Alkynes, partial reduction

Alkynes can be reduced to yield alkenes and alkanes. Complete reduction of the triple bond over a palladium hydrogenation catalyst yields an alkane partial reduction by catalytic hydrogenation over a Lindlar catalyst yields a cis alkene. Reduction of (he alkyne with lithium in ammonia yields a trans alkene. 

An obvious drawback in RCM-based synthesis of unsaturated macrocyclic natural compounds is the lack of control over the newly formed double bond. The products formed are usually obtained as mixture of ( /Z)-isomers with the (E)-isomer dominating in most cases. The best solution for this problem might be a sequence of RCAM followed by (E)- or (Z)-selective partial reduction. Until now, alkyne metathesis has remained in the shadow of alkene-based metathesis reactions. One of the reasons maybe the lack of commercially available catalysts for this type of reaction. When alkyne metathesis as a new synthetic tool was reviewed in early 1999 [184], there existed only a single report disclosed by Fiirstner s laboratory [185] on the RCAM-based conversion of functionalized diynes to triple-bonded 12- to 28-membered macrocycles with the concomitant expulsion of 2-butyne (cf Fig. 3a). These reactions were catalyzed by Schrock s tungsten-carbyne complex G. Since then, Furstner and coworkers have achieved a series of natural product syntheses, which seem to establish RCAM followed by partial reduction to (Z)- or (E)-cycloalkenes as a useful macrocyclization alternative to RCM. As work up to early 2000, including the development of alternative alkyne metathesis catalysts, is competently covered in Fiirstner s excellent review [2a], we will concentrate here only on the most recent natural product syntheses, which were all achieved by Fiirstner s team. 

Partial reduction of alkynes to Z-alkenes is an important synthetic application of selective hydrogenation catalysts. The transformation can be carried out under heterogeneous or homogeneous conditions. Among heterogeneous catalysts, the one that... 

Dissolving-Metal Reduction of Aromatic Compounds and Alkynes. Dissolving-metal systems constitute the most general method for partial reduction of aromatic rings. The reaction is called the Birch reduction,214 and the usual reducing medium is lithium or sodium in liquid ammonia. An alcohol is usually added to serve as a proton source. The reaction occurs by two successive electron transfer/proto-nation steps. 

RCM of dienes to cycloalkenes provides a useful method for the syntheses of carbo- and heterocycles and thus has been proved to be extremely effective in total synthesis of various natural products. Usually, however, mixtures of (E)- and (Z)-olefms result. In contrast, ring-closing alkyne metathesis provides a reliable route for synthesis of both (E)- and (Z)-macrocycloalkenes in a stereoslective manner taking advantage of stereoselective partial reduction of resulting cycloalkynes. A Lindlar reduction gives (Z)-cycloalkenes, whereas a hydroboration/ protonation sequence afford ( )-cycloalkenes (Equation (23)). Recently, Trost reported an alternative procedure for the synthesis of (E)-olefins from alkynes through hydrosilylation by a ruthenium catalyst. This procedure converts cycloalkyne 130, for example, to vinylsilane 131 and then to (E)-cycloalkene 132 in a stereoselective manner (Scheme 46)7 ... 

Alkyne metathesis is employed for constructing the a-chain of PGE2.methyl ester. Reaction of alkyne 144 and symmetrical alkyne 145 in a slight excess in the presence of the I4O/CH2CI2 catalyst produces the desired CM product 146 in 51% yield, which is then converted to PGE2.methyl ester by partial reduction with a Lindlar catalyst leading to (Z)-olefin 147 and subsequent deprotection (Scheme 49). 

Aldehydes are prepared by the hydroboration-oxidation of alkynes (see Section 5.3.1) or selective oxidation of primary alcohols (see Section 5.7.9), and partial reduction of acid chlorides (see Section 5.7.21) and esters (see Section 5.7.22) or nitriles (see Section 5.7.23) with lithium tri-terr-butox-yaluminium hydride [LiAlH(0- Bu)3] and diisobutylaluminium hydride (DIBAH), respectively. 

Partial reduction of alkynes with sodium in liquid ammonia or bycatalytic hydrogenation. 

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,... 

Scheme 34 Partial reduction of the alkyne-cobalt hexacarbonyl complexes under PK conditions in the presence of TFA...

The partial reduction of alkynes provides methods that are both regio-and stereospecific. Dissolving metal reductions tend to give trans alkenes, whereas catalytic methods of reduction generate the cis alkenes (Scheme 3.3). A Lindlar catalyst (Pd/CaCOj + PbO, partially poisoned with quinoline) has been recommended for use in this context. 

Selecting the catalyst and reaction conditions for partial reduction of a triple bond situated in a conjugated system is a challenge. Where the hydrogenation of an isolated alkyne can proceed with nearly complete selectivity, the partial saturation of an enyne takes place selectively with much more difficulty. Selectivities of 85-90% in these latter reactions are common and are considered to be reasonable for synthetic applications. 

The partial reduction of substrates containing triple bonds is of considerable importance not only in research, but also commercially for stereoselectively introducing (Z)-double bonds into molecular frameworks of perfumes, carotenoids, and many natural products. As with catalytic hydrogenation of alkenes, the two hydrogen atoms add syn from the catalyst to the triple bond. The high selectivity for alkene formation is due to the strong absorption of the alkyne on the surface of the catalyst, which displaces the alkene and blocks its re-adsorption. The two principal metals used as catalysts to accomplish semireduction of alkynes are palladium and nickel. 

Among the many available procedures for preparing alkenylsilanes are hydrosilylation of alkynes and partial reduction of alkynylsilanes. Hydrosilylation of 1-alkynes with triethylsilane in the presence of catalytic chloroplatinic acid results in regioselective... 

Reduction of 68a with L-selectride gave a 6 1 mixture of cyclopropyl carbinols in 92% with the (R)-alcohol predominating. Highly stereoselective hydroxyl-directed epoxidation from the a-face of the cyclopentane ring followed by silylation of the alcohol gave 69 (contaminated with a small amount of the product derived from the S-alcohol) in 84% yield. This intermediate was then coupled with the allenyl iodide 63 via the cuprate of 69 to afford an 86% yield of the diyne 70. Partial reduction of the alkynes followed by desilylation and chromatography afforded 71a and 71b in 79% and 13% yields, respectively. Conversion of the undesired major (R)-isomer 71a into the minor (5)-compound was accomplished via an oxidation-reduction sequence to provide 71b in 75% yield contaminated with 16% of the (R)-71a. Orthoester 71b was then cleaved... 

The synthesis of Z-alkenyl derivatives were carried out by partial reduction of triple bond with the Lindlar catalyst (route f). The fully saturated derivatives were obtained starting from the same alkynes by using palladium on charcoal as a catalyst (route g). 

No doubt joining the alkyne to the alkene could also have been done by a coupling reaction in the coordination sphere of a metal but an alternative is to imagine the alkene as coming from the dehydration of an alcohol 251. This allows disconnection to the known lactone 250. The synthesis of the alkyne uses DIBAL for partial reduction and the differential protection of the two OH groups by more or less hindered silyl groups. 

The most obvious method for the formation of alkenes from alkynes is by partial reduction. This reaction can be effected in high yield with a palladium-calcium carbonate catalyst that has been partially deactivated by addition of lead(II) acetate or quinoline (Lindlar s catalyst). It is aided by the fact that the more electrophilic alkynes are adsorbed on the electron-rich catalyst surface more strongly than the corresponding alkenes. An important feature of these reductions is their high stereoselectivity. In most cases the product consists very largely of the thermodynamically... 

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