Domino oxidation

A convenient procedure for the lactonization of alkenols has been recently revealed by Borhan and coworkers [19]. This methodology was successfully applied in the total synthesis of (+)-tanikolide (7-37), a natural product of marine origin which exhibits antifungal activities. Thus, when alkenol 7-36 is subjected to soluble oxone and a catalytic amount of 0s04, a smooth domino oxidative cleavage/lactonization process takes place which leads, after debenzylation, to the desired product in good overall yield (Scheme 7.12). 

Scheme 7.23. Domino oxidation/spirolactonization/Diels-Alder reaction sequence.

Scheme 7.28 DMP-induced domino oxidation/hetero-Diels-Alder sequence.

Scheme 7.30. DMP-induced domino oxidation/hetero-Diels-Alder procedure for the rapid entry into complex elisabethin and pseudopterosin structures.

En route to the total synthesis oftashironin (7-114a) and the debenzoylated compound 7-114b, which shows an interesting promotion of neurite growth, Danishefsky and coworkers have developed a domino oxidative dearomatization/trans-annular Diels-Alder reaction [54]. In this line, treatment of 7-115 with phenyl-iodine(III) diacetate (PIDA) led to an intermediate 7-116, which immediately underwent a transannular Diels-Alder reaction to furnish the complex cycloadducts 7-117 in good yields (Scheme 7.31). 

Scheme 7.31. Domino oxidative dearomatization/transannular-Diels-Alder reaction.

Scheme 7.36. Domino oxidation/twofold transannular-Diels-Alder reaction in the total synthesis of FR182877 (7-133).

The concept for the synthesis of4-hydroxy-4,5-dihydroisoxazoles by Righi and coworkers was discussed earlier, in Chapter 7. Here, an extension of this methodology by utilizing polymer-bound nitroacetate (hydroxylated Merrifield resin) is described [10], Thus, the one-pot domino oxidation/nitroaldol cyclization of aziridine 10-28 with immobilized nitroacetate 10-29 furnished 10-30 which, after detachment from the resin, led to the desired product 10-31 in good yield and excellent trans-selectivity (Scheme 10.7). 

Scheme 10.7. Domino oxidation/nitroaldol/1,3-dipolar cycloaddition process.

Scheme 10.12. Domino oxidation/hetero-Diels-Alder reaction.

In Fig. 14, the UV spectra of the domino oxidation products are shown. As the number of oxatetrasilacyclopentane rings increases, the lowest energy absorption maximum shifts bathochromically, and the molecular extinction coefficient becomes far larger (10 270 nm (s 3200), 11 273 nm (s 7600), 12 292 nm (s 25000), 13 297 nm (s 51900). The intense absorption of the order 104 is remarkable because these molecules contain no obvious chromo-phores which should give such intense absorption. Since the intense absorption is not observed in the ladder polysilanes, it is apparently due to the electronic effect of the oxygen atoms on the Si-Si a conjugation systems. 

Fundamental knowledge on the structures and properties of the ladder polysilanes has accumulated in our research for the past 15 years. Some results were unpredictable, including the silicon double helix structure, the domino oxidation, the formation of persistent radical anions, the Diels-Alder reactions at the 1,4-positions of anthracene, etc. These results let us recognize that the construction of novel structures will open the new chemistry. 

Scheme 5.7 Radical/cation-mediated domino oxidative coupling.

In Cramer s [60] heteroatom-nucleophile-induced C-C fragmentations, an allenic hydroxamic acid 162 was employed for a domino oxidative radical cyclization to afford the densely functionalized 1,2-oxazine 166 in 52% yield... 

This section deals with oxidation reactions as an initiative step of the domino process in combination with many other organic transformations. In 2004, Snaith and coworkers [3] demonstrated a simple and efficient method to synthesize 3-substituted 4-piperidinones 4 using a domino oxidation/carbonyl-ene/oxidation reaction (Scheme 9.1). This domino reaction comprises oxidation of unsaturated alcohol 1 using PCC (pyridinium chlorochromate) to give the corresponding aldehyde 2, followed by a carbonyl-ene type reaction to yield the secondary cyclic alcohol 3, which was oxidized under the reaction conditions to give 3-substituted 4-piperidinones 4 in good yields. 

Scheme 9.1 Domino oxidation/cyclization/oxidation process for the synthesis of 4.

Scheme 9.2 Total synthesis of 9 by domino oxidation/oxa-electrocyclization/oxidation process.

Scheme 9.5 Domino oxidative cyclization in the total synthesis of 24.

Scheme 9.27 Domino oxidation/Wittig/conjugate reduction.

Thus, oxidation of the allylic alcohol 363 to the corresponding aldehyde in the presence of a large excess of manganese dioxide initiated the domino oxidation/Diels-Alder/hetero-Diels-Alder sequence. After formation of 366 via an endo-E-syn transition state, the terminal aldehyde 367 then gave the tetracycle 364 in the concluding hetero-Diels-Alder step in 28% yield after 2 days. Intermediate 364 was then further transformed into the natural product 365 in an additional 14 steps, featuring an intramolecular Heck reaction and an iridium-catalyzed isomerization. 

Scheme 10.9 Domino oxidative dearomatisation-Michael reaction.

The synthesis of 2,5-disubstituted oxazoles from methyl ketones and benzylamines in a metal and peroxide-free environment is achieved using l2-promoted domino oxidative cyclization involving C-H bond cleavage and the formation of C-N and C-0 bonds. Slow oxidation of A-acetyl homocysteine thiolactone by iodate to A-acetyl homocysteine thiolacone sulfoxide occurs in a reaction S1 having 1 3 stoichiometry (oxidant reductant). The stoichiometric ratio in excess of 103 (reaction S2) is 2 5 because excess 103 oxidizes the r ion, generated in reaction SI, to I2. The stoichiometry ratio for the I2 oxidation (reaction S3) is 1 1. Complex kinetics are observed because reactions SI, S2 and S3 occur simultaneously with comparable rates. 

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