Recent Advances in the Synthesis of Propargyl Derivatives, and Their Application as Synthetic Intermediates and Building Blocks

Abstract

The propargyl group is a highly versatile moiety whose introduction into small-molecule building blocks opens up new synthetic pathways for further elaboration. The last decade has witnessed remarkable progress in both the synthesis of propargylation agents and their application in the synthesis and functionalization of more elaborate/complex building blocks and intermediates. The goal of this review is to highlight these exciting advances and to underscore their impact.

Developing Organometallic Nucleophilic Reagents Via Photoredox Catalysis

“…The key step in the transformation was the radical to polar cross over that allowed the formation of the chromium organometallic specie by reaction of the alkyl radical from the HE, 1,3-eneyne and the Cr(II) complex. The allenyl-and propargyl chromium are in equilibria 71 and because no traces of allenylic compounds are detected, the allenylic chromium species was more reactive. The collected data supported the proposed catalyst cycle, illustrated in Scheme 5.…”

Copper-Catalyzed Umpolung Reactivity of Propargylic Carbonates in the Presence of Diboronates: One Stone Four Birds

“…During the last several decades, both organocatalysts and transition metals have been widely exploited to achieve the polarity Umpolung of more diversified reagents such as allenes, ynones, imines, and others, and the related research has attracted the attention of global communities . On the other hand, the allylation and propargylation of carbonyl compounds have been recognized as particularly powerful strategies for C–C bond construction, and the corresponding homoallyl alcohol and homopropargyl alcohol products are highly valuable intermediates for the synthesis of complex molecules, especially natural products and pharmaceuticals. However, the conventional widely used allylation and propargylation reagents are organometallic reagents, which have certain limitations considering functional group tolerance, reagent stability, and reaction diversity (Scheme a). , Moreover, most of the readily available allylation reagents bear an E -configuration, which usually afford anti -products; syn -selective allylation employs reagents such as Z -allylic vicinal diboronates ( A1 ), Z -allylic germinal diboronates ( A2 ), and Z -allylic boronates ( A3 ), which are still challenging to be conveniently synthesized to date (Scheme b) .…”

“…On the other hand, the allylation and propargylation of carbonyl compounds have been recognized as particularly powerful strategies for C–C bond construction, and the corresponding homoallyl alcohol and homopropargyl alcohol products are highly valuable intermediates for the synthesis of complex molecules, especially natural products and pharmaceuticals. However, the conventional widely used allylation and propargylation reagents are organometallic reagents, which have certain limitations considering functional group tolerance, reagent stability, and reaction diversity (Scheme a). , Moreover, most of the readily available allylation reagents bear an E -configuration, which usually afford anti -products; syn -selective allylation employs reagents such as Z -allylic vicinal diboronates ( A1 ), Z -allylic germinal diboronates ( A2 ), and Z -allylic boronates ( A3 ), which are still challenging to be conveniently synthesized to date (Scheme b) . Different routes have to be designed to make each reagent since no general way can make all three types of Z -allylic reagents, and some methods suffer from harsh reaction conditions ( A3 ), ,, multiple step synthesis ( A3 ), limited substituent scope ( A2 and A3 ), ,, and the generation of Z / E mixtures ( A1 and A2 ). ,, In addition, diversity-oriented synthesis is another highly sought-after strategy that leads to molecular libraries and is valuable for new drug discovery .…”