Dihydrofurans from α-diazoketones due to facile ring opening – cyclization of donor–acceptor cyclopropane intermediates

Abstract

A series of a-diazoketones, 8, 25,28,31, and 34, have been synthesized and their reaction with ethyl vinyl ether examined under various reaction conditions. In the presence of metal salts (Rh,(OAc),, Pd(OAc),, CuC1) the ethoxydihydrofurans 12,37,39,41, and 43 are produced. Sensitized irradiation of the a-diazoketone 8 afforded the dihydrofuran 12 plus cyclobutanone 7, while direct photolysis of a-diazoketones 8,25,28,31, and 34 gave the cyclobutanones 7,38,40,42, and 44, respectively. A sample of the cyclopropylketone 45 was isolated from the rhodium(I1) acetate mediated reaction of 34 and its facile rearrangement to dihydrofuran 43 demonstrated. Collectively, these results indicate that the initial product from the reaction of an a-diazoketone with an electron-rich alkene such as ethyl vinyl ether is a cyclopropylketone. The donnor-acceptor substitution pattern of this intermediate results in spontaneous rearrangement to a dihydrofuran. Thus a direct dipolar cycloaddition mechanism is not involved when a-diazoketones react with en01 ethers under metal-mediated conditions. Instead, these reactions follow a cyclopropanation rearrangement or, more accurately, cyclopropanation -ring opening -cyclization pathway.Key words: diazoketone, rhodium acetate, dihydrofuran, cyclopropylketone, vinyl ether.RCsumC : On a synthttist une strie d'a-diazocttones 8,25,28,31 et 34 et on a ttudit, dans difftrentes conditions, leur rtaction avec l'tther tthylvinylique. En prtsence de sels mttalliques (RH,(OAc),, Pd(OAC),, CuC1) on obtient les tthoxydihydrofurannes 12,37,39,41 et 43. L'irradiation sensibiliste de l'a-diazocttones 8 produit le dihydrofuranne 12 et la cyclobutanone 7, tandis que la photolyse directe des a-diazocttones 8,25,28,31 et 34 donne les cyclobutanones 7,38,40,42 et 44 respectivement. On a isolt un tchantillon de cyclopropylcttone 45 de la rtaction du compost 34 en prtsence de l'acttate de rhodium et on dtmontre sa transposition facile en dihydrofuranne 43. Collectivement, ces rtsultats indiquent que le produit initial de la rtaction d'une a-diazocttone avec un alcbne riche en tlectrons tel l'tther Cthylvinylique est une cyclopropylcttone. Le modble de substitution donneur-accepteur de cet intermtdiaire provient d'une transposition spontante en dihydrofuranne. Ainsi un mCcanisme de cycloaddition dipolaire directe n'est pas impliqut lorsque une a-diazocttone rtagit avec des tthers tnoliques en prtsence d'un mCtal. Au lieu de cela ces rtactions suivent une transposition cyclopropanique ou plus prtcistment un processus de cyclopropanation, d'ouverture du cycle du cyclopropane et de cyclisation.Mots cle's : diazocttone, acttate de rhodium, dihydrofuranne, cyclopropylcCtone, tther vinylique.[Traduit par la rtdaction]

Donor−Acceptor-Substituted Cyclopropane Derivatives and Their Application in Organic Synthesis

“…For instance, metal-catalyzed reactions of cyclic diazoketones 326 with ethyl vinyl ether afforded dihydrofurans 328 with fair efficiency (Scheme ). In one case, the intermediate cyclopropyl ketone 327 was isolated and its smooth rearrangement to the dihydrofuran was demonstrated, suggesting that D−A cyclopropanes are generally intermediates in these formal [3 + 2] cycloadditions . This may also be the case in a related synthesis of fluoroalkyl-substituted dihydrofuran derivatives …”

“…In one case, the intermediate cyclopropyl ketone 327 was isolated and its smooth rearrangement to the dihydrofuran was demonstrated, suggesting that D-A cyclopropanes are generally intermediates in these formal [3 + 2] cycloadditions. 147 This may also be the case in a related synthesis of fluoroalkyl-substituted dihydrofuran derivatives. 148 An interesting route to 1,4-disubstituted furans employed Baylis-Hillman products 329 as starting materials, which were converted into dihydrofurans 331 via cyclopropyl ketones 330 (Scheme 92).…”

Synthetic Exploration of α‐Diazo γ‐Butyrolactams

“…This is due to the ring strain causing, in turn, weaker conjugation of the diazo function (or the resulting carbene center) to the carbonyl group . The reactivity of such diazo compounds is illustrated by the reported involvement of α‐diazo γ‐butyrolactones and α‐diazo cyclopentanones in such classic transition metal‐catalyzed reactions as cyclopropanation,, cyclopropenation, X–H insertion and 1,3‐dipolar cycloaddition (Scheme ).…”

Nucleophilic Metal Complexes as Acylation Catalysts: Solvent-Dependent “Switch” Mechanisms Leading to the First Catalyzed Staudinger Reaction

“…An optimal example would be the Staudinger reaction, namely the acylation of imines by ketenes to form β-lactams, involving only aprotic starting materials. , Our approach to making this reaction catalytic for the first time involves using a much less nucleophilic imine through attachment of electron-withdrawing groups onto the imine nitrogen and α to the imine unit. We determined that electron-deficient α-imino ester 7 does not react with diphenylketene 8 18a at room temperature. However, we found that 5 mol % of 1d catalyzes the addition of 7 to 8 to afford β-lactam 10 in 85% yield after only 5 min in BTF at room temperature (Scheme ) 18b…”

“…We determined that electron-deficient α-imino ester 7 does not react with diphenylketene 8 18a at room temperature. However, we found that 5 mol % of 1d catalyzes the addition of 7 to 8 to afford β-lactam 10 in 85% yield after only 5 min in BTF at room temperature (Scheme ) 18b 3 …”