Rhodium enantioselective cycloaddition

While copper and iron Lewis acids are the most prominent late transition metal Diels-Alder catalysts, there are reports on the use of other chiral complexes derived from ruthenium [97,98],rhodium [99],andzinc [100] in enantioselective cycloaddition reactions, with variable levels of success. As a comparison study, the reactions of a zinc(II)-bis(oxazoline) catalyst 41 and zinc(II)-pyridylbis(ox-azoline) catalyst 42 were evaluated side-by-side with their copper(II) counterparts (Scheme 34) [101]. The study concluded that zinc(II) Lewis acids catalyzed a few cycloadditions selectively, but, in contrast to the [Cu(f-Bubox)](SbFg)2 complex 31b (Sect. 3.2.1), enantioselectivity was not maintained over a range of temperatures or substitution patterns on the dienophile. An X-ray crystal structure of [Zn(Ph-box)] (01)2 revealed a tetrahedral metal center the absolute stereochemistry of the adduct was consistent with the reaction from that geometry and opposite that obtained with Cu(II) complex 31. 

Furthermore, an enantioselective cycloaddition was observed when the carbenoid was formed by the use of a chiral rhodium complex 37 derived from (S)-N-para (ferf-butylbenzene)sulfonylprolinate (TBSP). For example, decomposition of 38 by 37 in the presence of furan generated 39 with 80% ee, along with a triene containing side-product in 15-20% yield, Eq. 25. However the ee dropped significantly when other vinyldiazo compounds were studied under analogous conditions. 

Phosphates and phosphinates are also recommended as ligands. (R)- or (S)-Binaphthol phosphates 3.54 are used in palladium-catalyzed asymmetric hydro-carboxylation of olefins [923] or in rhodium-catalyzed cycloadditions of diazo compounds to olefins, albeit with modest selectivities in the latter case [924], Seebach and coworkers [925] tested phosphinates and phosphites prepared from diol 2.50 (R = R = Me, Ar = Ph) as ligands for rhodium and palladium in various enantioselective metal-catalyzed reactions [925], Rhodium-catalyzed hydrosilyla-tions of arylmethyl- or ethylketones by Ph2SiH2 were the only interesting reactions with these ligands. 

The reaction of [2+2+2] cycloaddition of acetylenes to form benzene has been known since the mid-nineteenth century. The first transition metal (nickel) complex used as an intermediate in the [2+2+2] cycloaddition reaction of alkynes was published by Reppe [1]. Pioneering work by Yamazaki considered the use of cobalt complexes to initiate the trimer-ization of diphenylacetylene to produce hexasubstituted benzenes [54]. Vollhardt used cobalt complexes to catalyze the reactions of [2+2+2] cycloaddition for obtaining natural products [55]. Since then, a variety of transition complexes of 8-10 elements like rhodium, nickel, and palladium have been found to be efficient catalysts for this reaction. However, enantioselective cycloaddition is restricted to a few examples. Mori has published data on the use of a chiral nickel catalyst for the intermolecular reaction of triynes with acetylene leading to the generation of an asymmetric carbon atom [56]. Star has published data on a chiral cobalt complex catalyzing the intramolecular cycloaddition of triynes to generate a product with helical chirality [57]. 

The first example of an enantioselective [5 + 2]-cycloaddition was reported for the tethered alkene-VCP 7a, which upon treatment with a chiral rhodium complex afforded the m-fused bicyclo[5.3.0]decene 8a in 80% yield and 63% enantiomeric excess (ee) (Equation (6)).39 A later study found that when a 2,2-bis(diphenyl-phosphanyl)-l,l-binaphthyl (BINAP)-modified rhodium(l) catalyst is used, good to excellent ee s and yields are achieved with a variety of substrates (Equation (7)).40... 

The enantioselective catalytic 1,3-dipolar cycloaddition of linear or cyclic nitrones to enals was accomplished using the half-sandwich rhodium(III) complex S, Rc)-[(ri -C5Me5)Rh (/ )-Prophos (H20)](SbF6)2 as catalyst precursor [33, 34]. At —25°C, quantitative conversions to the cycloadducts, with up to 95% ee, were achieved (Scheme 10). The intermediate with the dipolarophile coordinated to the rhodium has been isolated and completely characterized, including the X-ray determination of its molecular structure [33, 34]. 

The ability to produce 1,3-dipoles, through the rhodium-catalyzed decomposition of diazo carbonyl compounds, provides unique opportunities for the accomplishment of a variety of cycloaddition reactions, in both an intra- and intermolecular sense. These transformations are often highly regio- and diastereoselective, making them extremely powerful tools for synthetic chemistry. This is exemplified in the number of applications of this chemistry to the construction of heterocyclic and natural-product ring systems. Future developments are likely to focus on the enantioselective and combinatorial variants of these reactions. 

After completing his initial intramolecular cycloaddition, Hodgson utilized conditions that had been optimized for the intermolecular cycloaddition of DMAD with simple cyclic carbonyl ylides used by Hashimoto and co-workers (139). Hodgson et al. (140) found that the reaction indeed gave excellent overall chemical yield, but the enantioselectivity dropped to 1%, giving essentially a racemic mixture. It appeared that ee ratios were sensitive to the electronic nature of the dipole. Hodgson chose to screen several binaphthol derived rhodium catalysts of the type developed by McKervey and Pirrung, due in part to the reports of... 

Hashimoto and co-workers (206,207) recently published enantioselectivities of up to 92% ee in carbonyl ylide cycloadditions to acetylenic esters in the presence of a chiral rhodium catalyst (Scheme 11.58). 

The intermolecular version of the above reaction has also been reported (391). In the first example, a rhodium-catalyzed carbonyl yhde cycloaddition with maleimide was smdied. However, only enantioselectivities of up to 20% ee were obtained... 

Good yields of the bridged tetrahydropyran-3-one 38 are obtained when the a-diazoketones 37 are decomposed by chiral Rh(II)-catalysts in the presence of DMAD. It is proposed that an enantioselective intermolecular 13-dipolar cycloaddition follows the generation of a carbonyl ylide which is bound to the rhodium (Scheme 21) <99JA1417>. 

The rhodium-catalysed asymmetric 4 + 1-cycloaddition of vinylallenes (147) with CO furnishes 5-substituted 2-alkylidenecyclopent-3-enones (148) with up to 95% enantioselectivities (Scheme 56).276... 

An enantioselective rhodium(II)-catalysed intramolecular cyclopropanation, follow- (g) ed by a regioselective allylic alkylation and a diastereoselective rhodium(I)-catalysed 5 + 2-cycloaddition has been reported.102 ... 

The game is certainly not over, very recently catalytic enantioselective intermolecular cycloadditions of 2-diazo-3,6-diketoester of type 68 derived carbonyl ylides with alkene dipolarophiles have been developed [57]. Relying on chiral rhodium(II) clusters I and II, Hodgson et al. obtained very high enantioselectivities (up to 92% ee on 69) with norbornene as a trap, as disclosed in Scheme 31. 

The reaction of 3,4-dihydroisoquinoline A-oxide (74) and methacrylonitrile in the presence of cationic half-sandwich rhodium and iridium complexes containing a chiral diphosphine ligand was analyzed. The cycloadditions occurred with excellent regio- and diastereoselectivity and low-to-moderate enantioselectivity. Analysis of the catalytic system showed the formation of two epimeric complexes 75 containing the dipolarophile methacrylonitrile. The reaction of one of the isolated diastereopure complexes 75 with 74 afforded cycloadduct 76 with high enantioselectivity. A recycling procedure was developed in order to increase the adduct/catalyst ratio <07CEJ9746>. 

A review about the rearrangement and cycloaddition of carbonyl ylides generated from a-diazo compounds is available <2001CSR50>. Enantioselective intramolecular cyclopropanations of allyl 2-diazo-3-silanyloxybut-3-enoates to yield cyclopropyl 7-butyrolactones have been investigated with a variety of chiral rhodium catalysts. The best results were obtained with Rh2(PTTL)4, where enantioselectivity culminated at 89% ee (Equation 99) <2005TA2007>. 

The diphosphine (R,S)-BPPFA [(R,pS)-9] reacts analogously with acetic anhydride to give the corresponding acetate which can be derivatized. Replacement of the acetate by hydroxide leads to a useful ligand BPPFOH 1534, which has been used for the rhodium-catalyzed enantioselective reduction of a-oxo acids to a-hydroxy acids (Section D.2.3.1.). Recently, the chemistry of gold(I) complexes of such chiral phosphines has been developed they catalyze aldol-type cycloadditions of isocyanides to carbonyl compounds to give chiral dihydrooxazoles. which can be hydrolyzed to synthetically important chiral amino alcohols and amino acids 30,39,40. 

Hashimoto and coworkers [69] have recently begun to explore the use of chiral rhodium catalysts in the intramolecular dipolar cycloadditirai reactions of indoles, and have applied their methodology to the synthesis of the Aspidosperma ring system. Thus, the cycloaddition of the cyclopropyl carbonyl ylides derived from cyclopropyl diazo-5-imido-3-ketoesters 135 upon treatment with dirhodium (11) tetrakis[Af-tetrachlorophthaloyl-(5)-ferf-leucinate] gave cycloadducts 136 along with the spiro[2.3]hexanes 137 in only moderate yields (Scheme 34). Although the reaction proceeds with exclusive endo diastereoselectivity, only moderate enantioselectivities of up to 66% enantiomeric excess (ee) could be obtained. 

Development of chemo-, regio-, and enantioselective [2 + 2 + 2] cycloadditions (particularly, to form N-heterocycles) catalyzed by cationic rhodium(I)/BINAP-type bisphosphine complexes 07Y862. 

Chapter 4 concerns the cycloaddition of carbonyl ylides generated from diazo carbonyl compounds and rhodium or copper catalysts. In this framework chemoselective and enantioselective transformations leading to the formation of various heterocycles such as tetrahydrofurans, oxazolidines, mesoionic and bicyclic compoxmds, alkaloids, and other natural products are described. 

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