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1.
Frankowski KJ Golden JE Zeng Y Lei Y Aubé J 《Journal of the American Chemical Society》2008,130(18):6018-6024
A tandem Diels-Alder/azido-Schmidt reaction sequence provides rapid access to the core skeleton shared by several Stemona alkaloids including stenine, neostenine, tuberostemonine, and neotuberostemonine. The discovery and evolution of inter- and intramolecular variations of this process and their applications to total syntheses of (+/-)-stenine and (+/-)-neostenine are described. The stereochemical outcome of the reaction depends on both substrate type and reaction conditions, enabling the preparation of both (+/-)-stenine and (+/-)-neostenine from the same diene/dienophile combination. 相似文献
2.
A series of 2-(methylthio)-5-amidofurans containing tethered unsaturation were prepared via the reaction of dimethyl(methylthio)sulfonium tetrafluoroborate (DMTSF) with beta-alkoxy-gamma-dithiane amides 13-16 and 27-32 in 40-70% yield. Thermolysis of these furans resulted in an intramolecular Diels-Alder reaction (IMDAF). With the exception of 45 and 46, the oxa-bridged cycloadducts could not be isolated but immediately underwent a 1,2-methylthio shift to form bicyclic lactams in 60-100% yield. It was determined that incorporation of the amido carbonyl in the tether allowed the IMDAF reaction to proceed at a lower temperature. A dramatic example of this is seen in the IMDAF reaction of furan 35, in which the presence of an amido carbonyl as part of the dienophile tether, as opposed to the annealed ring (66) or the lack of a carbonyl (67), was necessary for the cycloaddition to occur. Furan 37, annealed to an azepine ring, underwent the IMDAF reaction at or below room temperature. To identify structural features that promote the IMDAF reaction, a computational study was undertaken. Ground-state and transition-state energies were calculated for furans 17, 33, 37, and 64 using the Becke 3LYP/6-31G model. The theoretical results were in good agreement with those observed. The results indicate that the incorporation of an amide carbonyl as part of the tether system works to place the dienophile in closer proximity to the furan ring, thereby lowering the activation energy needed to reach the transition state. 相似文献
3.
The total synthesis of several members of the hydroxylated phenanthridone subclass of the Amaryllidaceae alkaloid family has been carried out. (+/-)-Lycoricidine and (+/-)-7-deoxypancratistatin were assembled through a one-pot Stille/intramolecular Diels-Alder cycloaddition cascade to construct the core skeleton. The initially formed [4+2]-cycloadduct undergoes nitrogen-assisted ring opening followed by a deprotonation/reprotonation of the resulting zwitterion to give a rearranged hexahydroindolinone on further heating at 160 degrees C. The stereochemical outcome of the IMDAF cycloaddition has the side arm of the tethered vinyl group oriented exo with respect to the oxygen bridge. The resulting cycloadduct was used for the stereocontrolled installation of the remaining functionality present in the C-ring of the target molecules. Key features of the synthetic strategy include (1) a lithium hydroxide induced tandem hydrolysis/decarboxylation/elimination sequence to introduce the required pi-bond in the C-ring of (+/-)-lycoricidine, and (2) conversion of the initially formed Diels-Alder adduct into an aldehyde intermediate which then undergoes a stereospecific decarbonylation reaction mediated by Wilkinson's catalyst to set the trans-B-C ring junction of (+/-)-7-deoxypancratistatin. 相似文献
4.
[reaction: see text]. The intramolecular [4 + 2]-cycloaddition of a 2-methylthio-5-amidofuran was used to create the azepinoindole skeleton present in the Stemona alkaloid stenine. The rearranged cycloadduct was converted to stenine (1) in 11 additional steps via a sequence that features a Crabtree catalyst directed hydrogenation (9-->10), iodolactonization (2-->11), and a Keck allylation (11-->12). 相似文献
5.
The intramolecular Diels-Alder reaction of 2-substituted aminofurans (IMDAF) results in the formation of various indolines and tetrahydroquinolines. The isolation of these ring systems from the IMDAF reaction can be rationalized in terms of an initial [4 + 2]-cycloaddition that first produces an oxa-bridged cycloadduct, which was not detected since it readily underwent nitrogen-assisted ring opening. Proton exchange followed by an eventual dehydration provides the aromatic product. In certain cases, the intermediate cyclohexadienol can be isolated and independently converted to the final product in high yield. The starting 2-aminofurans were readily prepared from furanyl acyl azide by a Curtius rearrangement in the presence of an alcohol. Alkylation of the resulting N-alkyl carbamate with an alkenyl bromide allows for the synthesis of a wide variety of cycloaddition precursors. The scope of the IMDAF reaction was evaluated by using mono- and disubstituted alkenes, electron rich and electron deficient olefins, and acetylenic tethers. Cyclic 2-amidofurans were also synthesized using a related intramolecular Diels-Alder reaction of 2-amido-substituted oxazoles which contain a tethered alkyne. This transformation represents a new route to this rare heterocyclic ring system. The sequential cycloaddition method was used for a formal synthesis of the pyrrolophenanthridone alkaloid hippadine. 相似文献
6.
A convenient synthesis of various substituted hexahydroindolinones has been achieved by an intramolecular Diels--Alder cycloaddition reaction (IMDAF) of furanyl carbamates bearing tethered alkenyl groups. The initially formed [4 + 2]-cycloadduct undergoes nitrogen-assisted ring opening followed by deprotonation of the resulting zwitterion to give the rearranged ketone. The stereochemical outcome of the IMDAF cycloaddition has the sidearm of the tethered alkenyl group oriented syn with respect to the oxygen bridge. A synthetic route to (+/-)-mesembrane and (+/-)-crinane was accomplished using this methodology. It was possible to carry out a stereoselective reduction of the initially formed hexahydroindolinone ring to produce the cis-3a-aryl-hydroindole skeleton. A related [4 + 2]-cycloaddition/rearrangement sequence was also used for a formal synthesis of the Chinese ornamental orchid (+/-)-dendrobine. The tricyclic alkaloid core was formed stereoselectivity from the thermolysis of N-[(2-methyl-2-cyclopentenyl)methyl]-N-(4-isopropyl-furan-2-yl)carbamic acid tert-butyl ester. Kende's advanced intermediate 33 was prepared in seven additional steps by standard transformations, thereby completing a formal synthesis of (+/-)-dendrobine. 相似文献
7.
The total syntheses of gamma-lycorane and (+/-)-1-deoxylycorine were accomplished using an intramolecular Diels-Alder cycloaddition of a furanyl carbamate as the key step. The initially formed [4+2]-cycloadduct undergoes nitrogen-assisted ring opening followed by deprotonation/reprotonation of the resulting zwitterion to give a rearranged hexahydroindolinone. The stereochemical outcome of the IMDAF cycloaddition has the side arm of the tethered alkenyl group oriented syn with respect to the oxygen bridge. The key intermediate used in both syntheses corresponds to hexahydroindolinone 20. Removal of the t-Boc group in 20 followed by reaction with 6-iodobenzo[1,3]dioxole-5-carbonyl chloride afforded enamide 22. Treatment of this compound with Pd(OAc)(2) employing the Jeffrey modification of the Heck reaction provided the galanthan tetracycle 24 in good yield. Compound 24 was subsequently converted into (+/-)-gamma-lycorane using a four-step procedure to establish the cis-B,C-ring junction. A radical-based cyclization of the related enamide 33 was used for the synthesis of 1-deoxylycorine. Heating a benzene solution of 33 with AIBN and n-Bu(3)SnH at reflux gave the tetracyclic compound 38 possessing the requisite trans fusion between rings B and C in good yield. After hydrolysis and oxidation of 38 to 40, an oxidative decarboxylation reaction was used to provide the C(2)(-)C(3)(-)C(12) allylic alcohol unit characteristic of the lycorine alkaloids. The resulting enone was eventually transformed into (+/-)-1-deoxylycorine via known synthetic intermediates. 相似文献
8.
Heteroatom variants of the type 2 intramolecular Diels-Alder reaction provide an efficient method for the preparation of bridged bicyclic heterocycles. The type 2 variant of the intramolecular N-acylnitroso Diels-Alder reaction is an effective method for the synthesis of bridged bicyclic oxazinolactams. Structural studies of the cycloadducts have allowed for quantification of the deformations of the bridgehead functionalities and provided a strategy for the stereoselective synthesis of substituted seven- and eight-membered ring lactams. Diastereoselective cycloadditions followed by cleavage of the oxazine ring afford azepin-2-ones or azocin-2-ones. 相似文献
9.
Several 2-imido substituted furans were found to undergo a rapid intramolecular [4 + 2]-cycloaddition to deliver oxabicyclo adducts in good to excellent yields. By using a Rh(I)-catalyzed ring opening of the resulting oxabicyclic adduct, it was possible to prepare several highly functionalized tetrahydro-1H-indol-2(3H)-one derivatives which were then used to prepare several erythrina alkaloids. By taking advantage of the Rh(I)-catalyzed reaction, it was possible to convert tert-butyl 3-oxo-5-carbomethoxy-10-oxa-2-azatricyclo[5.2.1.0(1,5)]dec-8-ene-2-carboxylate into the ring opened boronate by reaction with phenylboronic acid. Treatment of the boronate with pinacol/acetic acid afforded the corresponding diol which was used in a successful synthesis of racemic 3-demethoxyerythratidinone. During the course of these studies, several novel rearrangement reactions were encountered while attempting to induce an acid-initiated Pictet Spengler cyclization of a key lactam intermediate. The IMDAF/Rh(I)-catalyzed ring opening cascade sequence was also applied to the total synthesis of (+/-)-erysotramidine as well as the lycorine type alkaloid (+/-)-epi-zephyranthine. 相似文献
10.
Fedor I. Zubkov Eugenia V. Nikitina Timur R. Galeev Vladimir P. Zaytsev Victor N. Khrustalev Roman A. Novikov Daria N. Orlova Alexey V. Varlamov 《Tetrahedron》2014
An efficient and versatile one-pot synthesis of 3,6a-epoxyisoindoles annelated with oxazine, oxazole, thiazine, thiazole, pyrimidine fragments and with their benzoannelated analogues is presented. The method is based on tandem N-acylation/intramolecular cycloaddition (the intramolecular Diels–Alder reaction of furan, IMDAF) reaction between α,β-unsaturated acid anhydrides and α-furyl substituted azaheterocycles. The latter can be easily prepared by condensation of diverse furfurals and 1,2- or 1,3-N,X-binucleophiles (aminoalcohols, aminothiols, diamines). The observed IMDAF reaction is stereoselective: exo-adducts are formed exclusively with large prevalence of one of the diastereoisomers. In most cases, the condensation/N-acylation/IMDAF reaction sequence may be carried out via a one-pot domino protocol. The scope and limitations of the proposed approach are thoroughly investigated. The obtained Diels–Alder adducts are attractive and useful substrates for further transformations. Fused isoindoles can be prepared from them in one-step by aromatization of the 7-oxabicyclo[2.2.1]heptene ring. Other transformations, including halogenation, ring cleavage, and Wagner–Meerwein skeletal rearrangement, are also demonstrated. The spatial structures of the obtained compounds have been established by X-ray diffraction analyses. 相似文献
11.
Prof. Dr. Hiromichi Fujioka Kenji Nakahara Naoyuki Kotoku Yusuke Ohba Yasushi Nagatomi Tsung‐Lung Wang Yoshinari Sawama Kenichi Murai Kie Hirano Tomohiro Oki Shintaro Wakamatsu Prof. Dr. Yasuyuki Kita 《Chemistry (Weinheim an der Bergstrasse, Germany)》2012,18(43):13861-13870
A route for the asymmetric synthesis of (?)‐stenine, a member of the Stemona alkaloid family used as folk medicine in Asian countries, is described. The key features of the sequence employed include stereoselective transformations on a cyclohexane ring controlled by a chiral auxiliary unit and an intramolecular Mitsunobu reaction to construct the perhydroindole ring system. By using an intermediate in the route to (?)‐stenine, an asymmetric synthesis of 9a‐epi‐stenine was also executed. The C(9a) stereocenter in 9a‐epi‐stenine was installed by using a Staudinger/aza‐Wittig reaction of a keto–azide precursor followed by reduction of the resulting imine. The results of this effort demonstrate the applicability of the chiral auxiliary based strategy to the preparation of naturally occurring alkaloids that contain highly functionalized cyclohexane cores. 相似文献
12.
The intramolecular Diels-Alder reaction of allenic ketones containing a furyl unit (IMDAF) to generate oxatricyclic systems in good yields is described. The alkene dienophiles 1ab give poor yields of the cycloadducts 2ab, presumably due to the facile retro Diels-Alder reaction. However, the analogous allenic dienophile 7 afforded the desired cycloadduct 8 in 91% yield on treatment with dimethylaluminum chloride. When the allene bears an alkyl substituent on the terminal carbon, complete diastereoselectivity is seen in the IMDAF, e.g. cyclization of 14 gave only the cycloadduct 15 in 80% yield presumably due to greater steric hindrance in the transition state II as compared to that in I. Finally we report complete chirality transfer of the stereochemistry of an allene to the carbon framework of the oxatricyclic system. Thus, the optically active allenic ketone 20 afforded only the desired cycloadduct 21 with the correct absolute stereochemistry needed for the synthesis of the arisugacin class of natural products. 相似文献
13.
[reaction: see text] Chiral precursors to the intramolecular Diels-Alder reaction using furan as a diene (IMDAF) have been prepared by diastereoselective addition of furyllithium to imines attached to perhydro-1,3-benzoxazines derived from (-)-8-aminomenthol. The acylation of the furylamines with alpha,beta-unsaturated acyl chlorides and subsequent IMDAF reaction under thermal conditions provided the corresponding cycloadducts as single diastereoisomers. The hydrolytic elimination of the chiral template yielded enantiopure perhydroepoxyisoindolones with up to five stereocenters. 相似文献
14.
The type two intramolecular Diels-Alder reaction (T2IMDA) is an efficient method for the formation of medium rings. The methodology is particularly effective for the construction of seven- and eight-membered rings. A strategy for the synthesis of functionalized cycloheptanes and cyclooctanes has been developed that involves a bridged to fused ring interchange. The T2IMDA provides a synthesis for rigid bridged bicyclic molecules that can be stereoselectively elaborated before ozonolysis of the bridgehead double bond. Following oxidative cleavage, aldol condensation provides fused bicyclic ring systems that otherwise are difficult to synthesize. This methodology is amenable to the synthesis of terpene natural products. This is demonstrated here through total syntheses of (+/-)-ledol and (+/-)-ledene and a formal synthesis of (+/-)-compressanolide. 相似文献
15.
The results presented here provide additional support for our hypothesis based on the relative basicity of the reaction controlling functional group to rationalize experimental observations on intramolecular Diels-Alder reactions with a furan diene (IMDAF) regarding the quantity (0.1 or 1.1 equiv) of Lewis acid required to facilitate the reaction most effectively. Heats of formation, DeltaH(f), and heats of reaction, DeltaH(R), have been obtained using AM1 calculations for 26 IMDAF reactions. These DeltaH(R) are generally exothermic (indicating that these IMDAF reactions are favorable) and can be qualitatively correlated with experimental yields of adduct, thereby providing a means of predicting the feasibility of the IMDAF promoted by 0.1 equiv of Lewis acid. The equilibria involved in the Lewis acid-promoted IMDAF reaction have been qualitatively interpreted using reaction coordinate diagrams and quantitatively investigated by generating a mathematical simulation of the reaction scheme. This demonstrates that the experimental behavior of the IMDAF reaction is well represented by the relative basicity hypothesis and that the LA concentration-dependent behavior should also be observed for other Lewis acid-promoted organic reactions. 相似文献
16.
Acylation of 4-α-furyl-4-N-benzylaminobut-1-enes with maleic anhydride gave 4-oxo-3-aza-10-oxatricyclo[5.2.1.01,5]dec-8-ene-6-carboxylic acid via amide formation followed by intramolecular Diels-Alder reaction of furan (IMDAF). The cycloaddition proceeded under mild reaction conditions (25 °C) and provided only the exo-adduct in quantitative yield. Treatment of this compound with PPA gave isoindolo[2,1-b][2]benzazepine derivatives via ring opening, aromatization and intramolecular electrophilic alkylation. In order to extend the scope of the reaction sequence, 7-oxo-5,11b,12,13-tetrahydro-7H-isoindolo[2,1-b][2]benzazepine-8-carboxylic acids were further transformed into useful synthetic intermediates. 相似文献
17.
Using an intramolecular [4 + 2] cycloaddition/rearrangement cascade of 3-(1,4-dioxaspiro[4.4]non-7-en-7-yl)-N-furan-2-ylpropionamide (23) as the key step, the BCD core of the lycopodium alkaloid fawcettidine was constructed. Heating the initially formed Diels-Alder cycloadduct at 180 °C results in a nitrogen-assisted ring opening followed by a deprotonation/reprotonation of the ensuing zwitterion to give a rearranged hexahydroindolinone. Our attempts to induce a related intramolecular furan Diels-Alder reaction (IMDAF) from the corresponding ketone of 23 failed to give any cycloaddition product. Instead, the only product obtained corresponded to a cyclopentenone derivative derived by isomerization of the double bond into the thermodynamically more stable α,β-position. Efforts toward construction of the final skeleton of fawcettidine by ring A closure of the rearranged cycloadduct derived from furanyl amide 23 are discussed. 相似文献
18.
The formal synthesis of the alkaloid (+/-)-dendrobine (4) was accomplished using the IMDAF cycloaddition/rearrangement sequence of a furanyl carbamate. Conversion of the rearranged cycloadduct to Kende's advanced intermediate in eight steps completed the formal synthesis of (+/-)-dendrobine. 相似文献
19.
A total synthesis of (+)-quassin from naturally occurring (S)-(+)-carvone is described. The total number of steps was 28, and the overall yield was about 2.6%. The synthetic strategy for the construction of the tetracyclic carbon framework was based on a C-->ABC-->ABCD ring annulation sequence, involving an aldol reaction, an intramolecular Diels-Alder reaction, and an intramolecular acylation as the key steps. Subsequent functionalization of ring A and ring C then afforded the target (+)-quassin. 相似文献
20.
[reaction: see text] A formal synthesis of (-)-apicularen A has been completed. The synthesis features a cyanohydrin acetonide coupling as a convergent approach to the C9-C18 segment and an intramolecular Diels-Alder addition sequence to create both the 10-membered macrocycle and the aromatic ring. 相似文献