Stereocontrolled C-O Ring Construction: The Fuwa/Sasaki Synthesis of Attenol A

Institute Of Technology ◽

Since five-membered ring ethers often do not show good selectivity on equilibration, single diastereomers are best formed under kinetic control. Aaron Aponick of the University of Florida demonstrated (Organic Lett. 2008, 10, 669) that under gold catalysis, the allylic alcohol 1 cyclized to 2 with remarkable diastereocontrol. Six-membered rings also formed with high cis stereocontrol. Ian Cumpstey of Stockholm University showed (Chem. Commun. 2008, 1246) that with protic acid, allylic acetates such as 3 cyclized with clean inversion at the allylic center, and concomitant debenzylation. J. Stephen Clark of the University of Glasgow found (J. Org. Chem. 2008, 73, 1040) that Rh catalyzed cyclization of 5 proceeded with high selectivity for insertion into Ha, leading to the alcohol 6. Saumen Hajra of the Indian Institute of Technology, Kharagpur took advantage (J. Org. Chem. 2008, 73, 3935) of the reactivity of the aldehyde of 7, effecting selective addition of 7 to 8, to deliver, after reduction, the lactone 9. Tomislav Rovis of Colorado State University observed (J. Org. Chem. 2008, 73, 612) that 10 could be cyclized selectively to either 11 or 12. Nadège Lubin-Germain, Jacques Uziel and Jacques Augé of the University of Cergy- Pontoise devised (Organic Lett. 2008, 10, 725) conditions for the indium-mediated coupling of glycosyl fluorides such as 13 with iodoalkynes such as 14 to give the axial C-glycoside 15. Katsukiyo Miura and Akira Hosomi of the University of Tsukuba employed (Chemistry Lett. 2008, 37, 270) Pt catalysis to effect in situ equilibration of the alkene 16 to the more stable regioisomer. Subsequent condensation with the aldehyde 17 led via Prins cyclization to the ether 18. Paul E. Floreancig of the University of Pittsburgh showed (Angew. Chem. Int. Ed. 2008, 47, 4184) that Prins cyclization could be also be initiated by oxidation of the benzyl ether 19 to the corresponding carbocation. Chan-Mo Yu of Sungkyunkwan University developed (Organic Lett. 2008, 10, 265) a stereocontrolled route to seven-membered ring ethers, by Pd-mediated stannylation of allenes such as 21, followed by condensation with an aldehyde.

Other Methods for Carbocyclic Construction: The Porco Synthesis of (-)-Hyperibone K

Organic Synthesis ◽

10.1093/oso/9780199965724.003.0081 ◽

2013 ◽

Author(s):

Douglass F. Taber

Keyword(s):

Oxidative Cyclization ◽

Florida State University ◽

State University ◽

Intramolecular Alkylation ◽

University Of Wisconsin ◽

Tokyo Institute ◽

Institute Of Technology ◽

University Of Bristol ◽

Varinder K. Aggarwal of the University of Bristol described (Angew. Chem. Int. Ed. 2010, 49, 6673) the conversion of the Sharpless-derived epoxide 1 into the cyclopropane 2. Christopher D. Bray of Queen Mary University of London established (Chem. Commun. 2010, 46, 5867) that the related conversion of 3 to 5 proceeded with high diastereocontrol. Javier Read de Alaniz of the University of California, Santa Barbara, extended (Angew. Chem. Int. Ed. 2010, 49, 9484) the Piancatelli rearrangement of a furyl carbinol 6 to allow inclusion of an amine 7, to give 8. Issa Yavari of Tarbiat Modares University described (Synlett 2010, 2293) the dimerization of 9 with an amine to give 10. Jeremy E. Wulff of the University of Victoria condensed (J. Org. Chem. 2010, 75, 6312) the dienone 11 with the commercial butadiene sulfone 12 to give the highly substituted cyclopentane 13. Robert M. Williams of Colorado State University showed (Tetrahedron Lett. 2010, 51, 6557) that the condensation of 14 with formaldehyde delivered the cyclopentanone 15 with high diastereocontrol. D. Srinivasa Reddy of Advinus Therapeutics devised (Tetrahedron Lett. 2010, 51, 5291) conditions for the tandem conjugate addition/intramolecular alkylation conversion of 16 to 17. Marie E. Krafft of Florida State University reported (Synlett 2010, 2583) a related intramolecular alkylation protocol. Takao Ikariya of the Tokyo Institute of Technology effected (J. Am. Chem. Soc. 2010, 132, 11414) the enantioselective Ru-mediated hydrogenation of bicyclic imides such as 18. This transformation worked equally well for three-, four-, five-, six-, and seven-membered rings. Stefan France of the Georgia Institute of Technology developed (Org. Lett. 2010, 12, 5684) a catalytic protocol for the homo-Nazarov rearrangement of the doubly activated cyclopropane 20 to the cyclohexanone 21. Richard P. Hsung of the University of Wisconsin effected (Org. Lett. 2010, 12, 5768) the highly diastereoselective rearrangement of the triene 22 to the cyclohexadiene 23. Strategies for polycyclic construction are also important. Sylvain Canesi of the Université de Québec devised (Org. Lett. 2010, 12, 4368) the oxidative cyclization of 24 to 25.

Alkenes

Organic Synthesis ◽

10.1093/oso/9780190646165.003.0027 ◽

2017 ◽

Author(s):

Allison K. Griffith ◽

Tristan H. Lambert

Keyword(s):

State University ◽

One Pot ◽

University Of Oxford ◽

University Of British Columbia ◽

University Of Wisconsin ◽

Unsaturated Carbonyl Compound ◽

Institute Of Technology ◽

University Of Zurich ◽

The α-C–H functionalization of piperidine catalyzed by tantalum complex 1 to produce amine 2 was developed (Org. Lett. 2013, 15, 2182) by Laurel L. Schafer at the University of British Columbia. An asymmetric diamination of diene 3 with diaziridine reagent 4 under palladium catalysis to furnish cyclic sulfamide 5 was developed (Org. Lett. 2013, 15, 796) by Yian Shi at Colorado State University. Enantioenriched β-fluoropiperdine 8 was prepared (Angew. Chem. Int. Ed. 2013, 52, 2469) via aminofluorocyclization of 6 with hypervalent iodide 7, as reported by Cristina Nevado at the University of Zurich. Erick M. Carreira at ETH Zürich disclosed (J. Am. Chem. Soc. 2013, 135, 6814) a ruthenium-catalyzed hydrocarbamoylation of allylic formamide 9 to yield pyrrolidone 10. Hans-Günther Schmalz at the University of Köln disclosed (Angew. Chem. Int. Ed. 2013, 52, 1576) an asymmetric hydrocyanation of styrene 11 with Ni(cod)₂ and phosphine–phosphite ligand 12 to yield exclusively the branched cyanide 13. A similar transformation of styrene 11 to the hydroxycarbonylated product 15 was catalyzed (Chem. Commun. 2013, 49, 3306) by palladium complex 14, as reported by Matthew L. Clarke at the University of St Andrews. Feng-Ling Qing at the Chinese Academy of Sciences found (Angew. Chem. Int. Ed. 2013, 52, 2198) that the hydrotrifluoromethylation of unactivated alkene 16 to 17 was catalyzed by silver nitrate. The same transformation was also reported (J. Am.Chem. Soc. 2013, 135, 2505) by Véronique Gouverneur at the University of Oxford using a ruthenium photocatalyst and the Umemoto reagent 18. Clark R. Landis at the University of Wisconsin, Madison reported (Angew. Chem. Int. Ed. 2013, 52, 1564) a one-pot asymmetric hydroformylation using 21 followed by Wittig olefination to transform alkene 19 into the γ-chiral α,β-unsaturated carbonyl compound 20. Debabrata Mati at the Indian Institute of Technology Bombay found (J. Am. Chem. Soc. 2013, 135, 3355) that alkene 22 could be nitrated stereoselectively with silver nitrite and TEMPO to form alkene 23. Damian W. Young at the Broad Institute disclosed (Org. Lett. 2013, 15, 1218) that a macrocyclic vinylsiloxane 24, which was synthesized via an E-selective ring closing metathesis reaction, could be functionalized to make either E- or Z-alkenes, 25 and 26.

Diels-Alder Cycloaddition: Fawcettimine (Williams), Apiosporic Acid (Helmchen), Marginatone (Abad- Somovilla), Okilactomycin (Hoye), Vinigrol (Barriault), Plakotenin (Bihlmeier/Klopper)

Organic Synthesis ◽

10.1093/oso/9780190200794.003.0079 ◽

2015 ◽

Author(s):

Douglass F. Taber

Keyword(s):

Natural Product ◽

Diels Alder ◽

State University ◽

University Of Minnesota ◽

Enantiomerically Pure ◽

Institute Of Technology ◽

La Jolla ◽

The University ◽

Stereogenic Center

Highly substituted dienes and dienophiles are often reluctant participants in intermolecular Diels-Alder cycloaddition. Nevertheless, Robert M. Williams of Colorado State University, in the course of a synthesis of fawcettimine 4, was able (J. Org. Chem. 2012, 77, 4801) to prepare 3 by combining the enone 1 with the diene 2. Günter Helmchen of the Universität Heidelberg set (J. Org. Chem. 2012, 77, 4491) the single stereogenic center of 5 by Ir-catalyzed allylic alkylation. The Lewis acid that promoted the cycloaddition also conveniently removed the trityl protecting group, leading to 6, that was saponified to apiosporic acid 7. Antonio Abad-Somovilla of the Universidad de Valencia prepared (J. Org. Chem. 2012, 77, 5664) the triene 8 in enantiomerically pure form from carvone. Despite the additional substitution on the diene, cycloaddition proceeded smoothly to give 9, which was carried on to marginatone 10. One could envision that okilactomycin 13 could be formed by an intramolecular Diels-Alder cycloaddition. Thomas R. Hoye of the University of Minnesota observed (Org. Lett. 2012, 14, 828) that the tetraene tetronic acid corresponding to 11 was inert, but that the methyl ether 11 cyclized smoothly to 12. Demethylation then gave the natural product The complex polycyclic structure of vinigrol 16 challenged organic synthesis chemists for many years, until a route was established by Phil Baran of Scripps/La Jolla (Highlights September 6, 2010). Louis Barriault cyclized (Angew. Chem. Int. Ed. 2012, 51, 2111) 14 to 15 en route to a late intermediate in the Baran synthesis It had been hypothesized that the natural product plakotenin 19 was formed naturally from a tetraene corresponding to 17. The tetraene 17 was prepared and the cyclization was successful, “confirming” both the structure of the natural product and the biosynthetic hypothesis. Angela Bihlmeier and Wim Klopper of the Karlsruhe Institute of Technology calculated (J. Am. Chem. Soc. 2012, 134, 2154) the relative energies of the four competing transition states for the cyclization, leading to a correction of the structure of 18, and so of the natural product 19.

Enantioselective Synthesis of Alcohols and Amines: The Ichikawa Synthesis of (+)-Geranyllinaloisocyanide

Organic Synthesis ◽

10.1093/oso/9780190200794.003.0034 ◽

2015 ◽

Author(s):

Douglass F. Taber

Keyword(s):

Allylic Alcohol ◽

Florida State University ◽

State University ◽

Quaternary Amine ◽

National University ◽

Cu Catalyst ◽

Enantioselective Addition ◽

Institute Of Technology ◽

The University ◽

University Of Manchester

Shuichi Nakamura of the Nagoya Institute of Technology reduced (Angew. Chem. Int. Ed. 2011, 50, 2249) the α-oxo ester 1 to 2 with high ee. Günter Helmchen of the Universität-Heidelberg optimized (J. Am. Chem. Soc. 2011, 133, 2072) the Ir*-catalyzed rearrangement of 3 to the allylic alcohol 4. D. Tyler McQuade of Florida State University effected (J. Am. Chem. Soc. 2011, 133, 2410) the enantioselective allylic substitution of 5 to give the secondary allyl boronate, which was then oxidized to 6. Kazuaki Kudo of the University of Tokyo developed (Org. Lett. 2011, 13, 3498) the tandem oxidation of the aldehyde 7 to the α-alkoxy acid 8. Takashi Ooi of Nagoya University prepared (Synlett 2011, 1265) the secondary amine 10 by the enantioselective addition of an aniline to the nitroalkene 9. Yixin Lu of the National University of Singapore assembled (Org. Lett. 2011, 13, 2638) the α-quaternary amine 13 by the addition of the aldehyde 11 to the azodicarboxylate 10. Chan-Mo Yu of Sungkyunkwan University added (Chem. Commun. 2011, 47, 3811) the enantiomerically pure 2-borylbutadiene 15 to the aldehyde 14 to give 16 in high ee. Because the allene is readily dragged out to the terminal alkyne, this is also a protocol for the enantioselective homopropargylation of an aldehyde. Lin Pu of the University of Virginia devised (Angew. Chem. Int. Ed. 2011, 50, 2368) a protocol for the enantioselective addition of 17 to the aldehyde 18 to give 19. Xiaoming Feng of Sichuan University developed (Angew. Chem. Int. Ed. 2011, 50, 2573) a Mg catalyst for the enantioselective addition of 21 to the α-oxo ester 20. Tomonori Misaka and Takashi Sugimura of the University of Hyogo added (J. Am. Chem. Soc. 2011, 133, 5695) 23 to 24 to give the Z-amide 25 in high ee. Marc L. Snapper and Amir H. Hoveyda of Boston College developed (J. Am. Chem. Soc. 2011, 133, 3332) a Cu catalyst for the enantioselective allylation of the imine 26. Jonathan Clayden of the University of Manchester effected (Org. Lett. 2010, 12, 5442) the enantioselective rearrangement of the amide 29 to the α-quaternary amine 30.

C–O Ring Construction: The Martín and Martín Synthesis of Teurilene

Organic Synthesis ◽

10.1093/oso/9780190646165.003.0043 ◽

2017 ◽

Author(s):

Tristan H. Lambert

Keyword(s):

Phenylboronic Acid ◽

Gold Catalysis ◽

State University ◽

Max Planck ◽

Amberlyst 15 ◽

University Of Toronto ◽

Palladium Catalyzed ◽

University Of Bristol ◽

Benjamin List at the Max-Planck-Institute in Mülheim reported (Angew. Chem. Int. Ed. 2013, 52, 3490) that the chiral phosphoric acid TRIP catalyzed the asymmetric SN2-type intramolecular etherification of 1 to produce tetrahydrofuran 2 with a selectivity factor of 82. The coupling of alkenol 3 with 4 to give the α-arylated tetrahydropyran 5 via a method that combined gold catalysis and photoredox catalysis was disclosed (J. Am. Chem. Soc. 2013, 135, 5505) by Frank Glorius at Westfälische Wilhelms-Universität Münster. Mark Lautens at the University of Toronto reported (Org. Lett. 2013, 15, 1148) the conversion of cyclohexanedione 6 and phenylboronic acid to bicyclic ether 8 using rhodium catalysis in the presence of dienyl ligand 7. Propargylic ether 9 was found (Org. Lett. 2013, 15, 2926) by John P. Wolfe at the University of Michigan to undergo conversion to furanone 10 upon treatment with dibutylboron triflate and Hünig’s base followed by oxidation with hydrogen peroxide. Tomislav Rovis at Colorado State University demonstrated (Chem. Sci. 2013, 4, 1668) that the spirocyclic compound 13 could be prepared in enantioenriched form from 11 by a photoisomerization- coupled Stetter reaction using carbene catalyst 12. Antonio C. B. Burtoloso at the University of São Paulo reported (Org. Lett. 2013, 15, 2434) the conversion of ketone 14 to lactone 15 using samarium(II) iodide and methyl acrylate. The merger of diketone 16 and pyrone 17 in the presence of Amberlyst-15 to produce (−)- tenuipyrone 18 was disclosed (Org. Lett. 2013, 15, 6) by Rongbiao Tong at the Hong Kong University of Science and Technology. Joanne E. Harvey at Victoria University of Wellington in New Zealand found (Org. Lett. 2013, 15, 2430) that tricyclic ether 20 could be generated efficiently from dihydropyran 19 and pyrone 17 via a palladium-catalyzed double allylic alkylation cascade. Two rings and four stereocenters were generated in the construction of bicyclic ether 23 from dienol 21 and acetal 22 via a Lewis acid-mediated cascade, as reported (Org. Lett. 2013, 15, 2046) by Christine L. Willis at the University of Bristol.

Enantioselective Construction of Arrays of Stereogenic Centers

Organic Synthesis ◽

10.1093/oso/9780199764549.003.0042 ◽

2011 ◽

Author(s):

Douglass Taber

Keyword(s):

Claisen Rearrangement ◽

Cinchona Alkaloid ◽

State University ◽

Henry Reaction ◽

University Of Pittsburgh ◽

Boston University ◽

Complementary Approach ◽

La Jolla ◽

An impressive array of new catalysts for enantioselective homologation have been reported. Carlos F. Barbas III of Scripps/La Jolla has found (Angew. Chem. Int. Ed. 2007, 46, 5572 ) that the commercial amino acid 3 mediated the addition of dihydroxyacetone 2 to an aldehyde such as 1 to give the triol 4 with high enantio- and diastereocontrol. Takashi Ooi of Nagoya University has devised (J. Am. Chem. Soc. 2007, 129, 12392) the catalyst 6 for the anti addition (Henry reaction) of nitro alkanes such as 5 to aldehydes. Takayoshi Arai of Chiba University has developed (Organic Lett. 2007, 9, 3595) a complementary catalyst (not shown) that mediated syn addition. Jonathan A. Ellman of the University of California, Berkeley has uncovered (J. Am. Chem. Soc. 2007, 129, 15110) the catalyst 10 for the aza-Henry reaction. Yian Shi of Colorado State University has found (J. Am. Chem. Soc. 2007, 129, 11688) ligands for Pd that direct the absolute sense of the addition of 13 to dienes such as 12. Bernhard Breit of Albert-Ludwigs-Universität, Freiburg has devised conditions (Adv. Synth. Cat. 2007, 349, 1891) for the Rh-catalyzed hydroformylation of α-olefins such as 15, and same-pot proline-catalyzed condensation of the linear aldehyde so produced with a branched aldehyde such as 17 to give, after reductive workup, the branched diol 18. Scott G. Nelson of the University of Pittsburgh has established (J. Am. Chem. Soc. 2007, 129, 11690) conditions, using Cinchona alkaloid derived catalysts, for the condensation of the imine surrogate 19 with the ketene precursor 20, to give the Mannich product 21. Scott E. Schaus of Boston University has developed (J. Am. Chem. Soc. 2007, 129, 15398) a complementary approach, based on catalyzed addition of isolated allyl borinates such as 23 to the activated imine 22. Kálmán J. Szabó of Stockholm University has found (J. Am. Chem. Soc. 2007, 129, 13723) that substituted allyl borinates can be prepared and reacted in situ. Martin Hiersemann of the Universität Dortmund has reported (Organic Lett. 2007, 9, 4979) the remarkable Cu*-catalyzed Claisen rearrangement of the prochiral 24, leading to 25 and thus to the versatile intermediate 27.

Construction of Stereochemical Arrays

Organic Synthesis ◽

10.1093/oso/9780190200794.003.0045 ◽

2015 ◽

Author(s):

Tristan H. Lambert

Keyword(s):

Kinetic Resolution ◽

Alder Reaction ◽

State University ◽

Rhodium Catalysis ◽

Allyl Sulfide ◽

Institute Of Technology ◽

Quaternary Stereocenters ◽

The University ◽

Technological University

The unprecedented enantioselective 1,8-addition of azlactone 1 to acylpyrrole 2 catalyzed by triaminophosphorane 3 was reported (J. Am. Chem. Soc. 2012, 134, 19370) by Takashi Ooi at Nagoya University. Tomislav Rovis at Colorado State University developed (Angew. Chem. Int. Ed. 2012, 51, 12330) the asymmetric oxidative hetero-Diels-Alder reaction of propionaldehyde (5) and ketone 6 to produce lactone 8, catalyzed by NHC catalyst 7 in the presence of phenazine. A related NHC catalyst 11 was utilized (Angew. Chem. Int. Ed. 2012, 51, 8276) by Xue-Wei Liu at Nanyang Technological University for the homoenolate addition of enal 9 to nitrodiene 10 to furnish 12 with high ee. The vinylogous conjugate addition of butenolide 13 to 15 to produce 16 with exquisite stereoselectivity was accomplished (Angew. Chem. Int. Ed. 2012, 51, 10069) by Kuo-Wei Huang at KAUST, Choon-Hong Tan at Henan University and Nanyang Technological University, and Zhiyong Jiang at Henan University. The enantioselective production of lactone 18 was achieved (J. Am. Chem. Soc. 2012, 134, 20197) by Jeffrey S. Johnson at the University of North Carolina at Chapel Hill by dynamic kinetic resolution (DKR) of α-keto ester 17. A related DKR strategy was employed (Org. Lett. 2012, 14, 6334) by Brinton Seashore-Ludlow at the KTH Royal Institute of Technology and Peter Somfai at Lund University in Sweden and the University of Tartu in Estonia for hydrogenation of α-amino-β-ketoester 19 to furnish aminoalcohol 21 with high Shigeki Matsunaga and Motomu Kanai at the University of Tokyo developed (Angew. Chem. Int. Ed. 2012, 51, 10275) a unique strategy for the selective production of the cross-aldol adduct 24 by in situ generation of an aldehyde enolate from allyloxyborane 23 under rhodium catalysis. The highly diastereoselective construction of adduct 26 bearing two adjacent quaternary stereocenters by ketone allylation with allyl sulfide 25 was reported (Angew. Chem. Int. Ed. 2012, 51, 7263) by Takeshi Takeda at the Tokyo University of Agriculture and Technology. Wen-Hao Hu at East China Normal University reported (Nature Chem. 2012, 4, 733) the enantioselective three-component coupling of diazoester 27, N-benzylindole (28), and imine 29 to furnish 31 under the action of Rh2(OAc)4 and phosphoric acid 30.

BUSINESS MODELS FOR ONLINE EDUCATION

Online Learning ◽

10.24059/olj.v10i2.1765 ◽

2019 ◽

Vol 10 (2) ◽

Author(s):

George Lorenzo

Keyword(s):

Online Education ◽

Business Models ◽

State University ◽

Central Florida ◽

University Of Georgia ◽

Community College District ◽

Institute Of Technology ◽

University Of Massachusetts ◽

Nine institutions—Colorado State University, Dallas County Community College District (DCCCD), Duquesne University, Georgia Institute of Technology, University of Central Florida, The University of Illinois at Springfield, University of Massachusetts Lowell, University of Michigan, University of Georgia—share information about their business models.

Preface: Modern Heterocycle Synthesis and Functionalization

Synlett ◽

10.1055/s-0040-1706679 ◽

2021 ◽

Vol 32 (02) ◽

pp. 140-141

Author(s):

Louis-Charles Campeau ◽

Tomislav Rovis

Keyword(s):

Active Pharmaceutical Ingredient ◽

Associate Professor ◽

Columbia University ◽

State University ◽

Heterocycle Synthesis ◽

University Of Toronto ◽

Process Chemistry ◽

The University ◽

Small Molecule Therapeutics

obtained his PhD degree in 2008 with the late Professor Keith Fagnou at the University of Ottawa in Canada as an NSERC Doctoral Fellow. He then joined Merck Research Laboratories at Merck-Frosst in Montreal in 2007, making key contributions to the discovery of Doravirine (MK-1439) for which he received a Merck Special Achievement Award. In 2010, he moved from Quebec to New Jersey, where he has served in roles of increasing responsibility with Merck ever since. L.-C. is currently Executive Director and the Head of Process Chemistry and Discovery Process Chemistry organizations, leading a team of smart creative scientists developing innovative chemistry solutions in support of all discovery, pre-clinical and clinical active pharmaceutical ingredient deliveries for the entire Merck portfolio for small-molecule therapeutics. Over his tenure at Merck, L.-C. and his team have made important contributions to >40 clinical candidates and 4 commercial products to date. Tom Rovis was born in Zagreb in former Yugoslavia but was largely raised in southern Ontario, Canada. He earned his PhD degree at the University of Toronto (Canada) in 1998 under the direction of Professor Mark Lautens. From 1998–2000, he was an NSERC Postdoctoral Fellow at Harvard University (USA) with Professor David A. Evans. In 2000, he began his independent career at Colorado State University and was promoted in 2005 to Associate Professor and in 2008 to Professor. His group’s accomplishments have been recognized by a number of awards including an Arthur C. Cope Scholar, an NSF CAREER Award, a Fellow of the American Association for the Advancement of Science and a Katritzky Young Investigator in Heterocyclic Chemistry. In 2016, he moved to Columbia University where he is currently the Samuel Latham Mitchill Professor of Chemistry.

C-O Ring Containing Natural Products: Paeonilactone B (Taylor), Deoxymonate B (de la Pradilla), Sanguiin H-5 (Spring), Solandelactone A (White), Spirastrellolide A (Paterson)

Organic Synthesis ◽

10.1093/oso/9780199764549.003.0050 ◽

2011 ◽

Author(s):

Douglass Taber

Keyword(s):

Oxidative Coupling ◽

Claisen Rearrangement ◽

Cyclic Carbonate ◽

Membered Ring ◽

State University ◽

Enantiomerically Pure ◽

University Of Cambridge ◽

Spirastrellolide A ◽

The University ◽

Oregon State University

Richard J. K. Taylor of the University of York has developed (Angew. Chem. Int. Ed. 2008, 47, 1935) the diasteroselective intramolecular Michael cyclization of phosphonates such as 2. Quenching of the cyclized product with paraformaldehyde delivered ( + )-Paeonilactone B 3. Roberto Fernández de la Pradilla of the CSIC, Madrid established (Tetrahedron Lett. 2008, 49, 4167) the diastereoselective intramolecular hetero Michael addition of alcohols to enantiomerically-pure acyclic sulfoxides such as 4 to give the allylic sulfoxide 5. Mislow-Evans rearrangement converted 5 into 6, the enantiomerically-pure core of Ethyl Deoxymonate B 7. The ellagitannins, represented by 10, are single atropisomers around the biphenyl linkage. David R. Spring of the University of Cambridge found (Organic Lett. 2008, 10, 2593) that the chiral constraint of the carbohydrate backbone of 9 directed the absolute sense of the oxidative coupling of the mixed cuprate derived from 9, leading to Sanguiin H-5 10 with high diastereomeric control. A key challenge in the synthesis of the solandelactones, exemplified by 14, is the stereocontrolled construction of the unsaturated eight-membered ring lactone. James D. White of Oregon State University found (J. Org. Chem. 2008, 73, 4139) an elegant solution to this problem, by exposure of the cyclic carbonate 11 to the Petasis reagent, to give 12. Subsequent Claisen rearrangement delivered the eight-membered ring lactone, at the same time installing the ring alkene of Solandelactone E 14. AD-mix usually proceeds with only modest enantiocontrol with terminal alkenes. None the less, Ian Paterson, also of the University of Cambridge, observed (Angew. Chem. Int. Ed. 2008, 47, 3016, Angew. Chem. Int. Ed. 2008, 47, 3021) that bis-dihydroxylation of the diene 17 proceeded to give, after acid-mediated cyclization, the bis-spiro ketal core 18 of Spirastrellolide A Methyl Ester 19 with high diastereocontrol.