Revisiting Aromatic Claisen Rearrangement Using Unstable Aryl Sulfonium/Iodonium Species: The Strategy of Breaking Up the Whole into Parts.

ConspectusSince Ludwig Claisen's discovery of the sigmatropic rearrangement of allyl aryl ethers in 1912, aromatic Claisen rearrangement has continuously attracted the attention of both experimental and theoretical chemists. Over more than a century of growth, this protocol has proven to be a practical and powerful synthetic tool in many aspects. However, the reaction scope has long been limited to aryl ethers and their S or N analogs until the serendipitous discovery of aromatic iodonium-Claisen rearrangement by Oh et al. in 1988 and the development of aromatic sulfonium-Claisen rearrangement by Kita et al. in 2004. Unlike traditional Claisen rearrangements, these hypervalent-bonding-based Claisen-type rearrangements can be performed by simply mixing electrophilically activated aryl sulfoxides/iodanes with certain nucleophiles to directly deliver rearrangement products. In addition to the simple operation, remarkable features, such as readily available substrates, valuable products and intriguing rearrangement patterns, have led to a dramatic resurgence of this rearrangement chemistry.In this Account, we summarize our recent works on developing new aromatic rearrangement modes using sulfonium/iodonium reagents. Interestingly, the program started with an accidental discovery that aryl sulfoxides could be coupled with alkyl nitriles in the presence of Tf 2 O and base. Mechanistic studies reveal that the reaction proceeds in three major steps, including the Tf 2 O-triggered assembly of both coupling partners, base-promoted deprotonation of in situ-generated aryl sulfonium-imine species leading to a key rearrangement precursor called aryl sulfonium-ketenimine species, and subsequent facile and rapid [3,3]-rearrangement. On the basis of the mechanistic underpinning, we divided the one-step operation into two steps called the "assembly/deprotonation" protocol for constructing unstable rearrangement precursors. Most notably, the switch from the commonly used one-step to mechanism-based multiple-step manipulation, which can be termed "breaking up the whole into parts", not only enables the independent control of each step of the reaction, thus significantly expanding the accessible synthetic scope, but also raises opportunities for developing new rearrangement patterns. For example, the "assembly/deprotonation" protocol has also been applied to the development of [5,5]-rearrangement of aryl sulfoxides and the asymmetric rearrangement of aryl iodanes, thus enabling the unprecedented regio- and stereocontrol of the rearrangement process. Furthermore, the "breaking up the whole into parts" thinking triggered us to merge the Morita-Baylis-Hillman (MBH) reaction into the rearrangement process to accomplish Z -selective MBH-type [3,3]-rearrangement of α,β-unsaturated nitriles and E -selective MBH-type [3,3]-rearrangement of α,β-unsaturated 2-oxazolines, which expands the scope of rearrangement partners to include α,β-unsaturated carbonyls. In addition, the impressive rapidity of the rearrangement process found in our initial discovery has also been recognized as a congestion-acceleration effect, which was further utilized to forge the rapid ortho -cyanoalkylative rearrangement of aryl iodanes, and thus leading to the first dearomatization of aryl iodanes. We anticipate that our protocols and ideas behind the methods will be complementary to the traditional thinking of the aromatic Claisen rearrangement.