Recent Advances in Total Synthesis via Metathesis Reactions

Abstract

The metathesis reactions, in their various versions, have become a powerful and extremely valuable tool for the formation of carbon–carbon bonds in organic synthesis. The plethora of available catalysts to perform these reactions, combined with the various transformations that can be accomplished, have positioned the metathesis processes as one of the most important reactions of this century. In this review, we highlight the most relevant synthetic contributions published between 2012 and early 2018 in the field of total synthesis, reflecting the state of the art of this chemistry and demonstrating the significant synthetic potential of these methodologies.1 Introduction2 Alkene Metathesis in Total Synthesis2.1 Total Synthesis Based on a Ring-Closing-Metathesis Reaction2.2 Total Synthesis Based on a Cross-Metathesis Reaction2.3 Strategies for Selective and Efficient Metathesis Reactions of Alkenes2.3.1 Temporary Tethered Ring-Closing Metathesis2.3.2 Relay Ring-Closing Metathesis2.3.3 Stereoselective Alkene Metathesis2.3.4 Alkene Metathesis in Tandem Reactions3 Enyne Metathesis in Total Synthesis3.1 Total Syntheses Based on a Ring-Closing Enyne-Metathesis Reaction3.2 Total Syntheses Based on an Enyne Cross-Metathesis Reaction3.3 Enyne Metathesis in Tandem Reactions4 Alkyne Metathesis in Total Synthesis4.1 Total Synthesis Based on a Ring-Closing Alkyne-Metathesis Reaction4.2 Other Types of Alkyne-Metathesis Reactions5 Conclusions

Acid‐Assisted Direct Olefin Metathesis of Unprotected Carbohydrates in Water

“…The exceptionals cientific impact of this methodh as led to al arge number of applications in many areas, such as organic synthesis, materials science, energy research, molecular topology, and medicinal chemistry. [4][5][6][7][8][9] Furthermore, the dynamic nature of the reaction is an attractive feature that has been exploited to generate, for example, dynamic systems, complexa rchitectures, and self-healing materials. [10][11][12][13][14][15][16][17][18][19][20] Ever since the introductiono ft he olefin metathesis reaction, much efforth as been invested in improving the catalysts.…”

“…One of the methods devised to accomplish this, olefin metathesis, is in this context highly useful since it results in efficient formation of new carbon–carbon double bonds under catalytic conditions. The exceptional scientific impact of this method has led to a large number of applications in many areas, such as organic synthesis, materials science, energy research, molecular topology, and medicinal chemistry . Furthermore, the dynamic nature of the reaction is an attractive feature that has been exploited to generate, for example, dynamic systems, complex architectures, and self‐healing materials …”

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

“…Alkene and alkyne metathesis [1][2][3][4], constituting highly versatile and powerful catalytic processes for constructing complex organic molecules [5][6][7][8][9][10][11][12], have found broad application in the fields of pharmaceutical synthesis [13][14][15], materials science [16][17][18][19][20], or in advanced techniques and technologies [21][22][23][24][25][26][27][28][29][30]. Thus, numerous multistep total syntheses of organic compounds, including bioactive molecules [31][32][33][34][35] and natural products [36,37], have been performed in a highly chemo-and stereoselective manner through metathesis routes [38][39][40][41][42][43].…”

“…carboxy-N-(4'-butenyl)-5-(2'piperidyl)piperidine)(20) and virgiboidine (3-but-3-en-1yl)decahydro-6H-1,5-methanopyrido[1,2-a][1,5]diazocin-6one)(21), two important pharmacologically active compounds containing dipiperidine and piperidino-quinolizidine units in their structure. Starting from the monoacetate of cyclopentene-1,4-diol that was obtained by the enzymatic desymmetrization of the corresponding diacetate, an enyne metathesis precursor was accessed by a Mitsunobu-type coupling reaction withScheme Synthesis of the AB subunits of manzamine A (16a) and E (16b) by enyne metathesis.…”

2-Methyltetrahydrofuran as a Solvent of Choice for Spontaneous Metathesis/Isomerization Sequence

“…Both these factors enable the use of OM in the final stages in numerous total syntheses. 4−7 Moreover, considering the high atom economy, as usually the only by-product is ethylene or other short alkenes, and the increasing tendency to utilize green solvents (e.g., dimethyl carbonate, 8−10 cyclopentyl methyl ether, 11 ethyl acetate, 11,12 2-methyltatrahydrofuran, 13,14 or water 15,16 ), which replace the traditionally applied toluene or chlorinated solvents (some of which are or will soon be abolished), 17 OM is recognized as a green technology, which suits perfectly the principles of circular economy. 18…”