Diastereospecific Nazarov Cyclization of Fully Substituted Dienones: Generation of Vicinal All‐Carbon‐Atom Quaternary Stereocenters

Abstract

The joining of two carbon atoms through a σ bond so as to form vicinal all-carbon atom quaternary centers remains a difficult challenge in organic synthesis. [1] An effective strategy to address the problem is to exploit an orbital symmetry controlled process. [2] We describe herein a diastereospecific Nazarov cyclization [3] that leads to cyclopentenones bearing adjacent all-carbon atom quaternary centers.We are aware of only the three examples of Nazarov cyclizations that lead to two contiguous all-carbon atom quaternary stereocenters during the ring forming step that are shown in Scheme 1. The first two examples in Scheme 1 describe Harding and coworkers' efforts that culminated in the total synthesis of (d,l)-trichodiene. [4] Reaction conditions in both cases were harsh but the yield of cyclic products 2 and 4 that lack sensitive functionality was high. Both reactions were diastereospecific, with the C3a,C3b relative stereochemistry (see compound 2) determined by the conrotation that is required by the selection rule governing the thermal 4π electron process. The third example in Scheme 1 is the oxidative Nazarov cyclization of allenyl ether 5 that was reported by Frontier and coworkers in 2011. [5] The oxyallyl zwitterion that forms spontaneously from the allene oxide following treatment of 5 with dimethyldioxirane (DMDO) underwent stereospecific cyclization to 6 in moderate yield. The zwitterion intermediate is strongly polarized, hence the mild reaction conditions.

The Nazarov Cyclization: A Valuable Method to Synthesize Fully Substituted Carbon Stereocenters

“…Tius has taken full advantage of the increased reactivity of polarized Nazarov substrates for the synthesis of vicinal all‐carbon‐atom quaternary stereocenters. The challenging task of joining two pro‐quaternary carbon atoms together to form vicinal all‐carbon‐atom centers was made possible by careful design of polarized dienones 17. Nazarov cyclization of 31 gives 32 , containing two adjacent all‐carbon centers, as a single diastereomer (Scheme ).…”

Retracted Article: An efficient one pot three-component synthesis of 2,4,6-triarylpyridines using triflimide as a metal-free catalyst under solvent-free conditions

“…It is found that triimide has also been used as a catalyst in numerous other organic reactions such as formation of oxime ethers, 32 Mukaiyama aldol reaction, 33 alkylation, 34 synthesis of indanes and tetralins, 35 allyl-allyl cross-coupling, 36 C-C bond formation 37 and Nazarov reaction. 38 In view of the efforts toward development of the potential of HNTf 2 as a catalyst, herein, we report an efficient one pot three-component synthesis of 2,4,6-triarylpyridines (Scheme 1).…”

1,4‐Diketones from Cross‐Conjugated Dienones: Potassium Permanganate‐Interrupted Nazarov Reaction

“…[9] On the other hand, the oxyallyl cation could undergo ac oncerted or stepwise [3+ +3] cycloaddition with permanganate to produce ah ypomanganate ester (Mechanism B), in ah omologous process to the [3+ +2] step that initiates alkene cleavage.T hrough equilibrium of the Mn V complexes,the aoxyanion could react with an additional Mn VII ,a ffording tricyclic manganese complex A.Considering the initial [3+ +3] cycloaddition provides syn-a,a' substituents,t he tricyclic complex A would be a cis,trans-angular structure bearing significant strain, which may disfavor this pathway.N otably, in either mechanism the discharge of carbon dioxide rather than carbon monoxide is proposed. Qualitative analysis via conversion of Ba(OH) 2 to BaCO 3 provides support for the formation of CO 2 . [13] However,f urther mechanistic studies entailing characterization of minor side-products and attempts to intercept proposed intermediates remain to be done.…”

“…There has been considerable development in the Nazarov reaction [1,2] over the past two decades,p articularly in the exploration of alternative substrates, [3] catalytic asymmetric variants, [4] skeletal rearrangement, [5] and domino/cascade processes [6] involving the Nazarov intermediate.T he latter approach (interrupted Nazarov reaction) entails trapping the oxyallyl cation intermediate with av ariety of p nucleophiles such as electron-rich arenes and enol derivatives or s nucleophiles from organoaluminum reagents. [7] Additionally, [4+ +3], [ 3 + +3],a nd [2+ +3] cycloadditions on the Nazarov intermediates to afford bridged bicyclic ring systems have been studied.…”