Diastereoselective ring closing

Scheme 9. Diastereoselective ring-closing metathesis and C8 methylation according to Kalesse et al. to synthesize C7-C2I (fragment A-B) (PMB = /i-methoxybenzyl).

Negishi E, Tan Z (2005) Diastereoselective, Enantioselective, and Regioselective Carbo-alumination Reactions Catalyzed by Zirconocene Derivatives. 8 139-176 Netherton M, Fu GC (2005)Pa]ladium-catalyzed Cross-Coupling Reactions of Unactivated Alkyl Electrophiles with Organometallic Compounds. 14 85-108 Nicolaou KC, King NP, He Y (1998) Ring-Closing Metathesis in the Synthesis of EpothUones and Polyether Natmal Products. 1 73-104 Nishiyama H (2004) Cyclopropanation with Ruthenium Catalysts. 11 81-92 Noels A, Demonceau A, Delaude L (2004) Ruthenium Promoted Catalysed Radical Processes toward Fine Chemistry. 11 155-171... 

Ring-closing reactions promoted by mercuric salts are valuable transformations which find an increasing use in the total synthesis of various natural products.130-140 Several examples of solvomercurations demonstrating the applicability of these transformations to the synthesis of natural product precursors are presented in Table 2. Piperidines (entry a), 141 pyrans (entries b-d), 142-144 and furans (entries e, f)14S>146 have been obtained in good yields and diastereoselectivity. These derivatives serve as starting materials for various natural products and can be demercu-rated under reducing conditions.147... 

Representatives of the bridged sulfone system 70 have been subjected to ruthenium catalysed ring-closing metathesis reactions (Grubbs catalyst) and shown to afford, in low yields, a few selected cyclic dimers and trimers, of all the possibilities available. The diastereoselectivities observed were rationalised in terms of kinetic control involved with internal ruthenium/sulfonyl oxygen coordination . 

Novel bicyclic imidazo-oxazaphosphinines have been synthesized in high diastereoselectivity by Marsault and Just <1996TL977>. In the first step, iV-tritylimidazole 209 was lithiated and, subsequently, treated with (.S )-propylcnc oxide as a chiral auxiliary and acetic acid to give the intermediate 210, which was reacted with alkyl dichlorophos-phite to yield the ring-closed product 211 as a single diastereomer (Scheme 33). Extension of these approaches for further derivatives 212 has also been published <1998NN939>. 

This chelation-controlled addition generated the homoallylic alcohols 86 with a diastereoselectivity of syn anti=S6ll4 , In contrast to the other syntheses described so far, the ring closing reaction was a 5 2 reaction but not a... 

The first diastereoselective total synthesis of ( )-guanacastepene A (rac-187) was published in a series of papers by Danishefsky and co-workers [107-110]. The tricyclic carbon framework was assembled by interplay of enolate alkylations and ring-closing carbon/carbon double bond forming reactions (Fig. 19). Commercially available cyclopentenone 90 was utilized as the A-ring precursor. 

Stabilized sulfonium ylides react with cyclopentenone to give the corresponding cyclopropane with high diastereoselectivity as a result of base- or ylide-mediated (g) equilibration of the intermediate betaine.38 When using chiral sulfonium ylides, betaine equilibration compromises enantioselectivity, because whereas one diastereomer ring closes rapidly, the other diastereomer undergoes epimerization at the ester stereocentre, ultimately leading to the opposite enantiomer of the cyclopropane. 

The spiro carbon is a stereogenic center in spiropyrans, but because of the achiral structure of the open merocyanine form, the photochromic process will always lead to racemization unless additional chiral moieties are present. When a chiral substituent was introduced, remote from the spiro center, it was possible to isolate diastereo-isomers of the spiropyrans, but rapid epimerization at the spiro center occurred.1441 Diastereoselective switching was successful with 28, in which a stereogenic center was present close to the spiro carbon (Scheme 15).[45] Distinct changes in CD absorption at 250 nm were monitored upon irradiation with UV (250 nm) and with visible light (>530 nm) and a diastereomeric ratio of 1.6 1.0 was calculated for the closed form 28. Furthermore, a temperature-dependent CD effect was observed with this system it was attributed to an inversion of the diastereomeric composition at low temperatures. It might be possible to exploit such effects in dual-mode chiral response systems. A diastereoselective ring-closure was also recently observed in a photochromic N6-spirobenzopyran tricarbonyl chromium complex. 451 ... 

Despite the unrivaled easy access to 1,4-dicarbonyl compounds, only a few examples of the application of Stetter reactions in the synthesis of natural products have been reported to date [55]. Tius et al. have employed a diastereoselective in-termolecular Stetter reaction and a ring-closing metathesis reaction as the key steps in their elegant synthesis of roseophilin (58 Scheme 9.16) [56]. The 1,4-... 

In a beautifully choreographed sequence of events, Judd and co-workers installed the C3 to C4 bridged bicyclic lactam moiety of 129 with diastereoselective control via an Ugi 4-component coupling, ring-closing metathesis, and Heck reaction <07OL5119>. 

Schmidt B, Westhus M (2000) Diastereoselectivity in a ring closing metathesis reaction with a remote stereogenic centre leading to quaternary dihydropyrans. Tetrahedron 56 2421-2426... 

Fustero, S., Bartolome, A., Sanz-Cervera, J. F., et al. (2003) Diastereoselective synthesis of fluorinated, seven-membered P-amino acid derivatives via ring-closing metathesis. Org. Lett., 5, 2523-2526. 

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