1 was found to be 1–2 orders of magnitude more potent than taxol against certain cancer cell lines. In contrast, ( )englerin B (2), lacking the glycolate at C10, was much less active and selective. An elegant total synthesis of the enantiomer of 1 from the naturally occurring terpene trans,cis-nepetalactone by the research group of Christmann established the absolute configuration of these guaianes as shown in Scheme 1. Recently, our research group has developed the gold(I)catalyzed [2+2+2] alkyne/alkene/carbonyl cycloaddition of 1,6-enynes bearing a carbonyl group in which two C C and one C O bonds are formed in a domino process. As has been shown in gold(I)-catalyzed reactions of enynes, this reaction is stereospecific. Furthermore, we have recently found that a propargylic stereocenter bearing an OR group exerts an exquisite stereocontrol in the cyclization process, which has been applied in the total synthesis of the oxatricyclic sesquiterpenes (+)-orientalol F (3) and ( )pubinernoid B (4). This cyclization is faster than the intramolecular 1,5-migration of propargylic OR groups that occurs in related systems. We planned to use the gold-catalyzed domino reaction for the synthesis of 1 and 2 from a 1,6-enyne 5 that is substituted by OR groups at the propargylic and allylic positions (Scheme 2). However, the allylic OR’ group would confer

Enantioselective Synthesis of (−)‐Englerins A and B

As a prelude to undertaking the total syntheses of the complex manzamine alkaloids, a series of model studies were conducted to establish the scope and limitations of intramolecular [4 + 2] cycloadditions of N-acylated vinylogous ureas with the trienic substrates 17a,b, 28a,b, and 34. These experiments clearly demonstrated that the geometry of the internal double bond and the presence of an electron-withdrawing group on the diene moiety were essential for the facile and stereoselective formation of the desired cycloadducts. The enantioselective syntheses of the manzamine alkaloids ircinol A (75), ircinal A (5), and manzamine A (1) were then completed by employing a convergent strategy that featured a novel domino Stille/Diels-Alder reaction to construct the tricyclic ABC ring core embodied in these alkaloids. Thus, the readily accessible chiral dihydropyrrole 58 was first converted in a single chemical operation into the key tricyclic intermediate 60. Two ring-closing metathesis reactions were then used to form the 13- and 8-membered rings leading to Z-72 and 74, the latter of which was quickly elaborated into ircinal A (5) via ircinol A (75). The synthetic 5 thus obtained was converted into manzamine A (1) following literature precedent. This concise synthesis of ircinal A required a total of 24 operations from commercially available starting materials with the longest linear sequence being 21 steps.

Enantioselective total syntheses of manzamine a and related alkaloids.

Phorbol, the flagship member of the tigliane diterpene family, has been known for over 80 years and has attracted attention from many chemists and biologists owing to its intriguing chemical structure and the medicinal potential of phorbol esters. Access to useful quantities of phorbol and related analogues has relied on isolation from natural sources and semisynthesis. Despite efforts spanning 40 years, chemical synthesis has been unable to compete with these strategies, owing to its complexity and unusual placement of oxygen atoms. Purely synthetic enantiopure phorbol has remained elusive, and biological synthesis has not led to even the simplest members of this terpene family. Recently, the chemical syntheses of eudesmanes, germacrenes, taxanes and ingenanes have all benefited from a strategy inspired by the logic of two-phase terpene biosynthesis in which powerful C-C bond constructions and C-H bond oxidations go hand in hand. Here we implement a two-phase terpene synthesis strategy to achieve enantiospecific total synthesis of (+)-phorbol in only 19 steps from the abundant monoterpene (+)-3-carene. The purpose of this synthesis route is not to displace isolation or semisynthesis as a means of generating the natural product per se, but rather to enable access to analogues containing unique placements of oxygen atoms that are otherwise inaccessible.

Nineteen-step total synthesis of (+)-phorbol

Enantioselective total syntheses of ircinal a and related manzamine alkaloids

In industries and academic laboratories, several late transition metal-catalyzed prerequisite reactions are widely performed during single and multistep synthesis. However, besides the desired products, these reactions lead to the generation of numerous chemical waste materials, by-products, hazardous gases, and other poisonous materials, which are discarded in the environment. This is partly responsible for the creation of global warming, resulting in climate adversities. Thus, the development of environmentally benign, cheap, easily accessible, and earth-abundant metal catalysts is desirable to minimize these issues. Certainly, iron is one of the most important metals belonging to this family. The field of iron catalysis has been explored in the last two-three decades out of its rich chemistry depending on its oxidation states and ligand cooperation. Moreover, this field has been enriched by the promising development of iron-catalyzed reactions namely, C–H bond activation, including organometallic C–H activation and C–H functionalization via outer-sphere pathway, cross-dehydrogenative couplings, insertion reactions, cross-coupling reactions, hydrogenations including hydrogen borrowing reactions, hydrosilylation and hydroboration, addition reactions and substitution reactions. Thus, herein an inclusive overview of these reaction have been well documented.

Havens J L

Papers

3,5-ジメチルピラゾールでのアリル酸化反応三酸化クロム錯体ステロイド性δ 5 -7-ケトン

Havens J L

Papers

3,5-ジメチルピラゾールでのアリル酸化反応 三酸化クロム錯体 ステロイド性δ 5 -7-ケトン

3,5-ジメチルピラゾールでのアリル酸化反応三酸化クロム錯体ステロイド性δ 5 -7-ケトン