reduction of indole acetamides

[megamole]

Hiya everybody,

I was just wondering what people would recommend for the reduction of indole acetamides to tryptamines. There are published examples of this being done using LiAlH₄, but hey're a little dated, and there are so many new and interesting commerically-available reducing agents out there now. Cost and availability aside, what would be the reagent of choice for maximum yields, with the minemum risk of side-products? Would superhydride or K-selectride be better choices?
"Give me ten minutes with your inner child, and I'll give you back an inner adult."

[megamole]

Nothing? No interest at all? What about Vitride - does anybody ahve details about its use as an amide reducing agent? Or what about the slightly more exotic tetrabutylammonium borohydride?

When it comes to synthesizing things like n,n-di-tert-butyltryptamine and other interesting sounding things that have yet to be explored, the question of how to reduce amides in a practical manner is important.

[terbium]

The problem is not just a reducing agent to reduce an amide but one that will reduce an amide but not the indole ring. LAH does this well and is so cheap and ubiquitous relative to some of these other reducing agents that no one other than a clandestine chemist would even consider using anything other than LAH.

[megamole]

I've been looking, and I found some interesting things. In J.Org.Chem. (1986) 51(12), 2332-2342, the authors managed to reduce a fairly sensitive indoleacetamide to a tryptamine with a 95% yield using DIBALH (diisobutylaluminum hydride). Its certainly somewhat expensive, but for results like that, its more than worth the money.

LAH has indeed been used a great deal. I guess the reason I was shy about it was that the yields for indoleacetamide reductions using it range from the mid 20% range to nearly quantitative, and I thought one of the more new reducing agents might be a little more selective and predictable. However, considering the amount of synthetic infrastructure based on it, and its ubiquitous nature in the modern lab, I decided to pay close attention to the techniques used in later examples in the literature based on LAH with high yields. The following represent the

Arzneim.Forsch. (1999) 49(2), 96 - 105. -- 85-90% yield of several tryptamines
J.Labelled Compd.Radiopharm. (1997) 39(, 677-684. -- 75% yields of 5-MeODMT, 76% yields of tryptamine
J.Med.Chem. (1999) 42(6), 1106 - 1111. -- 93% of a thienopyrolyl analog od DMT

So, DIBALH appears to be the reagent of choice, though LAH comes in a respectable second place.