Abstract
Commercially available Lindlar catalyst (10% by weight) in methanol, selectively hydrogenates various alkenes in the presence of benzyl ether and benzyl amine functionalities.
Graphical Abstract
While numerous methods are available in the literature for the reduction of alkynes and alkenes using a variety of catalysts, selective reduction of an alkene in the presence of benzyl ether and benzylamine functionalities has not been fully addressed.1 Selective reduction of an alkene was previously accomplished in the presence of a benzyl ether by a catalytic hydrogenation over 5% Rh-Al2O32a. Also, selective cleavage of benzyl ether in the presence of an olefin was carried out usinghydrogenation over 5% Pd-C.2b There are few known reports in the literature where reduction of a double bond or the cleavage a Cbz-group was achieved selectively in the presence of a benzyl ether by hydrogenation over 5% Pd-C and 5% butyl amine or ammonia.3 During the course of our studies towards synthesis of high affinity nonpeptidal ligands for the HIV-protease substrate binding site, we required a selective method for the conversion of dihydropyranone 1 to tetrahydropyranone 3. Attempted selective hydrogenation of 1 using 5% Pd-C or 5% Rh-Al2O3 catalyst was unsuccessful. However, catalytic hydrogenation of dihydropyranone 1 was carried out smoothly using Lindlar catalyst (Pd/CaCO3, PbO) in the absence of quinoline for 12 h to provide tetrahydropyranone 3 in 96% isolated yield. While Lindlar catalyst has been widely used for selective reduction of alkynes to alkenes4, its potential for selective olefin hydrogenation has not found precedent until recently.5 Herein, we report the chemoselective hydrogenation of a variety of olefins by commercially available (Aldrich) Lindlar catalyst in methanol.
To ascertain the generality of this selective reduction procedure, we applied it in several olefinic systems and found that this transformation is general to mono or di- or tri-substituted olefins. As shown in Table I, the reaction conditions are compatible to the presence of a benzyl ether (entries 1, 2 and 5), the benzyl amine (entries 3 and 4) functionality or substituted benzyl alcohol (entry 6).6 However, a Cbz-protecting group does not survive under these conditions. In conclusion, this method should find broad application in organic synthesis.
Table I.
Chemoselective reduction of various olefins with Lindlar catalyst
| Entry | Substrate | Time (method)a | Product | Yield% |
|---|---|---|---|---|
| 1. |  |
2 h (A) |  |
96 |
| 2. |  |
2h(A) |  |
98 |
| 3. |  |
50 min (B) |  |
97 |
| 4. |  |
45 min (B) |  |
95 |
| 5. |  |
40 min (B) |  |
98 |
| 6. |  |
2.5 h(A) |  |
96 |
Method A: using a Parr hydrogenation apparatus; Method B: using a hydrogen filled balloon
Acknowledgments
Financial support of this work by the National Institute of Health (GM-53386) is gratefully acknowledged.
References and Notes:
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- 6.In a typical procedure, a mixture of olefin (1 mmol) and Lindlar catalyst (10% by wt) in methanol (10 mL) was stirred under a hydrogen filled balloon or on a Parr apparatus under 20 psig for few hours. After this period, the mixture was filtered through a pad of celite, the solvent was evaporated and the residue was passed through a short silica gel column (50% ethyl acetate/hexane) to give the title hydrogenation product.