Dioxepinlerin dimetildiazomalonat/Bis(asetilasetonat) bakır (II) ile reaksiyonları

Abstract

Düz zincirli allil asetallerle diazoesterlerin tepkimeleri hakkında literatürde birçok çalışma bulunmasına rağmen, halkalı allil asetallerle diazo bileşiklerinin reaksiyonları konusunda detaylı bir çalışma yapılmamıştır. Bu konuda yapılan tek çalışma 1,3 dioxepinin diazoasetat/CuS04 sistemi ile reaksiyonu ve siklopropan türevinin sentezi ile ilgilidir. Katılma reaksiyonu dışında oxonyum ylid üzerinden yürüyebilecek olan, [l,2]-kayması (Stevens), [2,3]-sigmatropik göçler reaksiyonlarına hiç değinilmemiştir. Bu çalışmada l,3-dioxepin türevlerinin bis-(karbometoksi) karben-Bakır (II) asetil asetonat ile tepkimeleri incelenmiş ve siklopropan türevlerinin yanı sıra, diğer reakiyon ürünlerinin varlığı araştırılmıştır. Yapılan tepkimeler sonucu siklopropan türevlerinin yanında, [l,2]-kayması reaksiyonuna ait ürünlerin oluştuğu tespit edilmiştir. [2,3]-sigmatropik göç sonucu meydana gelebilecek ürüne rastlanmamıştır. l,3-dioxepindeki 2 nolu karbon atomuna bağlı substitüentler ürün dağılımını etkilemiştir. Her iki substitüent alkil olması durumunda, sadece siklopropan türevi elde edilmiş, tek alkil grubunun bulunduğu bileşiklerde, alkil grubunun hacimsel yapışma bağlı olarak farklı [l,2]-katılma ürünleri elde edilmiştir. Halkalı vinil asetal (2-metil-4,5-dihidro-l,3-dioxepin) reaksiyon ortamında parçalanarak asetaldehit ve furan vermiştir. DMDM parçalanma ürünlerine katılmıştır.

Carben and carbenoid reactions have great preparative value for the synthesis of cyclopropane and different heterocyclic compounds. Carbenes are highly reactive divalent carbon intermediates. Although they are neutral, carbenes usually have strong electrophilic character because of electron deficiency of the carben carbon, being a sextet not a stable octet. Electronically, carbenes can be either singlet or triplet state. Singlets are angular molecules, having their paired electrons in sp2 orbitals at the lowest state. Triplets have two unpaired electrons in two different degenerate sp orbitals. These carbenes, which are usually generated by photolysis or thermolysis of diazo compounds react with other molecules (especially alkenes, carbonylcompounds, ethers, etc.) yielding cyclopropanes, insertion products, dimers, etc. The addition of carbenes to suitable olefines are one of the most general procedure for the synthesis of cyclopropanes substituted with electron- withdrawing functions. %69 (exo) %4 (endo) Due to the concerted nature of the catalytic addition, the reaction is stereospecific. This type of reaction can be performed with or without the presence of a catalyst. Without catalyst the yield of cyclopropanes is low but the presence of copper-bronze vu raises the yield considerably. However, performing the reaction in the presence of rhodium(II)acetate gives better yields. In general it has been postulated that the substitution of an electron-donating group enhances the olefine reactivity towards carbenes and that substitution by electron with-drawing groups reduces this reactivity. R°\ /Rl N2CHCOOB/Cu Rj R2 90-120C * / "^COOEt TO f%94-95) < OR h/ N2CHPlç Ph -f - V- CN "*" Ph C (%70) Singlet carbenes can function as Lewis acids by interacting with a pair of non- bonding electrons contributed by a Lewis base. If the Lewis base is an uncharged species, the end result of such an acid-base reaction is an ylide. Ylides can be viewed as species in which a positively charged heteroatom is connected to a carbon atom possesing an shared pair of electrones. More recently, ylide generation has been achieved by the transition-metal catalyzed decomposition of diazo compounds in the presence of heteroatom. The reactive intermediate proceeding ylide formation is a carbenoid species. R-X-R + R2C=N2 ^^* R]C-XR metal d' %d "ylide" To generate oxonium ylides, one of the approach involves the interaction of carbenes with unshared electron pairs of an oxygen atom. Oxonium ylides are reactive species which readily undergo the Stevens rearragements, P-hidride elimination and [2,3]-sigmatropic reorganisation. For example, the reaction of allylic acetals with an vui alkyl diazoacetate in the presence of rhodium(II)acetate, three different kind of products could be obtained. R* R'x N,QR «^(0^)4 9 A ""«--v COOR N2CHCOOR ROOC m\ OR R\ ? ^=V COOR ? >-< OR OR (3) Compounds (1) was formed from the cyclopropanation of the olefinic bond. Compound (2) was originated from [2,3]-sigmatropic rearrangement of the oxygen ylide(4) while compounds (3) was formed by a [l,2]-insertion reaction. (Stevens rearrangement) Allylacetals undergo ylide formation when the reaction is carried out with the use of diazoesters. Cyclopropanation and Stevens rearrangement compete with the [2,3]- sigmatropic rearrangements. Ylide formation was favored by the factor of 3/2 to cyclopropanation. Steric factors, however were found to cause a variation in the ratio of products. Steric bulk near the allyl groups favours oxonium ylides formation, whereas steric bulk near the oxygen atom promotes the cyclopropanation reaction. There are a number of reports in the literature on the reaction of open chain allylic acetals and diazoesters. But a limited number of reports were found on the reactions of cyclic allylic acetals. The main study on this subject came from Jenderalla [103] on the reaction of ethyldiazoacetat with 1,3-dioxepin in the presence of CUSO4 who reported the formation of only cyclopropane derivative of 1,3-dioxepin. Other IX possible reaction pathways which involve oxonium ylide such as [2,3]-sigmatropic shifts, Stevens rearrangements and P-hidride elimination reactions were not mentioned by Jenderalla. N2CHCO2S (%90) In this study, several 1,3-dioxepin derivatives were reacted with dimethyldiazomalonate (DMDM) under bis(acetylacetonato)copper(II) catalyst in order to investigate the formation of oxonium ylide versus cyclopropanation. As seen in the Table, reactions were found to give the products derivated from Stevens rearrangement of the oxonium ylides as well as the cyclopropanated products. These result were quite different from Jenderalla' s result. As can be seen in the Table below, 2-Methyl-4,7-dihydro- 1,3-dioxepin gave both addition and C-0 insertion products in the yields of 40% and 60 % respectively, as major compounds. The minor compounds were carben dimer and decomposition product of cyclopropanated derivative. Cyclopropanation of 2-methyl-l,3-dioxepin afforded 70% of trans and 30% of cis isomers approximately. [l,2]-shift (Stevens rearrangement) reaction was realised in the O-CH-0 bond and also two isomers (R and S) yielded. Although these two isomers were detected by GC using chiral capiller column, the cis and trans isomers could not be determined by GC. This was probably due to its non-chiral structure. However, 13C-NMR and ^-NMR allowed to detect the cis and trans isomers because they have different chemical shifts in both spectral systems. Table-1. The products formed by the reaction of 4.7-Dihydro-l,3-dioxepin derivatives with DMDM. Reagents Products CH, HCrOC2^ OQtt HsCOzCO HC-OC^ Hjco^j C-QQ,^ CQaO-fe (VO) XI Table- 1. The products formed by the reaction of 4.7-Dihydro-l,3-dioxepin derivatives with DMDM. (Continued) Reagents Products ru Ph I CH- CH3 - CH3 -CH3 (H) w oc ~ (-> p-CIPh- c - CH J o o - s A lot of products were observed and it was not possible to separate them. Xll 2,2-dimethyl-4,7-dihydro-l,3-dioxepin gave only cis and trans cyclopropanated product. The products derivated from the [2,3]-sigmatropic shifts and Stevens rearrangement were not determined. From the reaction of 2-(l-phenyl ethyl)-l,3- dioxepin with DMDM, the products by the C-0 insertion of CH2-0 bond and cyclopropanation, in the yields of 30% and 70% respectively were obtained. 1,2-shift reaction (C-0 insertion) was occured in only O-CH2 bond as mentioned before, different from the O-C-O insertion product obtained from the reaction 2-methyl-l,3- dioxepin and DMDM. When studied started with the 10-fenil-l,6-dioxa-spiro(5,6)- dodec-3-en under the same experimental conditions, no dedectable amount of any insertion or addition products were obtained. Starting 1,3-dioxepin was not reacted with DMDM and recovered. Treatment of 2-(4-chloro-benzoyl)- 1,3-dioxepin with DMDM, gave such a completely resinous product mixture that pure substance could not be obtained by even TLC 2-methyl-4,7-dihydro-l,3-dioxepin was treated with potassium tert-butoxide in order to prepare the corresponding cyclic vinyl acetal-4,5-dihydro- 1,3-dioxepin because a notable study about the formation and rearrangements of the probable oxonium ylides derivated from cyclic vinyl acetals was not observed in the literature. This synthesized cyclic vinyl acetal was reacted with DMDM under the same experimental conditions used for 4,7-dihydro-l,3-dioxepins. From the spectral and chromatographic data it could be concluded that 4,7-dihydro-l,3-dioxepin decomposed to acetaldehyde and 2,3-dihydrofuran and these decomposed products reacted with DMDM in different reactions pathways and acetaldehyde formed a carbonyl ylide intermediate, then this intermediate reorganised to a 1,3-dioxalan derivative. As can be seen in Table- 1, steric factors caused the variation in the kinds and also in the ratios of product distribution. If two substituents are located in the C-2 position of 1,3-dioxepin only the cyclopropanated product (VIQ a and VIQ b) can be formed probably because of steric hindrance for the formation of the oxonium ylide. On the other hand if only one substituent is present in the C-2 position of 1.3- dioxepins both cyclo propaneted and C-0 insertion products can be obtained. But, the orientations oxonium of ylide to C-0 insertions are completely different related with the steric bulk of the present single substituent. If the single substituent is a small group like a methyl, C-0 insertion takes place in the only O-CH-0 bond. On the other hand if the substituent is bulky one such as 2-(l-phenyl ethyl)-l,3-dioxepin, C-0 insertion reaction takes part in only 0-CH2 bond.