Alkynes stereospecific synthesis

Reactions of 1-Alkenyl Metals with 1-Alkynyl Halides Reactions of Terminal Alkynes with -Carbon Halides General aspects Synthesis of terminal alkynes Stereospecific synthesis Phase-tranter catalysis... 

J. F. Normant and A. Alexakis, Carbometallation, C-Metallation of Alkynes, Stereospecific Synthesis of Alkenyl Derivatives , Synthesis, 1981, 841. 

A very efficient, stereospecific synthesis of DL-ribose was based26 on the use of l,l-diethoxy-5-(tetrahydropyran-2-yloxy)-2-pentyn-3-ol as the substrate. Catalytic hydrogenation of this alkyne to the cts-alkene was accompanied by cyclization, to give 2-ethoxy-2,5-dihydro-5-(tetra-hydropyran-2-yloxy)furan (35). cis-Hydroxylation of the double bond in 35 was effected with potassium permanganate, yielding the ethyl DL-ribofuranoside derivative 36, which was hydrolyzed to DL-ribose. 

In a similar manner, alkynes can undergo sequential carbometallation reactions, previously illustrated in equation (32).136 It is possible to combine carbocupration of alkynes with the use of a Michael acceptor as electrophile when that electrophile is a vinylphosphonium salt, carbocupration can be coupled to Wittig alkenation to result in a stereospecific synthesis of dienes via a one-pot, four-component, four carbon-carbon bond-forming reaction sequence.302... 

Brown et al.3 have now extended the Zweifel synthesis to a stereospecific synthesis of trisubstituted alkenes from an internal alkyne (equation III). Evidently a similar mechanism is involved franr-addition of I+ and OC H 3 followed by trans-elimination of I and BROCH3 resulting in tram-orientation of the two alkyl groupsof the alkyne. 

Evans, W.J., Hughes, L.A., Drummond, D.K. et al. (1986) Facile stereospecific synthesis of a dihydrox-yindenoindene unit from an alkyne and carbon monoxide via samarium-mediated carbon monoxide and CH activation. Journal of American Chemical Society, 108, 1722. 

The carbometallation of alkynes is also unique in its stereochemical pattern, since it is executed as an exclusive cis addition. For example, the stereoisomeric purity of pheromone 104, prepared as shown, is higher than 99.9% This feature is of special importance in the synthesis of natural pheromones, as the biological activity of these compounds is dramatically affected by the presence of an even negligible amount (less than 0.5% ) of the undesirable stereoisomer. Not surprisingly, this reaction has found numerous areas of application, especially in the stereospecific synthesis of the tri- and tetrasubstituted alkenes, a goal difficult to achieve by other methods. To illustrate the effectiveness of this approach, the synthesis of faranal 105, the trail-marking pheromone of the ant species Monomoriumpharaonis, is shown in Scheme 2.33. 

Advantage may be taken of the selective hydroboration of alkynes as compared to alkenes by dicy-clohexylborane or disiamylborane (Section 3.10.4.3) to provide syntheses of dienes and their deuteriated derivatives e.g. equation 62). Dibromoborane-dimethyl sulUde may be used similarly (Section 3.10.4.4)." The approach has been used for the stereospecific synthesis of an allylic hydroxydiene (equation 63). ... 

Ogawa, T., Kusume, K., Tanaka, M., Hayami, K., Suzuki, H. An alternative method for the stereospecific synthesis of conjugated alkenynes via the copper(l) iodide assisted cross-coupling reaction of 1-alkynes with haloalkenes. Synth. Commun. 1989,19, 2199-2207. 

Chemin, D. Linstrumclle, G. Palladium-catalyzed reaction of ( ) and (Z)-dichloroethenes with 1-alkynes. An efficient stereospecific synthesis of ( ) and (Z)-cncdiyncs. Tetrahedron 1994, 50, 5335-5344. 

Stereospecific synthesis of arylidene and allylidene cyclopentanes and cyclohexanes can be achieved by palladium-catalyzed cyclization of carbanions containing a C — C triple bond in the presence of aryl or vinyl halides52 33". The reaction is stereoselective, occurring with irans selectivity. Thus, a palladacyclic intermediate, resulting from initial aryl or vinyl carbapallada-tion, is ruled out in favor of primary carbanion addition to the alkyne unit. 

Additions of organometallic reagents to 1-alkynes continue to play a prominent role in the regio- and stereo-selective synthesis of olefins. A convenient procedure for the stereospecific synthesis of trisubstituted olefins, based on Normant s work on the addition of alkyl copper(l) complexes to 1-alkynes, is outlined in Scheme 10. The use of House s dimethyl sulphide-copper(i) bromide complex minimizes... 

A stereospecific synthesis of vinyl chlorides and bromides from alkynes via organocopper reagents has been reported (Scheme 37). Both vinyl and allyl... 

In 2002, Lett et al. published a convergent stereospecific synthesis of the resorcylic macolactone LL-Zl 640-2 (567) (Scheme 9.13) and hence hypothemycin (481) 382, 383). They started with the preparation of the three building blocks, 551, 555 (Scheme 9.11), and 564 (Scheme 9.12). Methyl ester 551 was produced from 4-methoxysalicylic acid (549) in four steps. Reaction of alkyne 552 with enantiopure (/ )-propylene oxide 490 afforded chiral alkyne 553, which then was converted into (Z)-vinyl iodide 555. 

General Procedures. - Normant and Alexakis have reviewed the use of alkyne metal compounds in the stereospecific synthesis of alkenyl compounds. The isomerisation of internal alkynes to ethynyl compounds effected by the catalyst derived from sodium or potassium hydride in 1,3-diaminopropane is illustrated in the conversion of nonadec-2-yn-l-ol (23) to nonadec-18-ynol (24) in 85% yield ... 

Lithium n butyl (phenylthio) cuprate has been used in nucleophilic substitution reactions of arenesulfonyl fluorides, al-lylic acetates, 9 BBN, propargyllc carbamates, and bromo-alkenes, as well as in nucleophilic additions to acetoxy-epoxides. It Is a good choice for 1,4-addItIon of an n-Bu group, having been used in 1,4 addition-elimination reactions of a-oxoketene dithloacetals and 3-halo-2-cycloalkenones, and in tandem vicinal dialkylation reactions of 5-methyleneoxa-zolones and alkynes. A typical example Is the use of the reagentin the stereospecific synthesis of (, -2-heptenoicacidfrom acetylene (eq 1). ... 

Stereospecific synthesis of c/5-disubstituted or trisubstituted olefins from mono- or di-substituted alkynes can be accomplished via hydroboration to dialkylvinylboranes followed by addition of sodium hydroxide and iodine. By treatment of the vinylborane with cyanogen bromide in methylene chloride solution, the complementary procedure, namely conversion into the /ra 5-olefin, may be effected. In the c/j-producing case, the stereochemistry is believed to be the result of /m 5-elimination of iodide and boron from the intermediate (64). In the corresponding intermediate (65) produced using... 

A new stereospecific synthesis " of 2-alkenenitriles (36) from 2-alkynenitriles and organocuprates overcomes problems associated with the synthesis from 1-alkynes. 2-Alkenenitriles are also liberated in good yield from the reaction of sodium sulphide with a-cyano-/3-nitro-sulphones (37) (Scheme 23). ... 

Pal et al. reported a facile and mild procedure for the regio- and stereospecific synthesis of novel enyne derivatives 131 via the copper-free palladium-catalyzed sequential coupling of 3-iodo(thio)flavone 130 with terminal alkynes [53] (Schane 6.34). 

The currently available methods for the synthesis of the title compounds are confined to the preparation of homo-1,1-dihalo-1-alkenes 180 while only a few reports are available for mixed 1,1-dihalo-1-alkenes of defined stereochemistry 18u. As the hy-droboration reaction proceeds in a stereospecific manner, the hydroboration-oxi-dation-bromination-debromoboration sequence of 1-chloro-l-alkynes produces selectively (Z)-l-bromo-l -chloro-l-alkenes (Eq. 116),82>. The oxidation with anhydrous trimethylamine oxide of the alkenylborane prior to the addition of bromine is necessary to avoid the competing transfer of one of 1,2-dimethylpropyl group from boron to the adjacent carbon atom. Similar reaction sequence provides 1,1-dibromo-l-alkenes (Eq. 117)182). 

Alkene synthesis is the most important and most widely used reaction in organic chemistry. Many review articles and research papers describe methods for the positioning and stereospecific introduction of carbon-carbon double bonds ". The three most important methods for the synthesis of alkenes described in this chapter are (1) elimination reactions, (2) aUcenation of carbonyl compounds and (3) reduction of alkynes. 

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