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1.
An efficient, syn-selective, all catalytic asymmetric protocol for the synthesis of alpha,omega-diheterofunctional deoxypolypropionates via Zr-catalyzed asymmetric carboalumination (ZACA reaction) was developed. The success of the method critically hinges on the one-pot conversion of unprotected allyl alcohol into TBS-protected (R)- or (S)-3-iodo-2-methyl-1-propanol (1) of 91% enantiomeric purity in 82% yield via (i) Zr-catalyzed asymmetric methylalumination, (ii) iodination, and (iii) protection with TBSCl. After zincation of 1, its Pd-catalyzed cross-coupling with various organic halides can give various organic derivatives, including 3 and 4, which can serve as key intermediates for efficient and selective syntheses of deoxypolypropionates, such as doliculide and 2,4,6,8-tetramethyldecanoic acid, and other chiral compounds, such as callystatin A. Selective monocarboalumination of 1,4-pentadiene (5 equiv) gave, after oxidation, the expected product 5, but it was 0% ee. A plausible mechanism for racemization has been proposed and experimentally supported. 相似文献
2.
A highly efficient method for the synthesis of stereochemically pure (>/=99% ee and >50/1 dr) alpha,omega-diheterofunctional reduced polypropionates has been developed. The essential features of the method are represented by the conversion of inexpensive styrene into 2-methyl-4-phenyl-1-pentanol (1) in 50% yield over two steps from styrene via Zr-catalyzed asymmetric carboalumination (ZACA) reaction in the presence of (NMI)2ZrCl2 and Pd-catalyzed vinylation of the in situ generated isoalkylalanes in the presence of Zn(OTf)2 and a catalytic amount of Pd(DPEphos)Cl2. This ZACA-Pd-catalyzed vinylation may be repeated as needed without purification. After the final ZACA reaction, oxidation with O2 provides alpha-hydroxy-omega-phenyl reduced polypropionates, which can be fully or partially purified by chromatography. After acetylation, Ru-catalyzed oxidative cleavage of the Ph ring, and reduction with BH3.THF, the second chromatographic purification provides stereoisomerically pure alpha,omega-diheterofunctional reduced polypropionates (e.g., 9 and 11) that can be further converted to key intermediates 6 and 7 for the synthesis of ionomycin (4) and borrelidin (5), respectively, by known reactions. 相似文献
3.
The ZACA reaction has been shown to proceed satisfactorily with internally OH-substituted 1-alkenes, provided that the OH group is unprotected and non-allylic. This reaction was used for reagent-controlled asymmetric construction of 3. Allylic alcohol was converted to 2 in seven steps via iterative ZACA processes and simple chromatography. (-)-Spongidepsin (1) was synthesized by using 2 and 3 through application of the esterification-amidation-ring-closing metathesis protocol previously reported. 相似文献
4.
[structure: see text]. A highly efficient and stereoselective protocol for the syntheses of symmetrical and unsymmetrical carotenoids involving Zr-catalyzed carboalumination of conjugated oligoenynes and Pd- and Zn-catalyzed alkenyl-alkenyl coupling has been developed and applied to the syntheses of beta- and gamma-carotene and vitamin A. gamma-Carotene of > or =99% isomeric purity was prepared in three linear steps (five steps overall) from beta-ionone, enyne 8, (E)-ICH=CHBr, and (E)-Me3SiC triple bond CCH=CHBr in 32% overall yield. 相似文献
5.
[reaction: see text] (+)-Epolactaene was synthesized in 14 steps in the longest linear sequence. The synthesis is highlighted by a highly efficient preparation of the lactone intermediate 4, which only requires three steps from the commercially available (S)-3-butyn-2-ol. It also features a fully stereocontrolled synthesis of the intermediate 9, which was constructed through the use of Zr-catalyzed methylalumination of alkynes and a series of Pd-catalyzed organozinc cross-coupling reactions, such as homopropargylation, direct ethynylation, and alkenylation of the methyl ester of (Z)-alpha-iodocrotonic acid (3). 相似文献
6.
Enantioselective Synthesis of Chiral Isotopomers of 1‐Alkanols by a ZACA–Cu‐Catalyzed Cross‐Coupling Protocol
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Dr. Shiqing Xu Akimichi Oda Prof. Dr. Ei‐ichi Negishi 《Chemistry (Weinheim an der Bergstrasse, Germany)》2014,20(49):16060-16064
Chiral compounds arising from the replacement of hydrogen atoms by deuterium are very important in organic chemistry and biochemistry. Some of these chiral compounds have a non‐measurable specific rotation, owing to very small differences between the isotopomeric groups, and exhibit cryptochirality. This particular class of compounds is difficult to synthesize and characterize. Herein, we present a catalytic and highly enantioselective conversion of terminal alkenes to various β and more remote chiral isotopomers of 1‐alkanols, with ≥99 % enantiomeric excess (ee), by the Zr‐catalyzed asymmetric carboalumination of alkenes (ZACA) and Cu‐catalyzed cross‐coupling reactions. ZACA‐in situ iodinolysis of allyl alcohol and ZACA‐in situ oxidation of TBS‐protected ω‐alkene‐1‐ols protocols were applied to the synthesis of both (R)‐ and (S)‐difunctional intermediates with 80–90 % ee. These intermediates were readily purified to provide enantiomerically pure (≥99 % ee) compounds by lipase‐catalyzed acetylation. These functionally rich intermediates serve as very useful synthons for the construction of various chiral isotopomers of 1‐alkanols in excellent enantiomeric purity (≥99 % ee) by introducing deuterium‐labeled groups by Cu‐catalyzed cross‐coupling reactions without epimerization. 相似文献
7.
Synthesis of isoxazoline N-oxides and its application in the formal synthesis of dehydroclausenamide
A protocol for the synthesis of isoxazoline N-oxides and its application in the formal synthesis of dehydroclausenamide are described. Sulfonium salt 1 reacts with substituted nitroalkenes smoothly to generate isoxazoline N-oxides in high to excellent yields with dr higher than 99/1. Its asymmetric version has been developed by using cinchona alkaloid-derived ammonium salts 6a and 6b instead of sulfonium salt 1 and higher than 96% ee values are achieved. This method has also been successfully applied to the formal synthesis of dehydroclausenamide. 相似文献
8.
A mechanism based on Michaelis-Menten kinetics with competitive inhibition is proposed for both the Zr-catalyzed carboalumination of α-olefins and the Zr-catalyzed chain growth of aluminum alkyls from ethylene. AlMe(3) binds to the active catalyst in a rapidly maintained equilibrium to form a Zr/Al heterobimetallic, which inhibits polymerization and transfers chains from Zr to Al. The kinetics of both carboalumination and chain growth have been studied when catalyzed by [(EBI)Zr(μ-Me)(2)AlMe(2)][B(C(6)F(5))(4)]. In accord with the proposed mechanism, both reactions are first-order in [olefin] and [catalyst] and inverse first-order in [AlR(3)]. The position of the equilibria between various Zr/Al heterobimetallics and the corresponding zirconium methyl cations has been quantified by use of a Dixon plot, yielding K = 1.1(3) × 10(-4) M, 4.7(5) × 10(-4) M, and 7.6(7) × 10(-4) M at 40 °C in benzene for the catalyst species [rac-(EBI)Zr(μ-Me)(2)AlMe(2)][B(C(6)F(5))(4)], [Cp(2)Zr(μ-Me)(2)AlMe(2)][B(C(6)F(5))(4)], and [Me(2)C(Cp)(2)Zr(μ-Me)(2)AlMe(2)][B(C(6)F(5))(4)] respectively. These equilibrium constants are consistent with the solution behavior observed for the [Cp(2)Zr(μ-Me)(2)AlMe(2)][B(C(6)F(5))(4)] system, where all relevant species are observable by (1)H NMR. Alternative mechanisms for the Zr-catalyzed carboalumination of olefins involving singly bridged Zr/Al adducts have been discounted on the basis of kinetics and/or (1)H NMR EXSY experiments. 相似文献
9.
Dr. Shiqing Xu Akimichi Oda Dr. Thomas Bobinski Dr. Haijun Li Yohei Matsueda Prof. Dr. Ei‐ichi Negishi 《Angewandte Chemie (International ed. in English)》2015,54(32):9319-9322
A new strategy for highly concise, convergent, and enantioselective access to polydeoxypropionates has been developed. ZACA‐Pd‐catalyzed vinylation was used to prepare smaller deoxypropionate fragments, and then two key sequential Cu‐catalyzed stereocontrolled sp3–sp3 cross‐coupling reactions allowed convergent assembly of smaller building blocks to build‐up long polydeoxypropionate chains with excellent stereoselectivity. We employed this strategy for the synthesis of phthioceranic acid, a key constituent of the cell‐wall lipid of Mycobacterium tuberculosis, in just 8 longest linear steps with full stereocontrol. 相似文献
10.
WANG Zhe 《高等学校化学研究》2001,17(3)
Part 1: A highly enantio-and diastereoselective Ireland-Claisen rearrangement of chiral C3(acyloxy)-vinyl silanes for the synthesis of anti-disubstituted succinic acid, an important intermediate for matrix metalloprotease inhibitors, has been developed (enantio-and anti/syn selectivities up to 95% and 38/1). The diastereoselectivity of this reaction was found to be sensitive to remote hydroxyl protecting groups, for example, with-OMOM group, the anti/syn ratio was 19/1, while with-OTBDMS, the ratio was 38/1. The resultant Ireland-Claisen rearrangement product was applied to the synthesis of macrocyclic MMP inhibitors, such as SL 422. 相似文献
11.
Soumitra Maity 《Tetrahedron》2009,65(45):9202-7242
A direct route for the synthesis of highly functionalized angularly substituted hydrindanes has been developed. The key step involves RO-RCM of an appropriately functionalized norbornene derivative. The hydrindane derivative obtained in this way has been used to accomplish a formal synthesis of bakkenolide-A. This protocol has also been extended for the synthesis of an advanced intermediate to the synthesis of the diterpene umbellactal. 相似文献
12.
Ramachandran PV Prabhudas B Chandra JS Reddy MV 《The Journal of organic chemistry》2004,69(19):6294-6304
Diastereoselective dihydroxylation of dihydropyranones and subsequent regioselective alpha-deoxygenation provides 1,3-trans-beta-hydroxy-delta-lactones stereoselectively. This protocol has been applied for the synthesis of C(1)-C(8) and C(15)-C(21) subunits of (+)-discodermolide. 相似文献
13.
Negishi E 《Dalton transactions (Cambridge, England : 2003)》2005,(5):827-848
Systematic explorations of organozirconium chemistry over the past quarter of a century have led to the discoveries and development as well as structural and mechanistic clarifications of novel Zr-catalyzed and -promoted carbon-carbon bond-forming reactions including (i) Ni- or Pd-catalyzed cross-coupling reaction of organozirconiums, (ii) Zr-catalyzed carboalumination of alkynes, (iii) Zr-catalyzed asymmetric carboalumination of alkenes, (iv) generation and carbometallative ring expansion of zirconacyclopropanes and zirconacyclopropenes and a myriad of their transformations and (v) various organozirconium migratory insertion reactions. 相似文献
14.
Shiqing Xu Akimichi Oda Thomas Bobinski Haijun Li Yohei Matsueda Ei‐ichi Negishi 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2015,127(32):9451-9454
A new strategy for highly concise, convergent, and enantioselective access to polydeoxypropionates has been developed. ZACA‐Pd‐catalyzed vinylation was used to prepare smaller deoxypropionate fragments, and then two key sequential Cu‐catalyzed stereocontrolled sp3–sp3 cross‐coupling reactions allowed convergent assembly of smaller building blocks to build‐up long polydeoxypropionate chains with excellent stereoselectivity. We employed this strategy for the synthesis of phthioceranic acid, a key constituent of the cell‐wall lipid of Mycobacterium tuberculosis, in just 8 longest linear steps with full stereocontrol. 相似文献
15.
Nucleophilic N-heterocyclic carbenes have been conveniently used as catalyst modifiers in amination reactions involving aryl chlorides, aryl bromides, and aryl iodides with various nitrogen-containing substrates. The scope of a coupling process using a Pd(0) or Pd(II) source and an imidazolium salt in the presence of a base, KO(t)Bu or NaOH, was tested using various substrates. The Pd(2)(dba)(3)/IPr.HCl (1, IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) system presents the highest activity with respect to electron-neutral and electron-rich aryl chlorides. The ligand is also effective for the synthesis of benzophenone imines, which can be easily converted to the corresponding primary amines by acid hydrolysis. Less reactive indoles were converted to N-aryl-substituted indoles using as supporting ligand the more donating SIPr.HCl (5, SIPr = 1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene). The Pd(OAc)(2)/SIPr.HCl/NaOH system is efficient for the N-arylation of diverse indoles with aryl bromides. The general protocol developed has been applied successfully to the synthesis of a key intermediate in the synthesis of an important new antibiotic. Mechanistically, palladium-to-ligand ratio studies strongly support an active species bearing one nucleophilic carbene ligand. 相似文献
16.
A short, high yielding protocol has been developed for the enantioselective and general synthesis of C2-functionalized, benzyl protected morpholines and orthogonally N,N'-protected piperazines from a common intermediate. 相似文献
17.
Girish PrabhuV.V. Sureshbabu 《Tetrahedron letters》2012,53(32):4232-4234
A simple protocol for the synthesis of 2-amino-1,3,4-oxadiazoles starting from the corresponding acylhydrazides by cyclodesulfurization of intermediate acylthiosemicarbazides mediated by o-iodoxybenzoic acid in good yields has been described. The protocol is mild with wide substrate scope, and thus a range of 2-amino-1,3,4-oxadiazoles have been prepared. 相似文献
18.
[formula: see text] The first total synthesis of (+)-thiazinotrienomycin E (1), member of a novel class of cytotoxic ansamycin antibiotics, has been achieved. The synthesis features a highly efficient construction of the aromatic fragment 3 incorporating TBS protection of the aniline, a significantly improved synthesis of (-)-19, an intermediate employed in our trienomycins A and F total syntheses, application of the Kocienski modified Julia protocol to elaborate the E,E,E-triene subunit, an efficient union of 3 and (+)-4, and Mukaiyama macrolactamization to access the thiazinotrienomycin macrolide. 相似文献
19.
An efficient method for acylation of isoquinolines has been developed using α-ketoacids under metal- and additive-free conditions in water. The protocol involves C(sp2)H functionalization of isoquinolines providing an easy access to C1-benzoylated isoquinolines, which constitute the core structure of a number of biological active compounds and serve as key intermediate in the synthesis of many alkaloids. 相似文献
20.
Efficient and highly regioselective direct C-2 arylation of azoles, including free (NH)-imidazole, -benzimidazole and -indole, with aryl halides 总被引:1,自引:0,他引:1
Fabio Bellina 《Tetrahedron》2007,63(9):1970-1980
The Pd- and Cu-mediated reaction of a large variety of π-electron sufficient heteroarenes, which include free (NH)-imidazoles, -benzimidazole and -indole, with aryl iodides under ligandless and base-free conditions provides regioselectively the required 2-arylheterocycle derivatives in high yields. 2-Aryl-1-phenyl-1H-imidazoles can also be prepared by a one-pot domino HALEX and Pd- and Cu-mediated arylation reactions of 1-phenyl-1H-imidazole with activated and unactivated aryl bromides under base-free and ligandless conditions. The protocol for the synthesis of 2-arylazoles involving the use of aryl iodides has been found to be suitable for the efficient preparation of three bioactive compounds and a key intermediate in the synthesis of a heparanase inhibitor. 相似文献