A convergent strategy has allowed access to bridgehead sultam 9 and the related carboxamides 10 and 11. The synthetic routing proceeds via the coupling of a suitably constructed dienamine to either o-iodobenzenesulfonyl chloride or o-iodobenzoyl chloride to generate the amides. The application in sequence of ring-closing metathesis and an intramolecular Heck reaction gave rise to advanced tricyclic intermediates. The final two steps involved bromination in liquid bromine and proper 2-fold dehydrobromination. The latter maneuver was best achieved with tetrabutylammonium fluoride in DMSO at elevated temperature. While the irradiation of 9 led principally via SO2-N bond homolysis and [1,5] sigmatropic rearrangement to generate 37, 10 proceeded via disrotatory cyclization to the exo cyclobutene 39, and 11 resisted photoisomerization. The inertness of 11 may stem from its distorted structural features which force its conjugated diene double bonds to be rigidly oriented 32 degrees out-of-plane. The unique ability of the sulfonamide linkage to excited-state homolysis holds comparative interest.
Triplet-sensitized irradiation of 8-thia-9-azatricyclo[7.2.1.0(2,7)]dodeca-2,4,6,10-tetraene (16) in acetone solution gives rise exclusively to tetracyclic sultam 20. This strong preference for benzo-vinyl bridging distal to the sulfonamide functional group has also been observed in eight derivatives carrying chemically diverse functional groups at C-10. In none of these examples is regiospecificity eroded. This overall result suggests that the added substituents act in harmony with the electronic rebonding pathway found operative in the parent system. From the structural perspective, this transformation constitutes a facile means for accomplishing the ring contraction of a bridgehead sultam.
Nearly a century after their original discovery, catalyzed enantioselective variants of the venerable Claisen rearrangement remain relatively rare. We have discovered a cooperative transition metal-Lewis acid cocatalyst system that affects highly enantio- and diastereoselective examples of archetypical Claisen rearrangements. The catalyzed rearrangements proceed using an easily prepared enantioenriched transition metal catalyst and a commercially available Lewis acid cocatalyst at ambient temperature in common solvents.
A ring-closing metathesis-based strategy has allowed access to an unreported pair of pyridoisoindolones and their previously unknown sultam counterparts. The synthetic routing takes advantage of the ready availability of N-allylphthalimide and N-allylsaccharin and proceeds via the proper incorporation of small side chains into the heterocyclic ring. Positionally selective introduction of the conjugated diene functionality was realized efficiently. Detailed study of the excited-state chemistry of 7 and 8 showed both lactams to be subject to [4 + 2] dimerization under acetone-sensitized conditions. Different regioselectivities are involved, with the response of 8 being far more efficient than that exhibited by 7. No dimers could be isolated from the photolyzates of 9 and 10 under any conditions. While the latter sultam undergoes extensive polymerization, 9 is transformed via direct irradiation at 350 nm into 46 and 47 via [1,3]-sigmatropy involving the S-N bond and heterocyclic ring cleavage, respectively.
Ketenes are among the few synthetic building blocks that undergo facile thermal [2 + 2] and [4 + 2] cycloadditions, yielding cyclobutanes, β‐lactones, β‐lactams, dioxins, quinoxalines, thiazinones, pyranones, and other useful carbo‐ and heterocycles. In addition to substrate structure, the presence of Lewis acids and bases can have a decisive effect on product outcome by diverting ketene reactivity to different cycloaddition manifolds.
This comprehensive review focuses on catalyzed enantioselective ketene [2 + 2] and [4 + 2] cycloadditions in which the asymmetric induction is derived solely from the catalyst complex. Accordingly, diastereoselective cycloadditions are described only when they are relevant to a catalytic asymmetric reaction variant. Molecular orbital interactions are correlated to the electronic structure of ketenes and used to explain ketene reaction pathways.
Cinchona
alkaloids play an important role in Lewis base catalyzed asymmetric carbonyl and imine cycloadditions, whereas Al(III)‐, Fe(II)‐, Ti(IV)‐, and Cu(II)‐complexes are mainly responsible for Lewis acid catalyzed asymmetric transformations. Carbene catalysts are also significant for both ketene–carbonyl and ketene–imine cycloadditions.
The subject cycloaddition protocol is also compared with other methods, including Mannich‐ and aldol‐based approaches to β‐lactams and β‐lactones, nitrone–alkyne and hetero Diels–Alder reactions, and the catalytic asymmetric allylation–lactonization.
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