Alkyne alcohols, reduction with

Now let s draw the forward scheme. 1,1-Dibromopentane is converted to 1-pentyne by reaction with excess sodium amide (to afford double elimination followed by deprotonation of the resulting alkyne), followed by aqueous woikup to protonate the terminal aUcynide. 1-Pentyne is converted to the aldehyde via hydroboration/oxidation. Subsequent reaction with sodium acetylide, followed by aqueous woikup, produces an alcohol. Reduction with H2 and Lindlar s catalyst converts the alkyne group to an alkene group. Ozonolysis converts the alkene to an aldehyde. Reaction with concentrated acid allows for elimination of the alcohol, producing the target compound. 

Another approach in the study of the mechanism and synthetic applications of bromination of alkenes and alkynes involves the use of crystalline bromine-amine complexes such as pyridine hydrobromide perbromide (PyHBts), pyridine dibromide (PyBn), and tetrabutylammonium tribromide (BiMNBn) which show stereochemical differences and improved selectivities for addition to alkenes and alkynes compared to Bn itself.81 The improved selectivity of bromination by PyHBn forms the basis for a synthetically useful procedure for selective monoprotection of the higher alkylated double bond in dienes by bromination (Scheme 42).80 The less-alkylated double bonds in dienes can be selectively monoprotected by tetrabromination followed by monodeprotection at the higher alkylated double bond by controlled-potential electrolysis (the reduction potential of vicinal dibromides is shifted to more anodic values with increasing alkylation Scheme 42).80 The question of which diastereotopic face in chiral allylic alcohols reacts with bromine has been probed by Midland and Halterman as part of a stereoselective synthesis of bromo epoxides (Scheme 43).82... 

Several cyclofunctionalization reactions of alkynic alcohols are synthetically useful. Metal ion-promoted cyclofunctionalization of ris-2-propargylcyclopentanol systems proceeds by the 5-exo mode (equation 77 and Table 23).197 Protiodemetallation or reductive demetallation provides the cyclic enol ether in high yields. This method has been used by Noyori in the synthesis of prostacyclin (PGh).197b,197c Reactions with catalytic amounts of mercury(II) or palladium(II) salts gave the endocyclic enol ether as the major product.197 -198 A related cyclization with Ag2C03 has been reported by Chuche.191 Schwartz... 

Indeed only alkynes could be reduced in (CH3)4N+ solutions while alkenes were inactive. Reduction of 1-hexyne, propargyl alcohol and 1,4-butyne diol were performed 13 at a mercury cathode with (CH3)4NC1 as the electrolyte. The corresponding olefins were formed and the respective yields were 45 %, 62 % and 82 %. The diacetate of 15 behaved similarly. However only the trans isomer 16 was formed from 15 while a mixture of trans and cis (6 4) isomers resulted from the reduction of the diacetate. Polarography of several alkynes in methanol with (C4H9)4N+ electrolytes showed, 3) that they react close to background decomposition. It was therefore proposed 14) that (CH3)4N+-mercury may be involved in the cathodic reduction of alkynes when (CH3)4N+ salts serve as the electrolytes. 

Midland and Graham completed a total synthesis of (-)-pestalotin (81)33 (Scheme 4.3bb). The asymmetric reduction of the ketone 82 gave the propar-gylic alcohol 83 with high enantioselectivity. Partial reduction of the alkyne,... 

Aldehydes, RCHO (Sec. 7.9) (Sec. 7.9) (Sec. 8.4) (Sec. 17.7, 19.2) (Sec. 19.2, 21.6) from disubstituted alkenes by ozonolysis from 1,2-diols by cleavage with sodium periodate from terminal alkynes by hydroboration followed by oxidation from primary alcohols by oxidation from esters by reduction with DIB AH [HA1(i-Bu)2]... 

Alkynic ketones have been used extensively in natural product synthesis, due in large part to the contributions of Midland and coworkers and the development of generd methods for enantioselective reduction of this moiety to afford optically active propargyl alcohols using chiral trialkylboranes. Furthermore, the derived alkynic alcohol is a versatile system which can be manipulated directly into cis-or rra 5-allylic alcohols and as a precursor for vinylorganometallic species. This section will briefly cover progress made in the direct acylation of alkynic organolithiums with the acylation protocol d veloped by Weinreb (see also Section 1.13.2.7). 

Semireduction of internal alkynes in the presence of a transition metal catalyst (e.g., Ni2B, Pd/C) provides disubstituted cw-alkenes. On the other hand, dissolving metal reduction of alkynes or reduction of propargylic alcohols with LiAlH4 or with Red-Al [sodium bis(2-methoxyethoxy)aluminum hydride] furnishes tran -disubstituted alkenes. ... 

Isomerizations. A convenient method for the conversion of alkynes to conjugated dienes is by treatment with Ph P. The synthetic application is shown in the preparation of 2,4-alkadienols from 2-alkynoic acids involving esterification with pentafluorophenol, isomerization with PhjP (PhMe, 50°), and reduction with DIBAL-H. Even propargyl bromide can be isomerized to give 1-bromopropadiene, albeit in 29% yield. Conjugated alkadienoic esters and amides are obtained in one step from the pentafluorophenyl alkynoates on reaction with alcohols and amines, respectively, after treatment with catalytic amount of PhjP. 

Synthesis of the acyclic portion began, as in the previous synthesis, with enantiomerically pure citronellol (25). Protection of the alcohol as the benzyl ether and oxidative cleavage of the olefin to the aldehyde gave 26 (85%). Chain extension via the masked acyl anion equivalent 27, alcohol protection, and concomitant -elimination and isomerization of the allene to die alkyne with butyl lithium gave 28. The resulting protected ketone must now be converted to the P-alcohol required for the completion of the synthesis. Thus hydrolysis to die ketone followed by enantioselective reduction with (—)-N-methylephedrine-... 

Metallation of l-methoxy-2-butyne with n-butyllithium at -78 C, followed by the addition of one equivalent of zinc chloride, generates the very reactive and unisolable organozinc intermediate. Reaction of this zinc reagent with cyclohexenone affords the alkynic alcohol in 95% yield as a 65 35 mixture of diasteieomers. Subsequent reduction of the triple bond provides either the trans alkene or the cis alkene, depending on the reaction conditions. A modified oxy-Cope rearrangement thus provides the dia-steieomeric ketones, which have been used for the synthesis of juvabione (Scheme 29). ... 

Anti addition across an alkyne can be accomplished with lithium aluminium hydride. This is particularly popular using propargylic alcohols and occurs with very high stereoselectivity. If the reduction is effected in the presence of sodium methoxide and the crude reduction product is treated with iodine, then the final product is exclusively the 3-iodoallylic alcohol (2.62). In contrast, reduction with lithivun aluminium hydride and alvuninium chloride, followed by iodination, gives the 2-iodoallylic alcohol (2.63). 

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