An Overview on Ynamines
Alkynes represent one of the most important and versatile building blocks in organic synthesis. Heteroatom-substituted alkynes, which can be considered as subgroups of alkynes, have also been vastly utilized in developing synthetic methods. In particular, ynamines [1-amino-alkynes or N-alkynyl amines] became the most valuable subgroup of alkynes after the establishment of their practical synthesis in the 1960's. The first attempt at preparation of an ynamine was reported by Bode1,2 in 1892. While well-characterized ynamines were reported in 19583 and 1960,4 a practical synthesis was not achieved until the effort led by Viehe5 in 1963 in addition to other subsequent works. In the ensuing twenty years, the synthetic significance of ynamines in organic and organometallic chemistry was firmly established by the work of many creative synthetic chemists. These elegant pioneer works have been informatively and carefully reviewed by Viehe in 19676 and 1969;7 Ficini in 1976;8 Pitacco and Valentin9 in 1979; Collard-Motte and Janousek10 in 1986; Himbert11 in 1993; and most recently by us12,13 and Katritzky14.





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The synthetic eminence of ynamines is well merited because of the predicable regioselectivity in their transformations as shown by the generalization in Scheme i, and more importantly, because they are inherently highly reactive. However, this latter attribute is also the source of the limitation that has seriously hampered the development of ynamine chemistry, thereby shortening the period of its prominence in synthesis. Ynamines are very sensitive toward hydrolysis, as protonation of the electron-rich alkynyl motif affords reactive keteniminium intermediates, which upon trapping with water leads to simple amides in a rather expensive manner (Scheme i). This hydrolytic instability has caused much difficulty in the experimental preparation and general handling of ynamines, and more detrimentally, rendered ynamine chemistry inaccessible.




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Scheme i



Consequently, the synthetic utility of ynamines has suffered a dramatic decline during the last thirty years.15 The most glaring limitations have been in the development of intramolecular and stereoselective reactions.7–14 The only reported intramolecular reaction of ynamines was Genet and Kahn's acid catalyzed addition of a hydroxyl group to an ynamine [i→ii in Scheme ii] in 1980,16 and although clever, it constitutes a hydrolytic process.






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Scheme ii



Besides Reinhoudt's17 sole account in 1987 reporting hetero-[4 + 2] cycloadditions of chiral ynamine iii with nitroalkenes that led to cycloadducts iv in modest de, the only other notable studies were reported ten years later by Fischer18 showcasing [2 + 2] cycloadditions of chiral ynamides v and vi with vinylidene chromium carbene complexes, and another three years later by Pericas19 in their Pauson-Khand cycloadditions using chiral ynamines vii.

Ynamides: A Modern Functional Group For The New Millennium

http://web4.uwindsor.ca/users/j/jlichaa/reference.nsf/0/10ff8b04ff3a317885256d88005720f6/$FILE/tet-2000-56-3262-brummond.pdf

Recent Advances in the Pauson–Khand Reaction and Related [2+2+1] Cycloadditions

Recent advances in the chemistry of ynamines and ynamides

Five membered carbocycles are important building blocks for many biologically active molecules. Moreover, substituted cyclopentenones (e.g. cyclopentenone prostaglandins) exhibit characteristic biological activity. The efficiency and atom economy of the Pauson-Khand reaction render this process potentially one of the most attractive methods for the synthesis of such compounds. Although it was discovered in its intermolecular form, the scope of the intermolecular Pauson-Khand reaction has always been limited by the poor reactivity and selectivity of the alkene component. The past decade, especially the last three years, has seen concerted efforts to broaden the scope of this reaction. In this overview, we provide a comprehensive and critical coverage of the intermolecular Pauson-Khand reaction based on the reactivity characteristics of different classes of alkenes and a rationalization of successes and misfortunes in this area.

The intermolecular Pauson-Khand reaction.

Chiral thioether ligands: coordination chemistry and asymmetric catalysis

A family of enantiomerically pure (2R)-10-(alkylthio)isoborneols [methylthio (1), neopentylthio (2), phenylthio (3)], specifically designed as chiral auxiliaries suitable for chirality transfer to cobalt in Pauson−Khand reactions, has been synthesized. The dicobalt hexacarbonyl complexes of the alkoxyacetylenes derived from these alcohols (10a−12a) can be converted to the rather stable, internally chelated, pentacarbonyl complexes 10b−12b by treatment with NMO. The intermolecular Pauson−Khand reactions of 10b−12b with strained olefins take place with synthetically useful rates at low temperatures (down to −20 °C), with high yields and diastereoselectivities:  norbornene (77%; 92:8), norbornadiene (82%; 96:4), bicyclo[3.2.0]hept-6-ene (91%; 93:7). The major diastereomer of the adduct of 10b with norbornadiene, 14, has been used as the starting point for a synthesis of (S)-(−)-4-alkyl-2-cyclopentenones through a sequence consisting of completely diastereoselective conjugate addition, reductive cleavage with...

Camphor-Derived, Chelating Auxiliaries for the Highly Diastereoselective Intermolecular Pauson−Khand Reaction: Experimental and Computational Studies

A family of dicobalt hexacarbonyl complexes of 1-(dialkylamino)-2-(trimethysilyl)acetylenes (3a−f) derived both from achiral and chiral amines [a, morpholine; b, (S)-2-methoxymethylpyrrolidine; c, (2R,5R)-2,5-bis(methoxymethyl)pyrrolidine; d, (±)-trans-2,5-bis(benzyloxymethyl)pyrrolidine; e, (2R,5R)-2,5-dimethylpyrrolidine; f, (S)-(α-methylbenzyl)benzylamine] has been prepared by a one-stage process from dichloroacetylene. The methanolysis at room temperature of these complexes (MeOH/K2CO3) induces the selective cleavage of the carbon−silicon bond, leading to the thermally unstable terminal ynamine complexes 12a−f. The Pauson−Khand reaction of 12a−f with strained olefins (norbornadiene and norbornene) takes place at unprecedentedly low temperatures (−35 °C) in the absence of chemical promoters. Diastereoselectivities of up to 94:6 are recorded in these reactions with the ynamine complexes derived from C2 symmetrical chiral auxiliaries (12c,d). The high reactivity depicted by terminal ynamines in the Pauso...

Jordi Vázquez

Papers

Camphor-Derived, Chelating Auxiliaries for the Highly Diastereoselective Intermolecular Pauson−Khand Reaction: Experimental and Computational Studies

Low-energy pathway for pauson-khand reactions: synthesis and reactivity of dicobalt hexacarbonyl complexes of chiral ynamines

Low-Energy Pathway for Pauson—Khand Reactions: Synthesis and Reactivity of Dicobalt Hexacarbonyl Complexes of Chiral Ynamines.

Camphor‐Derived, Chelating Auxiliaries for the Highly Diastereoselective Intermolecular Pauson—Khand Reaction: Experimental and Computational Studies.