Alkenols, synthesis

Schlosser, M., Coffinet, D. SCOOPY [a-substitution plus carbonyl olefinatlon via P-oxido phosphorus ylides] reactions. Regioselectivity of alkenol synthesis. Synthesis 1972, 575-576. 

The intramolecular oxidative earbonylation has wide synthetie applieation. The 7-lactone 247 is prepared by intramolecular oxycarbonylation of the alke-nediol 244 with a stoichiometric amount of Pd(OAc)2 under atmospheric pres-sure[223]. The intermediate 245 is formed by oxypalladation, and subsequent CO insertion gives the acylpalladium 246. The oxycarbonylation of alkenols and alkanediols can be carried out with a catalytic amount of PdCl2 and a stoichiometric amount of CuCb, and has been applied to the synthesis of frenolicin(224] and frendicin B (249) from 248[225]. The carbonylation of the 4-penten-l,3-diol 250, catalyzed by PdCl2 and CuCl2, afforded in the c -3-hydroxytetrahydrofuran-2-aeetie acid lactone 251[226J. The cyclic acetal 253 is prepared from the dienone 252 in the presence of trimethyl orthoformate as an accepter of water formed by the oxidative reaction[227]. 

For the formation of substituted THF rings (Route a, Scheme 8.1), Kishi developed a procedure based on the hydroxy-directed epoxidation of a y-alkenol [10]. Epoxidation of bishomoallylic alcohol 3 by TBHP/VO(acac)2 by this approach, followed by treatment of the intermediate epoxide 4 with acetic acid, gave the TH F derivative 5 of isolasalocid A (a 5-exo cydization Scheme 8.2) [11]. Further epoxidation of 5 (a y-alkenol) under the same conditions, followed by acetylation, afforded epoxide 6. For the synthesis of the natural product, the configuration of epoxide 6 had to be inverted before the second cydization reaction. Epoxide 6 was consequently hydrolyzed under acid conditions to the corresponding diol and was then selectively... 

A convenient procedure for the lactonization of alkenols has been recently revealed by Borhan and coworkers [19]. This methodology was successfully applied in the total synthesis of (+)-tanikolide (7-37), a natural product of marine origin which exhibits antifungal activities. Thus, when alkenol 7-36 is subjected to soluble oxone and a catalytic amount of 0s04, a smooth domino oxidative cleavage/lactonization process takes place which leads, after debenzylation, to the desired product in good overall yield (Scheme 7.12). 

When Wacker-type reactions are performed under a CO atmosphere, the (3-H elimination pathway can be suppressed in favor of CO insertion and subsequent nucleophilic cleavage of the acyl metal species.399 This alkoxycarbonylation process has found widespread utility, particularly in the synthesis of five- and six-membered oxacyclic natural products. For example, the THF core of tetronomycin was prepared by the Pd-catalyzed alkoxycarbonylation of 4-alkenol derivatives (Equations (117) and (118)), where stereocontrol was achieved by utilizing either the directing ability of a free hydroxyl or the conformational bias imposed by a bulky silyl ether.420 Additional examples making... 

The authors gratefully acknowledge the financial support for this research by the Natural Sciences and Engineering Research Council of Canada. Tony Liu and Chris Maxwell thank the Student Work Experience Program at Queen s University for financial support during the summer of 2005. We acknowledge Farhad Nowrouzi for synthesis of a precursor to 4-chlorophenyl -4-pentenoic acid and for preliminary measurements of the e.e. for the reaction of 14- Br+ with some l,co-alkenols and alkenoic acids. 

We have found that the secret to a successful synthesis of the alkenyl glycosides 64 lies in obtaining the pure -acetate 65 [47]. Condensation of the acetate 65 with the appropriate alkenol,in the presence of a small amount (5-20 mol% depending on the scale) of trimethylsilyl triflate, gave the alkenyl glycosides 64 in excellent yield. Oxidation of the alkene 64 with dimethyldioxirane, followed by deacetylation, then gave the putative enzyme inhibitors 60. 

A mechanism has been proposed for this synthesis involving initial electrophilic attack of protonated formaldehyde on the alkene. Proton abstraction leads to the alkenol and to the pyran via the chloromethyl ether. 

When five- or six-membered ring ethers can readily be formed by intramolecular alkoxymercuration of the initially formed alkenol, cyclic ethers are often the observed product (equation 219).341 This process has recently proven useful in the synthesis of spirocyclic acetals (equation 220).342... 

The mercury(ll)-promoted cyclization of alkenols to afford chromans continues to attract attention and is seen during the synthesis of a cannabinoid analogue 397 (Equation 165) <1998JME3596>. Intramolecular cyclization of the methyl ester 398 to form the 2,2-disubstituted chroman 399 can be achieved by a tandem demethylation/cyclization sequence using AlCb/EtSH via the intermediate 400 (Scheme 94) <2000MOL880>. Cyclizations of this type can also be effected by SnCLj- <1997S23>. 

Substituted maleic anhydrides have been directly exdted, but sensitization may also be used. In some cases the first method is better, and in some cases the second. In an approach to merrilactone A, which is closely related to the earlier-mentioned synthesis (Scheme 6.30), 2,3-dimethylmaleic anhydride was employed as a starting material in a sensitized [2 + 2]-photocydoaddition to 1,2-dichlorethene [114]. The reaction of tetrahydrophthalic anhydride (120) with alkenols and alkynols was conducted by direct irradiation in a Pyrex vessel. As an example, the reaction with allyl alcohol is depicted. The exo-product 121 was the preferred product with the endo-product cydizing spontaneously to lactone 122 (Scheme 6.43) [115]. Other alkenols reacted similarly. 

The reaction between phenyl cations and alkenols represents another example of a one-pot, tandem synthesis of cyclic ethers. Accordingly, 2-ben2yltetrahydrofurans are obtained by the addition of photogenerated phenyl cations to y-hydroxyalkenes. For example, 4-penten-l-ol (a terminal alkene) reacts with phenyl chlorides bearing EDGs under irradiation in polar protic solvents, suchasTFE oramixture MeCN/H20 (Scheme 10.57) [72],... 

Both Z- and E-configurations of carbon-carbon double bond are an important structural moiety of insect pheromones. The synthesis of unsaturated alcohols has attracted considerable attention of organic chemists in recent years because such alcohols and their acetates are known to be insect sex attractants. Recently, a very convenient, general, one pot synthesis of Z alkenols132) and Z-alkenols 133) via organoboranes has been reported. 

Reduction of la-alkynols to (E)-alkenols." This reaction is often one step in the synthesis of insect pheromones. Sodium in liquid ammonia is generally preferred for this reduction (5, 590). An alternative, general method is reduction with a large excess of lithium aluminum hydride in diglyme-THF. 

Synthesis of Tetrahydrofurans by Cyclization of 4-Alkenols Mediated by Palladium(II) or Palladiuin(O)... 

The synthesis of 5-substituted tetrahydro-2-vinylfurans, starting from 4-alkenols, proceeds with a catalytic amount of palladium(II) acetate, in the presence of copper(ll) acetate, under oxygen atmosphere in methanol/water. The resulting 2,5-disubstituted tetrahydrofurans are obtained in moderate yield. When (E)-1 -phenyl-4-hcxcn-1 -ol (1) is used as starting material, traus-tetrahydro-2-phenyl-5-vinylfuran (2) is the sole compound isolated from the reaction mixture, albeit in 40% yield40. 

Diastereoselective Synthesis of 2,6-Disubstituted Tetrahydro-2//-pyrans via Alkoxycarbonylation of Alkenols... 

Organoaluminium compounds have been utilized for alkynylation of alicyclic oxiranes in prostaglandin synthesis and for the preparations of m-alkenols (Eq. 252). ° ... 

On PhI(OAc)2-promoted oxidation in CH2CI2 containing alkenol (5 equiv.) at room temperature, 2-methoxyphenols such as 421 (R = Me and COOMe) were converted into the corresponding tricyclic compounds (444 and 445) in 77 and 75% yields, respectively (Scheme 86) via an intramolecular Diels-Alder reaction of the initially formed cyclohexa-2,4-dienones (446 and 447). These tricyclic compounds are recognized as promising synthetic intermediates for synthesis of natural products and related compounds . ... 

Larock and Kuo [68] investigated the Pd-catalyzed coupling of allylic alcohols and o-iodoaniline which provided a convenient, one-step synthesis of quinolines as represented by the reaction between o-iodoaniline and alkenol 156 to give quinoline 157. The optimal conditions for this reaction were found to be 5 mol% IklCk. 5 mol% PPh3, 3 equivalents NaHCO3, 1.5 equivalents alkenol and 10 mL of HMPA per mmol of o-iodoaniline at 140°C for 1 day under N2. The reaction was found to be fairly versatile and the use of a range... 

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