereoselectivity up to 98Vo. Sodium bis(trimethylsilyl)amide is a recommended base for this purpose. Electron withdrawing groups at the ylide carbon atom give rise to trans-stereoselectivity. If the carbon atom is connected with a polyene, mixtures of cis- and rrans-alkenes are formed. The trans-olefin is also stereoseiectively produced when phosphonate diester a-carbanions are used, because the elimination of a phosphate ester anion is slow (W.S. Wadsworth, 1977). 

Open-chain 1,5-polyenes (e.g. squalene) and some oxygenated derivatives are the biochemical precursors of cyclic terpenoids (e.g. steroids, carotenoids). The enzymic cyclization of squalene 2,3-oxide, which has one chiral carbon atom, to produce lanosterol introduces seven chiral centres in one totally stereoselective reaction. As a result, organic chemists have tried to ascertain, whether squalene or related olefinic systems could be induced to undergo similar stereoselective cyclizations in the absence of enzymes (W.S. Johnson, 1968, 1976). 

The early Escherunoser-Stork results indicated, that stereoselective cyclizations may be achieved, if monocyclic olefins with 1,5-polyene side chains are used as substrates in acid treatment. This assumption has now been justified by many syntheses of polycyclic systems. A typical example synthesis is given with the last reaction. The cyclization of a trideca-3,7-dien-11-ynyl cyclopentenol leads in 70% yield to a 17-acetyl A-norsteroid with correct stereochemistry at all ring junctions. Ozonolysis of ring A and aldol condensation gave dl-progesterone (M.B. Gravestock, 1978 see p. 279f.). 

Crotonaldehyde, hydrogenation of, 43-48 Cubane, isomerization of, 148 Cyclic dienes, metathesis of, 135 Cyclic polyenes, metathesis of, 135 Cycloalkenes, metathesis of, 134-136 kinetic model, 164 ring-opening polymerization, 143 stereoselectivity, 158-160 transalkylation, 142-144 transalkylidenation, 142-144 Cyclobutane configuration, 147 geometry of, 145, 146 Cyclobutene, metathesis of, 135 1,5,9-Cyclododecatriene, metathesis of, 135... 

The theory of stereoselectivity found in intramolecular hydrogen migration in polyenes was disclosed by Woodward and Hoffmann 51>. The HO—LU interaction criterion is very conveniently applied to this problem 64>. The LU of the C—H sigma part participates in interaction with the HO of the polyene n part. The mode of explanation is clear-cut... 

Similar schemes can be developed easily for analogous reactions of acceptor-substituted polyenes. For example, a triene with an acceptor group in 1-position can form six regioi-someric products of Michael addition and electrophilic capture, and each of these exists as E/Z stereoisomers, diastereomers and/or enantiomers. Thus, reactions of this type are only useful if both the regio- and stereoselectivity can be controlled fortunately, only one isomeric Michael adduct is formed in many cases. This is true in particular for polyunsaturated Michael acceptors which bear at least one triple bond besides one or more double bonds. An additional feature of the latter substrate type is that nucleophilic additions can... 

Brevetoxin B (79) is one of the most representative polyether compounds, which was isolated by Nakanishi, Clardy, and co-workers, from Gymnodynium breve Davis [36]. Nakanishi and co-workers postulated the biosynthetic pathway of 79 as shown in Scheme 7.21, that is, stereoselective oxidation of polyene 80 would give... 

A closely related special case of metathesis is the conversion of cycloalkenes under metathesis conditions, known as ring-opening polymerization or metathesis polymerization (see Section 12.2). Macrocyclic polyenes and polymers, called poly-alkenamers, are formed with high stereoselectivity ... 

Johnson in 1993 described an approach to racemic p-amyrin involving application of a biomimctic polyene cyclization.7 In the same year Corey accomplished the enantioseleetive synthesis of compound 4. a key intermediate that opened the way to stereoselective preparation of compounds I, 2. and 3 8 A key step in the synthesis of P-amyrin (1) was the introduction of chiral oxazaboroli-dines for enantioseleetive carbonyl reduction. Ba ed on these methods, generation of an enantiomerically pure epoxide and its stereoselective cationic cyclization led to the pentacyclic system of structure 1 Diastereoselective cyclopropanation and an intramolecular protonation of a carbanion represent other interesting steps in this total synthesis. 

The Shi epoxidation has found several applications in total synthesis [15]. Particularly attractive are examples in which it has been used to establish the stereochemistry of polyepoxides which can undergo cascade cyclizations to polyether products, mimicking possible biosynthetic pathways. An example is the construction of the tetahydrofuran rings of the natural product glabrescol via highly stereoselective formation of the tetraepoxide 10 from the polyene 9 (Scheme 12.6) [22]. 

Figure 8.13 Stereoselective syntheses of (Z)-alkenes, and all-(Z)-dienes and polyenes.

Condensations between aldehydes and metalated phosphonic acid dialkyl esters other than those mentioned previously are also referred to as Homer-Wadsworth-Emmons reactions. Nevertheless, in these esters, too, the carbanionic center carries a substituent with a pi electron withdrawing group, for example, an alkenyl group, a polyene or a C=N group. The Homer-Wadsworth-Emmons reactions of these reagents are also stereoselective and form the new C=C double bond /ra/ ,v-selectively. 

Stereoselective synthesis of the C11-C16 fragment of the polyene macro-lide antibiotic, pentamycin, has also been accomplished under the aldolase protocol.45 A formyl and benzyl protected aldehyde, available from D-glucose by chemical methods, reacts with DHAP under the influence of FDP aldolase. After phosphatase hydrolysis the essential C11-C16 skeleton of pentamycin is generated. Removal of an additional hydroxyl group at position 1 and isolation of the C11-C16 fragment as a thioacetal, is accomplished in several steps (Scheme 5.23). 

Rychnovsky and his group have recently developed new synthetic methods that lead to the total syntheses of the polyene macrolides roxaticin [2], roflamycoin [3], and filipin III [4]. The polyol chains of all three natural products were constructed by iterative, stereoselective alkylation of lithiated cyanohydrin acetonides and subsequent reductive decyanation, illustrated here by the synthesis of the polyol framework of filipin III (1) (Scheme I). The bifunctional cyanohydrin acetonide 2, prepared by ruthenium/BINAP catalyzed enantioselective hydrogenation of the corresponding ) -keto ester (BINAP = [ 1,1 -binaphthyl]-2,2 -diylbis(diphenylphosphane)), is deprotonated with LiNEt2 and alkylated with 2-benzyloxy-l-iodoethane. The alkylation product 3 is converted by a Finkelstein reaction into the iodide 4, which is used to alkylate a second... 

Tetrabromocyclohexadienone has been shown to be an efficient alternative to A -bromosuccinimide for the preparation of terminal bromohydrins of polyenes like squalene/° A stereoselective synthesis of mokupalide (4), an unusual head-to-tail linked hexaprenoid from a marine sponge, is summarized in the Scheme. ... 

Polyene cyclization. Cyclization of dienes by oxymercuration ordinarily is not stereoselective. However, the presence of an allylic hydroxyl groups can increase the stereoselectivity. Thus oxymercuration-demercuration of linalool (1) under the best conditions leads mainly to the iridanols 2 and 3, which constitute 85% of the... 

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