Cationic-Initiated MBFTs

The following examples will show the power of cationic-initiated MBFTs utilized in the total synthesis of natural products. 

3-oxidosqualene 38 was easily prepared in two steps from squalene, followed by a reported procedure. Treatment of epoxide 38 with HCl in ether gave a 1 1 

Treatment of amine 58 with formaldehyde under acidic conditions led to the formation of the methylene iminium ion 59, which induced a Mannich cyclization at the C3 position of the indole to produce the spiroindolenine 60. Compound 60 underwent 

The first one-pot cascade reaction was used to introduce the pyrrole moiety. The 2-amino-4-bromoimidazole 65, an amidine tautomer of 64, first underwent a nucleophilic substitution of the bromine atom by reaction with the pyrrole surrogate 66, producing compound 67, which was subsequently treated with TEA leading to the desired Al-coupled pyrrole-2-carboxylic acid 69 through oxonium 68. This one-pot cascade reaction involved no less than five chemical transformations. 

The second one-pot cascade reaction was used to complete the synthesis of the natural product from acid 69. Reduction of the two azide groups of 69 produced the highly polar diamine 70, which was treated with EDC and HOBt to induce an intramolecular lactam cyclization and deliver the macro-palau amine 71. When the crude reaction mixture of 71 was heated in TEA, compound 72, proceeding through amidine tautomer 71, elicited the key transannular cyclization and delivered the palau amine in 17% overall yield from 69. The outcome stereochemistry was all in the control of the stereocenters within the substrate. 

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The goal of this chapter is to highlight and discuss a selection of MBTFs employed in the total synthesis of natural products during the past 10 years. As MBTFs usually involve many distinct steps, which make it hard to classify them, this chapter is divided into five parts anionic-initiated MBFTs, cationic-initiated MBFTs, radical-mediated MBFTs, pericyclic MBFTs, and transition-metal-catalyzed MBFTs, hoping that the division can help show the MBFTs employed in the synthesis of natural products clearly and concisely. 

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