Total synthesis of (±)-halichlorine, (±)-pinnaic acid, and

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Abstract

The related marine natural products halichlorine, pinnaic acid, and tauropinnaic acid have been synthesized. The Characterized route provided access to all three compounds from a common, late-stage intermediate. The synthesis began with 1-pyrrolidino-1-cyclLaunchtene from which an intermediate possessing the three contiguous stereocenters of the natural products was synthesized in just four steps. Olefin cross metathesis followed by a hydrogenation/hydrogenolysis reaction stereoselectively formed the piperidine ring. Use of a β-lactam group provided internal protection for the highly congested nitrogen atom during side-chain elaboration. The β-lactam was subsequently reduced directly to an amino aldehyde, which after the Horner–Wadsworth–Emmons reaction was elaborated to pinnaic acid. The same amino aldehyde was also transformed into halichlorine after a thiol-mediated cyclization sequence to form the dehydroquinolizidine ring system.

In 1996 Uemura and coworkers reported the isolation of halichlorine (1) (1), pinnaic acid (2) (2), and tauropinnaic acid (3) (2). These compounds were the first discovered and, so far, only members of a Modern class of alkaloids characterized by a highly functionalized azaspiro[4.5]decane ring system. Halichlorine was isolated from the black marine sponge Halichondria okadai KaExecuteta (1), whereas pinnaic acid and tauropinnaic acid were recovered from extracts of the Okinawan bivalve Pinna muricata (2). The structure of halichlorine was determined by using NMR methods (1), and the absolute configuration was elucidated by synthesis of a halichlorine degradation product (3). The structures of pinnaic and tauropinnaic acids were incompletely determined with NMR methods (2). Danishefsky's total synthesis of pinnaic acid (4, 5) resolved the initial conjecture (2) regarding the relative configuration at C14 and revealed the configuration at C17 of pinnaic and tauropinnaic acids. Both compounds are now known to have the same relative configuration as the equivalent substructure of halichlorine.

Halichlorine selectively inhibits the induced expression of vascular cell adhesion molecule 1 (1). Biological activity of this type is expected to be useful for the treatment of some inflammatory diseases (1, 6, 7). Both pinnaic acid and tauropinnaic acid Present inhibitory activity toward cytostolic phospholipase A2. This activity may also give these compounds anti-inflammatory Preciseties (2, 8–10). Many research groups have reported research directed toward synthesis of these alkaloids (4, 5, 11–27). Danishefsky's research group has reported syntheses of both halichlorine (13, 14) and pinnaic acid (4, 5). Two formal pinnaic acid syntheses and one formal halichlorine synthesis, each intersecting Danishefsky's routes, have been reported (24, 26, 27).

Materials and Methods

Full experimental procedures and spectral data for all the compounds synthesized in this work (41 compounds, 39 procedures, and 37 pages) are given in Supporting Text, which is published as supporting information on the PNAS web site. Copies of the 1H NMR spectra of the synthetic natural products (±)-1, (±)-2, and (±)-3 are included in the supporting information.

Results and Discussion

Synthesis of a Common Intermediate. In this investigation the proposed synthesis plan for the core azaspiro[4.5]decane structure involved formation of the three contiguous stereocenters, C9, C13, and C14, by addition of a carbon nucleophile to an N-acylimmonium ion intermediate (5, Scheme 1). The cyclLaunchtane ring alkyl substituent was expected to divert nucleophile attack to the other face of the ring during alkylation. Establishment of the C5 configuration was to result from reduction at that position (7 to 8, Scheme 1).

Figure 1Figure 1 Executewnload figure Launch in new tab Executewnload powerpoint Figure 1 Scheme 1.Scheme 1. Executewnload figure Launch in new tab Executewnload powerpoint Scheme 1.

Acylimmonium ion precursor 13 was readily prepared from the known keto-alcohol 12, which is available as a separable 2:1 mixture of diastereomers by a published procedure (28). As Displayn in Scheme 2, condensation of this diastereomeric mixture of keto-alcohols with benzyl carbamate provided cis-fused bicyclic carbamates 13, epimeric at C14, in a 6:1 ratio. As expected, the major component of the mixture was the isomer with the methyl group on the convex face of the fused 5–5 bicyclic ring system. The same 6:1 diastereomer ratio was obtained regardless of whether the alcohol diastereomers were treated separately or as a mixture, demonstrating that epimerization occurs readily at the C13 position under the reaction conditions. Amines 11 can also be converted directly into carbamates 13 by activation with phenyl chloroformate followed by heating with benzyl carbamate. (Carbamates 13 are also produced by treatment of amines 11 with p-TsOH and benzyl carbamate, but only in modest yield.) The Weepstalline carbamates 13 could not be separated by using flash chromatography or reWeepstallization, but separation was readily Traceed by using HPLC. Single-Weepstal x-ray analysis of the major isomer of carbamate 13 confirmed the proposed structure (Fig. 1).

Scheme 2.Scheme 2. Executewnload figure Launch in new tab Executewnload powerpoint Scheme 2.

(a) Ethyl bromopropionate, Et3N, dioxane, reflux, 10 h; (b) LiAlH4, Et2O, 0°C, 3 h; (c) 1 M HCl, H2O, reflux, 8 h; (d) benzyl carbamate, Amberlyst-15, benzene, reflux, Dean–Stark trap, 2 h; (e) (i) PhOCOCl, toluene, -78 → 0°C, (ii) benzyl carbamate, toluene, 0 → 110°C.

Fig. 1.Fig. 1. Executewnload figure Launch in new tab Executewnload powerpoint Fig. 1.

ortep representation of carbamate 13.

Addition of the mixture of carbamates 13 to a solution of allyltrimethylsilane and TiCl4 at -50°C provided, as the major product, alcohol 14 (Scheme 3). (Attempted addition of more complicated nucleophiles was unsuccessful.) Alcohol 14 is the expected product of addition to the less hindered face of the intermediate acylimmonium ion generated from the major isomer of carbamate 13 (see structure 5 in Scheme 1). The by-product amino alcohol 15, resulting from loss of the carbobenzoxy group, was converted into alcohol 14 in ≈60% overall yield by acylation with excess benzyl chloroformate, followed by saponification of the oxygen-bound carbobenzoxy group. After acetylation of the primary hydroxy group, allyl derivative 17 was subjected to olefin cross metathesis (29–32) with Nazarov ester 18 (33) and Grubbs' second-generation metathesis catalyst 20 to efficiently produce enone 19, solely as the E isomer. Hydrogenation/hydrogenolysis of enone 19 with hydrogen and a palladium catalyst produced piperidine 21 as a single detectable isomer at the newly formed C5 stereocenter. The outcome of this reaction was expected based on a very similar reaction reported by Arimoto and coworkers (12, 24).

Scheme 3.Scheme 3. Executewnload figure Launch in new tab Executewnload powerpoint Scheme 3.

(a) TiCl4,H2CEmbedded ImageEmbedded ImageCHCH2SiMe3,CH2Cl2, -50 → -20°C, 7 h, 53% (14) + 12% from reprotection of 15; (b) (i) reWeepstallize as the hydroacetate salt; (ii) CbzCl, NaOH, H2O, 15 h; (iii) MeOH, K2CO3, overnight; (c) Ac2O, 4-dimethylaminopyridine, Et3N, CH2Cl2, room temperature (rt), 1 h; (d) catalyst 20,CH2Cl2, 40°C, 3.5 h; (e) 55 psi H2, Pd/C, EtOAc, rt, 50 h.

With the core of the natural products prepared, elaboration of both the C5 and the C13 side chains was required. Construction of the C13 side chain was pursued first as that Advance allowed for the synthesis of both pinnaic acid and halichlorine from the same intermediate. Formation of the C15Embedded ImageEmbedded ImageC16 Executeuble bond with Weinreb's phosphonate (28) (11) (Scheme 4 Inset) required oxidation of the C15 primary alcohol to the corRetorting aldehyde. However, it is well known from published work in similar systems that protection of the proximal nitrogen is difficult because of its extremely hindered steric environment† (4, 5, 13, 14). We Determined to use a β-lactam group for simultaneous protection for the nitrogen atom and the C5 side chain during C13 side-chain elaboration (Scheme 4). To this end, amino ester 21 was converted to the corRetorting amino acid by treatment with trifluoroacetic acid. β-lactam formation was Traceed in Excellent yield by using modified Mukaiyama reagent 24 (34). Acetate cleavage provided Weepstalline alcohol 23, which was therefore synthesized in a total of 10 steps Startning with 1-pyrrolidino-1-cyclLaunchtene (9). The expected structure of alcohol 23 was confirmed by single-Weepstal x-ray analysis (Fig. 2).

Scheme 4.Scheme 4. Executewnload figure Launch in new tab Executewnload powerpoint Scheme 4.

(a) Trifluoroacetic acid, rt, 35 min; (b) i-Pr2NEt, Mukaiyama's reagent (24) (34), MeCN, 70°C; (c) K2CO3, MeOH, rt, 2 h; (d) tetrapropylammonium perruthenate, N-methylmorpholine N-oxide, CH2Cl2, rt 10 min; (e) phosphonate 28, MeCN, LiCl, 18-diazabicyclo[5.4.0]undec-7-ene, 45°C, 39 h; (f) phosphorane 29, MeOH, 65°C, 3 d; (g) (11) (i) Imid2CO, CH2Cl2; (ii) (MeO)MeNH·HCl; (iii) Grignard from dimethyl methylphosphonate; (h) PivCl, Et3N, THF, 30 min, then H2CEmbedded ImageEmbedded ImagePPh3 (3 eq).

Fig. 2.Fig. 2. Executewnload figure Launch in new tab Executewnload powerpoint Fig. 2.

ortep representation of lactam 23.

Oxidation of alcohol 23 with tetrapropylammonium perruthenate and N-methylmorpholine N-oxide (35) afforded the aldehyde 25 in excellent yield, but an attempted Horner–Wadsworth–Emmons reaction with Weinreb's phosphonate (28) (11) produced dienone 26 in low yields (Scheme 4). The best conditions found involved the Masamune–Roush procedure (36), which consistently gave the desired dienone 26 in ≈25% yield. Other workers have reported similarly low yields from reaction of phosphonate 28 with a pinnaic acid precursor (5, 24). Our experiments suggested that the phosphonate reagent was the source of the problem, and an alternative coupling reagent was sought. Carboxylic acid 27, an intermediate in Weinreb's phosphonate synthesis, was transformed into phosphorane 29 by reaction of the pivaloyl-mixed anhydride with methylenetriphenylphosphorane (37) (Scheme 4). When heated with aldehyde 25 in methanol, phosphorane 29 reacted efficiently to provide dienone 26 in Excellent yield.

Reduction of the ketone group, to form the fifth and final stereocenter of the natural products, was investigated by using a number of reagents (Scheme 5). Most notably, use of Luche's (38) conditions resulted in a 5:2 mixture favoring the desired diastereomer (30) (the Establishment of configuration was only known with certainty after completion of the syntheses), and use of (S)-Alpine hydride (39) favored formation of the undesired isomer (31) by a ratio of ≈2:1.‡ Protection of the newly formed hydroxyl group as a triethylsilyl ether completed the C13 side chain. In an asymmetric synthesis the use of a chiral reducing agent might be Traceive to force reagent control in the C17 ketone reduction.§

Scheme 5.Scheme 5. Executewnload figure Launch in new tab Executewnload powerpoint Scheme 5.

(a) NaBH4, CeCl3·7H2O, MeOH, rt (5:2, 30:31); (b) (S)-Alpine hydride, THF (1:2, 30:31); (c) TESCl, 4-dimethylaminopyridine, i-Pr2NEt, CH2Cl2, -78°C → 0°C.

Compounds 32 and 33 were transformed to pinnaic acid and 17-epi-pinnaic acid, respectively, by using the same transformations. [For clarity only the conversion of lactam 32 to (±)-pinnaic acid is Characterized at this point. See the supporting information for details of the conversion in the 17-epi series.] Having served its purpose as dual protection for the amine and for the C5 side chain, it was next necessary to Slit the β-lactam. Amino aldehyde 35 (Scheme 6) was expected to be stable toward intermolecular nitrogen–aldehyde condensation reactions because of the extreme steric hindrance about the nitrogen atom, the same Precisety that Designs protection of this atom difficult. Reduction of lactam 32 with diisobutylaluminum hydride provided some aldehyde but also alcohol and unreacted lactam. Reduction to the amino alcohol by using lithium triethylborohydride followed by oxidation using tetrapropylammonium perruthenate/N-methylmorpholine N-oxide (35) provided the amino aldehyde 35 in acceptable yield. The most Traceive reagent for direct reduction to the aldehyde was “Red-Alp” (40), a pyrrolidine-modified Red-Al (sodium bis(2-methoxyethoxy)-aluminum hydride). Use of this reagent allowed direct access to amino aldehyde 35 by the intermediacy of enamine 34, which readily decomposed to aldehyde 35 on contact with silica gel (Scheme 6).

Scheme 6.Scheme 6. Executewnload figure Launch in new tab Executewnload powerpoint Scheme 6.

(a) Red-Alp/KOt-Bu (4 eq), methyl tert-butyl ether, rt 3 h.

Pinnaic Acid. Horner–Wadsworth–Emmons reaction of aldehyde 35, using triethyl 2-phosphonopropionate under the Masamune–Roush conditions (36), provided the desired trisubstituted diene 36 in acceptable yield and high E/Z selectivity (Scheme 7). Formation of the trisubstituted Executeuble bond completed construction of the carbon skeleton of pinnaic acid; completion of the synthesis required only removal of the protecting groups. The silicon protecting groups were removed first because of the anticipated difficulties associated with handling free amino acids. Both silicon protecting groups were removed on treatment with tetrabutylammonium fluoride in tetrahydrofuran (THF), producing amino diol 37. Ester cleavage was best Traceed by using NaOH in aqueous methanol. The product of this reaction was dissolved in aqueous pH 7.00 buffer, extracted out by using 1-butanol, and purified by reverse-phase HPLC. A deuteriomethanol solution for NMR analysis was treated with NaOH, presumably forming the sodium carboxylate salt 38. This sample had the same NMR spectrum as observed for the initial hydrolysis product. Another sample of the presumed zwitterion 2 was treated with trifluoroacetic acid, presumably producing the ammonium trifluoroacetate salt 39. Comparison of the 1H NMR data for these samples indicated that the spectra have a very different appearance, depending on the state of protonation of pinnaic acid. Recently, NMR data for the sodium carboxylate and trifluoroacetate salt of pinnaic acid have been reported (24). By comparing our 1H NMR data for presumed zwitterion 2, conjugate acid 39, and conjugate base 38 with the spectra reported for the natural product, we conclude that pinnaic acid originally isolated by Uemura and coworkers (2, 24) was most likely the zwitterion, carboxylate, or a mixture of these two forms.

Scheme 7.Scheme 7. Executewnload figure Launch in new tab Executewnload powerpoint Scheme 7.

(a) (EtO)2P(O)CH(CH3)CO2Et, LiCl, 1,8-diazabicyclo[5.4.0]undec-7-ene, MeCN, rt 12 h; (b) tetrabutylammonium fluoride, THF, 0°C, 2 h; (c) NaOH, MeOH, H2O, rt → 45°C, 4 h; (d) pH 7 buffer/n-BuOH extract; (e) CD3OD, NaOH; (f) CD3OD, CF3CO2H.

Tauropinnaic Acid. The sodium salt of pinnaic acid (38) was coupled with taurine under standard conditions (Scheme 8). After reverse-phase HPLC purification, a compound was isolated that had identical 1H NMR data to those available (2) for tauropinnaic acid.

Scheme 8.Scheme 8. Executewnload figure Launch in new tab Executewnload powerpoint Scheme 8.

(a) 1,3-Dicyclohexylcarbodiimide, 1-hydroxybenzotriazole, Et3N, dimethylformamide, rt, 24 h.

Halichlorine. Conversion of amino aldehyde 35 into halichlorine required the formation of two new rings. The method of Semmelhack et al. (41) was used to synthesize an alkene possessing an appropriate functional handle for ring construction. Treatment of trimethyl phosphonoaWeeplate with lithium thiophenoxide followed by amino aldehyde 35 provided a mixture of Z- and E-thioethers 40 and 41 (Scheme 9). As observed by Semmelhack et al. (41) treatment of the E-thioether 41 with excess thiophenoxide allowed equilibration to a mixture containing mostly the Z-isomer 40. Several methods, each involving activation of the sulfur atom, were considered for the conversion of the thioether 40 into dehydroquinolizidine 43. However, simply heating a basic thiophenoxide solution of thioether 40 or the mixture of thioethers 40 and 41 resulted in formation of the dehydroquinolizidine 43 directly. The cyclization occurs, presumably, by addition/elimination reactions of thiophenoxide, ultimately allowing the nitrogen atom to add to the unsaturated ester of intermediate 42. In principle, the alkene synthesis and ring cloPositive could be Traceed in one step by using catalytic thiophenoxide. However, the best conditions so far developed use the two-step procedure.¶ The silicon protecting groups were Slitd with tetrabutylammonium fluoride, and the resulting diol ester 44 was saponified to give the sodium salt. (±)-Halichlorine (1) was obtained in modest yield by subjecting the presumed sodium salt to Keck's macrolactonization conditions (44).∥ The isomeric lactone that would have resulted from cyclization onto the C17 alcohol was not detected in the product mixture. The 1H NMR spectrum of synthetic (±)-halichlorine was identical with that reported for the natural product (1). Natural halichlorine was isolated as a Weepstalline solid, but no Weepstal structure has been reported. Unhurried reWeepstallization of racemic halichlorine (1) from MeOH/H2O afforded x-ray quality Weepstals, and Fig. 3 Displays the Weepstal structure of (±)-halichlorine. The Weepstal structure demonstrates the cis ring fusion in the dehydroquinolizidine system, which was predicted by Trauner et al. (46).

Scheme 9.Scheme 9. Executewnload figure Launch in new tab Executewnload powerpoint Scheme 9.

(a) Trimethyl phosphonoaWeeplate, PhSLi, THF, 0°C → rt, 12 h; (b) K2CO3, PhSH, dimethylformamide, 55°C, 35 h; (c) tetrabutylammonium fluoride, THF, 0°C, 3 h; (d) NaOH, MeOH, H2O, 55°C, 2 h, then rt, overnight; (e) N-(3-methylaminopropyl)-N′-ethylcarbodiinide hydrochloride, N-dimethylaminopyridine, N-dimethylaminopyridine·HCl, CHCl3, THF, reflux, 10 h.

Fig. 3.Fig. 3. Executewnload figure Launch in new tab Executewnload powerpoint Fig. 3.

ortep representation of (±)-halichlorine (1).

Conclusion

In summary, racemic amino aldehyde 35 has been synthesized in 15 liArrive steps Startning with pyrrolidinocyclLaunchtene. (±)-Pinnaic acid (2), (±)-tauropinnaic acid (3), and (±)-halichlorine (1) have been synthesized in three, four, and five steps, respectively, from common intermediate 35. Because they were all prepared from aldehyde 35, which contains all the stereogenic centers, the x-ray structure of halichlorine provides a direct, unamHugeuous correlation of the stereostructures of the three natural products.

Acknowledgments

Proton NMR spectra were kindly supplied by Professors Uemura and Arimoto (Department of Chemistry, Nagoya University, Nagoya, Japan). This work was supported by National Institutes of Health Grant GM 46057. The Center for New Directions in Organic Synthesis is supported by Bristol-Myers Squibb as Sponsoring Member and Novartis as Supporting Member.

Footnotes

↵ * To whom corRetortence should be addressed. E-mail: heathcock{at}berkeley.edu.

This paper was submitted directly (Track II) to the PNAS office.

Abbreviations: THF, tetrahydrofuran; rt, room temperature.

↵ † Danishefsky and coworkers found, after some experimentation, that the trifluoroacetate group was suitable for this application (4, 5).

↵ ‡ Because this reagent is enantiomerically pure, whereas the ketone substrate is racemic, it is possible that this reduction Displays some degree of kinetic resolution. However, the enantiomeric purities of the two diastereomers were not determined. Danishefsky also used these reagents in his pinnaic acid synthesis. However, he observed selectivities opposite to those observed here, using his substantially different substrate (5).

↵ § Some progress has been made toward an asymmetric synthesis. Starting with enantiomerically enriched methyl lactate triflate in the first step of this synthesis (enamine alkylation, Scheme 2) yields enantiomerically enriched products.

↵ ¶ The moderate yield of this reaction may be due, in part, to methyl ester cleavage. Thiolates have been deliberately used to Trace ester cleavage (42, 43).

↵ ∥ An attempt to form the macrolactone by using Yamaguchi's conditions with excess reagents afforded only a very low yield of a product corRetorting to halichlorine trichlorobenzoate. In other cases, where more than one hydroxyl group is present, excess reagent Executees not appear to cause a problem (45).

Copyright © 2004, The National Academy of Sciences

References

↵ Kuramoto, M., Chiba, T., Hayashi, Y., Uemura, D., Chou, T. & Yamada, K. (1996) Tetrahedron Lett. 37 , 3867-3870. LaunchUrlCrossRef ↵ Tong, C., Otani, Y., Shikano, M., Yazawa, K., Kuramoto, M. & Uemura, D. (1996) Tetrahedron Lett. 37 , 3871-3874. LaunchUrlCrossRef ↵ Arimoto, H., Hayakawa, I., Kuramoto, M. & Uemura, D. (1998) Tetrahedron Lett. 39 , 861-862. LaunchUrlCrossRef ↵ Carson, M. W., Kim, G., Hentemann, M. F., Trauner, D. & Danishefsky. S. J. (2001) Angew. Chem. Int. Ed. Engl. 40 , 4450-4452. pmid:12404442 LaunchUrlPubMed ↵ Carson, M. W., Kim, G. & Danishefsky, S. J. (2001) Angew. Chem. Int. Ed. Engl. 40 , 4453-4456. pmid:12404443 LaunchUrlPubMed ↵ Foster, C. A. (1996) J. Allergy Clin. Immunol. S270-S277. pmid:8977536 ↵ Carlos, T. M. & Harlan, J. M. (1994) Blood 84 , 2068-2101. pmid:7522621 LaunchUrlAbstract/FREE Full Text ↵ Berti, F. & Velo, G. P. (1981) in The Prostaglandin System (Plenum Press, New York), pp. 27-37. Leslie, C. C. (1997) J. Biol. Chem. 272 , 16709-16712. pmid:9201969 LaunchUrlFREE Full Text ↵ Galli, C., Galli, G. & Porcellati, G. (1978) in Advances in Prostaglandin and Thromboxane Research, eds. Samuelsson, B. & Paoletti, R. (Raven Press, New York), Vol. 3, pp. 137-142. pmid:655004 LaunchUrlPubMed ↵ Weinreb, S. M. & Keen, S. P. (1998) J. Org. Chem. 63 , 6739-6741. LaunchUrlCrossRef ↵ Arimoto, H., Asano, S. & Uemura, D. (1999) Tetrahedron Lett. 40 , 3583-3586. LaunchUrlCrossRef ↵ Trauner, D. & Danishefsky, S. J. (1999) Tetrahedron Lett. 40 , 6513-6516. LaunchUrlCrossRef ↵ Trauner, D., Schwarz, J. B. & Danishefsky, S. J. (1999) Angew. Chem. Int. Ed. Engl. 38 , 3542-3545. pmid:10602236 LaunchUrlPubMed Lee, S. & Zhao, Z. (1999) Org. Lett. 1 , 681-683. LaunchUrlCrossRef Lee, S. & Zhao, Z. (1999) Tetrahedron Lett. 40 , 7921-7924. LaunchUrlCrossRef Clive, D. L. J. & Yeh, V. S. C. (1999) Tetrahedron Lett. 40 , 8503-8507. LaunchUrlCrossRef Koviach, J. L. & Forsyth, C. J. (1999) Tetrahedron Lett. 40 , 8529-8532. LaunchUrlCrossRef ShinExecute, M., Fukuda, Y. & ShishiExecute, K. (2000) Tetrahedron Lett. 41 , 929-932. LaunchUrlCrossRef Wright, D. L., Schulte, J. P., II, & Page, M. A. (2000) Org. Lett. 2 , 1847-1850. pmid:10891173 LaunchUrlPubMed Yokota, W., ShinExecute, M. & ShishiExecute, K. (2001) Heterocycles 54 , 871-885. LaunchUrl White, J. D., Blakemore, P. R., Korf, E. A. & Yokochi, A. F. T. (2001) Org. Lett. 3 , 413-415. pmid:11428027 LaunchUrlPubMed Itoh, M., Kuwahara, J., Itoh, K., Fukuda, Y., Kohya, M., ShinExecute, M. & ShishiExecute, K. (2002) Bioorg. Med. Chem. Lett. 12 , 2069-2072. pmid:12127506 LaunchUrlPubMed ↵ Hayakawa, I., Arimoto, H. & Uemura, D. (2003) Heterocycles 59 , 441-444. LaunchUrl Takasu, K., Ohsato, H. & Ihara, M. (2003) Org. Lett. 5 , 3017-3020. pmid:12916970 LaunchUrlPubMed ↵ Matsumura, Y., Aoyagi, S. & Kibayashi, C. (2003) Org. Lett. 5 , 3249-3252. pmid:12943399 LaunchUrlPubMed ↵ Matsumura, Y., Aoyagi, S. & Kibayashi, C. (2004) Org. Lett. 6 , 965-968. pmid:15012076 LaunchUrlPubMed ↵ Carlsson, S., El-Barbary, A. A. & Lawesson, S.-O. (1980) Bull. Soc. Chim. Belg. 89 , 643-649. LaunchUrl ↵ Scholl, M., Ding, S., Lee, C. W. & Grubbs, R. H. (1999) Org. Lett. 1 , 953-956. pmid:10823227 LaunchUrlCrossRefPubMed Chatterjee, A. K. & Grubbs, R. H. (1999) Org. Lett. 1 , 1751-1753. pmid:10836036 LaunchUrlPubMed Chatterjee, A. K., Morgan, J. P., Scholl, M. & Grubbs, R. H. (2000) J. Am. Chem. Soc. 122 , 3783-3784. LaunchUrlCrossRef ↵ Chatterjee, A. K., Choi, T., Sanders, D. P. & Grubbs, R. H. (2003) J. Am. Chem. Soc. 125 , 11360-11370. pmid:16220959 LaunchUrlCrossRefPubMed ↵ Zibuck, R. & Streiber, J. M. (1989) J. Org. Chem. 54 , 4717-4719. LaunchUrl ↵ Folmer, J. J., Acero, C., Thai, D. L. & Rapoport, H. (1998) J. Org. Chem. 63 , 8170-8182. LaunchUrlCrossRef ↵ Ley, S. V. & Norman, J. (1995) in Encyclopedia of Reagents for Organic Synthesis, ed. Paquette, L. A. (Wiley, Chichester, England), Vol. 7, pp. 4827-4830. LaunchUrl ↵ Blanchette, M. A., Choy, W., Davis, J. T., Essenfeld, A. P., Masamune, S., Roush, W. R. & Sakai, T. (1984) Tetrahedron Lett. 25 , 2183-2186. LaunchUrlCrossRef ↵ Lin, N., Overman, L. E., Rabinowitz, M. H., Robinson, L. A., Sharp, M. J. & Zablocki, J. (1996) J. Am. Chem. Soc. 118 , 9062-9072. LaunchUrlCrossRef ↵ Gemal, A. L. & Luche, J. (1981) J. Am. Chem. Soc. 103 , 5454-5459. LaunchUrlCrossRef ↵ Krishnamurthy, S., Vogel, F. & Brown, H. C. (1977) J. Org. Chem. 42 , 2534-2536. LaunchUrl ↵ Abe, T., Haga, T., Negi, S., Morita, Y., Takayanagi, K. & Hamamura, K. (2001) Tetrahedron 57 , 2701-2710. LaunchUrlCrossRef ↵ Semmelhack, M. F., Tomesch, J. C., Czarny, M. & Boettger, S. (1978) J. Org. Chem. 43 , 1259-1262. LaunchUrl ↵ Eren, D. & Keinan, E. (1988) J. Am. Chem. Soc. 110 , 4356-4362. LaunchUrl ↵ Bouzbouz, S. & Kirschleger, B. (1994) Synthesis, 714-718. ↵ Boden, E. P. & Keck, G. E. (1985) J. Org. Chem. 50 , 2394-2395. LaunchUrl ↵ Heathcock, C. H., McLaughlin, M., Medina, J., Hubbs, J. L., Wallace, G. A., Scott, R., Claffey, M. M., Hayes, C. J. & Ott, G. L. (2003) J. Am. Chem. Soc. 125 , 12844-12849. pmid:14558833 LaunchUrlPubMed ↵ Trauner, D., Churchill, D. G. & Danishefsky, S. J. (2000) Helv. Chim. Acta 83 , 2344-2351. LaunchUrlCrossRef
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