Electronic and Steric Control of Regioselectivities in Rh(I)-Catalyzed (5 + 2) Cycloadditions: Experiment and Theory

Abstract

The first studies on the regioselectivity of Rh(I)-catalyzed (5 + 2) cycloadditions between vinylcyclopropanes (VCPs) and alkynes have been conducted experimentally and analyzed using density functional theory (DFT). The previously unexplored regiochemical consequences for this catalytic, intermolecular cycloaddition were determined by studying the reactions of several substituted VCPs with a range of unsymmetrical alkynes. Experimental trends were identified, and a predictive model was established. VCPs with terminal substitution on the alkene reacted with high regioselectivity (>20:1), as predicted by a theoretical model in which bulkier alkyne substituents prefer to be distal to the forming C-C bond to avoid steric repulsions. VCPs with substitution at the internal position of the alkene reacted with variable regioselectivity (ranging from >20:1 to a reversed 1:2.3), suggesting a refined model in which electron-withdrawing substituents on the alkyne decrease or reverse sterically controlled selectivity by stabilizing the transition state in which the substituent is proximal to the forming C-C bond.

Permuting Diels–Alder and Robinson annulation stereopatterns

“…Adding to the patterns accessible by this logic was the fact that the chemistry is also extendable to the situation where the Diels-Alder diene contains a methyl substituent group at a terminal carbon 30 (Table 2). Once again, the levels of face selectivity in the cycloadditions were excellent, giving rise to the major adducts shown.…”

Synthesis of Highly Functionalized Cyclohexenone Rings: Rhodium‐Catalyzed 1,3‐Acyloxy Migration and Subsequent [5+1] Cycloaddition

“…Our research group [5] and that of others [20,21] have found that the regioselectivity for the cleavage of CÀC s bonds in cyclopropanes depends on the stereochemistry of the cyclopropane ring, the electronic properties of the substituents, and the nature of the metal catalysts. Our research group [5] and that of others [20,21] have found that the regioselectivity for the cleavage of CÀC s bonds in cyclopropanes depends on the stereochemistry of the cyclopropane ring, the electronic properties of the substituents, and the nature of the metal catalysts.…”

Computational Studies and Experimental Results—An Example of Excellent Teamwork in Studying Carbocyclization

“…A large array of different ACPs were transformed into the corresponding cis-fused bicyclohexenones with high yields and stereoselectivities by application of the optimized catalyst system consisting of [Rh(PPh 3 ) 3 Cl] and silver trifluoroacetate. All three tested catalyst systems-[{Rh(CO) 2 Cl} 2 ]/PPh 3 , [Rh(CO)(PPh 3 ) 2 Cl], and [Rh(PPh 3 ) 3 Cl]-displayed good to excellent activity and furnished the cis-fused bicyclohexenones in high stereoselectivity (cis/trans !…”

“…[1] Beside unsaturated substrates also strained carbocycles like cyclopropanes and cyclobutanes and their derivatives were identified to be suitable participants in these formal "higher-order" cycloaddition reactions. [3] In a recent publication Baik and Evans et al followed a somewhat different approach. The linkage of the single reaction participants in a chemo-, regio-, and stereoselective manner continues to display a significant challenge for preparative chemists since it provides the possibility to construct unusual structures difficult to assemble stepwise.…”