Diastereoselective Three-Component 3,4-Amino Oxygenation of 1,3-Dienes Catalyzed by a Cationic Heptamethylindenyl Rhodium(III) Complex

Abstract

The direct oxyamination of olefins is a compelling tool to rapidly access β-amino alcohols–a privileged motif ubiquitous in natural products, pharmaceuticals and agrochemicals. Although a variety of expedient methods are established for simple alkenes, selective amino oxygenation of 1,3-dienes is less explored. Within this context, methods for the oxyamination of 1,3-dienes that are selective for the internal position remain unprecedented. We herein report a modular three-component approach to perform an internal and highly diastereoselective amino oxygenation of 1,3-dienes catalyzed by a cationic heptamethylindenyl (Ind*) Rh­(III) complex.

Highly regioselective and diastereodivergent aminomethylative annulation of dienyl alcohols enabled by a hydrogen-bonding assisting effect

“…1 In particular, the two-component Pd-catalyzed annulation of dienes involving the formation of π-allylpalladium species and intramolecularly intercepting them with a nucleophile allows for the rapid construction of cyclic molecules, and significant progress has been achieved. 2,3 However, a serious limitation is that most of these reactions are performed via formation of a π-allylpalladium intermediate like I or II , 2 which leads to the generation of 1,2 or 1,4-difunctionalization products (Scheme 1A). A different type of π-allylpalladium intermediate III would be expected that can deliver the 3,4-difunctionalized cyclic products via its subsequent intramolecular interception with a nucleophile.…”

“… 4 However, in stark contrast to 1,2- and 1,4-annulations, the 3,4-annulation of 1,3-dienes has remained elusive. 3 The underlying reason might be attributed to the lack of efficient strategy and appropriate alkylpalladium species to enable the Heck insertion to occur across the internal C C bond for regioselective formation of intermediate III. Moreover, intramolecular interception of intermediate III may generate an inseparable mixture of trans - and cis -isomers, which makes such reactions more challenging.…”

Rh(III)-Catalyzed Intra- and Intermolecular 3,4-Difunctionalization of 1,3-Dienes via Rh(III)-π-Allyl Amidation with 1,4,2-Dioxazolones

“…Beyond these seminal examples, direct installation of unprotected β-amino alcohols (amino hydroxylation) across 1,3-dienes has remained elusive. In contrast to oxidizing the more accessible terminal olefin of 1,3-dienes, our group recently disclosed a unique protocol to selectively access 3,4-amino oxygenated products leaving behind an exempted vinyl group, which can be exploited for further derivatization (Figure C) . One of the key features involves the generation of a cationic, Lewis acidic Rh­(III) complex from the heptamethylindenyl (Ind*) dichloride precursor ([Ind*RhCl 2 ] 2 ), − which readily invites coordination of 1,3-dienes.…”

“…In alcoholic solvents (>15 equiv of the nucleophile), 1,3-nonadiene 1a is converted into the methoxy amidated product 3a when treated with methyl dioxazolone 2a (3.0 equiv) in the presence of 2.0 mol % [Ind*RhCl 2 ] 2 ( Rh-1 ) and 10 mol % of AgSbF 6 (70% yield, >15:1 d.r.). To facilitate transition to elaborate nucleophiles, a series of organic solvents were evaluated using MeOH as a stoichiometric nucleophile (5.0 equiv).…”

“…Over the last years, 1,4,2-dioxazol-5-ones 2 have evolved into extremely practical acyl amino sources, which are readily available from carboxylic acids. ,− ,− Along these lines, fluorinated amide 6b (49%) as well as n -alkyl substituted amides 6c , 6d (61–67%) are successfully incorporated in the amino hydroxylation protocol. Furthermore, sterically more demanding groups such as α-tertiary amides 6e – g (37–61%) and benzyl substituents ( 6h , 44%) are compatible.…”