Autocatalytic Carbonyl Arylation through In Situ Release of Aryl Nucleophiles from N-Aryl-N'-Silyldiazenes

Abstract

A method for the catalytic generation of functionalized aryl alkali metals is reported. These highly reactive intermediates are liberated from silyl-protected aryl-substituted diazenes by the action of Lewis basic alkali metal silanolates, resulting in desilylation and loss of N₂ . Catalytic quantities of these Lewis bases initiate the transfer of the aryl nucleophile from the diazene to carbonyl and carboxyl compounds with superb functional-group tolerance. The aryl alkali metal can be decorated with electrophilic substituents such as methoxycarbonyl or cyano as well as halogen groups. The synthesis of a previously unknown cyclophane-like [4]arene macrocycle from a 1,3-bisdiazene combined with a 1,4-dialdehyde underlines the potential of the approach.

Keywords: Lewis bases; autocatalysis; chemoselectivity; nucleophilic addition; silicon.

Scheme 1

Silicon‐based aryl pronucleophiles in transition‐metal‐free 1,2‐addition to aldehydes (alcohols after hydrolysis). EWG=electron‐withdrawing group, EDG=electron‐donating group, FG=functional group, X=aryl substituent. MW=microwave irradiation, R=alkyl or aryl group, tBu‐P4=3‐tert‐butylimino‐1,1,1,5,5,5‐hexakis(dimethylamino)‐3‐{[tris(dimethylamino)phosphoranylidene]amino}‐1λ ⁵,3λ ⁵,5λ ⁵‐1,4‐triphosphazadiene (Schwesinger base), TBAF=tetrabutylammonium fluoride.

Figure 1

Scope II: Various diazene/aldehyde combinations.^[a] [a] Unless noted otherwise, the reactions were performed on a 0.40 mmol scale with 10 mol % Me₃SiONa in THF at room temperature. [b] Me₃SiOK instead of Me₃SiONa. [c] Formed along with the corresponding silyl enol ether in 30 % yield. [d] Yield determined by NMR spectroscopy using CH₂Br₂ as an internal standard. [e] The reaction was performed on a 1.8 mmol scale with 5.0 mol % Me₃SiONa in THF at room temperature.

Scheme 2

Scope III: Ketones and esters as electrophiles. [a] Formed along with the corresponding 1,4‐adduct in 6 % yield.

Scheme 3

Scope IV: Equivalent of an aryl bisnucleophile in the reaction with an aldehyde (left) or a dialdehyde (right); molecular structure of a cyclophane‐like [4]arene macrocycle (middle, thermal ellipsoids are shown at the 50 % probability level and all hydrogen atoms except the two pointing toward the center are omitted for clarity).

Scheme 4

Proposed autocatalytic cycle. M=alkali metal, R and R′=alkyl or aryl, Ar=aryl.