Recent Applications in the Use of Sulfoxides as Chiral Auxiliaries for the Asymmetric Synthesis of Natural and Biologically Active Products

The contribution of chiral sulfoxides as versatile auxiliaries in the field of organic chemistry has shown a prevalent interest in the asymmetric synthesis of natural products during the last 45 years. In this short review, we report the recent applications of these chiral auxiliaries to the synthesis of natural and biological active products highlighted from 2010 to 2019. We hope to allow the reader to have an overview of the potential of sulfoxide chemistry in the field of enantio­selective synthesis.1 Introduction2 Diastereoselective Additions to Ketones2.1 Reduction of β-Keto Sulfoxides2.2 Reduction of β-Keto Sulfoxides Followed by Bromohydrin Forma tion3 Synthesis of an α-Amino α′-Sulfinyl Ketone Followed by Diastere oselective Reduction of the β-Keto Sulfoxide4 Diastereoselective Addition of Carbanionic Chiral Sulfoxides4.1 Addition to an Aldehyde4.1.1 Aldol Reactions4.1.2 Reformatsky-Type Reactions4.2 Additions to Chiral Sulfinimines5 Diastereoselective Cyclization Reactions Directed by a Chiral Sulf oxide5.1 1,4-Radical Additions5.2 Intramolecular Conjugate Additions5.3 Nazarov Cyclizations5.4 Diels–Alder Reactions6 Atropodiastereoselective Synthesis7 Conclusion

Alkoxyallenes as Starting Materials for the Syntheses of Natural Products

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. Dedicated to Dr. Reinhold Zimmer, a pioneer of alkoxyallene chemistry, on the occasion of his 60th birthday.