The Overman Synthesis of Briarellin F

Central Feature ◽

Soft Corals ◽

Enantiomerically Pure ◽

Single Diastereomer ◽

Convergent Approach ◽

The University ◽

Polycyclic Ethers

Briarellin F 4 is an elegant representative of the complex polycyclic ethers produced by soft corals such as Briareum abestinum. Larry E. Overman of the University of California, Irvine, developed (J. Org. Chem. 2009, 74, 5458) a triply convergent approach to 4, the central feature of which was the Prins-pinacol combination of 1 with 2 to give 3. The aldehyde 2 was assembled by Wittig homologation of the aldehyde 5 with the phosphorane 6, followed by metalation and formylation. The aldehyde 10 was prepared by opening the enantiomerically pure epoxide 8 with the acetylide 9. Hydroboration of carvone 11 could not be effected with sufficient diastereocontrol. As an alternative, the mixture of diols was oxidized to the lactone 12 . Kinetic quench of the derived silyl ketene acetal followed by reduction led to the diastereomerically pure crystalline diol 13. This key intermediate will have many other applications in target-directed synthesis. The ketone 14 was converted to the alkenyl iodide 15 by stannylation of the enol triflate, followed by exposure of the stannane to N-iodosuccinimide. Addition of the alkenyl iodide 15 to the aldehyde 10 gave the diol 1 as an inconsequential 3:1 mixture of diastereomers. This mixture was combined with the aldehyde 2 to give, via Lewis acid–mediated rearrangement of the initially prepared acetal, the aldehyde 3 . The aldehyde 3 was readily decarbonylated by irradiation in dioxane. Face-selective Al-mediated epoxidation of the derived homoallylic alcohol proceeded with 10:1 selectivity, and subsequent MCPBA epoxidation of the cyclohexene was also secured with 10:1 facial control. This set the stage for the triflic anhydride–mediated closure of the six-membered ring ether. The Nozaki-Hiyama-Kishi cyclization of 18 proceeded with remarkable selectivity, delivering briarellin E 19 as a single diastereomer. Dess-Martin oxidation converted 19 into briarellin F 4.

The Bergman-Ellman Synthesis of (-)-Incarvillateine

Organic Synthesis ◽

10.1093/oso/9780199764549.003.0092 ◽

2011 ◽

Author(s):

Douglass Taber

Keyword(s):

High Temperature ◽

Ferulic Acid ◽

Bond Formation ◽

Reductive Elimination ◽

Enantiomerically Pure ◽

Single Diastereomer ◽

Symmetry Properties ◽

Starting Point ◽

The monoterpene alkaloid (-)-incarvillateine 3 has interesting symmetry properties. The central cyclobutane diacid core is not itself chiral, but the appended alkaloids are. The key step in the total synthesis of 3 recently (J. Am. Chem. Soc. 2008, 130, 6316) described by Robert G. Bergman and Jonathan A. Ellman of the University of California, Berkeley was the diastereoselective Rh-catalyzed cyclization of 1 to 2. The cyclobutane diacid core 5 was assembled from ferulic acid 4 following the procedure of Kibayashi (J. Am. Chem. Soc. 2004, 126, 16553). The starting point for the preparation of 1 was the commercial aldehyde 6. Enantioselective allylation followed by silylation delivered 7, which on cross metathesis with methacrolein gave the diene aldehyde 8. Imine formation then completed the construction of 1. The cyclization of 1 was effected by warming (45 °C, 6 h) with 2.5 mol % [RhCl(coe)2]2 and 5.5 mol % (DMAPh)Pet2 ligand. While eight products were possible from the cyclization (four diastereomers, two geometric isomers of the exo alkene), only two were observed, with one predominating. Since the product mixture was easily susceptible to tautomerization, it was carried on directly to reduction and cyclization, to form the lactam 8. Hydrogenation of 8 to 9 required high temperature and pressure, but delivered 9 as a single diastereomer. Reduction and desilylation then set the stage for Mitsunobu coupling with 5, to give 11. Dissolving metal conditions removed the tosyl groups from 5 to give (-)-incarvillateine 3. It will be interesting to see how general this Rh catalyzed cyclization will be. It will also be interesting to establish the mechanism. The authors described the cyclization of 1 as proceeding via initial metalation of the alkene C-H bond, followed by insertion of the ester-bearing alkene into the C-Rh bond to form a new C-Rh bond, and finally reductive elimination. Their previous observation of metalation of such an unsaturated imine with maintenance of the alkene geometry suppported this mechanism. The high diastereocontrol also suggested intramolecular C-C bond formation. Whatever the mechanism, the enantiomerically-pure cyclopentane 2, having four of its five carbons functionalized, is a versatile intermediate for further transformation.

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.

The Nakada Synthesis of (+)-Ophiobolin A

Organic Synthesis ◽

10.1093/oso/9780190646165.003.0084 ◽

2017 ◽

Author(s):

Douglass F. Taber

Keyword(s):

Second Generation ◽

Selective Reduction ◽

Membered Ring ◽

Magnesium Bromide ◽

Enantioselective Hydrolysis ◽

Central Feature ◽

The University ◽

Stereogenic Center ◽

Hydrolysis Of ◽

Useful Yield

Ophiobolin A 3 shows nanomolar toxicity toward a range of cancer cell lines. A central feature of this sesterterpene, isolated from the rice fungus Ophiobolus miyabeanus, is the highly-substituted eight-membered ring. A key step in the synthesis of 3 described (Chem. Eur. J. 2013, 19, 5476; Angew. Chem. Int. Ed. 2011, 50, 9452) by Masahisa Nakada of Waseda University was the acid-mediated cyclization of 1 to 2. The preparation of 1 began with the enantioselective hydrolysis of 4 to the monoester 5. Selective reduction followed by protection gave 6, that was carried on via 7 to 8. The ethoxyethyl group was selectively removed, and the alcohol was converted to an iodide (not illustrated) that was condensed with the lactone 9 to give 1. The cyclization of 1 could jeopardize the stereogenic center adjacent to the masked carbonyl, so eight diastereomers were possible. Careful optimization led to a preparatively useful yield of the desired product 2. Hydroboration gave 10, that was carried on to the aldehyde 11. The cyclopentanone 15 was prepared from the enantiomerically-enriched epoxide 12. Opening with vinyl magnesium bromide followed by exposure to the second-generation Grubbs catalyst gave the diol 13, that was selectively protected, leading to 14. The derived bromohydrin was a mixture of regioisomers and diastereomers, from which, after oxidation, 15 dominated. Generation of the boron enolate from 15 in the presence of 11 gave the aldol product, that could be dehydrated with the Burgess reagent. Reduction with Raney nickel set the stereogenic center adjacent to the ketone, that was carried on to 16. Metathesis to close the eight-membered ring was not trivial. Finally, it was found that 17 could be induced to cyclize to 18 at an elevated temperature using the second-generation Hoyveda catalyst. Protecting group exchange gave 19. Routine functional group manipulation then completed the synthesis of (+)-ophiobolin 3. Some years ago, Neil E. Schore of the University of California, Davis showed (Tetrahedron Lett. 1994, 35, 1153) that the opening of Sharpless-derived epoxides such as 12 with vinyl nucleophiles was unexpectedly flexible. One set of conditions gave the expected inversion, but alternative conditions led to opening with clean retention (or double inversion) of absolute configuration.

Diels–Alder Cycloaddition: Sarcandralactone A (Snyder), Pseudopterosin (−)-G-J Aglycone (Paddon-Row/Sherburn), IBIR-22 (Westwood), Muironolide A (Zakarian), Platencin (Banwell), Chatancin (Maimone)

Organic Synthesis ◽

10.1093/oso/9780190646165.003.0080 ◽

2017 ◽

Author(s):

Douglass F. Taber

Keyword(s):

Absolute Configuration ◽

Alder Reaction ◽

Diels Alder ◽

Enantiomerically Pure ◽

Protein Protein Interaction ◽

South Wales ◽

National University ◽

The Absolute ◽

En route to sarcandralactone A 3, Scott A. Snyder of Scripps Florida effected (Angew. Chem. Int. Ed. 2015, 54, 7842) Diels–Alder cycloaddition of the activated enone 1 to the Danishefsky diene. On exposure to trifluoroacetic acid, the adduct was unraveled to the ene dione 2. Michael N. Paddon-Row of the University of New South Wales and Michael S. Sherburn of the Australian National University prepared (Nature Chem. 2015, 7, 82) the allene 4 in enantiomerically-pure form. Sequential cycloaddition with 5 followed by 6 gave an adduct that was decarbonylated to 7. Further cycloaddition with nitroethylene 8 led to the pseudopterosin (−)-G-J aglycone 9. The protein–protein interaction inhibitor JBIR-22 12 contains a quaternary α-amino acid pendant to a bicyclic core. Nicholas J. Westwood of the University of St. Andrews set (Angew. Chem. Int. Ed. 2015, 54, 4046) the absolute configuration of the core 11 by using an organocatalyst to activate the cyclization of 10. Metal catalysts can also be used to set the absolute configuration of a Diels–Alder cycloaddition. In the course of establishing the structure of the marine natural product muironolide A 15, Armen Zakarian of the University of California, Santa Barbara cyclized (J. Am. Chem. Soc. 2015, 137, 5907) the enol form of 13 preferentially to the diastereomer 14. Unactivated intramolecular Diels–Alder cycloadditions have been carried out with more and more challenging substrates. A key step in the synthesis (Chem. Asian. J. 2015, 10, 427) of (−)-platencin 18 by Martin G. Banwell, also of the Australian National University, was the cyclization of 16 to 17. In another illustration of the power of the unactivated intramolecular Diels–Alder reaction, Thomas J. Maimone of the University of California, Berkeley cyclized (Angew. Chem. Int. Ed. 2015, 54, 1223) the tetraene 19 to the tricycle 20. Allylic chlorination followed by reductive cyclization converted 20 to chatancin 21.

The Zakarian Synthesis of ( + )-Pinnatoxin A

Organic Synthesis ◽

10.1093/oso/9780199764549.003.0097 ◽

2011 ◽

Author(s):

Douglass Taber

Keyword(s):

Claisen Rearrangement ◽

Aldol Condensation ◽

Primary Alcohol ◽

Allylic Alcohol ◽

Santa Barbara ◽

Enantiomerically Pure ◽

Calcium Channel Activator ◽

The University ◽

Nabh4 Reduction

( + )-Pinnatoxin A 3, isolated from the shellfish Pinna muricata, is thought to be a calcium channel activator. A key transformation in the synthesis of 3 reported (J. Am. Chem. Soc . 2008, 130, 3774) by Armen Zakarian, now at the University of California, Santa Barbara, was the diastereoselective Claisen rearrangement of 1 to 2. The alcohol portion of ester 1 was derived from the aldehyde 4, prepared from D-ribose. The absolute configuration of the secondary allylic alcohol was established by chiral amino alcohol catalyzed addition of diethyl zinc to the unsaturated aldehyde 5. The acid portion of the ester 1 was prepared from (S)-citronellic acid, by way of the Evans imide 7. Methylation proceeded with high diasterocontrol, to give 8. Functional group manipulation provided the imide 9. Alkylation then led to 10, again with high diastereocontrol. In each case, care had to be taken in the further processing of the α-chiral acyl oxazolidinones. Direct NaBH4 reduction of 8 delivered the primary alcohol. To prepare the acid 10, the alkylated acyl oxazolidinone was hydrolyzed with alkaline hydrogen peroxide. On exposure of the ester 1 to the enantiomerically-pure base 11, rearrangement proceeded with high diastereocontrol, to give the acid 2. This outcome suggests that deprotonation proceeded to give the single geometric form of the enolate, that was then trapped to give specifically the ketene silyl acetal 12. This elegant approach is dependent on both the ester 1 and the base 11 being enantiomerically pure. The carbocyclic ring of pinnatoxin A 3 was assembled by intramolecular aldol condensation of the dialdehyde 11. This outcome was remarkable, in that 11 is readily epimerizable, and might also be susceptible to β-elimination. Note that the while the diol corresponding to 11 could be readily oxidized to 11 under Swern conditions, attempts to oxidize the corresponding hydroxy aldehyde were not fruitful.

Stereoselective C-N Ring Construction

Organic Synthesis ◽

10.1093/oso/9780199764549.003.0054 ◽

2011 ◽

Author(s):

Douglass Taber

Keyword(s):

Organic Chemistry ◽

Diels Alder ◽

Wolff Rearrangement ◽

Enantiomerically Pure ◽

Amino Esters ◽

Shanghai Institute ◽

Single Diastereomer ◽

Peking University ◽

Convenient Route ◽

Ryoichi Kuwano of Kyushu University showed (J. Am. Chem. Soc. 2008, 130, 808) that diastereomerically and enantiomerically pure pyrollidines such as 2 could be prepared by hydrogenation of the corresponding pyrrole. Victor S. Martín of Universidad de la Laguna found (Organic Lett. 2008, 10, 2349) that the stereochemical outcome of the pyrrolidine-forming Nicholas cyclization could be directed by the protecting group on the N. Jianbo Wang of Peking University established (J. Org. Chem. 2008, 73, 1971) a convenient route to diazo esters such as 6. N-H insertion led to the pyrrolidine, which Zhen-Jiang Xu of the Shanghai Institute of Organic Chemistry and Chi-Ming Che of the University of Hong Kong showed (Organic Lett. 2008, 10, 1529) could be reduced with high diastereoselectivity to the hydroxy ester 7. Alternatively, Professor Wang found that photochemical Wolff rearrangement of 6 delivered the pyrrolidone 8 . Martin J. Slater and Shiping Xie of GlaxoSmithKline optimized (J. Org. Chem. 2008, 73, 3094) the hydroquinine catalyzed enantioselective 3+2 cycloaddition of 9 and 10, leading to the pyrrolidine 11 with high diastereocontrol. Shu Kobayashi of the University of Tokyo developed (Adv. Synth. Cat. 2008, 350, 647) a practical protocol for the aza Diels-Alder construction of enantiomerically-pure piperidines such as 14 . Biao Yu of the Shanghai Institute of Organic Chemistry cyclized (Tetrahedron Lett. 2008, 49, 672) the product from the proline-catalyzed enantioselective aldol of 15 and 16, leading to the substituted piperidine 17 . Michael Shipman of the University of Warwick described (Tetrahedron Lett. 2008, 49, 250) the cyclization of the aziridine derived from 18, that proceeded to give 19 as a single diastereomer, apparently via kinetic side-chain protonation. Takeo Kawabata of Kyoto University found (J. Am. Chem. Soc. 2008, 130, 4153) that intramolecular alkylation to form four, five and six-membered rings from amino esters such as 21 proceeded with remarkable enantioretention. Géraldine Masson and Jieping Zhu of CNRS, Gif-sur-Yvette, condensed (Organic Lett. 2008, 10, 1509) cinnamaldehyde 23 with cyanide and an ω-alkenyl amine to give the intramolecular aza-Diels-Alder substrate 24. Hongbin Zhai of the Shanghai Institute of Organic Chemistry acylated (J. Org. Chem. 2008, 73, 3589) 26 with 27, leading to the ring-closing metathesis precursor 28.

Enantioselective Construction of Alkylated Stereogenic Centers

Organic Synthesis ◽

10.1093/oso/9780199764549.003.0040 ◽

2011 ◽

Author(s):

Douglass Taber

Keyword(s):

Ni Catalyst ◽

Max Planck ◽

Enantiomerically Pure ◽

University Of Oxford ◽

Princeton University ◽

Oxidation Reduction ◽

Single Diastereomer ◽

Rh Catalyst ◽

The University ◽

Diastereomeric Excess

Carsten Bolm of RWTH Aachen developed (Angew. Chem. Int. Ed. 2008, 47, 8920) an Ir catalyst that effected hydrogenation of trisubstituted enones such as 1 with high ee. Benjamin List of the Max-Planck-Institut Mülheim devised (J. Am. Chem. Soc. 2008, 130, 13862) an organocatalyst for the enantioselective reduction of nitro acrylates such as 3 with the Hantzsch ester 4. Gregory C. Fu of MIT optimized (J. Am. Chem. Soc. 2008, 130, 12645) a Ni catalyst for the enantioselective arylation of propargylic halides such as 6. Both enantiomers of 6 were converted to the single enantiomer of 8. Michael C. Willis of the University of Oxford established (J. Am. Chem. Soc. 2008, 130, 17232) that hydroacylation with a Rh catalyst was selective for one enantiomer of the allene 9, delivering 11 in high ee. Similarly, José Luis García Ruano of the Universidad Autónoma de Madrid found (Angew. Chem. Int. Ed. 2008, 47, 6836) that one enantiomer of racemic 13 reacted selectively with the enantiomerically- pure anion 12, to give 14 in high diastereomeric excess. Ei-chi Negishi of Purdue University described (Organic Lett. 2008, 10, 4311) the Zr-catalyzed asymmetric carboalumination (ZACA reaction) of the alkene 15 to give the useful chiron 16. David W. C. MacMillan of Princeton University developed (Science 2008, 322, 77) an intriguing visible light-powered oxidation-reduction approach to enantioselective aldehyde alkylation. The catalytic chiral secondary amine adds to the aldehyde to form an enamine, that then couples with the radical produced by reduction of the haloester. Two other alkylations were based on readily-available chiral auxiliaries. Philippe Karoyan of the Université Pierre et Marie Curie observed (Tetrahedron Lett . 2008, 49, 4704) that the acylated Oppolzer camphor sultam 20 condensed with the Mannich reagent 21 to give 22 as a single diastereomer. Andrew G. Myers of Harvard University developed the pseudoephedrine chiral auxiliary of 23 to direct the construction of ternary alkylated centers. He has now established (J. Am. Chem. Soc. 2008, 130, 13231) that further alkylation gave 24, having a quaternary alkylated center, in high diastereomeric excess.

C-N Ring Construction: The Synthesis of Decursivine by Mascal and by Jia

Organic Synthesis ◽

10.1093/oso/9780199965724.003.0056 ◽

2013 ◽

Author(s):

Douglass F. Taber

Keyword(s):

Pyridinium Salt ◽

Reductive Coupling ◽

University Of Arkansas ◽

Santa Barbara ◽

University Of Illinois ◽

Enantiomerically Pure ◽

Du Bois ◽

Duke University ◽

Barry M. Trost and Justin Du Bois of Stanford University described (Org. Lett. 2011, 13, 3336) the cyclization of 1 to the activated aziridine 2. Liming Zhang of the University of California, Santa Barbara, rearranged (Angew. Chem. Int. Ed. 2011, 50, 3236) the propergylic amine 3 to the azetidinone 4 by N-H insertion of an intermediate Au carbene. Xiao Zheng and Pei-Qiang Huang of Xiamen University effected (J. Org. Chem. 2011, 76, 4952) reductive coupling of 6 with 7 to deliver the ester 8 . Eiji Tayama of Niigata University found (Tetrahedron Lett. 2011, 52, 1819) that 9 could be alkenylated with 10 with substantial retention of absolute configuration. Duncan J. Wardrop of the University of Illinois at Chicago, en route to a synthesis of (-)-swainsonine, observed (Org. Lett. 2011 , 13, 2376) high diastereocontrol in the cyclization of 12 to 13. Iain Coldham of the University of Sheffield also observed (J. Org. Chem. 2011, 76, 2360) substantial diastereoselection in the cyclization of 14 to 15. Robert E. Gawley of the University of Arkansas established (Org. Lett. 2011, 13, 394) that exposure of metalated 16 to just 5 mol % of a chiral ligand was sufficient to enable enantioselective coupling, to deliver 17. Christian Nadeau of Merck Frosst effected (J. Am. Chem. Soc. 2011, 133, 2878) enantioselective addition to the pyridinium salt 19 to give 20. Jiyong Hong of Duke University observed (Org. Lett. 2011, 13, 796) that enantiomerically pure 21 cyclized to the cis diastereomer of 22. With the Hayashi catalyst, cyclization could be driven toward the trans diastereomer, 22, enabling the synthesis of (+)-myrtine. Dawei Ma of the Shanghai Institute of Organic Chemistry found (Org. Lett. 2011, 13, 1602) that the Hayashi catalyst also directed the relative and absolute outcome in the addition of 24 to 23 , to give the piperidine 25. Donn G. Wishka of Pfizer/Groton devised (J. Org. Chem. 2011, 76, 1937) a practical route to the cis-substituted azepane 27, by Beckmann rearrangement of the enantiomerically pure 26 followed by reduction and oxidative cleavage.

C-O Ring Construction: The Theodorakis Synthesis of (-)-Englerin A

Organic Synthesis ◽

10.1093/oso/9780199965724.003.0049 ◽

2013 ◽

Author(s):

Douglass F. Taber

Keyword(s):

Ring Expansion ◽

Propargyl Alcohol ◽

Oxidative Cyclization ◽

Hydroxy Ketone ◽

Santa Barbara ◽

University Of Pittsburgh ◽

Enantiomerically Pure ◽

Boston University ◽

Liming Zhang of the University of California, Santa Barbara, described (J. Am. Chem. Soc. 2010, 132, 8550) the remarkable transformation of a propargyl alcohol 1 into the oxetanone 2. The transformation proceeded without loss of ee, as did the ring expansion of 3 to 5 reported (J. Org. Chem. 2010, 75, 6229) by Peter R. Schreiner of Justus-Liebig University, Giessen, and Andrey A. Fokin of the Kiev Polytechnic Institute. Takeo Taguchi of the Tokyo University of Pharmacy and Life Sciences developed (Chem. Commun. 2010, 46, 8728) a catalyst for the stereoselective conjugate addition of 7 to 6. Mitsuru Shindo of Kyushu University devised (Org. Lett. 2010, 12, 5346) the thioester 10, which condensed smoothly with an α-hydroxy ketone 9 to deliver the lactone 11. Zili Chen of the Renmin University of China and Lin Guo of the Beijing University of Aeronautics and Astronautics developed (Org. Lett. 2010, 12, 3468) the diastereoselective double addition of propargyl alcohol 13 to 12 to give 14. Jian-Wu Xie of Zhejiang Normal University uncovered (J. Org. Chem. 2010, 75, 8716) the catalyzed enantioselective addition of 16 to 15 to give the dihydrofuran 17. James S. Panek of Boston University extended (Org. Lett. 2010, 12, 4624) the utility of the enantiomerically pure allenic nucleophile 19, adding it to the acceptor 18 to give 20 with both ring and sidechain stereocontrol. Biswanath Das of the Indian Institute of Chemical Technology, Hyderabad, showed (Tetrahedron Lett. 2010, 51, 6011) that the epoxide of the tartrate-derived acetonide 21 could be rearranged to the fully substituted, differentially protected tetrahydrofuran 22. Paul E. Floreancig of the University of Pittsburgh uncovered (Angew. Chem. Int. Ed. 2010, 49, 5894) the highly stereocontrolled oxidative cyclization of 22 to 23. Dirk Menche of the University of Heidelberg found (Angew. Chem. Int. Ed. 2010, 49, 9270) that the Pd-mediated addition of 24 to 25 also proceeded with high diastereocontrol. Dipolar cycloaddition to a furan is of increasing importance in target-directed synthesis. Emmanuel A. Theodorakis of the University of California, San Diego, added (Org. Lett. 2010, 12, 3708) the diazo ester 27, prepared from the inexpensive chiral auxiliary pantolactone, to the furan 28.

Stereocontrolled Carbocyclic Construction: The Trauner Synthesis of the Shimalactones

Organic Synthesis ◽

10.1093/oso/9780199764549.003.0080 ◽

2011 ◽

Author(s):

Douglass Taber

Keyword(s):

Allylic Alcohols ◽

Max Planck ◽

Chiral Amine ◽

Ene Reaction ◽

Enantiomerically Pure ◽

University Of Wisconsin ◽

Single Diastereomer ◽

Enantioselective Epoxidation ◽

The University ◽

Technological University

Benjamin List of the Max Planck Institute, Mülheim devised (J. Am. Chem. Soc. 2008, 130, 6070) a chiral primary amine salt that catalyzed the enantioselective epoxidation of cyclohexenone 1 . Larger ring and alkyl-substituted enones are also epoxidized with high ee. Three- and four-membered rings are versatile intermediates for further transformation. Tsutomu Katsuki of Kyushu University developed (Angew. Chem. Int. Ed. 2008, 47, 2450) an elegant Al(salalen) catalyst for the enantioselective Simmons-Smith cyclopropanation of allylic alcohols such as 3. Kazuaki Ishihara of Nagoya University found (J. Am. Chem. Soc. 2007, 129, 8930) chiral amine salts that effected enantioselective 2+2 cycloaddition of α-acyloxyacroleins such as 5 to alkenes to give the cyclobutane 7 with high enantio- and diastereocontrol. Gideon Grogan of the University of York overexpressed (Adv. Synth. Cat. 2008, 349, 916) the enzyme 6-oxocamphor hydrolase in E. coli . The 6-OCH so prepared converted prochiral diketones such as 8 to the cyclopentane 9 in high ee. Richard P. Hsung of the University of Wisconsin found (Organic Lett. 2008, 10, 661) that the carbene produced by oxidation of the ynamide 10 cyclized to 11 with high de. Teck-Peng Loh of Nanyang Technological University extended (J. Am. Chem. Soc. 2008, 130, 7194) butane-2,3-diol directed cyclization to the preparation of the cyclopentane 15. Note that sidechain relative configuration is also controlled. We established (J. Org. Chem. 2008, 73, 3467) that the thermal ene reaction of 17 delivered the tetrasubstituted cyclopentane 18 as a single diastereomer. Tony K. M. Shing of the Chinese University of Hong Kong devised (J. Org. Chem. 2007, 72, 6610) a simple protocol for the conversion of carbohydrate-derived lactones such as 19 to the highly-substituted, enantiomerically-pure cyclohexenone 21. Hiromichi Fujioka and Yasuyuki Kita of Osaka University established (Organic Lett. 2007, 9, 5605) a chiral diol-mediated conversion of the cyclohexadiene 22 to the diastereomerically pure cyclohexenone 24. Dirk Trauner, now of the University of Munich, reported (Organic Lett. 2008, 10, 149) an elegant assembly of the neuritogenic polyketide shimalactone A 28.