Why do thioureas and squaramides slow down the Ireland–Claisen rearrangement?

Abstract

A range of chiral hydrogen-bond-donating organocatalysts was tested in the Ireland–Claisen rearrangement of silyl ketene acetals. None of these organocatalysts was able to impart any enantioselectivity on the rearrangements. Furthermore, these organocatalysts slowed down the Ireland–Claisen rearrangement in comparison to an uncatalyzed reaction. The catalyst-free reaction proceeded well in green solvents or without any solvent. DFT calculations showed that the activation barriers are higher for reactions involving hydrogen-donating organocatalysts and kinetic experiments suggest that the catalysts bind stronger to the starting silyl ketene acetals than to transition structures thus leading to inefficient rearrangement reactions.

Reshuffle Bonds by Ball Milling: A Mechanochemical Protocol for Charge-Accelerated Aza-Claisen Rearrangements

“…Despite their synthetic relevance as bond forming reactions, all of these original protocols have one disadvantage in common: a high energy demand [ 21 , 30 , 31 ]. Consequently, catalytic protocols that make use of transition metal complexes [ 55 , 56 , 57 , 58 , 59 , 60 , 61 ], Lewis or Brønsted acids [ 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 ], or organocatalysts [ 75 , 76 , 77 , 78 , 79 , 80 ], were developed to shape the (energy) efficiency of the Claisen rearrangement. Along these lines, the ‘on-water’-effect was explored to reduce the reaction temperatures, too [ 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 ].…”

Tandem Insertion/[3,3]-Sigmatropic Rearrangement Involving the Formation of Silyl Ketene Acetals by Insertion of Rhodium Carbenes into S–Si Bonds

“…Initially, we explored the reaction of PhO−SiMe 3 with allylα-phenyl-α-diazoacetate 1 using typical conditions for O−H insertion (1 mol % Rh 2 (OAc) 4 , 2 equiv PhO−SiMe 3 , CH 2 Cl 2 , 40 °C, slow addition over 1 h; Table 1). 15 Ireland−Claisen rearrangements of silylketene acetals generally proceed at or below room temperature, 16 but after 1 h syringe pump addition of the diazo compound, the reaction was allowed to run for an additional 1 h to ensure completion of the rearrangement. Addition of the diazo compound by syringe pump reduces unwanted carbene dimer formation.…”