Subject: Summary of responses. 1,3-dipolar cycloadditions

From: Jose Ignacio Garcia <[email-masked]>
Date: Mon, 18 Apr 94 9:39:06 MET

Dear netters,

Thanks to everyone who replied to my request about semiempirical calculations
of 1,3-dipolar cycloadditions. Here is the summary of the responses received.

=============================== Original question =============================

 Dear netters,

 I intend to start a study about the reaction between diazomethane and a series
 of complex dipolarophiles. Given that the important size of these systems, I
 have planned to use semiempirical methods (AM1 and PM3). I have some references
 dealing with the use of these type of calculations to locate transition
 structures in this kind of reactions, but the conclusions seem some controversial.
 I would acknowledge any ideas or suggestions on this topic.
 Of course, I will summarize the responses to the net.

===============================================================================

Jim Blake wrotes:

Carlos Sosa and myself published a paper on the using DFT to locate
the transition states of a few 1,3-dipolar cycloadditions.  We also
compared this to HF and MPx levels of theory.  The reference is

International journal of quantum chemistry vol 49, 511-526, 1994.

  Jim

===============================================================================

Dave Winkler wrotes:

We have not had much success predicting regiochemistry of these types of 
reactions using semiempirical MO.  Please send me summary.

Cheers,

Dave
__________________________________________________________________________

   Dr. David A. Winkler                        Voice: 61-3-542-2244      
   Principal Research Scientist                Fax:   61-3-543-8160      
   CSIRO Division of Chemicals and Polymers
   Private Bag 10       
   Clayton, Australia.

   "Life is what happens to you while you're making other plans"

===============================================================================

Mike Robb wrotes:

We did MC-SCF computations on this reaction in 1987

JACS vol 109 4642-4648 1987

I believe that these are delicate problems because if the
competition with a biradical mechanism. Semi-empirical methods
will certainly be unreliable.  Further SCF cannot describle the
biradical path.

Mike Robb

===============================================================================

Konrad Koehler wrotes:

Dear Dr. Ignacio,

   Thank you for your detailed response to my questions.  I now have a much 
better idea of what you are trying to do.

   I would agree that > 20 heavy atoms is probably too large a problem to 
handle with ab initio theory, even with a relatively fast workstation.

   As far as the reaction mechanism of dipolar cycloaddition reactions, this 
of course goes back to the argument between Firestone and Huisgen.  The former 
argued in favor a stepwise mechanism while Huisgen and most others argue in 
favor of concerted, asynchronous reaction.  Most of the experimental evidence 
favors the concerted reaction (stereoslectivity of reactions, relatively small 
rate enhancement with increasing solvent polarity, etc.).  I don't have these 
references at my finger tips, but could pull them out if you are interested.

   If you are specifically interested in the reaction mechanism, in my 
opinion, ab initio calculations are the only way to go.  If you can't model 
the full structures of your reactants with ab initio theory, use a model 
system.  If you are interested in the face (i.e., stereo) selectivity 
question, especially for large systems, perhaps a molecular mechanics approach 
is worth trying.

   The strategy is to obtain a transition state geometry at a high level of ab 
initio theory, and then use this transition state structure to parameterize a 
force field using special atom types for the atoms directly involved in bond 
formation/breakage so that the transition state becomes a minimum on the 
molecular mechanics potential energy surface.  Houk and others have shown that
it is possible to predict the stereochemical outcome of certain cycloaddition
reactions using this approach (for a review see [1]), although this technique
has been criticized by Menger.[2,3]  Finally enhancements to recent versions
of the MacroModel program have [4] been made so that it is relatively easy to
set up (although it is non-trivial to parameterize) molecular mechanics
transition state calculations. 

[1] Eksterowicz, J. E.; Houk, K. N. Transition-state modeling with 
    empirical force fields.  Chem. Rev.   1993, 93, 2439-2461. 
[2] Sherrod, M. J.; Menger, F. M. "Transition-state modeling" does not always
    model transition states.  J. Am. Chem. Soc.   1989, 111, 2611-2613. 
[3] Menger, F. M.; Sherrod, M. J. Origin of high predictive capabilities in
    transition-state modeling.  J. Am. Chem. Soc.   1990, 122, 8071-8075. 
[4] Mohamadi, F.; Richards, N. G. J.; Guida, W. C.; Liskamp, R.; Caufield, C.;
    Chang, G.; Hendrickson, T.; Still, W. C. MacroModel V3.5X.    1990, 11,
    440-467. 

    I hope this information is helpful.

    Ciao,

 ------------------------------------------------------------------
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===============================================================================

David White wrotes:

Dear Dr. Garcia-Laureiro,

Professor Tony Ford of the University of Natal in South Africa and I 
are just about finished a study of
1,3-dipolar additions between diazomethane and some dipolarophiles.
However, we have done the entire study using ab initio.  We have 
completed the transition state optimizations and are in the process
of doing the frequency calculations.  We would be very interested 
to know the dipolarophiles you are using in your study for potential
comparrison of the ab initio and semiempirical results.

Sincerely,

David White
  
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===============================================================================

E. Lewars wrotes:

I believe a semiemp study of the Diels-Alder reaction of heterodienophiles
(HNO, HN=NH, etc will appear in THEOCHEM this year; this is related to 
the topic you asked about.

===============================================================================

Again, thank you very much.

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Dr. Jose Ignacio Garcia-Laureiro              Phone : 34-(9)76-350475
Departamento de Quimica Organica              Fax   : 34-(9)76-567920
Instituto de Ciencia de Materiales de Aragon  e-mail: [email-masked]
C.S.I.C.-Universidad de Zaragoza                      [email-masked]
50009 ZARAGOZA (SPAIN)                                [email-masked]
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