Lindlar reduction

An alternative method for the conversion of an alkyne to an alkene uses sodium or lithium metal as the reducing agent in liquid ammonia as solvent. This method is complementary to the Lindlar reduction because it produces... 

The masked propargylic anfz-l,3-diols obtained in these reactions are useful precursors to more functionalized systems. Lindlar reduction of alkyne 171 generated the (Z)-allylic diol 172, which underwent diastereoselective osmium tetraoxide-catalyzed dihydroxylation to provide the partially protected tetraol 173 (Scheme 28). The propargylic anfz-l,3-dioxane 175,obtained in 88% yield from... 

The yield in the metathesis reaction was 80% and was followed by a Lindlar reduction. The synthesis was completed by epoxidation with DMDO. 

The coupled fragments were then converted to a vinyl iodide. The key steps were a Z-selective Lindlar reduction and iodinolysis of the vinyl silane, which was done using NIS in acetonitrile (sequence F-l to F-ll). 

C3-trifluoroacetamide 27 were synthesized by deprotection of Boc-macrocycle 15, followed by acylation, to give macrocycles 24 and 25. Subsequent Lindlar reduction and Stille reaction gave the C3-acylated derivatives 26 and 27. 

Akita and Ohta disclosed one of the earliest Sonogashira reactions of chloropyrazines and their A-oxides [24, 25]. The union of 2-chloro-3,6-dimethylpyrazine (23) and phenylacetylene led to 2,5-dimethyl-3-phenylethynylpyrazine (29). Subsequent Lindlar reduction of adduct 29 then delivered (Z)-2,5-dimethyl-3-styrylpyrazine (30), a natural product isolated from mandibular gland secretion of the Argentine ants, Iridomyrmex humilis. 

Fiirstner succeeded in the synthesis of ambrettolide from a diyne using this catalyst system. Treatment of diyne 148a with Mo(CO)6 (5 mol%) and p-chlorophenol (1 equiv) in chlorobenzene at 140°C gave cycloalkyne 149a in 69% yield. Subsequent Lindlar reduction proceeded smoothly in a stereoselective manner to alford ambrettolide ... 

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 ... 

Total synthesis of motuporamide C is achieved by alkyne metathesis as a key step/ Diyne 133 is readily transformed into macrocyclic alkyne 134 with either catalyst. Lindlar reduction of 134 gives cycloalkene 135, which is further derivatized to motuporamine C-2HC1 (Scheme 47). 

A simple alternative to the Lindlar reduction process has been recognized.95 The palladium(II) acetate-catalyzed polymerization of triethoxysilane in water produces finely divided palladium metal dispersed on a polysiloxane matrix with concomitant hydrogen evolution. Addition of (EtO)3SiH to the mixture of an alkyne and all other necessary constituents allows facile and selective reduction of the alkyne without an external hydrogen source ... 

Conversion of 5 to PGE2 (6) requires Lindlar reduction, saponification to the acid group, desilylation (HF), and deoximation. Usual methods for the last step are ineffective, but deoximation was achieved with the solid Ti reagent (1) in 73% yield. 

Numerous applications of this chemistry to the synthesis of leukotrienes have been reported, as illustrated for the preparation of 12-hydroxyeicosatetraenoic acid (189 Scheme 41).154 Reaction of the carbe-noid precursor (190) with furan in the presence of rhodium(II) acetate generated a furanocyclopropane, which on standing reverted to predominantly the (Z, )-isomer (191). Reduction of the dicarbonyl compound (191) gave the diol (192), which was then selectively converted to the bromide (193). Subsequently, (193) was coupled with the alkynide (194), followed by Lindlar reduction and deprotection to produce (189). The overall procedure is quite general and has been applied to a range of related compounds (195-199)135-138 and useful synthetic fragments (200 and 201).153... 

The leaving group will come from an alcohol so the basic skeleton is a 1,2,3-triol 36 that is nearly symmetrical and becomes symmetrical with a C-C disconnection to the symmetrical epoxide 37. Both starting materials 34 and 37 are available and are symmetrical we just have to make 37. The epoxide comes from the Z-alkene 38 and that can be made by Lindlar reduction of the alkyne 39. 

In a process that is complementary to Lindlar reduction of cyclic alkynes, Fiirstner and Radkowski reported the chemo- and stereoselective reduction of cycloalkynes (formed by ringclosing alkyne metathesis) to (E)-cycloalkenes using ruthenium-catalyzed (nms-selective hydrosilylation followed by desilylation by AgF (dark, rt) (Scheme 1) <02CC2182>. Employing this process, the 21-membered macrocycle is formed in 85% yield with almost complete -stereoselectivity. 

These two / f( -reactions have been used for a stercospecific synthesis of dihydrone-petalactone (7) from norbomenone (3).- Addition of propynylmagnesium bromide, followed by Lindlar reduction of the triple bond, acetylation, and reaction with 2. provides the allylsilane 4. Epoxidation of 4 and dcsilylation results in 5. Oxy-Cope rearrangement of 5 results in a single ketone (6) with the desired four chiral centers. The remaining steps to 7 involve conventibnal reactions. 

Pd on CaC03 lead acetate-quinoline (Lindlar reduction)... 

Preparation of Derivatives. Enoate derivatives are prepared from the corresponding chiral alcohol by treatment with acry-loyl chloride in the presence of Triethylamine and catalytic 4-Dimethylaminopyridine or the appropriate carboxylic acid chloride and Silveril) Cyanide. Alkynyl ethers are readily available from the potassium alkoxide by treating with Trichloroethylene, in situ dechlorination with n-Butyllithium, and electrophilic trapping. Trapping the intermediate anion with a proton source or lodomethane followed by Lindlar reduction of the alkynyl ether affords the corresponding vinyl and l-(Z)-propenyl ether, respectively, while reduction of the alkynyl ether with Lithium Aluminum Hydride affords the l-( )-propenyl ether. 

The second sapphyrin analog reported by Sessler and coworkers is derived directly from macrocycle 6.26. Here, subjecting the alkyne-containing macrocycle 6.26a to Lindlar reduction conditions was found to afford a near quantitative conversion to the partially reduced macrocycle 6.27a (Scheme 6.3.3). As inferred from H NMR spectroscopic analysis, the specific structure of this reduction product is the tra 5-alkene 6.27. This compound may formally be regarded as being a true isomer of pentaazasapphyrin, and is thus referred to as [22]sapphyrin-(2.1.0.0.1) or [22]pentaphyrin- 2.1.0.0.1). 

Reduction of an alkyne. The best-known reactions of this type are Lindlar reduction, the McMurry reaction and Birch reduction. 

When we first introduced the concept of enantiomers and chirality in Chapter 16, we stressed that any imbalance in enantiomers always derives ultimately from nature. A laboratory synthesis, unless it involves an enantiomerically pure starting material or reagent, will always give a mixture of enantiomers. Here is just such a synthesis of the Japanese beetle pheromone you have just met. You can see the Z-selective Lindlar reduction in use—only one geometrical isomer of the double bond is formed— but, of course, the product is necessarily racemic and therefore useless as beetle bait, because in the original addition of the lithiated alkyne to the aldehyde there can be no control over stereochemistry. If all the starting materials and reagents are achiral, the product must be... 

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