THE FORMATION OF DIENONES THROUGH AR<sub>1</sub>-PARTICIPATION

Winstein, S.; Baird, Robert D.

doi:10.1021/ja01560a076

Cited by 60 publications

(16 citation statements)

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“…This may be attributed largely to the increased entropy of activation required for the Ar-4′ spirocyclization and is not reflective of the relative stabilities of the resulting products. In contrast, the slow rate of ring closure relative to an Ar-5′ spirocyclization8 may be related to the corresponding enthalpy of activation and is likely reflective of the relative stabilities of the resulting products.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Characterization of a Cyclobutane Duocarmycin Derivative Incorporating the 1,2,10,11-Tetrahydro-9H-cyclobuta[c]benzo[e]indol-4-one (CbBI) Alkylation Subunit

Lajiness

Boger

2010

J. Am. Chem. Soc.

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The synthesis of 1,2,10,11-tetrahydro-9H-cyclobuta [c]benzo [e]indol-4-one (17, CbBI), containing a deep-seated fundamental structural modification in the CC-1065 and duocarmycin alkylation subunit with the incorporation of a ring expanded fused cyclobutane (vs cyclopropane), its chemical and structural characterization, and its incorporation into a key analogue of the natural products are detailed. The approach to the preparation of CbBI was based on a precedented (Ar-3′ and Ar-5′), but previously unknown Ar-4′ spirocyclization of a phenol onto a tethered alkyl halide to form the desired cyclobutane. The conditions required for the implementation of the Ar-4′ spirocyclization indicate that the entropy of activation substantially impacts the rate of reaction relative to the much more facile Ar-3′ spirocyclization, while the higher enthalpy of activation slows the reaction relative to an Ar-5′ spirocyclization. The characterization of the CbBI-based agents revealed their exceptional stability and exquisite reaction regioselectivity, and a single crystal X-ray structure analysis of N-Boc-CbBI (13) revealed their structural origins. The reaction regioselectivity may be attributed to the stereoelectronic alignment of the two available cyclobutane bonds with the cyclohexadienone π-system, which resides in the bond that extends to the less substituted cyclobutane carbon for 13. The remarkable stability of N-Boc-CbBI (stable even at pH 1) relative to N-Boc-CBI (t 1/2 = 133 h at pH 3) containing a cyclopropane may be attributed to a combination of the increased extent of vinylogous amide conjugation, the nonoptimal geometric alignment of the cyclobutane with the activating cyclohexadienone, and the intrinsic but modestly lower strain energy (1.8 kcal/mol) of a cyclobutane versus cyclopropane.

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Section: Resultsmentioning

confidence: 99%

Synthesis and Characterization of a Cyclobutane Duocarmycin Derivative Incorporating the 1,2,10,11-Tetrahydro-9H-cyclobuta[c]benzo[e]indol-4-one (CbBI) Alkylation Subunit

Lajiness

Boger

2010

J. Am. Chem. Soc.

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“…The function of a spiro cyclohexadienone as a transient intermediate has been previously (13) proposed in order to interpret a related reaction, i.e. the alkaline solvolysis of 2-p-hydroxyphenylethyl bromide.…”

Section: Resultsmentioning

confidence: 99%

Studies on the condensation of lignins in alkaline media. Part II. The formation of stilbene and arylcoumaran structures through neighbouring group participation reactions

Gierer¹,

Pettersson²

1977

Can. J. Chem.

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JOSEF GIERER and INGEGERD PETTERSSON. Can. J. Chem. 55, 593 (1977). The alkaline condensation of p-hydroxyarylglycerol-a-aryl ether units in lignin with other phenolic structures and the subsequent reactions of the condensation products have been elucidated using appropriate model compounds. It is shown that the primary condensation of simple phenols (2,6-xylenol or resorcinol) into the a-position of phenolic compounds of the f3-aryl ether type is followed by an aryl participation (A,-3) reaction resulting in the cleavage of the a-aryl ether bond and formation of the corresponding stilbene derivative. When resorcinol is used as reaction partner, the condensation is also followed by the cleavage of the P-aryl ether linkage through another type of neighbouring group participation reaction involving the phenolate anion ortho to the site of condensation and giving rise to the corresponding arylcoumaran derivative.The consequences of these findings for the course of alkaline delignification processes are briefly discussed. Chem. 55, 593 (1977). On a ClucidC, utilisant des composes modiles approprits, le mecanisme de la condensation alcaline d'unites d'ether p-hydroxyarylglycCro1 a-aryle de la lignine avec d'autres structures phCnoliques et les rCactions subsCquentes des produits de condensation. On a montr6 que la condensation primaire de phenols simples (xylenol-2,6 ou rCsorcino1) en position a des composes phCnoliques du type ether a-aryle est suivie par une reaction de participation du groupe aryle (A1-3) qui conduit au bris du lien ether P-aryle et a la formation du derive stilbene correspondant. Quand on utilise le resorcinol comme partenaire de la rCaction, la condensation est aussi suivie par une coupure du lien ether a-aryle par un autre type de reaction de participation de groupe voisin impliquant I'anion phenolate ortho par rapport au site de condensation et donnant lieu au dCrivC arylcoumarane correspondant.On discute des consCquences de ces resultats pour les processus de delignification alcaline. [Traduit par le journal]Numerous studies on the alkaline condensation of lignins have shown that the benzylic position in phenolic units constitutes the main site of reaction in this complex process (1-6). In most of these studies, model compounds of the phydroxybenzyl alcohol type were reacted with simple phenols and the resulting diarylmethanes were isolated. The condensation reaction was formulated as a nucleophilic addition of an ortho-or para-cyclohexadienone carbanion to the appropriate para-quinonemethide, followed by proton or side-chain elimination with rearomatization (7). Results from studies using model compounds of the y-hydroxyaryl coumaran (8) and P-arylglycerol (9) types indicated that this conjugate addition reaction is not prevented by the presence of an aryi or an aroxy group in the adjacent P-position (cf. also condensations in acidic media (10)). Thus, carbanions formed from phenolic lignin structures compete, in fact, with the other nucleophiles present in the pulping liquor (SH-, OH-ions) ...

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“…Also, perhaps the additional ortho ‐alkoxy substituent at C15 participates in a precedented but now arcane intramolecular Ar 1 participation reaction, generating a methylated spirocyclohexadienone (cf. 24 ) 11. This participation results in a hitherto unnoticed first inversion around C13.…”

Section: Methodsmentioning

confidence: 96%

The Solution to a Deep Stereochemical Conundrum: Studies toward the Tetrahydroisoquinoline Alkaloids

et al. 2006

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THE FORMATION OF DIENONES THROUGH AR₁-PARTICIPATION

Cited by 60 publications

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Synthesis and Characterization of a Cyclobutane Duocarmycin Derivative Incorporating the 1,2,10,11-Tetrahydro-9H-cyclobuta[c]benzo[e]indol-4-one (CbBI) Alkylation Subunit

Synthesis and Characterization of a Cyclobutane Duocarmycin Derivative Incorporating the 1,2,10,11-Tetrahydro-9H-cyclobuta[c]benzo[e]indol-4-one (CbBI) Alkylation Subunit

Studies on the condensation of lignins in alkaline media. Part II. The formation of stilbene and arylcoumaran structures through neighbouring group participation reactions

The Solution to a Deep Stereochemical Conundrum: Studies toward the Tetrahydroisoquinoline Alkaloids

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THE FORMATION OF DIENONES THROUGH AR1-PARTICIPATION

Cited by 60 publications

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Synthesis and Characterization of a Cyclobutane Duocarmycin Derivative Incorporating the 1,2,10,11-Tetrahydro-9H-cyclobuta[c]benzo[e]indol-4-one (CbBI) Alkylation Subunit

Synthesis and Characterization of a Cyclobutane Duocarmycin Derivative Incorporating the 1,2,10,11-Tetrahydro-9H-cyclobuta[c]benzo[e]indol-4-one (CbBI) Alkylation Subunit

Studies on the condensation of lignins in alkaline media. Part II. The formation of stilbene and arylcoumaran structures through neighbouring group participation reactions

The Solution to a Deep Stereochemical Conundrum: Studies toward the Tetrahydroisoquinoline Alkaloids

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THE FORMATION OF DIENONES THROUGH AR₁-PARTICIPATION