Oxazolidinones cyclopropanation

Another recent example of the use of chiral C2-symmetric bis(oxazoline) ligands is the work by Mamai and co-workers.This group studied the cyclopropanation reaction of oxazolidinones 80a and 80b using diphenylsulfonium isopropylide 248,... 

An internal diastereoselective alkylation reaction leading to cyclopropane formation 24 has been reported40. Although the 2-oxazolidinone moiety employed was not chiral, it should be possible to perform this reaction using a chiral auxiliary of the oxazolidinone type. 

Stereosectivity is a broad term. The stereoselectivity in cyclopropanation which has been discussed in the above subsection, in fact, can also be referred to as diastereoselectivity. In this section, for convenience, the description of diastereoselectivity will be reserved for selectivity in cyclopropanation of diazo compounds or alkenes that are bound to a chiral auxiliary. Chiral diazoesters or chiral Ar-(diazoacetyl)oxazolidinone have been applied in metal catalysed cyclopropanation. However, these chiral diazo precursors and styrene yield cyclopropane products whose diastereomeric excess are less than 15% (equation 129)183,184. The use of several a-hydroxy esters as chiral auxiliaries for asymmetric inter-molecular cyclopropanation with rhodium(II)-stabilized vinylcarbenoids have been reported by Davies and coworkers. With (R)-pantolactone as the chiral auxiliary, cyclopropanation of diazoester 144 with a range of alkenes provided c yield with diastereomeric excess at levels of 90% (equation 130)1... 

Chiral Rh(II) oxazolidinones Rh2(BNOX)4 and Rh2(IPOX)4 (25a,b) were not as effective as Rh2(MEPY)4 for enantioselective intramolecular cyclopropanation, even though the steric bulk of their chiral ligand attachments (COOMe versus i-Pr or CH2Ph) are similar. Significantly lower yields and lower enantioselectivides resulted from dinitrogen extrusion from prenyl diazoacetate catalyzed by either Rh2(4.S -lPOX)4 or Rh2(4S-BNOX)4. This difference, and those associated with butenolide formation [91], can be attributed to the ability of the carboxylate substituents to stabilize the carbocation form of the intermediate metal carbene (3b), thus limiting the Rh2(MEPY)4-catalyzed reaction to concerted carbene addition onto both carbon atoms of the C-C double bond. 

The capabilities of 5-8 for enantioselective cyclopropanation were determined (34) from reactions at room temperature of d- and/or /-menthyl diazoacetate (MDA) with styrene (Table 1), which allows direct comparison with results from both the Aratani (A-Cu) and Pfaltz (P-Cu) catalysts (19, 24). Cyclopropane product yields ranged from 50 to 75%, which were comparable to those obtained with chiral copper catalysts, but enantiomeric excesses were considerably less than those reported from use of either P-Cu or A-Cu. Furthermore, these reactions were subject to exceptional double diastereoselectivity not previously seen to the same degree with the chiral copper catalysts. Although chiral oxazolidinone ligands proved to be promising, the data in Table 1 suggested that steric interactions alone would not sufficiently enhance enantioselectivities to advance RI12L4 as an alternative to A-Cu or P-Cu. 

Table 1. Diastereoselectivities for the Cyclopropanation of Styrene by Menthyl Diazoacetate with Chiral Rhodium(H) Oxazolidinone Catalysts...

Chiral dirhodium(II) tetrakis(methyl-2-oxopyrrolidine-5-carboxylates) and dirhodium(ll) tetrakis(4-benzyl-2-oxazolidinones) have been studied to determine factors influencing the enantiocontrol in metal-carbene transformations. Doyle et al. used the Tektronix CAChe molecular modeling system to examine the steric control on the optical yields of cyclopropanation products.Details of the force field are not available in the open literature. The low energy conformation of the proposed metal-carbene intermediate predicted absolute configurations of the product that conflicted with experiment. However, when the metal-carbene was weakly bonded to styrene, the low energy conformer... 

Chiral Ligands. Bidentate chelation of dirhodium(II) compounds by chiral oxazolidinones creates asymmetric sites on the metal, leading to induction in cyclopropanations and carbon-hydrogen insertion reactions. The oxazolidinones are less effective in this capacity than are the pyrrolidines. ... 

Groaning and Meyers have recently synthesized the (5)-( + )-enantiomer of Danishefsky s early intermediate 65 by a short alternative route (Scheme 9) (57). In one of the key steps, cyclopropanation of the chiral unsaturated bicyclic oxazolidinone 77 took place preferentially on the convex face (>20 1). Subsequent treatment of the product 78, a masked acyliminium ion, with aliyltrimethylsilane and titanium tetrachloride introduced the allyl group at the angular position, again with good stereocontrol (20 1). The preparation of (+ )-65 in effect represents a formal synthesis of (- )-indolizomycin (63). 

In early attempts at rhodium-catalyzed diastereoselective asymmetric cyclopropanation chiral 3-diazoacetyl-2-oxazolidinones 1 were added to styrene73. After tram esterification with ethanol, optically active cis- and /rans-cyc opropanes 2 were isolated with 13-14% ee. 

Tandem coupling and cycliasth a-arylvinylated cyclopropanes and het and oxazolidinones. Furan derivatises i... 

Tandem coupling and cyclization. Functionalized allenes are converted to a-arylvinylated cyclopropanes and heterocycles including epoxides, tetrahydrofurans, and oxazolidinones. Furan derivatives are formed from allenyl ketones." ... 

Whereas the preceding processes involving ring openings of cyclopropanes provide useful [3+2] entries to cyclopentanes, the use of simpler substrates in [3+2] cycloadditions is made possible by the development of reductive cycloaddition pathways. Such reactions were initially developed in the context of stoichiometric processes, where metallacycles were prepared by oxidative cyclizations of enones and alkynes, followed by either protonation or alkylation of the nickel 0-enolate functionality. Catalytic protocols involving various intramolecular combinations of 7t-systems include formal [3+2] reductive cycloadditions of bis-enones to form bicyclooctanols (Scheme 3-33), of enones with unsaturated acyl oxazolidinones to form triquinane derivatives, and of enals with alkynes to form bicyclooctenols. ... 

In the course of their seminal study on the amine-catalyzed cyclopropanation of a,(3-unsaturated aldehydes by p-oxosulfonium ylides, Kunz and MacMillan [89] found that while first- and second-generation oxazolidinones failed to promote the reaction, proline afforded the expected product in good yields and poor enantiose-lectivity (Scheme 2.15). 

The Ti-mediated reactions for construction of cyclopropane derivatives in the presence of Grignard reagents have also been reported [188]. These methodologies have provided convenient approaches to the synthesis of spirocyclopropane oxazolidinones or trifunctionalized propane derivatives. 

Motherwell et al. reported the formation of a nitrogen-substituted methylene-transfer reagent from amide acetal 82 using zinc and cupric chloride or zinc chloride (Scheme 1.45) [77]. Aminocyclopropanes 83 were isolated in good yields. Asymmetric induction using chiral oxazolidinone 84 was examined [78]. Intramolecular cyclopropanation progressed, and p-lactam-fused multicarbocyclic cyclopropanes 85 were obtained [79]. 

The use of the Simmons-Smith reaction of allenes provides an efficient synthesis of novel spiro cyclopropanes. The use of chiral oxazolidinone-attached allenes 89 afforded chiral spiro[2.2]pentanes 90 and 91 (Scheme 1.48) [82]. 

Chiral oxazolidinone also controlled the stereochemistry of cyclopropanation of enamides 102 (Scheme 1.53) [88]. Cyclopropane 103 was obtained in good yields with high diastereomeric excesses. 

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