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The structures of three racemic (tetrahydro-[1,3]dioxino[5,4-d][1,3]dioxin-4-yl)methanol derivatives are reported, namely, 4-[(methylsulfonyloxy)methyl]-2,4,4a,6,8,8a-hexahydro-[1,3]dioxino[5,4-d][1,3]dioxine, C8H14O7S,1, 4-[(benzyloxy)methyl]-2,4,4a,6,8,8a-hexahydro-[1,3]dioxino[5,4-d][1,3]dioxine, C14H18O5,2, and 4-[(anilinocarbonyl)methyl]-2,4,4a,6,8,8a-hexahydro-[1,3]dioxino[5,4-d][1,3]dioxine, C14H17NO6,3. Mesylate ester1at 173 K has triclinicP\overline{1} symmetry and both benzyl ether2at 173 K and phenyl urethane3have monoclinicP21/csymmetry. These structures are of interest because of the conformation of thecis-fused tetraoxadecalin ring system. Thiscis-bicyclo[4.4.0]decane ring system,i.e. cis-decalin, can undergo conformational equilibration. In the two most stable conformers, both six-membered rings adopt a chair conformation. However, there are significant consequences in these two stable conformers, with heteroatom substitution at the 1,3,5,7-ring positions as described. Only one conformation, denoted as `concave' or `inside', is found in these crystal structures. This is consistent with previously reported structures of the 1,1-geminal dihydroxy aldehyde and tosylate analogs.
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Nitrene C−H Bond Insertion Approach to Carbazolones and Indolones, and a Reactivity Departure for 7‐Membered Analogues
A modular platform for facile access to 1,2,3,9‐tetrahydro‐4H‐carbazol‐4‐ones (H4‐carbazolones) and 3,4‐dihydrocyclopenta[b]indol‐1(2H)‐ones (H2‐indolones) is described. The requisite 6‐ and 5‐membered 2‐arylcycloalkane‐1,3‐dione precursors were readily obtained through a Cu‐catalyzed arylation of 1,3‐cyclohexanediones or by a ring expansion of aryl succinoin derivatives. Enolization of one carbonyl group in the diones, conversion to a leaving group, and subsequent azidation gave 2‐aryl‐3‐azidocycloalk‐2‐en‐1‐ones. This two‐step, one‐pot azidation is highly regioselective with unsymmetrically substituted 2‐arylcyclohexane‐1,3‐diones. The regioselectivity, which is important for access to single isomers of 3,3‐disubstituted carbazolones, was analyzed mechanistically and computationally. Finally, a Rh‐catalyzed nitrene/nitrenoid insertion into theorthoC−H bond of the aryl moiety gave the H4‐carbazolones and H2‐indolones. One carbazolone was elaborated to an intermediate reported in the total synthesis ofN‐decarbomethoxychanofruticosinate, (−)‐aspidospermidine, (+)‐kopsihainanine A. With 2‐phenylcycloheptane‐1,3‐dione, prepared from cyclohexanone and benzaldehyde, the azidation reaction was readily accomplished. However, the Rh‐catalyzed reaction unexpectedly led to a labile but characterizable azirine rather than the indole derivative. Computations were performed to understand the differences in reactivities of the 5‐ and 6‐membered 2‐aryl‐3‐azidocycloalk‐2‐en‐1‐ones in comparison to the 7‐membered analogue, and to support the structural assignment of the azirine.
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- Award ID(s):
- 1953574
- PAR ID:
- 10538642
- Publisher / Repository:
- Wiley
- Date Published:
- Journal Name:
- Chemistry – A European Journal
- Volume:
- 29
- Issue:
- 72
- ISSN:
- 0947-6539
- Subject(s) / Keyword(s):
- indole, carbazolone, indolone, nitrene, rhodium catalysis
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript
- Journal Article:
- https://doi.org/10.1002/chem.202302995
