There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

The biaryl structural motif is a predominant feature in many pharmaceutically relevant and biologically active compounds. As a result, for over a century 1 organic chemists have sought to develop new and more efficient aryl -aryl bond-forming methods. Although there exist a variety of routes for the construction of aryl -aryl bonds, arguably the most common method is through the use of transition-metalmediated reactions. 2-4 While earlier reports focused on the use of stoichiometric quantities of a transition metal to carry out the desired transformation, modern methods of transitionmetal-catalyzed aryl -aryl coupling have focused on the development of high-yielding reactions achieved with excellent selectivity and high functional group tolerance under mild reaction conditions. Typically, these reactions involve either the coupling of an aryl halide or pseudohalide with an organometallic reagent (Scheme 1), or the homocoupling of two aryl halides or two organometallic reagents. Although a number of improvements have developed the former process into an industrially very useful and attractive method for the construction of aryl -aryl bonds, the need still exists for more efficient routes whereby the same outcome is accomplished, but with reduced waste and in fewer steps. In particular, the obligation to use coupling partners that are both activated is wasteful since it necessitates the installation and then subsequent disposal of stoichiometric activating agents. Furthermore, preparation of preactivated aryl substrates often requires several steps, which in itself can be a time-consuming and economically inefficient process.

http://aether.cmi.ua.ac.be/artikels/Artikels%20Gitte/Artikels/Reviews/Heck-Type-lautens.pdf

Aryl-aryl bond formation by transition-metal-catalyzed direct arylation.

Electrochemistry represents one of the most intimate ways of interacting with molecules. This review discusses advances in synthetic organic electrochemistry since 2000. Enabling methods and synthetic applications are analyzed alongside innate advantages as well as future challenges of electroorganic chemistry.

Synthetic Organic Electrochemical Methods Since 2000: On the Verge of a Renaissance

Since the discovery of organic azides by Peter Griess more than 140 years ago, numerous syntheses of these energy-rich molecules have been developed. In more recent times in particular, completely new perspectives have been developed for their use in peptide chemistry, combinatorial chemistry, and heterocyclic synthesis. Organic azides have assumed an important position at the interface between chemistry, biology, medicine, and materials science. In this Review, the fundamental characteristics of azide chemistry and current developments are presented. The focus will be placed on cycloadditions (Huisgen reaction), aza ylide chemistry, and the synthesis of heterocycles. Further reactions such as the aza-Wittig reaction, the Sundberg rearrangement, the Staudinger ligation, the Boyer and Boyer-Aube rearrangements, the Curtius rearrangement, the Schmidt rearrangement, and the Hemetsberger rearrangement bear witness to the versatility of modern azide chemistry.

Organic Azides: An Exploding Diversity of a Unique Class of Compounds

https://chemistry.mdma.ch/hiveboard/rhodium/pdf/archive/merbst/quinoline1999.pdf

Quinoline, quinazoline and acridone alkaloids

A six-step formal total synthesis of a natural alkaloid, mappicine (3), has been achieved. The highlight of our synthetic strategy is an intramolecular hetero Diels-Alder reaction that was used for the construction of the CD ring system of mappicine (3). In addition, it was demonstrated that the Sonogashira coupling reaction of 2-chloro-3-hydroxymethylquinoline (8c) with trimethylsilylacetylene proceeded at room temperature in excellent yield.

A concise formal total synthesis of mappicine and nothapodytine B via an intramolecular hetero Diels-Alder reaction.

Total synthesis of (±)-methyl atis-16-en-19-oate (5c), a tetracyclic diterpenoid possessing a bicyclo[2.2.2]octane ring system, was accomplished. Intramolecular Diels−Alder reaction of tetraene 14 was employed in a construction of kaurene skeleton 13. The pivotal step involved a homoallyl−homoallyl radical rearrangement process of (±)-methyl 12-hydroxykaur-16-en-19-oate monothioimidazolide 12, which led to 5c in good yield. Interestingly, treatment of methyl 12-oxo-kaur-16-en-19-oate 30 with hydrazine monohydrate in the presence of KOH in bis(ethylene glycol) at 200 °C resulted in cyclopropanation to furnish, directly, trachyloban-19-oic acid (4b), together with kaur-16-en-19-oic acid (6b).

Total Synthesis of (±)-Methyl Atis-16-en-19-oate via Homoallyl−Homoallyl Radical Rearrangement

Stereocontrolled construction of a spiro fused bicyclo[2.2.2]octane ring system by the intramolecular double Michael reaction

Asymmetric total syntheses of (−)-methyl atis-16-en-19-oate (1c), (−)-methyl kaur-16-en-19-oate (2c), and (−)-methyl trachyloban-19-oate (3c) have been achieved by employing a hybrid strategy of palladium-catalyzed cycloalkenylation and homoallyl−homoallyl radical rearrangement The common synthetic intermediate 5 was prepared from 2-allylcyclohexanone (4) with 98% ee using d'Angelo's asymmetric Michael addition A series of functional group modifications in 5 via palladium-catalyzed cycloalkenylation led to (+)-14, which had already been prepared by us as racemate (−)-Methyl atis-16-ene-19-oate (1c) was generated via homoallyl-homoallyl radical rearrangement On the other hand, Wolff−Kishner reduction of 18 followed by esterification yielded (−)-methyl kaur-16-en-19-oate (2c) together with (−)-methyl trachyloban-19-oate (3c)

Total syntheses of (-)-methyl atis-16-en-19-oate, (-)-methyl kaur-16-en-19-oate, and (-)-methyl trachyloban-19-oate by a combination of palladium-catalyzed cycloalkenylation and homoallyl-homoallyl radical rearrangement.

Full details of three approaches to an entirely regio- and stereoselective synthesis of the well-known target reserpine are described, culminating in a total synthesis which efficiently meets these requirements.

Masahiro Toyota

Papers

A concise formal total synthesis of mappicine and nothapodytine B via an intramolecular hetero Diels-Alder reaction.

Total Synthesis of (±)-Methyl Atis-16-en-19-oate via Homoallyl−Homoallyl Radical Rearrangement

Stereocontrolled construction of a spiro fused bicyclo[2.2.2]octane ring system by the intramolecular double Michael reaction

Total syntheses of (-)-methyl atis-16-en-19-oate, (-)-methyl kaur-16-en-19-oate, and (-)-methyl trachyloban-19-oate by a combination of palladium-catalyzed cycloalkenylation and homoallyl-homoallyl radical rearrangement.

Regiospecific and stereoselective syntheses of (+/-)-reserpine and (-)-reserpine.