- Large-Scale Synthesis of Eldecalcitol
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Industrial-scale synthesis of eldecalcitol is described. AA highly diastereoselective epoxidation of p-methoxybenzyl (PMB) protected dienol at room temperature provides the key epoxide intermediate with a secondary hydroxyl group, which is alkylated with a triflate to set up all of the subunits at the C-1, C-2, and C-3 positions of the A-ring fragment. Selective protecting group manipulation followed by palladium-catalyzed cyclization then provides the A-ring synthon. The C/D-ring fragment is obtained by (1) direct C-H hydroxylation of Grundman's ketone using in situ prepared trifluoropropanone dioxirane and (2) protection. Finally, the coupling of the A-ring with the C/D-ring fragment, global deprotection, and recrystallization provide the highly crystalline eldecalcitol.
- Moon, Hyung Wook,Lee, Seung Jong,Park, Seong Hu,Jung, Se Gyo,Jung, In A.,Seol, Chang Hun,Kim, Seung Woo,Lee, Seon Mi,Gangganna, Bogonda,Park, Seokhwi,Lee, Kee-Young,Oh, Chang-Young,Song, Juyoung,Jung, Jaehun,Heo, Ji Soo,Lee, Kang Hee,Kim, Hae Sol,Lee, Won Taek,Baek, Areum,Shin, Hyunik
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- Total synthesis of 1α,25-dihydroxy-2β-(3-hydroxypropoxy)vitamin D3 (ED-71)
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A convergent method for the synthesis of ED-71 has been developed. Starting from the reported epoxide 5 which could be easily prepared from D-mannitol, ED-71 was synthesized in 11 linear steps with 17% overall yield.
- Deng, Wutong,Gong, Yimou,Pu, Qingyin,Sun, Jian,Wang, Chao,Zhou, Li
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- Synthesis of highly functional carbamates through ring-opening of cyclic carbonates with unprotected α-amino acids in water
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The present work shows that it is possible to ring-open cyclic carbonates with unprotected amino acids in water. Fine tuning of the reaction parameters made it possible to suppress the degree of hydrolysis in relation to aminolysis. This enabled the synthesis of functionally dense carbamates containing alkenes, carboxylic acids, alcohols and thiols after short reaction times at room temperature. When Glycine was used as the nucleophile in the ring-opening with four different five membered cyclic carbonates, containing a plethora of functional groups, the corresponding carbamates could be obtained in excellent yields (>90%) without the need for any further purification. Furthermore, the orthogonality of the transformation was explored through ring-opening of divinylenecarbonate with unprotected amino acids equipped with nucleophilic side chains, such as serine and cysteine. In these cases the reaction selectively produced the desired carbamate, in 70 and 50% yield respectively. The synthetic design provides an inexpensive and scalable protocol towards highly functionalized building blocks that are envisioned to find applications in both the small and macromolecular arena.
- Olsén, Peter,Oschmann, Michael,Johnston, Eric V.,?kermark, Bj?rn
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p. 469 - 475
(2018/02/07)
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- Cyclic allylic carbonates as a renewable platform for protecting chemistry in water
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The present work explores different cyclic allylic carbonates as a potential class of allylcarbamate precursors. The 5-membered carbonate formed a carbamate with very good thermal and pH stability, which could be cleanly deprotected in aqueous solution, in just 30 min with 2 mol% Pd(OAc)2 as catalyst. The polar nature of the installed motif made it possible to deprotect highly unpolar substrates in water as solvent.
- Olsén, Peter,Morvan, Jennifer,Sawadjoon, Supaporn,Shatskiy, Andrey,Johnston, Eric V.,?kermark, Bj?rn
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supporting information
p. 3186 - 3190
(2018/07/29)
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- Hydrogen Bonding-Assisted Enhancement of the Reaction Rate and Selectivity in the Kinetic Resolution of d,l-1,2-Diols with Chiral Nucleophilic Catalysts
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An extremely efficient acylative kinetic resolution of d,l-1,2-diols in the presence of only 0.5 mol% of binaphthyl-based chiral N,N-4-dimethylaminopyridine was developed (selectivity factor of up to 180). Several key experiments revealed that hydrogen bonding between the tert-alcohol unit(s) of the catalyst and the 1,2-diol unit of the substrate is critical for accelerating the rate of monoacylation and achieving high enantioselectivity. This catalytic system can be applied to a wide range of substrates involving racemic acyclic and cyclic 1,2-diols with high selectivity factors. The kinetic resolution of d,l-hydrobenzoin and trans-1,2-cyclohexanediol on a multigram scale (10 g) also proceeded with high selectivity and under moderate reaction conditions: (i) very low catalyst loading (0.1 mol%); (ii) an easily achievable low reaction temperature (0 °C); (iii) high substrate concentration (1.0 M); and (iv) short reaction time (30 min). (Figure presented.).
- Fujii, Kazuki,Mitsudo, Koichi,Mandai, Hiroki,Suga, Seiji
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supporting information
p. 2778 - 2788
(2017/08/23)
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- Isocyanate-free route to poly(carbohydrate-urethane) thermosets and 100% bio-based coatings derived from glycerol feedstock
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Glycerol serves as the exclusive bio feedstock for the preparation of high purity sorbitol tricarbonate (STC) as new intermediate for poly(carbohydrate-urethane) thermosets and 100% bio-based non-isocyanate polyhydroxyurethane (NIPU) coatings. In this process, glycerol-based acrolein is dimerized, carbonated, and oxidized, thus producing the highly reactive diepoxy functional ethylene carbonate (DOC), which by facile chemical CO2 fixation yields high purity STC. Opposite to most state-of-the-art multifunctional five-membered cyclic carbonates and regardless of the feedstock used for its manufacture, STC enables amine curing at ambient temperature even in the absence of catalysts. According to FT-IR and NMR spectroscopic analyses of the amine/carbonate reaction kinetics, the internal cyclic carbonate group is 3 times more reactive with respect to the two terminal carbonate groups. This is attributed to the electron-withdrawing effect of terminal cyclic carbonates. Curing STC with a blend of bio-based flexible and rigid diamines such as dimer fatty acid-based diamine (Priamine 1074) and isophorone diamine affords poly(carbohydrate-urethane) thermosets and NIPU coatings exhibiting substantially improved thermal and mechanical properties.
- Schmidt, Stanislaus,Ritter, Benjamin S.,Kratzert,Bruchmann, Bernd,Mülhaupt, Rolf
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p. 7268 - 7276
(2016/10/22)
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- Synthesis of the tetracyclic core of exiguaquinol
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A Diels-Alder reaction, a desymmetrizing aldol reaction, and a reductive Heck cyclization are employed in a short synthesis of a tetracycle relevant to exiguaquinol, a potential antibiotic. Ground-state energies of this advanced model system and the natural product rationalize the incorrect hemiaminal configuration experimentally obtained and point to the importance of the sulfonate in dictating the relative configuration of the natural product.
- Schwarzwalder, Gregg M.,Steinhardt, Sarah E.,Pham, Hung V.,Houk,Vanderwal, Christopher D.
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supporting information
p. 6014 - 6017
(2014/01/06)
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- Palladium-mediated phosphine-dependent chemoselective bisallylic alkylation leading to spirocarbocycles
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Cycles everywhere: The selectivity in the transformations of 1,3-diones to carbocycles by palladium-catalyzed bisallylic alkylations is strongly dependent on the phosphine that is employed (see scheme). Moreover, synthesized vinylcyclopentenes can be easily transformed into cycloheptadiene derivatives through a carboncarbon allylic bond cleavage.
- Clavier, Hervé,Giordano, Laurent,Tenaglia, Alphonse
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supporting information; experimental part
p. 8648 - 8651
(2012/09/22)
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- Readily accessible chiral diene ligands for Rh-catalyzed enantioselective conjugate additions of boronic acids
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Enabled by the broad scope of the Pd-catalyzed asymmetric alkylation of meso- and d,l-divinylethylene carbonate, several chiral diene ligands were prepared in two steps from commercial materials. Subsequently, these ligands were evaluated in the Rh-catalyzed asymmetric conjugate addition of boronic acids to enones.
- Trost, Barry M.,Burns, Aaron C.,Tautz, Thomas
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supporting information; body text
p. 4566 - 4569
(2011/10/09)
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- Convergent total synthesis of squamostolide
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A convergent total synthesis of the Annonaceous acetogenin squamostolide, in a longest linear sequence of nine steps from d-mannitol, is reported. Central to the efficiency of the synthesis is a highly selective tandem ring-closing/cross metathesis step in which lactone formation and fragment coupling are accomplished.
- Quinn, Kevin J.,Smith, Austin G.,Cammarano, Carolyn M.
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p. 4881 - 4886
(2008/02/01)
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- Synthesis of dihydrofurans and dihydropyrans with unsaturated side chains based on ring size-selective ring-closing metathesis
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Enantiomerically pure 1,5-hexadiene-3,4-diol, derived from D-mannitol in a few steps, may serve as a starting material for enantiopure dihydropyrans and dihydrofurans bearing an unsaturated side chain which is amenable for further synthetic transformations. The synthesis relies on a ring size- selective ring-closing metathesis reaction of a triene. Most likely, a catalyst-directing effect of an allylic hydroxy group is responsible for the selectivity.
- Schmidt, Bernd,Nave, Stefan
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p. 215 - 230
(2008/02/03)
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- A convergent Pd-catalyzed asymmetric allylic alkylation of dl- And meso-divinylethylene carbonate: Enantioselective synthesis of (+)-australine hydrochloride and formal synthesis of isoaltholactone
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The use of a mixture of dl-and meso-divinylethylene carbonate as an electrophile in palladium-catalyzed asymmetric allylic alkylation reactions is reported. From the diastereomeric mixture of meso and chiral racemic starting materials, a single product is obtained in high optical purity employing either oxygen or nitrogen nucleophiles. The resulting dienes have proven to be versatile synthetic intermediates as each carbon is functionalized for further transformation and differentiated by virtue of the reaction. A mechanism for this intriguing transformation is proposed and a concise enantioselective total synthesis of (+)-australine hydrochloride is reported as well as a formal synthesis of isoaltholactone.
- Trost, Barry M.,Aponick, Aaron,Stanzl, Benjamin N.
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p. 9547 - 9560
(2008/12/20)
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- Palladium-catalyzed asymmetric allylic alkylation of meso- and dl-1,2-divinylethylene carbonate
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The palladium-catalyzed asymmetric allylic alkylation of a 1:1 mixture of DL- and meso-1,2-divinylethylene carbonate is reported. For the first time, both the ionization and nucleophilic addition steps of the catalytic cycle act as enantiodiscriminating steps to give a single product in high enantiomeric excess. The reactions proceed in >98% ee to efficiently generate useful chiral building blocks from acrolein. The absolute and relative configurations of iso-cladospolide B and 11-epi-iso-cladospolide B were verified by total synthesis, solving an apparent discrepancy in the literature. Copyright
- Trost, Barry M.,Aponick, Aaron
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p. 3931 - 3933
(2007/10/03)
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- Regioselective cleavage of the bis-benzylidene acetal of D-mannitol under oxidative and reductive conditions: A new approach to C2-symmetric chiral ligands
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A highly regioselective oxidative cleavage of 1,3:4,6-di-O-benzylidene-d- mannitol was carried out using NBS and the resultant product was readily converted to the C2-symmetric chiral ligand, (R,R)-3,4-dihydroxy-1,5- hexadiene. On the other hand, reductive cleavage of 1,3:4,6-di-O-benzylidene-d- mannitol was achieved in a highly regioselective manner using BF 3?OEt2 and Et3SiH to give a highly functionalized benzyl ether, which was converted to a synthetically useful C2-symmetric bis-amino alcohol derivative.
- Aravind, Appu,Mohanty, Subhendu K.,Pratap, T. Veerabhadra,Baskaran, Sundarababu
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p. 2965 - 2968
(2007/10/03)
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- Total synthesis of 3-deoxy-D-manno-2-octulosonic acid (KDO) and 2-deoxy-β-KDO
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(equation presented) Total syntheses of KDO and 2-deoxy-β-KDO are reported. The C2-symmetric dienediol 4 was desymmetrized by conversion to its corresponding 1,4-dioxanone 5. Ireland-Claisen rearrangement of 5 provided the 6-vinyldihydropyran-2-carboxylate template 6. Double-Sharpless asymmetric dihydroxylation gave the tetraol 7a, which was converted to KDO and 2-deoxy-β-KDO using methods similar to those previously reported. This synthetic scheme provides a flexible route to KDO and KDO analogues.
- Burke, Steven D.,Sametz, Geoffrey M.
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- Kinetic resolution of chiral auxiliaries with C2-symmetry by lipase-catalyzed alcoholysis and aminolysis
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Three cyclic diols, 1,2-cyclohexanediol (1), 1,3-cyclohexanediol (2), and 1,3-cyclopentanediol (3), two acyclic unsaturated diols, 1,5-hexadiene-3,4-diol (4) and 1,7-octadiyne-3,6-diol (5), and a cyclic diamine, 1,2-cyclohexanediamine (6), have been kinetically resolved in alcoholysis and aminolysis reactions, catalyzed by Candida antarctica component B lipase, using S-ethyl thiooctanoate or ethyl octanoate as acyl donors. Acceptable stereoselectivity was achieved in most cases. Acta Chemica Scandinavica 1996.
- Mattson, Anders,Orrenius, Christian,Oehrner, Niklas,Unelius, C. Rikard,Hult, Karl,Norin, Torbjoern
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p. 918 - 921
(2007/10/03)
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- Double asymmetric iodoamination; synthesis of C2 symmetric and meso-amino alcohols
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Alkenic diols 2 and 14 are iodocyclized providing dihydro-1,3-oxazine 3 and dihydrooxazole 15 in 90 and 93% de, respectively, which are precursors of various C2 symmetric and meso-amino alcohols.
- Kang, Sung Ho,Ryu, Do Hyun
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p. 355 - 356
(2007/10/03)
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- SYNTHESIS OF (3R,4R)-1,5-HEXADIEN-3,4,-DIOL AND ITS UNSYMMETRICAL DERIVATIVES : APPLICATION TO (R)-(+)-α-LIPOIC ACID
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(3R,4R)-1,5-Hexadien-3,4-diol and its umsymmetrical derivatives were prepared starting from D-mannitol and their utility in the synthesis of (R)-(+)-α-lipoic acid has been explored.
- Rama Rao, A. V.,Mysorekar, S. V.,Gurjar, M. K.,Yadav, S. J.
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p. 2183 - 2186
(2007/10/02)
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