The Predominant Potions Professors

In 1980, Ranganathan et. al published a paper entitled “Nitroethylene: a stable, clean, and reactive agent for organic synthesis” which reported on several properties of nitroethylene; one of the most important properties focused on was its propensity to perform cycloadditions.

Nitroethylene was indeed found to undergo (4 + 2) addition with cyclopentadiene even at -100 "C. For practical reasons, however, the additions involving sensitive 5-substituted cyclopentadienes were carried out at -15 "C and the others at around 0 "C. We believe that nitroethylene is an effective 2 component in cyclopentadiene cycloadditions, as illustrated with adducts 1-7 (Chart I).

Chart I essentially showed the following cycloaddition (Diels-Alder) reaction, where R varied between several chemical groups.

 

 

 

 

 

While not specifically mentioned in great detail, it is worthy to note that all of the reactions proposed in this paper have the product formed in the endo- conformation only.

In 1985, E. J. Corey and A. G. Myers cited Ranganathan’s paper during a Diels-Aler reaction they performed with nitroethylene as the dieneophile.  Their reaction is below:

 

 

 

 

 

Already the similarities between this reaction and the key reaction we are focused on are readily apparent. On the topic of the stereochemistry of this reaction, the authors discussed how:

The beta-orientation of the nitroethylene bridge and the endo stereochemistry of the nitro group follow from the observation of…strong deshielding by nitro of protons at C(5) and C(6) in 14 relative to 13…

Unfortunately, there was no clarification on which carbons they had labeled C(5) and C(6), but in short, the Nitro- group were strongly and favorably deshielded while in this endo conformation.

 

 

 

 

 

In 2004, Lazarski et al. referenced Corey’s paper while performing early syntheses of Maoecrystal V.  The reaction they were using Corey’s information for is shown below:

This paper was then used by Lazarski’s group in their 2014 synthesis of Maoecrystal V as their reference for why they thought they could utilize the Diels-Alder reaction that is the focus of our Leading Question.

Citations:

Ranganathan, D.; Rao, B.; Ranganathan, S.; Mehrotra, A.; Iyengar, R. J. Org. Chem. 1980, 45, 1185-1189.

Corey, E. J.; Myers, A. G. J. Am. Chem. Soc. 1985, 107, 5574-5576.

Lazarski, K.; Hu, D.; Stern, C.; Thomas, R. Org. Lett. 2010, 12, 3010-3013.

Zheng, C.; Dubovyk, I.; Lazarski, K.; Thomson, R. J. Am. Chem. Soc. 2014, 136, 17750-17756.