Solvent effectDonor-acceptor-substituted vinylcyclopropanes such as l a , 3a, 5a, 5b, 7a, 9a, 9b, and 12a smoothly undergo thermal ring enlargement to functionalized cyclopentene derivatives 2, 4, 6, 8, 10, and 13 at relatively low temperatures (150-190 "C) in good yields. This vinylcyclopropane-cyclopentene rearrangement proceeds with low ( l a , 3a), moderate (9a, b) or high (7a, 12a) stereoselectivity. In the case of 7a and 12a almost complete retention of configuration with respect to the migrating (methoxy)(phenyl)-substituted carbon atom was observed. The definite mechanistic interpretation of these results is complicated by the stereoisomerization of the starting donor-acceptor-substituted vinylcyclopropanes which proceeds as competing reaction during ring enlargement. Nevertheless, all observations together, in particular the recorded solvent effects, support a stepwise mechanism of the rearrangement with a highly stabilized 1,3-zwitterionic species as common intermediate for cyclopropane stereoisomerization and ring enlargement.The rearrangement of vinylcyclopropanes opens a synthetically very valuable route to cyclopentene derivatives and meanwhile it has often been employed in natural product synthesis [2]. Despite its preparative importance the mechanism of this reaction is still under discussion, and it is not clear whether this rearrangement can occur as concerted process ['] or whether it always involves (diradical) intermediate~r~]. Also, metal-catalyzed rearrangements were describedr5]. In recent publicationsrh1 we reported on the smooth and highly flexible synthesis of donor-acceptorsubstituted vinylcyclopropanes A which are available from Fischer carbene complexes and electron-deficient dienes, in many examples even in diastereomerically pure form.In a few of these formal [2 + 11 cycloadditions we observed small amounts of cyclopentene derivatives B which can arise either from a direct [4 + 11 cycloadditi~n [~] or thermal rearrangement of A. These observations motivated us to investigate the thermolyses of cyclopropanes A since we felt that a rearrangement under relatively mild conditions may be uncovered and could be due to the donoracceptor-substitution pattern. Here we describe our results which support this idea and discuss their mechanistic implications. ResultsDiastereomerically pure vinylcyclopropane 1 a rearranged in refluxing decalin (190'C) and after 13 d gave a mixture of four diastereomers 2a-2d in 74% yield. In this case and in all subsequent examples the reaction progress was monitored by NMR spectroscopy. The rearrangement was considerably faster by running the experiment in refluxing benzonitrile (190 "C) giving 2a-2d in slightly different diastereomeric composition and in excellent yield. In contrast, in dimethylformamide at 150°C (6 h) no consumption of the starting material l a could be observed.Rather similar results were obtained for the thermal rearrangement of starting material 3a which afforded a mixture of 4a-4d in 7 I YO yield. The regioselectivity of this process m...
Thermal reactions of the a,bunsaturated Fischer carbene complexes 3 ± 5 with the siloxydienes 6 and 7 mainly furnished the expected cyclohepta-1,4-dienes such as 9, 10, 12, 14, and 15, whose formation is explained by a formal [21] cycloaddition followed by Cope rearrangement. The rather electron-rich carbene complex 5 also afforded the cyclopentene derivatives 11 and 16 as by-products, which are probably formed by two distinct mechanisms. Single diastereomers of the cyclopentene derivatives 17 and 18 were isolated as the exclusive products of the reactions of 3 and 4, respectively, with the donor/ acceptor-substituted 1,3-diene 8. This process is interpreted as a metalla Diels ± Alder reaction to form a chromacyclohexene intermediate 25, which subsequently undergoes fragmentation to give cyclopentene derivatives with the required constitution. Most surprisingly, the reactions of simple carbene complexes 1 or 2 with the siloxydienes 7 or 8 yielded cyclopentene derivatives 19 and 20 that do not contain the carbene ligand of the precursor complexes. Instead, the constitution of the isolated products can be accounted for by a formal diene dimerization with fragmentation of a methylene unit. Their formation can be interpreted by an unprecedented sequence of carbene-ligand metathesis followed by a metalla Diels ± Alder reaction and reductive fragmentation. All these results illustrate the great importance of electronic fine-tuning in the precursors involved in reactions of Fischer carbene complexes with 1,3-dienes.
Thermal reactions of Fischer carbene complex 1 with trisub-nerally fairly high in preference of cyclopropanes with the stituted electron-deficient 1,3-dienes 7, 8, 23, 25, 32, and 35 methoxy group cis-positioned with respect to the olefin provided highly substituted vinylcyclopropanes in good moiety. The reaction of methylcarbene complex 2 with diene yields. The carbene transfer proceeds highly regioselectively ester 8 displays inversed regioselectivity. These observations favouring cyclopropanation of the double bond not bearing are discussed together with solvent effects, and a mechanisthe ester function. In addition, the diastereoselectivity is ge-tic rationale is presented.In a preceding reportL2I we described thermal reactions of Fischer carbene complexes A with 1 ,Cdisubstituted electron-deficient dienes B which furnished vinylcyclopropene derivatives C. Gratifyingly, these reactions occurred with complete periselectivity, in favour of formal [2 + 11 cycloadditions, and with excellent regioselectivity and good diastereoselectivity producing compounds C in high preference. DSince not many studies on the reactivity of Fischer carbene complexes with dienesr41 are known, we further investigated 1,3-dienes with different substitution patterns, in particular trisubstituted electron-deficient compounds, in order to study the dependence of the selectivities with regard to the diene structure. ResultsAs Fischer carbene complex we generally employed the phenyl-substituted compound 1, but in one example we also studied the considerably less reactive methyl-substituted complex 2. Whereas thermal reactions of 1 with diene esters 3-5 provided only polymers or intractable mixtures of many compounds, we could receive clear results when dienes 6-8 were used as carbene acceptors. The slow reaction (9OoC, 3 d) of complex 1 with methyl 4-methyl-2,4-pentadienoate (6) regioselectively afforded a mixture of the two diastereomers 9alb (67:33) in moderate yield. This transformation thus proceeds with the lowest diastereoselectivity observed with diene esters as studied in
The thermal reaction of Fischer carbene complex 1 with electron-deficient 1,3-dienes such as methyl (E,E)-2,4-hexadienoate (2) provided functionalized vinylcyclopropanes like 3 in good yields. Similar results were obtained by employing related unsaturated esters 4, 17, and 21 or nitrile 6. The periselectivity as well as regioselectivity of these carbene-transfer reactions are generally very high, and the diastereomer with the methoxy group cis-positioned with respect to the olefinic moiety is largely favoured (>85: 15). A mechanistic rationale of these observations is given. Double adducts were only formed as minor sideproducts in these reactions, but by employing amide 13 as electron-deficient diene they were very easily formed with 1. The [2 + 11 cycloaddition could also be extended to methylcarbene complex 24 and diene 2, but the corresponding vinylcyclopropane 25a was so far only obtained in low yield. cycloaddition would provide cyclopentene derivative E. In addition, diastereomers can be formed along these routes. Therefore, a first systematic study addresses to the questions of regio-, peri-, and diastereoselectivity. It has also to be investigated which substituents R' and X (acceptor) are appropriate for this reaction. M e 0 R __We concentrated on electron-deficient 1,Cdisubstituted 1,3-dienes, since monosubstituted dienes such as methyl 2,4-pentadienoate were unsuitable substrates -probably due to their high tendency to polymerize [' I. The reactions of carbene complexes with higher substituted 1,3-dienes will be described in due ResultsThe thermal reaction of standard carbene complex 1 with methyl (E,E)-2,4-hexadienoate (2) in cyclohexane proceeded rather slowly but cleanly afforded vinylcyclopropane derivatives 3a/b in good yield and with surprisingly high dia-
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.