Ring expansion, asymmetric

In 2003, Bonini et al. reported a new synthesis of ferrocenyloxazolines based on an iodide-mediated ring expansion of A-ferrocenoyl-aziridine-2-carboxylic esters. The thus-formed ligands were successfully employed as palladium chelates for the test reaction, since they allowed the product to be formed in quantitative yields and good to high enantioselectivities (Scheme 1.69). According to the results, it seemed that the additional chiral centre present in the oxazoline backbone of these ligands did not play a major role for the asymmetric induction and the activity of the corresponding catalysts. 

This chapter begins by classifying the combinations of oxidation/reduction processes with subsequent cationic transformations, though to date the details of only two examples have been published. The first example comprises an asymmetric epoxidation/ring expansion domino process of aryl-substituted cyclopropyl-idenes (e. g., 7-1) to provide chiral cyclobutanones 7-3 via 7-2, which was first described by Fukumoto and coworkers (Scheme 7.1) [2]. 

Scheme 7.1. Domino asymmetric epoxidation/ring expansion reaction.

Scheme 7.2. Asymmetric expoxidation/ring-expansion reaction using chiral (salen)Mn111 complex 7-6.

The reaction of vinylcarbenoids with vinyl ethers can lead to other types of [3 + 2] cycloadditions. The symmetric synthesis of 2,3-dihydrofurans is readily achieved by reaction of rhodium-stabilized vinylcarbenoids with vinyl ethers (Scheme 14.17) [107]. In this case, (J )-pantolactone is used as a chiral auxihary. The initial cyclopropanation proceeds with high asymmetric induction upon deprotection of the silyl enol ether 146, ring expansion occurs to furnish the dihydrofuran 147, with no significant epi-merization during the ring-expansion process. 

Delair and colleagues found that an asymmetric pyrrolidone 344 might serve as a common precursor of (+)-Retronecine 345 and (+)-Amphorogynine A and D (equation 132). The ring expansion was a key and efficient step during the synthetic process and was performed with Tamura s Beckmann reagent. 

Asymmetric induction in the ylide formation/[l,2]-shift has also been studied with chiral metal complexes. Katsuki and co-workers examined the reaction of ( )-2-phenyloxetane with 0.5 equiv. of /< //-butyl diazoacetate in the presence of Gu(i) catalyst. With chiral bipyridine ligand 53, trans- and m-tetrahydrofurans 54 and 55 are obtained with 75% and 81% ee, respectively (Equation (6)). This asymmetric ring expansion was applied by the same group to their enantioselective synthesis of translactone. 

When the above-mentioned ring expansion with diazomethane 74) of trimethyl-dioxo[2.2]metacyclophane 65 (methylation was necessary to increase the inversion barrier to > 130 kJ) was performed in the presence of optically active alcohols at —60 °C, asymmetric induction occurred to an extent of ca. 40% ee (enantiomeric excess as determined by nmr-spectroscopy in the presence of chiral shift reagents)85). (+)-DibutyI tartrate favoured the dextrorotatory diketone 66 ([a]D 160° for the optically pure product) — the isomeric 67 was formed only with 3% ee (—)-ethyl lactate on the other hand led to an excess of (+)-67 ([a]D +240°) but gave (+)-66 with only 10% ee85). 

In cycloadditions of enones to alkenes novel strategies have been adopted for ring expansion of the cycloadducts, either by the choice of appropriate alkenes, e.g. 2-(trimethylsiloxy)buta-1,3-diene,70 vmv-2-trimethylsiloxybuten-2-oales71 or 3,3-dimethylcyclopropene,72 or by using 3-oxo-l-cyeloalkene-l-carboxylates as enones.73 Asymmetric [2 + 2] photocycloaddition of cyclopent-2-enone to a (+ )-dihydrofuran acetonide constitutes the cornerstone of the synthetic strategy in the first total synthesis of the novel antitumor metabolite ( )-echinosporin.74 The cycloaddition product 25 from treatment of 2-(2-carbomethoxyethyl)-2-cyclopentenone (24) with ethene has been used as a precursor for the preparation of tricyclo[4.2.0.01,4]octane.75... 

In addition, a proline- or phenylalanine-based Rh(II) can catalyze intramolecular asymmetric carbene reactions such as aromatic ring expansion and C—H insertion with moderate selectivity (Scheme 95) (229). Rh(II) carboxamides are also effective catalysts for asymmetric C—H or N—H insertion (228c). 

Asymmetric hydroboration.1 The key step in a synthesis of natural (+ )-hir-sutic add-C (1), based on an earlier synthesis of racemic 1, is an efficient asymmetric hydroboration of the meso-alkene 2. Reaction of 2 with (+ )-diisopinocampheyl-borane (90% ee) followed by oxidation provides the exo-alcohol 3 in 73% yield and in 92% optical purity. Ring expansion of the corresponding ketone with ethyl diazoacetate is not regioselective even in the presence of BF3 etherate or (C2H5)30+ BF4, but does afford the desired a-keto ester in the presence of SbCl5 (8, 500-501). Decarboxylation of the crude product gives (— )-4 in 90% ee after chromatography. 

An asymmetric Schmidt ring expansion of the 4-substituted cyclohexanones 312 using chiral azido alcohols 313 gave the azepan-2-ones 314 in high yields and good diastereomeric ratios depending on the nature and position of R1 (Scheme 40) <2003JA7914>. 

An asymmetric [1,2]-Wagner-Meerwein shift has been achieved under Pd catalysis, allowing ring expansion of l-(alkyloxyallenyl)cyclobutanol and simple derivatives to ... 

Asymmetric IRDARs of optically active furfuryl fumarates 91 were investigated under thermal and high-pressure conditions. The diastereoselectivities observed increased with the size of the tether substituents, achieving up to 86% in the case of R = f-Bu, though in the case of R = neo-Pen only 38% de was obtained. It is concluded the diastereoselectivity observed was thermodynamically controlled (Scheme 27) [65]. An IRDA ring-expansion approach toward taxinine (a carbocylic compound) [66] utilizing both Lewis acids and high pressure has been reported [67]. 

The reaction of the silyloxypyrroles 47 possessing a chiral substituent at the nitrogen atom, with cyclobutanone in the presence of a Lewis acid, followed by an acid induced ring expansion of the cyclobutanol intermediate 48, offers an asymmetric route to the l-azaspiro[4.4]nonanes 49 in good diastereoisomeric excess <02SL1629>. In this context it might also be interesting to... 

Many unusual biocatalytic asymmetric oxidation reactions like oxidative cychza-tion, oxidative ring expansion, oxidative deamination, or oxidative decarboxylation were discovered in the course of studies in natural product biosynthesis and the involved enzyme functions continue to be of great interest. 

Simpkins and co-workers were the first to use an asymmetric catalytic process in (-)-anatoxin-a synthesis (Newcombe and Simpkins, 1995) instead of resorting to the chiral pool strategy. Their total synthesis of (-)-anatoxin-a relied on an enantioselective enolisation reaction of a readily available ( )-3-tropinone (33), by a chiral lithium amide base (34) (Bunn et al. 1993a, 1993b) and subsequent cyclopropanation/ring expansion reaction giving the ketone 37 (Scheme 7.8). 

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