A Practical Solution to Stereodefined Tetrasubstituted Olefins

Abstract

Olefins, compounds with a carbon-carbon double bond, are of fundamental importance, and stereodefined construction of tetrasubstituted carbon-carbon double bond is a significant challenge. Here we show a unique and practical method for the preparation of stereodefined, fully substituted olefins via conjugate addition of organozinc reagents to readily available 2,3-allenals. Through mechanistic studies, it is confirmed that the geometry of the newly formed double bond is controlled by unique regiospecific oxygen-protonation of the enolate intermediates, generating 1,3-alkadienols. Such alkadienols would undergo a concerted 1,5-H-transfer reaction via a six-membered transition state to ensure the configuration of the carbon-carbon double bond in the final products. Using the readily available organozinc reagents and 2,3-allenals provides a very rapid access to a wide range of tetrasubstituted olefins with defined stereochemistry, bearing an extremely versatile aldehyde functionality.

Mechanochemical C−X/C−H Functionalization: An Alternative Strategic Access to Pharmaceuticals

“…[93] ln view of the green and sustainable features of mechanochemistry and CDC reaction, the Yu and Su group paid a longstanding interest in mechanochemical CDC reactions for the synthesis of APIs and bioactivate molecules involving tetrahydroquinoline (THIQ) (33) and indole cores (34) (Scheme 13). [13b,94] In 2011, they pioneered a DDQ-mediated solvent-free CDC reaction to afford three types of THIQ derivatives in good yields (35)(36)(37) using nitroalkanes (32), alkynes (33) and indoles (34) as pronucleophile, respectively (Scheme 14A). [94a] When alkynes (33) and indoles (34) were used as pronucleophiles, the reactions could be catalyzed by recoverable copper balls without any additional metal catalyst.…”

Synthesis of Stereodefined Multi-Functionalized Tetrasubstituted Olefins via a Catalyst-Free Oxidative Coupling Strategy and Their Application for Hpochlorite Anion Detection

“…Reported efficient methods for accessing such unsaturated structures are mainly relied on transition‐metal catalysis, such as carbofunctionalization of alkynes, olefin metathesis, cross‐coupling reactions, cylcoaddition reactions, direct C−H functionalization of alkenes, and oxidation dehydrogenation of alkanes . Examples for the successful synthesis of tetrasubstituted olefins under metal free conditions are rarely documented . Within these systems, the main drawback of the existing approaches is, in most cases, an E / Z ‐ or regio‐isomeric mixtures rather than a stereodefined fully substituted olefins was obtained.…”

“…[17] Examples for the successful synthesis of tetrasubstituted olefins under metal free conditions are rarely documented. [18] Within these systems, the main drawback of the existing approaches is, in most cases, an E/Z-or regio-isomeric mixtures rather than a stereodefined fully substituted olefins was obtained. Therefore, the development of direct and practical access to novel and more exotic polyfunctionalized stereodefined tetrasubstituted olefins from readily available feed stocks under mild reaction conditions, especially in a metal free manner, still remains challenging and highly desirable.…”

Pd‐Catalyzed Decarboxylative Allylation for Stereoselective Syntheses of Allylic Alcohols bearing a Quaternary Carbon Center

“…Recently, Ma and coworkers demonstrated a practical approach for the syntheses of stereodefined tetrasubstituted olefins with high yields and stereoselectivities. [11] Vinyl cyclic carbonates (VCCs) are important in modern organic chemistry, recently, Pd-catalyzed decarboxylative of VCCs [12][13][14][15][16] has been regarded as a useful approach for the synthesis of important allylic manifolds. Here, we focus our attention on the stereo-and regiodefined, highly substituted olefins and limited reports of tetrasubstituted olefins.…”