Stereochemical and Mechanistic Investigations of a Palladium‐Catalyzed Annulation of Secondary Alkyl Iodides

Abstract

Inversion versus retention: A palladium‐catalyzed annulation with enantioenriched secondary alkyl iodides gives mechanistic insight into the stereochemistry of this CH bond functionalization reaction (see scheme) involving a proposed PdII/PdIV catalytic cycle.

Alkylating Reagents Employed in Catellani‐Type Reactions

“…[11] Notably,i fe nantioenriched secondary alkyl iodides were incorporated, the solventp layed ap ivotal role in chirality transfer.N o significant loss of stereochemical information was observed in MeCN, but severe racemization took place in DMF. [10,11] In 2016, the group of Gu developed an ortho-silylmethylationr eaction by applying (iodomethyl)cyclohexyloxydimethylsilane as the alkylating reagent (Table 1, entry 9). [19] It is worth mentioning that the [(cyclohexyloxy)dimethylsilyl]methyl group can be readily oxidizedu nder Fleming-Tamao conditions or by ceric ammonium nitrate to give the benzylic alcohol derivatives.…”

“…Since then, a number of bifunctionalized alkyl halides were developed to access synthetically useful benzo‐fused carbo‐ and heterocycles (Section 3). Apart from isopropyl iodide, sterically hindered secondary alkyl halides were only applicable in this reaction through an intramolecular fashion . In 2015, the group of Lautens reported a general protocol for the incorporation of challenging secondary alkyl iodides intermolecularly in Catellani reaction, for the first time (Section 2) .…”

“…In 2015, the group of Lautens reported a general protocol for the incorporation of challenging secondary alkyl iodides intermolecularly in Catellani reaction, for the first time (Section 2) . Notably, chiral secondary alkyl halides could be incorporated inter‐ or intramolecularly without loss of stereochemical information, while an overall inversion of the stereoconfiguration was observed . In addition to alkyl halide, highly strained 2 H ‐azirines were utilized by the group of Lautens in 2010 as the novel alkylating reagent to react with aryl iodides and provide indoles (Section 4) .…”

“…Apart from isopropyl iodide, [9] sterically hindered secondary alkyl halidesw ere only applicable in this reaction through an intramolecular fashion. [10] In 2015, the group of Lautens reported ag eneral protocol for the incorporation of challenging secondary alkyl iodides intermolecularly in Catellani reaction, for the first time (Section 2). [11] Notably,c hiral secondary alkyl halides could be incorporated inter-or intramolecularly without loss of stereochemical information, while an overall inversion of the stereoconfiguration was observed.…”

“…[11] Notably,c hiral secondary alkyl halides could be incorporated inter-or intramolecularly without loss of stereochemical information, while an overall inversion of the stereoconfiguration was observed. [10] In addition to alkyl halide, highly strained 2H-azirines were utilized by the group of Lautens in 2010 as the novel alkylating reagentt or eact with aryl iodides and provide indoles (Section 4). [12] In 2018, epoxides were demonstrated to be elegant alkylating reagents independently by the groups of Dong and Zhou.…”