Cyanoacetylenic Alcohols: Molecules of Interstellar Relevance in the Synthesis of Essential Heterocycles, Amino Acids, Nucleobases and Nucleosides

Abstract

Cyanoacetylenic alcohols, R1R2C(OH)C≡C-CN, the closest derivatives of cyanoacetylene, an interstellar abundant molecule, are now becoming acknowledgeable in modern organic synthesis which tends to mimic nature. Highly reactive C≡C and C≡N bonds in close vicinity of the hydroxyl group makes these molecules a chemical trinity of mutually influencing functions ensuring an endless number of chemical transformations. All reactions of cyanoacetylenic alcohols parallel modern organic synthesis, being biomimetic. They do not need transition metals (and in most cases, the metals at all except for physiologically indispensible Na+, K+), proceed at ambient temperature and often in aqueous media. Fundamentally, these reactions are 100% atom-economic because they are almost exclusively addition processes. Usually, in the cyanoacetylenic alcohols, cyano, acetylene and hydroxyl functions behave as inseparable entity providing the multiple functionalizations of the forming molecules. This allows hydroxyl, carbonyl, carboxylic, imino, amino, amido, cyanoamido, cyano, various P-containing, ether and ester functions, along with the double bonds and different fundamental heterocycles (furans, furanones, pyrazoles, oxazoles, pyridines, pyrimidines, purins, etc.) and diverse polycyclic systems to be integrated in a one molecular architecture. This review focuses on analysis and generalization of the knowledge accumulated in the chemistry of these cyanoacetylenic alcohols, mostly over the past 15 years.

Quantum‐Chemical Insight into Self‐Organization of Complex Molecules from Acetylene and Anilines Catalyzed by Superbase KOH/DMSO: One‐Pot Cascade Assembly of 1,3‐Bis(arylamines)

“…[1][2][3][4] Later, replaced by cheaper ethylene and propylene, acetylene and its derivatives kept their leading positions as building blocks in fine organic synthesis. [5][6][7] Recently, a multi-molecular self-organization of complex molecules from several acetylene units and simple nucleophiles in special superbase systems like KOH/DMSO and KO t Bu/DMSO was discovered and started being unfolded and shaped. [5][6][7] This was proved [8] to be triggered and driven specifically by acetylene due to its capacity to play a role of both electrophile and nucleophile, which is particularly expressed in superbase media.…”

“…[5][6][7] Recently, a multi-molecular self-organization of complex molecules from several acetylene units and simple nucleophiles in special superbase systems like KOH/DMSO and KO t Bu/DMSO was discovered and started being unfolded and shaped. [5][6][7] This was proved [8] to be triggered and driven specifically by acetylene due to its capacity to play a role of both electrophile and nucleophile, which is particularly expressed in superbase media. For example, this dichotomy of the acetylene reactivity allowed 6,8-dioxabicyclo[3.2.1]octanes, congeners of insect pheromones and mammal hormones, [9] to be diastereoselectively assembled from two molecules of acetylene and two molecules of ketones in the KOH/DMSO system in one synthetic operation.…”

“…Acetylene remained a basic feedstock for most commodity and specialty chemicals for more than a half of the twentieth century [1–4] . Later, replaced by cheaper ethylene and propylene, acetylene and its derivatives kept their leading positions as building blocks in fine organic synthesis [5–7] …”

“…This was proved [8] to be triggered and driven specifically by acetylene due to its capacity to play a role of both electrophile and nucleophile, which is particularly expressed in superbase media. For example, this dichotomy of the acetylene reactivity allowed 6,8‐dioxabicyclo[3.2.1]octanes, congeners of insect pheromones and mammal hormones, [9] to be diastereoselectively assembled from two molecules of acetylene and two molecules of ketones in the KOH/DMSO system in one synthetic operation [7] . This four‐molecule self‐organization, as confirmed by quantum‐chemical investigations, [10] involves the alternating addition of ketone carbanions to the triple bond and addition of acetylenic carbanions to the carbonyl groups (Favorsky reaction).…”

The Structure of Biologically Active Functionalized Azoles: NMR Spectroscopy and Quantum Chemistry

“…Due to their intensive use in various branches of medicine, technology and agriculture, azoles attract the closest attention of researchers. Different monographs and reviews are devoted to the chemistry, properties and application of azoles [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34].…”