Alcohols, functionalized dienes

The use of alkylhydroperoxides as epoxidizing agents for allylic alcohols under catalytic conditions was soon expanded into enantioselective epoxidation with use of the more mild titanium alkoxides in the presence of chiral tartaric esters116. As concerns the epoxidation of functionalized dienes, these now so-called Sharpless conditions [Ti(OPr )4, dialkyl tartrate, TBHP] have been utilized to enantioselectively epoxidize 1,4-pentadiene-... 

Dimerization of Alkynes and Propargyl Alcohols into Functional Dienes or Cyclobutenes... 

Ruthenium-based catalysts are relatively easy to synthesise and are tolerant of alcohol functionality in the acyclic diene monomer [26]. 

Catalyst 10 allows the production of cyclo-pentene (21 —> 22) and cyclohexene derivatives (23 —+ 24) in high yields 11] (Scheme 3). The tolerance of many different functional groups is remarkable. For example, dienes of the type 23, possessing an unprotected carboxylic acid, aldehyde, or alcohol function, can be used in ringclosing metathesis, employing catalyst 10. 

A solution of sodium in ammonia may be considered as a source of solvated electrons. The alcohol functions as a proton source. The aromatic molecule accepts an electron from the solution to form a radical anion 1, protonation of which by the alcohol forms the radical 2 (Scheme 11.2). Acceptance of a second electron generates a new carbanion, which is also protonated and gives the 1,4-diene 3. The overall transformation is reduction of the aromatic compound to the 1,4-diene. 

Cycloadditions of Acyl Nitroso Derivatives. In situ formation of the acyl nitroso derivative by oxidation of the hydroxy carbamic acid under Swem-Moffat conditions in the presence of a functionalized diene affords the corresponding cycloadduct in 94% yield and 96% diastereomeric excess (eq 4). The resulting cycloadduct can be further elaborated to prepare optically active functionalized amino alcohols. 

TBHP yielded an allylic alcohol, which was benzylated to provide 97. This highly functionalized diene underwent RCM with Schrock s catalyst affording cyclopentene 98 in a yield of 91%. Under the action of hydrogen and Pd/C, hnal reduction and debenzylation were performed simultaneously to give 5a-carba-(3-D-fmctofuranose [54]. 

Palladium(II)-catalyzed 1,4-additions to conjugated dienes, in which at least one alkoxide function is added, require the presence of an alcohol function. In all cases known so far, this involves an alkoxypalladation of tlie conjugated diene to give an intermediate 4-alkoxy-l,2,3-(jr-allyl)palladium complex. Subsequent nucleophilic attack on the jr-allyl... 

A keteneacetal, the Brassard diene, has also been bound to polystyrene-based resin (308). This has been achieved by the reaction of diketene with alcohol functions on polystyrene resin. The ketone function of the resulting acet-oacetate could readily be enolized by TMOF (trimethyl orthoformate) and a catalytic amount of H, giving the methyl enolate. The remaining ester function was then deprotonated with LDA and subsequently silylated with TBDMSCl. The resulting diene (311) was used in many hetero-Diels-Alder reactions (HDA) with aldehydes and ketones as dienophiles, giving a library... 

The synthesis of (5S,15S)-diHETE is shown in Scheme 4.16 and makes use of Pd-Cu coupling of a terminal acetylene to trans vinyl bromides (48 + 50 —> 51 and 51 + 49 — 52) to obtain eneynes. The acetylenes are reduced by catalytic hydrogenation to give the requisite cis-trans dienes. Acetylenes 46 and 47 bear the suitable optically active secondary alcohols for the (5S)and (155)-alcohol functions in the natural product and are derived from chiral reductions of the corresponding ketones. ... 

Whitesell and Minton have synthesized (- )-xylomollin (408), the only trans-fiised iridoid, from the racemic bicyclic diene 409. Control of the stereochemistry was effected in the first step by addition of the glyoxylate 410. The two products were separated and the major one, 411, was reduced with lithium aluminum hydride. Conversion of the primary alcohol to a methyl group, with concomitant inversion of stereochemistry at the secondary alcohol carbon atom was carried out by protection of the primary alcohol function (fert-butyldimethylsilyl), tosylation of the secondary hydroxyl, then removal of the silyl group with formation of an epoxide with inversion, and reduction (LiEtaBH) of the epoxide. The remaining steps are shown in Scheme 36. It remains to point out that isoxylomoUin (412) was produced preferentially, and is indeed formed from xylomollin (408) slowly in methanolic solution. ... 

JV-Isobutyroylbuxaline-F (194) (N-isobutyroylbaleabuxaline-F ), isolated from B. balearica, is related to the. buxidienines. It is transparent in the u.v. above 220 nm, and n.m.r. indicates tne presence of a single ethylenic proton. The fourth oxygen atom is part of a tertiary alcohol function and gives a diene of the buxidienine type on dehydration. This structure requires confirmation. 

Furthermore, this regio- and stereoselective bond formation between unsaturated carbon atoms was applied to the synthesis of functionalized dienes under extremely mild conditions. Thus, even vinylic boronic esters containing an allylic acetal moiety and alkenylboronate having a chiral protected allylic alcohol were successfully accomplished with vinylic iodides under aqueous conditions in 60-90% yield [30]. In addition, an exceptionally simple and efficient synthesis of a prostaglandin (PGEj) precursor was reported by Johnson, applying a DMF/THF/ water solvent mixture with a bis(diphenylphosphino)ferrocene palladium catalyst [31]. It is curious that the presence of water is an absolute necessity in order to succeed in this approach (Scheme 3). 

The retrosynthetic disconnection of isocomene leads primarily to the intermediate tertiary carbenium ion 1, which may arise from the intermediate carbenium ion 2 by anionotropic 1,2-alkyl shift. The latter turns out to be the protonation product of the tricycle 3 containing an exocyclic CC-double bond which is generated by a WiT-TiG-methylenation of the tricyclic ketone 4. The concept behind this is formation of the cyclobutane ring in 4 by means of an intramolecular [2-l-2]-photocycloaddition of the 1,6-diene 5. The enone substructure in 5 results from hydrolysis of the enolether and dehydration of the tertiary alcohol function in (65)-l-alkoxy-2,4-dimethyl-3-(2-methyl-l-penten-5-yl)cyclohexene 6. The tertiary alcohol 6 emerges from a nucleophilic alkylation of (65)-3-alkoxy-2,6-dimethyl-2-cyclohexen-l-one 7 with metallated 5-halo-2-methyl-l-pentene obtained by GrigNARD reaction or... 

In 1985, O Malley et al. published the total syntheses of rac-averufin (103) and rac-nidurufin (104) (65). These are both early precursors of the aflatoxins in their biosynthesis. Nidurufin (104) is the direct successor of averufin (103) and the direct precursor of versiconal hemiacetal acetate (12, see Scheme 2.1). Nidurufin (104) and averufin (103) are accessible by the same synthesis route only the two last steps differ firom each other (see Scheme 2.17). The first reaction was a double Diels-Alder reaction with dichloro-p-benzoquinone (97) and two equivalents of diene 98. Then, three of the four alcohol functions were selectively MOM-protected (—> 99). The remaining alcohol was converted into the allyl ether and then subjected to a reductive Claisen rearrangement, followed by MOM-protection of the redundant alcohol ( 100). By addition/elimination of PhSeCl, 101 was formed. Deprotonation of t-butyl 3-oxobutanoate, followed by reaction with 101 yielded the pivotal intermediate 102. This could be converted into rac-averufin (103) by deprotection of the alcohols and decarboxylation at the side chain. The last step was a p-TsOH-catalyzed cyclization to give 103. By treating 102 with /m-CPBA, the double bond is epoxidized. rac-Nidurufin (104) was then formed by cyclization of this epoxide under acidic conditions. 

After masking of the alkyne function by a dicobalthexacarbonyl complex, RCM was used to cyclize the diene 573 (Scheme 9.15). Then, decomplexation enabled a Diels-Alder reaction with the disiloxydiene 575, ensued by elimination of isobutylene. Two hydroxy groups of the resorcylic macrolide (576) obtained were protected and the TBS-ether was cleaved. Thus, dehydration with concluding deprotection of all alcohol functions furnished aigialomycin D (482), in an overall yield of 8%. 

Hydroformylation involves the reaction of C=C bonds with syngas (i.e., a mixture of carbon monoxide and hydrogen) and produces aldehyde functional groups. Hydroformylation of diene-based polymers is mostly performed by means of providing sites for further derivations. The most commonly explored secondary modification of aldehyde functional groups is hydrogenation to give primary alcohol functionality however, aldehyde may also be converted to nitrile, acetate, or amine functionalities. " ... 

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