4-exo-dig cyclocarbopalladation, discovery and application in the synthesis of complex polycyclic molecules
01 Jan 2022-Vol. 15, pp 365-415
TL;DR: A series of 4-exo-dig cyclocarbopalladations has been efficiently used to produce molecular complexity in a straightforward manner as mentioned in this paper, usually under microwave irradiation, in high yields.
Abstract: A series of 4-exo-dig cyclocarbopalladations has been efficiently used to produce molecular complexity in a straightforward manner. Strained 1,2-cyclobutanediols are rapidly obtained, usually under microwave irradiation, in high yields. In many cases, the cyclocarbopalladation cascade reaction is associated with 6π- or 8π-electrocyclic reactions. Polycyclic skeletons of unnatural or natural products can be prepared in a few steps from simple starting materials. Very strained aromatic polycycles, the taxane framework, cyclooctatrienes, cyclooctatetraenes, fenestranes, and fenestrenes have been obtained using this methodology.
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TL;DR: The total synthesis of taxol is reported by a convergent strategy, which opens a chemical pathway for the production of both the natural product itself and a variety of designed taxoids.
Abstract: Taxol, a substance originally isolated from the Pacific yew tree (Taxus brevifolia) more than two decades ago, has recently been approved for the clinical treatment of cancer patients. Hailed as having provided one of the most significant advances in cancer therapy, this molecule exerts its anticancer activity by inhibiting mitosis through enhancement of the polymerization of tubulin and consequent stabilization of microtubules. The scarcity of taxol and the ecological impact of harvesting it have prompted extension searches for alternative sources including semisynthesis, cellular culture production and chemical synthesis. The latter has been attempted for almost two decades, but these attempts have been thwarted by the magnitude of the synthetic challenge. Here we report the total synthesis of taxol by a convergent strategy, which opens a chemical pathway for the production of both the natural product itself and a variety of designed taxoids.
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TL;DR: The Heck reaction has been a topic of fluctuating interest; however, in the last six years activity in this area has flourished as discussed by the authors, leading to impressive sequences consisting of even different reaction types that occur not only in a consecutive mode, but also in a single operation.
Abstract: The palladium-catalyzed coupling of haloarenes and haloalkenes with alkenes, which was discovered by Richard F. Heck in the late sixties, has been a topic of fluctuating interest; however, in the last six years activity in this area has flourished. Careful choice of substrates and skillful tailoring of reaction conditions lead to impressive sequences consisting of even different reaction types that occur not only in a consecutive mode, but also in a single operation. The wellestablished Heck reaction, together with other mechanistically related palladiumcatalyzed transformations with arene, alkene, and alkyne derivatives, opens the door to a tremendous variety of elegant and highly convergent routes to structurally complex molecules. The reaction is not disturbed by heteroatoms such as oxygen and nitrogen (nor by sulfur and phosphorus with some limitations). The spectrum of recent achievements starts with a range of chemoselective and regioselective monocouplings of highly functionalized substrates with unsymmetrical and multisubstituted reaction partners. Other advances include cascade reactions in which three, four, five, and even eight new CC bonds are formed to yield oligofunctional and oligocyclic products with impressive molecular complexity. Even the enantioselective construction of complex natural products with quaternary stereocenters has been achieved with Heck reactions in key steps, as exemplified by the synthesis of crinan, picrotoxinin, and morphine. Today, the Heck reaction is indispensible in the arsenal of synthetic methods available to organic chemists. Certainly it is only a matter of time before the Heck reaction is applied in industrial syntheses.
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