In studying the evolution of organic chemistry and grasping its essence, one comes quickly to the conclusion that no other type of reaction plays as large a role in shaping this domain of science than carbon-carbon bond-forming reactions. The Grignard, Diels-Alder, and Wittig reactions are but three prominent examples of such processes, and are among those which have undeniably exercised decisive roles in the last century in the emergence of chemical synthesis as we know it today. In the last quarter of the 20th century, a new family of carbon-carbon bond-forming reactions based on transition-metal catalysts evolved as powerful tools in synthesis. Among them, the palladium-catalyzed cross-coupling reactions are the most prominent. In this Review, highlights of a number of selected syntheses are discussed. The examples chosen demonstrate the enormous power of these processes in the art of total synthesis and underscore their future potential in chemical synthesis.

Palladium-catalyzed cross-coupling reactions in total synthesis.

The design and implementation of cascade reactions is a challenging facet of organic chemistry, yet one that can impart striking novelty, elegance, and efficiency to synthetic strategies. The application of cascade reactions to natural products synthesis represents a particularly demanding task, but the results can be both stunning and instructive. This Review highlights selected examples of cascade reactions in total synthesis, with particular emphasis on recent applications therein. The examples discussed herein illustrate the power of these processes in the construction of complex molecules and underscore their future potential in chemical synthesis.

Cascade reactions in total synthesis.

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Advances in transition metal (Pd, Ni, Fe)-catalyzed cross-coupling reactions using alkyl-organometallics as reaction partners.

http://aether.cmi.ua.ac.be/artikels/Artikels%20Gitte/Artikels/Reviews/Trans.%20Metal.%20catal.%20reactions%20Chem.%20rev.%20042127.pdf

Transition-Metal-Catalyzed Reactions in Heterocyclic Synthesis

Synthesis of oxygen- and nitrogen-containing heterocycles by ring-closing metathesis.

A concise approach to a family of potent herbicidal 10-membered lactones is described on the basis of ring-closing metathesis (RCM) as the key step for the formation of the medium-sized ring. This includes the first total syntheses of herbarumin I (1) and II (2) as well as the synthesis of several possible macrolides of the pinolidoxin series. A comparison of their spectral and analytical data with those of the natural product allowed us to establish the stereostructure of pinolidoxin, a potent inhibitor of induced phenylalanine ammonia lyase (PAL) activity, as shown in 46. This finding, however, makes clear that a previous study dealing with the relative and absolute stereochemistry of this phytotoxic agent cannot be correct. An important aspect from the preparative point of view is the fact that the stereochemical outcome of the RCM reaction can be controlled by the choice of the catalyst. Thus, use of the ruthenium indenylidene complex 16 always leads to the corresponding (E)-alkenes, whereas the secon...

Total syntheses of the phytotoxic lactones herbarumin I and II and a synthesis-based solution of the pinolidoxin puzzle.

Against the rules: during the hundred years following Sabatier's groundbreaking work on catalytic hydrogenation, syn delivery of the H atoms to the π system of a substrate remained the governing stereochemical rule. An exception has now be found with the use of cationic [Cp*Ru] templates, which accounts for the first practical, functional-group-tolerant, broadly applicable and highly E-selective semihydrogenation method for alkynes.

A Functional-Group-Tolerant Catalytic trans Hydrogenation of Alkynes

Reactions of internal alkynes with R3M-H (M = Si, Ge, Sn) follow an unconventional trans-addition mode in the presence of [Cp*Ru(MeCN)3]PF6 (1) as the catalyst; however, the regioselectivity is often poor with unsymmetrical substrates. This problem can be solved upon switching to a catalyst comprising a [Ru-Cl] bond, provided that the acetylene derivative carries a protic functional group. The R3M unit is then delivered with high selectivity to the alkyne-C atom proximal to this steering substituent. This directing effect originates from the ability of the polarized [Ru-Cl] bond to engage in hydrogen bonding with the protic substituent, which helps upload, activate, and lock the alkyne within the coordination sphere. An additional interligand contact of the chloride with the -MR3 center positions the incoming reagent in a matching orientation that translates into high regioselectivity. The proposed secondary interactions within the loaded catalyst are in line with a host of preparative and spectral data and with the structures of the novel ruthenium π-complexes 10 and 11 in the solid state. Moreover, the first X-ray structure of a [Ru(σ-stannane)] complex (12a) is presented, which indeed features peripheral Ru-Cl···MR3 contacts; this adduct also corroborates that alkyne trans-addition chemistry likely involves σ-complexes as reactive intermediates. Finally, it is discussed that interligand cooperativity might constitute a more general principle that extends to mechanistically distinct transformations. The presented data therefore make an interesting case for organometallic chemistry that provides inherently better results when applied to substrates containing unprotected rather than protected -OH, -NHR, or -COOH groups.

Interligand Interactions Dictate the Regioselectivity of trans-Hydrometalations and Related Reactions Catalyzed by [Cp*RuCl]. Hydrogen Bonding to a Chloride Ligand as a Steering Principle in Catalysis

The first total synthesis of a major component of the microbial biosurfactant sophorolipid has been achieved This approach to the 26-membered macrolide 1 containing a Z-configured alkene group in its lipidic tether spanning the sophorose backbone is based on a ring-closing metathesis reaction of diyne 21 catalyzed by Mo[N(t-Bu)(Ar)]3 (5; Ar = 3,5-dimethylphenyl) activated in situ by CH2Cl2, followed by Lindlar reduction of the resulting cycloalkyne 22 The two β-glycosidic linkages of compound 21 were installed by means of the glucal epoxide method and a modified Koenigs−Knorr reaction promoted by AgOTf/lutidine, respectively

Karin Radkowski

Papers

Total syntheses of the phytotoxic lactones herbarumin I and II and a synthesis-based solution of the pinolidoxin puzzle.

A Functional-Group-Tolerant Catalytic trans Hydrogenation of Alkynes

Interligand Interactions Dictate the Regioselectivity of trans-Hydrometalations and Related Reactions Catalyzed by [Cp*RuCl]. Hydrogen Bonding to a Chloride Ligand as a Steering Principle in Catalysis

Ring-closing alkyne metathesis. Application to the total synthesis of sophorolipid lactone.

A chemo- and stereoselective reduction of cycloalkynes to (E)-cycloalkenes