Rhodium (Chief Bee)
09-26-02 07:17
No 360757
      New tryptamine synthesis?  Bookmark   



Couldn't (S)-2-tert-butoxycarbonylaminopropyl methanesulfonate used for the alkylation somehow be used for 3-alkylation to form alpha-methyltryptamines? Or could it be applied to amphetamines, by some kind of aryl halide/mesylate coupling?
 
 
 
 
    Barium
(Hive Bee)
09-26-02 07:31
No 360763
      I have no clue if it could be used.  Bookmark   

I have no clue if it could be used. But Im pretty sure Os or Lillienthal have ideas about it.

Catalytic hydrogenation freak
 
 
 
 
    pHarmacist
(Hive Bee)
10-05-02 19:04
No 364924
      To Rhodium  Bookmark   

I think that this would be fully possible, and of course much easier from indolum.... A little reminder of our conversation of my Wolff/Kishner thread in Stimulants :)



[pH]armacist - Never, never ever shall you underestimate the power of retrosynthesis...
 
 
 
 
    Rhodium
(Chief Bee)
10-05-02 21:38
No 364950
      Oh - do you have any references for the first ...  Bookmark   

Oh - do you have any references for the first reaction? I have never seen anything being alkylated by the sulfur equivalent of an orthoester before...
 
 
 
 
    pHarmacist
(Hive Bee)
10-05-02 21:53
No 364955
      On monday  Bookmark   

My professor is constantly talking about that particular reaction, I have no reference but I can ask the old geezer  about his refs on monday, although I don't like arguing with him when it comes to chemistry, what he saiz goez..

[pH]armacist - Never underestimate the power of retrosynthesis. Svenskar suger p fotboll!
 
 
 
 
    pHarmacist
(Hive Bee)
10-05-02 22:06
No 364957
      When I look at it it seems logical, CH3S goes, ...  Bookmark   

When I look at it it seems logical, CH3S goes, carbocation is formed, attack from the 3-carbon of indole, works fine...

[pH]armacist - Never underestimate the power of retrosynthesis. Svenskar suger p fotboll!
 
 
 
 
    hest
(Hive Adickt)
10-06-02 03:09
No 365004
      Beilstain  Bookmark   

A beilstein search on the thiothing(and related structure) gave no hits, that might bee a hint ?.
 
 
 
 
    pHarmacist
(Hive Bee)
10-06-02 03:21
No 365006
      OrgSyn  Bookmark   

This could also be a hint, exacly the reaction I was talking about:

3-ALKYLATED AND 3-ACYLATED INDOLES FROM A COMMON PRECURSOR: 3-BENZYLINDOLE AND 3-BENZOYLINDOLE
Submitted by: P. Sttz and P. A. Stadler
Published in Annual Volume 56, page 8; Collective Volume 6, page 109

http://www.orgsyn.org

[pH]armacist - Never underestimate the power of retrosynthesis. Svenskar suger p fotboll!
 
 
 
 
    dmitri
(Stranger)
10-06-02 10:44
No 365075
      The mesylate ester is being used as an ...  Bookmark   

The mesylate ester is being used as an N-alkylating agent. This reaction follows a classic SN2 mechanism, and I have a hard time imagining that the 3-position is going to be an option.

I'm kind of surprised that they're using NaCNBH3 to remove the protecting group; TFA or even HCl in EtOAc will do this nicely for a lot less money.
 
 
 
 
    GC_MS
(Hive Bee)
10-06-02 14:39
No 365156
      Looks...  Bookmark   

Looks like some sort of Friedel-Crafts with BF3 as the Lewis acid. The dithiane can be converted to -CH2- with Raney Ni (or hydrazine), as said by pHarmacist.



R1   S---CH2
  \ /     \
   C      CH2  +  Ra-Ni or H2N-NH2 ----> R1-CH2-R2
  / \     /
R2   S---CH2



Some more information on that reaction can be found on http://www.tciamerica.com/news/newslib/94sum_a.htm
I don't completely see how MeS- interacts in the reaction though, how/why it leaves. I suggest there is formation of MeSH in the first step of the reaction? Anyway, as it looks related to Friedel-Crafts, I postulated the following mechanism:



           (d-)                       
  H2C---S   S--Me         F           
   /     \ /              |           
H2C       C(d+)     + (d+)B--F    ----> 
   \     / \              |            
  H2C---S   R             F            
 


            Me
            |
  H2C---S   S~~~BF3          H2C---S                F
   /     \ /                  /     \ (+)           |
H2C       C         ---->  H2C       C     +   MeS~~B--F
   \     / \                  \     / \             |
  H2C---S   R                H2C---S   R            F
 
 

  H2C---S   R               HC---CH
   /     \ /          (2)   /     \
H2C       C ----*     HC---C       CH   ---->
   \     / (+)  |      |    \     /
  H2C---S       *--->  |     C---CH
                       |    /
                      HC---N
                      (3)
                     
                     
  H2C---S   R
   /     \ /
H2C       C   H  HC---CH
   \     / \ /   /     \
  H2C---S   C---C       CH  --[MeS~BF3]-->
            |    \     /
            |     C---CH
            |    /
         (+)C---N
           /
          H
         
         
  H2C---S   R
   /     \ /
H2C       C      HC---CH
   \     / \     /     \
  H2C---S   C---C       CH  +  BF3  +  MeSH
            |    \     /
            |     C---CH
            |    /
           HC---N



Theory: in the 2-methylthio-1,3-dithiane, there is one C atom bound by 3 sulphur atoms and an R group. S drains electrons from C, by which C ends up with a partial negative current. In this case, a Lewis acid (BF3) interacts with the methylthio group. I don't know exactly why the BF3 wouldn't interact with the dithiane S atoms... stereochemical factors, or a lower partial negative current, or... ? Anyway, MeS- is the leaving group and form some kind of complex with BF3 (don't think it can form a bond, since B can only form 3 sigma bonds according to hybridisation theorem). The dithiane carbonium ion can now interact with the indole structure, as shown in the sketch. But I think the carbonium ion can interact both on C2 and C3 of the indole. I show the reaction in the way you would like it most... wink. The hydrogen on C2 is "cought" by the MeS-BF3 complex, by which the indole derivative becomes a stable molecule and MeS-BF3 falls appart in MeSH and BF3. This is 100% theoretical, I might be selling you a bag of elephant dung as well... but as I look at this reaction, you'll end up with two alkylated indoles: one alkylated on C2, the other on C3.

Might be interesting as well:

[1] L Micouin, A Diez, J Castells, D Lopez, M Rubiralta, JC Quirion, HP Husson - Synthetic applications of 2-(1,3-dithian-2-yl)indoles V. Asymmetric synthesis of dasycarpidone-type indole alkaloids, Tetrahedron Lett 36 1693-1696.
[2] Seung-Hwa Baek, Chan-Nam Yook, and No-Yeun Park - Boron Trifluoride Etherate-Catalyzed Formation of 3,4,5,6-Tetrahydro-7-hydroxy-2-(1,3-dithian-2-yl)-9-alkyl-2,6-methano- 2H-1-benzoxocin Derivatives, Bulletin of the Korean Chemical Society 12(6) (1991) 633-635. http://www.kcsnet.or.kr/publi/bul/bu91n6/633.pdf

PS: pi-bond in sketches not shown due to estetical considerations... you (should) know where they are wink.


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    GC_MS
(Hive Bee)
10-06-02 15:15
No 365173
      aldehydes...  Bookmark   

It might be interesting to note that the method might also be applicable for the synthesis of aldehydes... If the following dithiane is used:


  H   S---CH2
   \ /     \
    C      CH2
   / \     /
MeS   S---CH2



and the yielding indole-1,3-dithiane is hydrolyzed with Hg(II) (for instance HgCl2) instead of reduced with Ra-Ni, the end product is an aldehyde.


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