Intermolecular Diels–Alder Cycloaddition/Cross-Coupling Sequences of 2-Bromo-1,3-butadienes

Abstract

2-Bromo-1,3-butadienes are demonstrated to be effective substrates for tandem Diels–Alder/transition metal cross-coupling reaction sequences. Intermolecular cycloaddition of a 2-bromo-1,3-diene with activated dienophiles proceeded under Lewis acid catalysis in generally high yields with good to excellent endo diastereoselectivity. The resulting vinyl bromide cycloadducts underwent subsequent Stille and Suzuki cross-couplings under standard conditions in good yields. Both the Diels–Alder and cross-coupling steps were highly tolerant of a range of functionalities and protecting groups. The use of the bromine substituent as both a cycloaddition directing group and cross-coupling nucleofuge avoids extra steps required to install and remove the more commonly used silyl enol ethers and enol sulfonates for each transformation and gives full control of the alkene regiochemistry throughout the reaction sequence. The 2-bromo-1,3-dienes were conveniently prepared in three steps from readily available aldehydes and established as hydrolytically stable and practical synthetic intermediates.

Synthetic Studies Towards Spirocyclic Imine Marine Toxins Using N-Acyl Iminium Ions as Dienophiles in Diels–Alder Reactions

“…21 Meanwhile, the most recent study from our group in 2019 has demonstrated 2-bromo-1,3-butadiene systems (e.g., 103, Scheme 17) as highly effective substrates for tandem Diels-Alder-transition-metal cross-coupling reaction sequences. 58 Intermolecular cycloaddition of 2-bromodiene 103 with a variety of activated dienophiles was shown to proceed in generally high yield, with good to excellent endo diastereoselectivity. The resulting vinyl bromide cycloadducts 104 readily underwent subsequent Stille and Suzuki cross-couplings under standard conditions to provide access to novel substituted cyclohexene products 105.…”

“…Scheme 17 Use of 2-bromodiene 103 in Diels-Alder cycloadditions to access 5,6-spirocyclic imine 106 by Brimble and Furkert et al58 …”

Leveraging Metal and Ligand Reactive Sites for One Pot Reactions: Ligand‐Centered Borenium Ions for Tandem Catalysis with Palladium

“…Brimble, Furkert, and co‐workers recently described such stepwise reactions starting with Lewis acid catalysed cycloaddition of the 2‐bromo‐1,3‐butadiene 1 using BF 3 ⋅ Et 2 O (Scheme 2). [11] After workup and isolation, the brominated cycloaddition products were then functionalized with Stille and Suzuki cross‐coupling reactions using 10 mol% Pd(PPh 3 ) 4 . Depending on the dienophile, some of the cycloaddition reactions required heating to 60 °C, the use of neat BF 3 ⋅ Et 2 O, and/or other Lewis acid catalysts like neat TiCl 4 to afford the cycloaddition products in good yields and at reasonable timescales [11] .…”

“… [11] After workup and isolation, the brominated cycloaddition products were then functionalized with Stille and Suzuki cross‐coupling reactions using 10 mol% Pd(PPh 3 ) 4 . Depending on the dienophile, some of the cycloaddition reactions required heating to 60 °C, the use of neat BF 3 ⋅ Et 2 O, and/or other Lewis acid catalysts like neat TiCl 4 to afford the cycloaddition products in good yields and at reasonable timescales [11] . The more forcing catalysis conditions required for cycloaddition reactions to occur with 1 made them ideal candidates for challenging the reactivity of ligand‐centered borenium ions generated in ( R TBDPhos)PdCl 2 complexes.…”

Zn–Catalyzed Direct Synthesis of 3-Iodo-1,3-dienes from α-Allenols

“…On the other hand, iododienes are interesting species for organic chemistry because of their wide reactivity. These compounds are precursors in Diels-Alder reactions [4], palladium-catalyzed reactions [5] such as Stille [6], Negishi [7], and Sonogashira [8] and carbonylation cross-couplings [9], solvolysis [10] and metalation reactions [11].…”