Origins of Regio- and Stereochemistry in Type 2 Intramolecular N-Acylnitroso Diels–Alder Reactions: A Computational Study of Tether Length and Substituent Effects

Abstract

Quantum mechanical calculations have been used to investigate type 2 intramolecular Nacylnitroso Diels–Alder reactions. Experimentally observed regioselectivities and diastereoselectivities of these reactions have been reproduced using B3LYP/6-31+G(d) DFT calculations. The factors that govern selectivity (i.e. tether length, tether substitution and diene substitution) were systematically investigated. Tethers less than 6 carbon atoms lead to 1,3 regioisomers due to conformational restrictions. Substituents on the tether lead to diastereoselective outcomes dictated by transannular interactions in the transition states. The modest diastereoselectivity of diene-substituted substrates is rationalized as arising from reduction of eclipsing interactions in the flattened diene transition states. This method should prove valuable for planning syntheses involving type 2 intramolecular Diels–Alder reactions.

An Experimental and Computational Approach to Understanding the Reactions of Acyl Nitroso Compounds in [4 + 2] Cycloadditions

“…Unlike intramolecular NDA pathways where predictions of relative transition energies are straightforward, 30 intermolecular The Journal of Organic Chemistry NDA pathways are difficult to model given that there are many possible starting points, different conformers, and local minima of the two reactant molecules. This difficulty is compounded by super-reactive acyl nitroso species, such as MeOCONO and MeNHCONO, where the endo-NDA transition state can be only 2.0 kcal mol −1 higher than the starting diene and nitroso species.…”

Generation and Trapping of Nitrosocarbonyl Intermediates

“…Besides the specific studies done by the Pavia group in connection with ene reaction of nitrosocarbonyls 1i , 1n , and 1eb already discussed in previous sections, , recently, Shea, Rychnovsky, and co-workers presented quantum mechanical calculations to investigate the intramolecular NC HDA cycloaddition to account for the origin of regio- and stereoselectivities. Scheme reports the reaction and the DFT calculated TS predicting the observed selectivities …”

“…Scheme 190 reports the reaction and the DFT calculated TS predicting the observed selectivities. 355 From the theoretical point of view the cycloreversion process of the 3,5-diphenyl-1,2,4-oxadiazole-4-oxide 294 was investigated by peforming DFT calculations at the B3LYP/6-31G(d,p) level. Figure 8 shows the enthalpic profile connecting the intermediates and the TS along with the energy values (kcal/ mol) nearby the structures.…”

Facile generation of bridged medium-sized polycyclic systems by rhodium-catalysed intramolecular (3+2) dipolar cycloadditions

“…Type I IMDA cycloadditions (linked at the 1-position of the diene) are great for synthesizing fused bicyclo[m.4.0] ring systems. The pioneering Shea type II IMDA cycloadditions (linked at the 2-position of the diene) are powerful for the preparation of a few of bridged bicyclo[m.3.1] ring systems 15 – 17 ; however, these are very rarely used for the creation of all-carbon bicyclo[m.2.2] ring systems 18 , because the formation of such bicyclo[m.2.2] ring systems ( m = 3, 4, or 5) also with an unfavorable strained bridgehead olefin 19 (Bredt’s rule) 20 are usually more challenging than their regioisomeric products 21 (Fig. 1b ).…”