Rhodium-Catalyzed Enantioselective Cycloaddition

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. 

Mori, R, Fukawa, N., Noguchi, K., Tanaka, K. (2011). Asymmetric synthesis of axially chiral biaryl diphosphine ligands by rhodium-catalyzed enantioselective intramolecular double [2+2+2] cycloaddition. Organic Letters, 13, 362-365. 

Shibata, T., Kawachi, A., Ogawa, M., Kuwata, Y., Tsuchikama, K., Endo, K. (2007). Rhodium-catalyzed enantioselective [2+2+2] cycloaddition of diynes with unfunctionalized aUcenes. Tetrahedron, 63, 12853-12859. 

RHODIUM-CATALYZED ENANTIOSELECTIVE [2 + 2 + 2] CYCLOADDITION 269 9.4.3 Synthesis of Heterobiaryls... 

Axially chiral pyridines as well as axially chiral pyridones could be synthesized via rhodium-catalyzed enantioselective [2 + 2 + 2] cycloaddition. The reaction of 1,6-diyne 68 with ethyl cyanoformate (69) in the presence of the cationic rhodium(I)/Segphos catalyst furnished axially chiral arylpyridine 70 as a single regioi-somer with excellent ee value (Scheme 9.25) [19],... 

Scheme 2.33 Rhodium-catalyzed enantioselective [2-1-2-1-2] cycloaddition of 1,6-diynes with ynamides.

Scheme 2.54 Rhodium-catalyzed enantioselective [24-24-2] cycloaddition reactions of 1-alkynylphosphine oxides with 1,6-diynes.

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. 

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... 

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. 

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. 

Substituted tetraphenylenes are known as interesting biaryl-based chiral cyclic scaffolds. The cationic rhodium(l)/Cy-BINAP or QuinoxP complex-catalyzed enantioselective double homo-[2+2+2] cycloaddition of triynes afforded chiral tetraphenylenes with high enantioselec-tivity (Scheme 21.20) [24]. 

Anilides, bearing a sterically demanding orfho-substituent, are known to exist as atropisomers due to a high rotational barrier around aryl-nitrogen single bond. The cationic rhodium(I)/xyl-BINAP complex-catalyzed enantioselective [2+2+2] cycloaddition of 1,6-diynes with trimethylsilylynamides afforded axiaUy chiral anilides with good to excellent enantioselectivity (Scheme 21.21) [25]. 

Scheme 27 Enantioselective rhodium catalyzed [5+2] cycloaddition of alkenyl-tethered vinylcyclopropanes...

Rovis and coworkers reported the first enantioselective rhodium-catalyzed [4-I-2-I-2] cycloaddition of terminal alkynes 131 with ( i-dienyl isocyanates 132 to construct the bicyclo[6.3.0]azocines [48]. Heating a toluene solution (110 °C) of 131 and 132 in the presence of a catalytic amount of [Rh(C2H4)2Cl]2 and chiral phosphoramidite afforded the [4-I-2-I-2] cycloadducts 133 in good yields with excellent enantiomeric excesses [49], Initial oxidative cyclization between the diene and the isocyanate moiety of 132 afforded rhodacycle 134. Coordination and insertion of alkyne 131 to 134 followed by reductive elimination of the resulting rhodacycle 135 provided the [4-I-2-I-2] adduct 133 (Scheme 4.27). 

Yu, R. T., Friedman, R. K., Rovis, T. (2009). Enantioselective rhodium-catalyzed [4-I-2-I-2] cycloaddition of dienyl isocyanates for the synthesis of bicyclic azocine rings. Journal of the American Chemical Society, 131, 13250-13251. 

The cationic rhodium(I)/axially chiral biaryl diphosphine complex catalyzed the enantioselective desymmetrization of symmetric dialkynylphosphine oxides via rhodium-catalyzed [2- -2-1-2] cycloaddition with 1,6-diynes to give / -stereogenic alkynylphosphine oxides (Scheme 4.50) [53]. This method was also applied to... 

Use of the phosphoramidite ligand (-)-199 proved to be crucial for the enantioselective rhodium-catalyzed crossed [2 + 2 + 2] cycloaddition of alkenyl isocyanate 197 with phenylacetylene 198, which provided the vinylogous amide 200 in 62% yield (98% ee). Thereafter, cycloaddition product 200 underwent a diastereoselective hydrogenation followed by a Mitsunobu reaction to complete the total synthesis of (+)-lasubine II (201). 

The enantioselective completely intramolecular [2 + 2 + 2] cycloaddition also furnishes Cz-symmetric axially chiral biaryls. Shibata et al. reported the cationic rhodium(I)/tol-BINAP complex-catalyzed enantioselective [2 + 2 + 2] cycloaddition of symmetric hexaynes 58 to give Cz-symmetric axially chiral biaryls 59 with good yields and ee values (Scheme 9.21) [21]. This is the first example of an axially chiral bis(biphenylene) skeleton. 

As shown in Sections 9.4.1 and 9.4.2, electron-deficient and coordinating alkynyl carbonyl compounds showed high reactivity in cationic rhodium(I)/biaryl bispho-sphine complex-catalyzed enantioselective [2- -2-1-2] cycloaddition. Therefore, Tanaka et al. investigated the use of alkynylphosphonates or alkynylphosphine oxides instead of alkynyl carbonyl compounds for the practical synthesis of axially chiral biaryl phosphorus compounds. The enantioselective [2- -2-1-2] cycloadditon... 

The enantioselective synthesis of axially chiral P—N ligands was also accomplished by rhodium-catalyzed [2 + 2+-2] cycloaddition. The reactions of 1,6-diynes 75 with diphenylphosphinoyl-substituted isoquinolinyl acetylenes 76 furnished diphenylphosphinoyl-substituted axially chiral 1-arylisoquinolines 77 with high yields and ee values (Scheme 9.28) [23], The new diphenylphosphinoyl-substituted axially chiral 1-arylisoquinoline 77 (Z = NTs, R = Me) was derivatized to the corresponding axially chiral P—N ligand 78 and isoquinoline A-oxide 79 without racemization, which could be used in the rhodium-catalyzed hydroboration and Lewis base-catalyzed allylation, respectively [23],... 

Tanaka et al. overcame this limitation by designing the enantioselective completely intramolecular double [2- -2-1-2] cycloaddition. The reaction of diphenylphosphinoyl-substituted hexayne 94, prepared from triyne 93 in two steps, in the presence of the cationic rhodium(I)/tol-BINAP catalyst furnished C2-symmetric axially chiral biaryl bisphosphine oxide 95 in moderate yield with high enantioselectivity (Scheme 9.32) [25]. Subsequent recrystallization andreduction of bisphosphine oxide 95 furnished the corresponding enantiopure bisphosphine 96, which could be used as an effective chiral ligand for rhodium-catalyzed asymmetric hydrogenation and cycloaddition [25]. 

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]. 

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