One-Pot Synthesis of α-Alkyl Styrene Derivatives

Abstract

There is a significant need to develop more rapid and efficient routes to styrene derivatives, since they are extensively used in polymer sciences. This manuscript reports a one-pot synthesis of an array of α-alkyl styrene derivatives from readily available natural products (i.e., estragole and safrole). This method is regioselective, producing a rearranged adduct, under transition metal-free conditions. This methodology has broad nucleophile scope, even tolerating sterically hindered nucleophiles; it is general for carbon, nitrogen, oxygen, and sulfur nucleophiles.

Synthesis of a New α-Azidomethyl Styrene from Safrole via a Dearomative Rearrangement

“…Initially, it was found that allylaryl bearing electron poor and electron-neutral functional groups favors the formation of ( E )-allylic compounds such as ( E )-allylic azide 3 ( Scheme 1 ) [ 26 ]. On the other hand, in electron-rich systems (e.g., estragole or safrole), a dearomative rearrangement occurs to preferentially form adducts such as 4 (α-azidomethyl styrene) [ 27 ]. At the same time, it was also observed that the formation of regioisomers mainly occurred during the bromination step [ 28 ].…”

“…5-(2,3-dibromopropyl)benzo[ d ][1,3]dioxole ( 2a ) was obtained in a 22% yield, while 5-(1,3-dibromopropan-2-yl)benzo[ d ][1,3]dioxole ( 2b ) was isolated in a 63% yield. 1,3-dibromide 2b was then reacted under our standard azidation conditions [ 26 , 27 ] using sodium azide as the nucleophile and 1,8-diazabicyclo [5.4.0]undec-7-ene (DBU) as the base. To our delight, the expected product [5-(3-azidoprop-1-en-2-yl)benzo[ d ][1,3]dioxole 4 ] was obtained in a 91% yield ( Scheme 1 ).…”

“…The spectra of compound 4 can be found in the Supplementary Materials . In addition, it is worth noting that full mechanism details can be found in our prior reports [ 25 – 27 ].…”

Regiodivergent sulfonylation of terminal olefins via dearomative rearrangement

“…In 2021, we reported a straightforward protocol for the synthesis of a-alkyl styrenes (Scheme 1, eqn (3)). 39 It was observed that the bromination step plays a decisive role in determining the adduct regioselectivity and yield. Specifically, the bromination solvent and temperature.…”

Quantum Chemical Insight into 1,2-Shift Rearrangement in Bromination of Allylaryls

“…Recently, we reported the synthesis of α-alkyl styrene using transition metal-free one-pot reaction conducted under mild conditions. − Interestingly, this reaction resulted in a mixture of two distinct styrene derivatives, a and b (Scheme ). Based on the experimental observations in our previously reported work and the bromine-mediated rearrangement reaction studies done by Dubois and Costa, it was proposed that allylaryl undergoes an alkene bromination to form bromonium intermediate I , which later on undergoes an intramolecular rearrangement, a 1,2-shift by the electron-rich aryl moiety to form the spiro[2.5] intermediate II . , The spiro[2.5] intermediate II can be ring-opened by a nucleophilic attack by a Br – anion on the three-membered ring to produce either a 2,3-dibromo derivative ( a ) or a 1,3-dibromo derivative ( b ).…”