Scheme 1. 1,2-Dicarbonyl or monocarbonyl compounds directly serve as surrogates for diazo compounds in Mo-catalyzed deoxygenative cyclopropanation reactions.
The first enantioselective polyene cyclization initiated by a BINOL-derived chiral N-phosphoramide (NPA) catalyzed protonation of an imine is described. The ion-pair formed between the iminium ion and chiral counter anion of the NPA plays an important role for controlling the stereochemistry of the overall transformation. This strategy offers a highly efficient approach to fused tricyclic frameworks containing three contiguous stereocenters, which are widely found in natural products. In addition, the first catalytic asymmetric total synthesis of (-)-ferruginol was accomplished with an NPA catalyzed enantioselective polyene cyclization, as the key step for the construction of the tricyclic core, with excellent yield and enantioselectivity.
The polyene cyclization of E-polyenes has evolved into a reliable and widely used strategy for the construction of trans-decalin frameworks of terpene and steroid natural products. However, the polyene cyclization approach to cis-decalin framework is considerably challenging because such a reaction requires more difficult accessed Z-polyenes. Furthermore, polyene cyclization of Z-polyene to cis-decalin was usually accompanied by the formation of trans-isomer. We herein report a "universal" polyene cyclization approach to cis-decalin frameworks by employing ynamide-capped polyenes (YCPs), in which the central alkene can be either Z-or E-configuration. A broad range of YCPs are compatible to furnish the cis-decalin frameworks in good to excellent yields with excellent diastereoselectivity. No detectable trans-isomer has been observed for all the substrates used in this study. Both experimental and DFT calculation results revealed that the ynamide protonationinitiated polyene cyclization proceeds in a stepwise manner involving an unprecedented double protonation mechanism, wherein the steric repulsion between the iminium and the forming decalin
The substituted benzene derivatives are essential to
organic synthesis,
medicinal chemistry, and material science. However, the 1,3-di- and
1,3,5-trisubstituted benzenes are far less prevalent in small-molecule
drugs than other substitution patterns, likely due to the lack of
robust, efficient, and convenient synthetic methods. Here, we report
a Mo-catalyzed intermolecular deoxygenative benzene-forming reaction
of readily available ynones and allylic amines. A wide range of unsymmetric
and unfunctionalized 1,3-di- and 1,3,5-trisubstituted benzenes were
obtained in up to 88% yield by using a commercially available molybdenum
catalyst. The synthetic potential of the method was further illustrated
by synthetic transformations, a scale-up synthesis, and derivatization
of bioactive molecules. Preliminary mechanistic studies suggested
that this benzene-forming process might proceed through a Mo-catalyzed
aza-Michael addition/[1,5]-hydride shift/cyclization/aromatization
cascade. This strategy not only provided a facile, robust, and modular
approach to various meta-substituted benzene derivatives
but also demonstrated the potential of molybdenum catalysis in the
challenging intermolecular deoxygenative cross-coupling reactions.
The first enantioselective polyene cyclization initiated by a BINOL‐derived chiral N‐phosphoramide (NPA) catalyzed protonation of an imine is described. The ion‐pair formed between the iminium ion and chiral counter anion of the NPA plays an important role for controlling the stereochemistry of the overall transformation. This strategy offers a highly efficient approach to fused tricyclic frameworks containing three contiguous stereocenters, which are widely found in natural products. In addition, the first catalytic asymmetric total synthesis of (−)‐ferruginol was accomplished with an NPA catalyzed enantioselective polyene cyclization, as the key step for the construction of the tricyclic core, with excellent yield and enantioselectivity.
The transition‐metal‐catalyzed cyclopropanation of alkenes by the decomposition of diazo compounds is a powerful and straightforward strategy to produce cyclopropanes, but is tempered by the potentially explosive nature of diazo substrates. Herein we report the Mo‐catalyzed regiospecific deoxygenative cyclopropanation of readily available and bench‐stable 1,2‐dicarbonyl compounds, in which one of the two carbonyl groups acts as a carbene equivalent upon deoxygenation and engages in the subsequent cyclopropanation process. The use of a commercially available Mo catalyst afforded an array of valuable cyclopropanes with exclusive regioselectivity in up to 90 % yield. The synthetic utility of this method was further demonstrated by gram‐scale syntheses, late‐stage functionalization, and the cyclopropanation of a simple monocarbonyl compound. Preliminary mechanistic studies suggest that phosphine (or silane) acts as both a mild reductant and a good oxygen acceptor that efficiently regenerates the catalytically active Mo catalyst through reduction of the Mo‐oxo complexes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.