Current Organic Chemistry - Volume 23, Issue 27, 2019

Alkoxyallenes are easily available and versatile building blocks for the preparation of a variety of natural products (terpenes, polyketides, alkaloids, amino acids, carbohydrates etc.) originating from different classes. The synthetic use of the three allene carbon atoms frequently follows the “normal” reactivity pattern showing that alkoxyallenes can be regarded as special enol ethers. Additions of alcohols or amines to alkoxyallenes form vinyl-substituted O,O- or N,O-acetals that are frequently used in ring-closing metathesis reactions. This methodology delivers crucial heterocyclic units of the target compounds. Enantioselective additions provide products with high enantiopurity. Alternatively, an “Umpolung” of reactivity of alkoxyallenes is achieved by lithiation at C-1 and subsequent reaction with electrophiles, such as alkyl halides, carbonyl compounds, imines or nitrones. High stereoselectivity of the addition step can be achieved by substrate control or auxiliary control. The high diastereo- or enantioselectivity is transferred to the subsequent acyclic or cyclic products. The cyclization of primary addition products occurs efficiently under mild conditions and provides functionalized dihydrofuran, dihydropyrrole or 1,2-oxazine derivatives. These are valuable intermediates for the synthesis of a variety of heterocyclic natural products. Nazarov cyclizations or gold catalyzed rearrangements allow the synthesis of five- and six-membered carbocyclic compounds that are also used for natural product synthesis.

Vinylallenes have been synthesized and used as reagents for many years. However, the number of reviews covering the advances in the chemistry of vinylallenes are scarce. Most of the information lies in general reviews about allenes or in reviews dedicated to specific areas of research. Today, vinylallenes are used in the synthesis due to the special characteristics of this moiety, a diene with a non-conjugated double bond and the capacity to generate axial chirality. In this review, the most relevant publications involving vinylallenes, published in the last fifteen years, are compiled. The review includes new or improved synthetic methods and the reactivity of vinylallenes prepared by classical or new methods. The reactions of vinylallenes have been classified as Nazarovtype processes, cycloaddition reactions, and reactions in which vinylallenes are key intermediates, usually non-isolated but essential for the process to occur. Other types of reactivity are also included.

Allenes represent an extremely important class of organic molecules, which, as a result of their twisted orthogonal π-systems can possess axial chirality. A wide array of methods for allene synthesis have been reported, such as the substitution of propargylic electrophiles, isomerization of alkynes and sigmatropic rearrangement. An alternative approach for the synthesis of allenes is 1,2-elimination of an appropriately substituted precursor. This mini-review highlights recent examples of 1,2-elimination processes, which target allenes including both polar and radical processes. The main focus is upon how control over the stereospecificity (e.g. syn- or anti-) of the 1,2-elimination process can enable the synthesis of enantioenriched axially chiral allenes. Recent developments in this field are presented including both enantiospecific and catalytic asymmetric methods.

The present review article summarizes the synthesis of allenes, which bear an adjacent functional group, by [3,3]- or [2,3]-sigmatropic rearrangement of appropriate propargyl substrates. Functionalized allenes, such as allenyl isothiocyanates, isoelenocyanates, isocyanates, thiocyanates, azides, azo compounds and others, are easily available by these methods. In several cases, however, the title compounds show high reactivity, which leads to rapid intermolecular or intramolecular successive reactions. Consequently, synthesis of the allenes by sigmatropic rearrangement has to be combined with special techniques, for example, flash vacuum pyrolysis or in situ generation and trapping reactions. The high tendency of the presented functionalized allenes to undergo cyclization reactions can be utilized to prepare heterocyclic products, for instance, thiazoles, selenazoles, 1,2,3-triazoles and pyrazoles. The synthesis of functionalized 1,3-butadienes by a second sigmatropic rearrangement of the title compounds is also successful.

The 1,3-dipolar cycloaddition reaction is a powerful and versatile strategy for the synthesis of carbocyclic and heterocyclic five-membered rings. Herein, the most recent developments on the [3+2] cycloaddition reactions using allenes acting either as dipolarophiles or 1,3-dipole precursors, are highlighted. The recent contributions on the phosphine- and transition metal-catalyzed [3+2] annulations involving allenes as substrates are also covered, with the exception of those in which the formation of a 1,3-dipole (or synthetic equivalent) is not invoked. This review summarizes the most relevant research in which allenes are used as building blocks for the construction of structurally diverse five-membered rings via [3+2] annulation reactions.