Suggested 2 step reaction to AMT

[Rhenium]

Hello everyone, it's been a long while since I walked these hallowed halls, but I had an idea kind of spring itself upon me as I sat in the lab musing over a few synthetic papers...
 

http://rhodium.lycaeum.org/chemistry/it-290.html

As everyone knows, the above link is to the synthesis of AMT located on Rhodium's page. Being more interested in synthetic chemistry than it's personal use, I wondered about a synthesis starting from that ubiquitous material Tryptophan.

Ok, here's the plan...

1) Reduction of Tryptophan or it's ester by the usual routes i.e. LiAlH4 or BH3/THF.

2) Elimination of that pesky alcohol group to it's corresponding methyl which takes us to our finished compound.

Ok, the first part is relatively simple, but what about the second? You can't reduce the group using standard methods, so how about these two papers which have definitely graced the Hive before...

1) Olah, G.A. et. al., J. Org. Chem., 44(, 1979, pp 1247.

2) Sakai, T., et. al., Tet. Let., 28(33), 1987, pp 3817.

Both of these papers are different spins on Me3SiCl and NaI. The first turns the alcohol into a Iodide, and the second eliminates it all together. Both sets of reaction proceed at room temperature in good to excellant yield.
Three question therefore arise, 1) Can this chemistry be applied to indole containing system for the elimination of the slcohol, 2) what if any side-reactions may occur, and 3) if the iodide is isolated, what subsequent reaction can be used to eliminate that?

I leave these questions in your capable hands for further pondering...

Yours, as always...

Rhenium

[rev drone]

Say, if memory serves, I think NaBH4/I2 as a reducing system is effective at facilitating the reduction of amino acids cheaply and effectively. I remember posting

------------------
-the good reverend drone

Ipsa scientia potestas est

[Rhodium]

Synthesis of S(+)- and R(-)-3-(2-Aminopropyl)indole from Ethyl-D- and L-Tryptophanate
David B. Repke and Wilfred J. Ferguson

J. Heterocyclic Chem., 13, 775 (1976)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/ethyl.tryptophanate2amt.pdf)

Abstract
A stereospecific requirement for hallucinogenesis applies to certain molecules containing an asymmetric center. Thus, only the R-isomers of substituted phenylisopropylamines and lysergic acid diethylamide are psychotomimetic. The enantiomers of a minor hallucinogen, S(+)- and R(-)-3-(2-aminopropyl)indole (?-methyltryptamine) (6a and 6b) were synthesized via a 5-step manipulation from D- and L-tryptophan ethyl ester hydrochloride, respectively. Optical purity of these two isomers was determined by pmr spectroscopy of their complexes with a europium chiral shift reagent using the indole C₂ H signal.

[Sedrick]

[Fastandbulbous]

Surely that means that, by the above method, that phenylalanine can be converted into amphetamine, tyrosine to 4-hydroxyamphetamine and best of all DOPA to 3,4-dihydroxyamphetamine (then methylenation to MDA), and as phenolic OH groups don't undergo substitution reactions in the same way that aliphatic OH groups do, mean that they will be stable to reagents that convert the OH from reduction of the carboxylic acid to the intermediate iodo compound, or am I overlooking something simple (my area is pharmacology, with only a bit of org chem synth proceedures)?

[Beard]

You can't reduce the group using standard methods, so how about these two papers which have definitely graced the Hive before...</p><p>1) Olah, G.A. et. al., J. Org. Chem., 44(, 1979, pp 1247.</p><p>2) Sakai, T., et. al., Tet. Let., 28(33), 1987, pp 3817.</p><p>Both of these papers are different spins on Me3SiCl and NaI. The first turns the alcohol into a Iodide, and the second eliminates it all together. Both sets of reaction proceed at room temperature in good to excellant yield.
</p>

Referenced papers available here (no javascript required to download them):

* J. Org. Chem., Vol. 44 ( Issue 8 ), 1979, pp 1247. @ https://file.io/Cat32X or https://dropfile.to/oLDMK0S (24 hours)
* Tet. Let., Vol. 28 (Issue 33), 1987, pp 3817. @ https://file.io/hxGP7G or https://dropfile.to/JySchWf (24 hours)

Alts ( Javascript required, no SSL but always available ):
* http://www.xup.in/dl,58488579/J.org.chem1979%2844%291247.pdf/
* http://www.xup.in/dl,51447552/Tet._Let._1987_28(33)_pp3187.pdf/

I tried to upload them directly & attach to this post, but I kept getting an error:

An Error Has Occurred!
Cannot access attachments upload path!

[Tsathoggua]

How about conversion of the aliphatic -OH to the halide via a modified Appel rxn. This (Appel reaction) relies on conversion of PPh3 to a diphenylphosphonium halide, which is the active halogenation agent.

The classic rxn uses carbon tet and PPh3, which (the latter) can be used in catalytic quantities apparently. Yes toady once asked if chloroform could be used in place of carbon tet, for chlorinations, but seemingly whilst the reaction would proceed it would be exceedingly slow. It seems remarkably versatile, at least, inasmuch as one wishes to react an alcohol to an alkyl halide. The versatility comes from being able to utilize carbon tetrachloride, tetrabromide, tetraiodide (this last is thermodynamically unstable and should be stored if it must be so at 0'C or preferably, prepared and immediately cooled prior to use). It can be produced, reportedly via reaction of C-tet with I2, but MeI, I2, Br2 and even alkali metal ionic salts have been used for this modified Appel. It converts alcohols into alkyl halides. Quite a kick ass rxn. Been contemplating its use for synthesis of chlormethiazole or bromethiazole in fact, for times I've run out of SOCl2.

[enone]

what about indole-3-acetic acid -> indole-3-acetone -> alpha-methyltryptamine?

IAA is sold in bulk all over. basically treat it like phenylacetic acid and distill the ketone from a mixture of it and lead (II) acetate, then run the leuckart with ammonium formate. really quick (and dirty) stuff, feasible for sure

[micro]

Very interesting.
IAA is indeed quite available.

[enone]

on second thought, maybe reductive amination with ammonium acetate and sodium cyanoborohydride wouldn't be the worst idea

https://anonimag.es/image/JJ7k

fixed link

[Beard]

That's probably the way to go.

Though here, after all, nearly two decades after the OP, attached are the aforementioned papers.