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1.
[reaction: see text] A biosynthetic proposal for ring formation in the antitumor agent halichomycin is presented in which macrocyclization of the putative prehalichomycin intermediate 1 is the first step. Compound 2 then undergoes dehydration to the alpha-keto N-acylimine 3 followed by tandem nucleophilic addition of the C(16)-hydroxyl to form the hemimacrolactam. A stereospecific Michael ring closure and enol protonation complete C-ring assembly. So far, synthetic efforts toward 1 have resulted in 8. 相似文献
2.
It has been experimentally reported that PMe(3) catalyzes the cycloalkylation of the pendant halogenated α,β-unsaturated ketones (e.g., 1) at the C(α) position, whereas NHC catalyzes the cycloalkylation of the pendant halogenated α,β-unsaturated esters (e.g., 2) at the C(β) position. A DFT study has been performed to understand the detailed reaction mechanisms and the causes for the different ring closure positions in the two cycloalkylations promoted by the similar catalysts. Both reactions undergo three stages that include the nucleophilic addition of the catalysts (PMe(3) or NHC) to the substrates (1 or 2) and subsequent ring closure via S(N)2 mechanism, the H-elimination by the bases (KOH or K(3)PO(4)), and the catalyst release giving the final products. The first stage in the NHC-catalyzed reaction involves a favorable H-transfer step leading to the umpolung Michael acceptor, which is more stable than the nucleophilic addition complex. The H-transfer turns off the possibility to close ring at C(α) position for the reaction. In contrast, the similar H-transfer in the PMe(3)-catalyzed reaction is thermodynamically unfavorable. According to the electronic structure of the addition complex of PMe(3) to substrate (1), we rationalize why the experimentally isolated intermediate in the PMe(3)-catalyzed reaction is the trans-cyclic ketophosphonium salt, rather than its cis isomer that favors electrostatic attraction. The differences and the similarities among the two reactions and the traditional MBH reaction are discussed. 相似文献
3.
Several spiroperoxy antimalarial compounds were designed and synthesized using the hydrogen peroxide in UHP (urea-H2O2 complex) as the source of the peroxy bond. Incorporation of the H2O2 into the organic molecule framework through ketal exchange reaction in the present cases was greatly facilitated by the potential to form a five- or six-membered cyclic hemiketal due to the presence of a hydroxyl group γ or δ to the ketone carbonyl group. When the electron-withdrawing group in the Michael acceptor was a nitro group, the closure of the peroxy ring occurred readily under the hydroxidation conditions. Presence of a benzene ring fused to the peroxy ring effectively reduced the degrees of freedom in the transition state for the ring-closure step and made the otherwise very difficult seven-membered 1,2-dioxepane rather easy to form through the intramolecular Michael addition. 相似文献
4.
5.
Qi Zhang 《Tetrahedron》2006,62(50):11627-11634
Bicyclo[3.2.1] type 1,2,4-trioxanes are readily synthesized from precursors that may form intramolecular hemiketals using UHP (H2O2-urea complex) as the source of the peroxy bond and p-TsOH or CSA as the catalyst. The ring closure through an intramolecular Michael addition occurred in a highly stereoselective way, giving only one diasteromer as shown by the NMR spectra. 相似文献
6.
Trost BM Yang H Brindle CS Dong G 《Chemistry (Weinheim an der Bergstrasse, Germany)》2011,17(35):9777-9788
This article describes chemoselective and atom-economic methods for the stereoselective assembly of the ring A and B subunits of bryostatins. A Ru-catalyzed tandem alkene-alkyne coupling/Michael addition reaction was developed and applied to the synthesis of bryostatin ring B. We explored an acetylide-mediated epoxide-opening/6-exo-dig cyclization route to access the bryostatin ring A, although ring A was eventually furnished through an acid-catalyzed tandem transketalization/ketalization sequence. In addition, a dinuclear zinc-catalyzed methyl vinyl ketone (MVK) aldol strategy was evaluated for the construction of the polyacetate moiety. Utilization of these methods ultimately led to the rapid assembly of the northern bryostatin fragment containing both the ring A and B subunits. 相似文献
7.
Bart Vanderhoydonck 《Tetrahedron》2007,63(32):7679-7689
Syntheses of 5-phosphono-2-oxazolidinones and 5-phosphono-2-imidazolidinones were achieved from the corresponding 1-vinyl-2-phosphonoaziridines. Regioselective aziridine ring opening employing methyl chloroformate affords 1-amido-2-chloroethylphosphonates, which were easily transformed into the corresponding 2-oxazolidinones upon heating in dimethyl sulfoxide. Treatment of the aziridine ring opening products with ammonia furnishes vinylphosphonates, which undergo a Michael type addition with several amines. In situ ring closure of the addition products yields the corresponding phosphonylated 2-imidazolidinones. 相似文献
8.
Dialkyl amides of L-valine, L-isoleucine, and L-tert-leucine (2) are excellent chiral auxiliaries for the construction of quaternary stereocenters at ambient temperature. Enaminoesters 3, prepared from these auxiliaries 2 and Michael donors 1, undergo a copper-catalyzed asymmetric Michael reaction with methyl vinyl ketone (MVK, 4) to afford products 5 in 70-90% yield and 90-99% ee (enantiomeric excess). The exclusion of moisture or oxygen is not necessary. The auxiliaries 2 are readily available by standard procedures. After workup they can be recovered almost quantitatively. 相似文献
9.
E. V. Suslov D. V. Korchagina K. P. Volcho N. F. Salakhutdinov 《Chemistry of Heterocyclic Compounds》2009,45(5):560-566
The application of the basic zeolite Csβ as catalyst for the interaction of methyl vinyl ketone (MVK) with 5-methoxybenzimidazole-2-thiol
leads to a Michael heteroreaction exclusively at the N-nucleophilic center with the formation of a fairly unusual product
of di-addition of MVK to thiol. The reaction of 1,2,4-triazole-3-thiol with MVK in the presence of zeolite Csβ proceeds both
at the S- and also at the N-nucleophilic center and leads to the formation of products of mono- and diaddition according to
Michael, and also to the product of heterocyclization. On interacting crotonaldehyde with salicylaldehyde in the presence
of Csβ 2-methyl-2H-chromene-3-carbaldehyde is formed. 相似文献
10.
The nitrovinyl-substituted quinones 2-(2-nitrovinyl)-1,4-benzoquinone and 2-(2-nitrovinyl)-1,4-naphthoquinone react with a variety of cyclic and acyclic enol ethers via two competing pathways. In one pathway, the nitrovinylquinone acts as an inverse electron-demand [4 + 2] diene. This gives quinoid carbocycles, which readily tautomerize to their hydroquinone form. The other pathway involves conjugate (Michael) addition of the enol ether to the nitrovinylquinone, followed by ring closure. This gave dihydrobenzofurans, which can eliminate an alcohol to give benzofurans. Hindered enol ethers tended to favor the conjugate addition pathway, while less hindered enol ethers favored cycloaddition. 相似文献
11.
[structure: see text] The synthesis of the A,B,C-ring system (2) of hexacyclinic acid (1) is achieved starting from a selective Diels-Alder reaction followed by vinyl cuprate addition. The diastereoselective reduction of the ketone carbonyl at C16 could be achieved with LiAlH(4). An intramolecular Michael addition established the ring system stereoselectively, providing access to the selective generation of 9 out of the 14 stereocenters of hexacyclinic acid. 相似文献
12.
Xiaohui Du 《Tetrahedron letters》2004,45(48):8843-8846
The six membered ring of guanacastepene A was constructed by a Diels-Alder reaction of 1,1,4-trisubstituted diene to set up the correct relative stereochemistry at the C8 quaternary center and the remote C5 stereocenter. In 10 efficient steps from the Diels-Alder adduct 9, the desired highly functionalized [5-7-6] tricyclic skeleton 2 was synthesized. Key steps involve trimethylsilyl chloride (TMSCl) assisted Michael addition to form enol ether and the usage of the enol ether in the following intramolecular Mukaiyama aldol reaction to form the middle seven membered ring of guanacastepene A. 相似文献
13.
Anthony J. Nocket Prof. Dr. Steven M. Weinreb 《Angewandte Chemie (International ed. in English)》2014,53(51):14162-14165
The first total synthesis of the tetracyclic antimalarial Myrioneuron alkaloid (±)‐myrioneurinol has been accomplished using three highly diastereoselective reactions as pivotal steps: 1) an intramolecular Michael addition of a benzyloxycarbonyl‐protected lactam titanium enolate to an α,β‐unsaturated ester for construction of the spirocyclic C5 quaternary center and the a/d rings, 2) a malonate anion conjugate addition to a transient nitrosoalkene to install the requisite functionality and configuration at the C7 position, and 3) an intramolecular sulfonyliminium aza‐Sakurai reaction to form the b ring and the attendant C9/C10 configuration of the natural product. 相似文献
14.
The chiral nitrogen Lewis base, tricyclic cinchona alkaloid derivative TQO, is an effective promoter in the catalytic, asymmetric aza‐Baylis–Hillman reaction of N‐sulfonated imines Ar? CH?NR′ 1 (R′ = Ts, Ms, Ns, SES) with various activated olefins such as methyl vinyl ketone (MVK), ethyl vinyl ketone (EVK), acrolein, methyl acrylate, phenyl acrylate, or α‐naphthyl acrylate to give the corresponding adducts in moderate to good yields with good to high ee (up to 99 %) at ?30 °C or 45 °C in various solvents, including DMF/MeCN (1:1, v/v). The first such reaction of 1 with the simplest Michael acceptor MVK and methyl acrylate has been achieved with excellent enantioselectivity. The adducts derived from MVK and EVK had the opposite absolute configuration to those from acrolein, methyl acrylate, phenyl acrylate, and α‐naphthyl acrylate. A plausible mechanism has been proposed on the basis of previous reports and the authors’ investigations. An effective bifunctional chiral nitrogen Lewis base–Brønsted acid system has been revealed in this type of aza‐Baylis–Hillman reaction. 相似文献
15.
Total synthesis of natural and unnatural lamellarins with saturated and unsaturated D-rings 总被引:1,自引:0,他引:1
Ploypradith P Petchmanee T Sahakitpichan P Litvinas ND Ruchirawat S 《The Journal of organic chemistry》2006,71(25):9440-9448
Twenty-eight natural and unnatural lamellarins with either a saturated or an unsaturated D-ring were synthesized according to our developed synthetic route. The key step involved the Michael addition/ring closure (Mi-RC) of the benzyldihydroisoquinoline and alpha-nitrocinnamate derivatives, which provided the 2-carboethoxypyrrole intermediates in moderate to good yields (up to 78% yield). Subsequent hydrogenolysis/lactonization furnished lamellarins with a saturated D-ring in excellent yields (up to 93% yield). DDQ oxidation of the saturated lamellarin acetates led directly to the corresponding unsaturated analogues in 54-95% yield. In addition, only two steps in our developed strategy require column chromatography. 相似文献
16.
Valrie Braud Laurent Businelli Yves Gnanou Bernard Maillard 《Macromolecular rapid communications》2000,21(13):901-904
The polymerisation of styrene in the presence of methyl vinyl ketone (MVK) and triethylborane (BEt3)was studied. The mixture of these two compounds was found to form a bicomponent complex that functions as a transfer agent for growing polystyryl radicals (CT = 0.7; benzene, 60 °C). The analysis of the polymer chains formed by MALDI‐TOF‐MS showed that they were fitted with CH2—CH3 and CH2—CH2—C(O)—CH3 as end groups which obviously emanated from MVK and BEt3. In contrast, no such transfer occurred on using each of them as single compound. 相似文献
17.
Maya CM Cámpora J Carmona E Matas I Palma P Gutiérrez-Puebla E Monge A 《Chemistry (Weinheim an der Bergstrasse, Germany)》2007,13(13):3675-3687
The reaction of nickel enolates displaying a metallacyclic structure with the alpha,beta-unsaturated ketones methyl vinyl ketone (MVK) or methyl propenyl ketone (MPK) takes place in two stages, affording initially bicyclic adducts, which subsequently isomerize to the corresponding open-chain products. The former are generated with high stereoselectivity and can be considered as the products of the [2+4] cycloaddition of the enolate to the enone. The ring opening process involves a prototropic rearrangement that can be catalyzed by water. In the case of the reaction of the parent nickel enolate complex 1 (which displays an unsubstituted Ni-O=C(R)CH2 arrangement) with MVK, a double-addition process has been observed, consisting of two successive cycloaddition/isomerization reactions. The carbonylation of the different cyclic and noncyclic products affords the corresponding lactones that retain the stereochemistry of the organometallic precursors. This methodology allowed trapping the primary product of the reaction of 1 with MPK as the corresponding organic lactone, demonstrating that the cycloaddition process takes place with exo selectivity. DFT modeling of the latter reaction provides further support for a quasi-concerted cycloaddition mechanism, displaying a nonsymmetric transition state in which the C-C and the C-O bond are formed in an asynchronous manner. 相似文献
18.
Gury Zvilichovsky Mordechai David Eliahu Nemes 《Journal of heterocyclic chemistry》1980,17(2):299-304
4-Aryl-3,5-dihyroxyisoxazoles which are strong organic acids add spontaneously to mesityl oxide to form 4-aryl-2-(1,1-dimethyl-3-oxobutyl)isoxazolidine-3,5-dione. This reaction was found to be reversible and the equilibrium is solvent dependent. These acids add to 2 moles of methyl vinyl ketone. The adducts obtained from mesityl oxide undergo ketalization to form derivatives of 2H,7H-isoxazolo[3,2-b][1,3]oxazine on exposure to alcohols. The rate of this ring closure reaction is dependent on the nature of the alcohol and on the nature of the substituent on the phenyl group which is at position 4 of the isoxazole ring. The mechanisms of the non catalyzed Michael addition and of the ketalization reaction are discussed. The structure of the polymers which are obtained by the reaction of phenyldisic acids with acrolein and crotonaldehyde is also discussed. 相似文献
19.
20.
P. V. Gushchin M. Haukka N. A. Bokach V. Yu. Kukushkin 《Russian Chemical Bulletin》2008,57(10):2125-2131
The reaction of the trans-[PtCl4(EtCN)2] complex with diphenylguanidine (DPG) in a molar ratio of 1: 2 proceeds via the nucleophilic addition of DPG to coordinated nitrile and the coordination of DPG to the metal center to form the [PtCl4{NH=C(NHPh)2}{NH=C(Et)-N=C(NHPh)2}] complex with the open-chain 1,3,5-triazapentadiene ligand. The latter undergoes chelation in solution (84 h, 50 °C, CDCl3), and the ring closure is accompanied by the replacement of the coordinated chloride and the formation of the cationic complex
[PtCl3{NH=C(NHPh)2}{NH=C(Et)NHC(NHPh)=NPh}](Cl). The reaction of the trans-[PtCl4(EtCN)2] complex with DPG in a molar ratio of 1: 4 affords the [PtCl3{NH=C-(NHPh)2}{NH=C(Et)NC(NHPh)=NPh}] complex with the chelating 1,3,5-triazapentadienate ligand. 相似文献