DMSO as a carbon source for sp3 CH olefination

DMSO as a carbon source for sp3 CH olefination

There are increasing examples of dimethyl sulfoxide acting as a carbon source for methylation reactions. (See the recent Synthesis Corner post of January, 2018 – “DMSO as a carbon source in transition-metal-free α-Csp3-H methanylation” and March, 2018—”DMSO as a carbon source in the transition-metal-free synthesis of quinolones.”) Recently, Namidharan et al., the first to demonstrate an αSP of hypervalent aryliodides and DMSO. Reported on the synthesis of multisubstituted arylamidines in a one-pot sequential approach using3 Palladium-catalyzed SP after CH olefination2 CH arylation.1

In the first step of a one-pot, two-step sequence, sulfonylamidine 1 α sp. passes by3 CH olefination to produce terminal olefin 2e And 2Z (figure 1). When only this step was performed, good ablation yields were achieved with a variety of electron-donating, electron-withdrawing or sterically-seeking substituents at all R positions. Since the impedance of isomerization of imine bonds in these compounds is relatively low, most reactions result in a mixture of about 1:1. I And jade isomer of the product.

Figure 1: α sp3 CH olefination of amidine to form a terminal olefin

When both steps were executed sequentially in the same reaction vessel, good overall yields (51–70%, Figure 2) were obtained in most instances. However, the addition of aromatic rings with electron-withdrawing substituents at the para position reveals a moiety of the product. Additionally, the high substitution of the amine nitrogen (R2 and R3 = alkyl) also yielded only a trace amount of the desired product.

Figure 2: Tandem One-Pot Synthesis of Multisubstituted Sulfonylamidines

The mechanism of the olefination reaction was explored using d6-DMSO as the solvent. This resulted in the production of deuterated terminal olefins and indicated that DMSO was the carbon source for methylene. With this information and references to the literature, the arrangement below (Scheme 1) was proposed.

In the proposed mechanism, DMSO reacts with the hypervalent iodine reagent resulting in an active DMSO species a, species a Thionium decomposes into cation b and releases iodosobenzene. Cation’s reaction b Produces thiomethyl intermediate with amidine C Which undergoes oxidation of sulfoxide I Through the reaction with iodoisobenzene. sulfoxide I Then the terminal alkene undergoes a Chugaev-type reaction to produce F, In addition to the palladium catalyst, alkene F pairs with iodobenzene generated in the olefination reaction to produce the final product Yes,

Scheme 1: Proposed Mechanism for the Olefination Reaction with DMSO and Phenyliodine Diacetate

In summary, this work demonstrates a new metal-free route to produce a terminal alkene at the alpha position of an amidine. DMSO serves as a carbon methylene source for this reaction and also acts as a solvent. Additionally, this reaction can be used as the first step of a one-pot terminal olefination and arylation sequence that generates highly substituted sulfonylamidines.

Debra D. Dolliver, Ph.D.

Reference
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