Cyclic rhodium -catalyzed synthesis

SCHEME 3.10 Rhodium-catalyzed synthesis of cyclic sulfonamides [9]. 

The signature application for the G-H insertion in synthesis is probably the total synthesis of (—)-tetrodotoxin 126 by Du Bois and Hinman.233 Two stereospecific G-H activation steps, rhodium-catalyzed carbene G-H insertion and carbamate-based nitrene C-H insertion, have been used to install the two tetrasubstituted centers C6 and C8a (Scheme 12). Diazoketone 122 was treated with 1.5mol% Rh2(HNCOCPh3)4, and cyclic ketone 123 was selectively formed in high yield without purification. The reaction of carbamate 124 with 10mol% Rh2(HNCOCF3)4, PhI(OAc)4, and MgO in C6H6 solvent furnished the insertion product 125 in 77% yield. 

The simple macrocyclic ether 18 was synthesized as shown in Figure 16. Chain elongation of L-leucine via the Amdt-Eistort synthesis, followed by reduction, provided the basic 13-aminoalcohol building block. The ether linkage was formed by rhodium-catalyzed caibene insertion, and the phosphonate was introduced by an Arbusov reactkm on the bromoethyl derivative. Coupling to L-leucine and fomation of the macro-cyclic lactam proceeded as described above for the more rigid analog. 

Scheme 6.20 Rhodium-catalyzed arylation of cyclic W-sulfonyl ketimines using arylboroxines and the corresponding ring-opening step leading to the synthesis of chiral (triaryl)-methylamines, as described by...

The synthesis of macrocycles is very important due to their versatile applications in medicinal and naturtil product chemistry [123]. The rhodium-catalyzed one-pot synthesis of functionalized polyether macrocycles, at high concentrations from four components, was achieved under mild conditions by Lacour et aL the synthesis of 16- to 18-membered macrocycles by the regioselective condensation of two a-ditizo-p-ketoesters, and two cyclic ethers, in the presence of RhjlOct) is depicted in Scheme 9.11 [124]. Various diazo esters have been successfully employed as substrates with up to 75% yields. 

The synthesis and the catalytic activity in the rhodium-catalyzed hydroformylation of styrene as well as quantum-chemical estimation of structure-activity relationship of novel cyclic amidophosphonite ligands bearing polyfluorinated tails were reported [52]. 

Han J, Kang S, Lee HK. Dynamic kinetic resolution in the stereoselective synthesis of 4,5-diaryl cyclic sulfami-dates by using chiral rhodium-catalyzed asymmetric transfer hydrogenation. Chem. Commun. 2011 47 (13) 4004- 06. 

There have been many other independent reports of excellent S/C ratios using rhodium DuPHOS systems. For the synthesis of an (R)-metalaxyl intermediate 19 [21], a turnover number of 50000 has been demonstrated using Me-DuPHOS-Rh. Hoffmann la Roche have reported the Et-DuPHOS-Rh-catalyzed hydrogenation at S/C 10000-20000 of a cyclic enol acetate 21 to provide an intermediate 22 to Zeaxanthin in 98% ee [22] (Fig. 12). 

The intermolecular and especially intramolecular carbenoid C-H insertion is a very useful method for the synthesis of cyclic organic compounds as well as other products [59-63]. For example, the remote functionalization of C-H bonds by a-diazoketones, which is efficiently catalyzed by rhodium(II) complexes, gives cyclopentanones, lactams and lactones according to the general equation ... 

Reactions of acylpalladium complexes involving acylpalladation with arenes or formally equivalent processes have been much less exploited compared with those involving acylpalladation with alkenes or alkynes discussed in the previous section, and to the best of our knowledge, their examples are limited to intramolecular reactions. A few reactions that may include the intramolecular acylmetallation with arenes are known in the case of a rhodium catalyst, but the products are limited to a narrow range of compounds such as indenones.t In contrast, the Pd-catalyzed carbonylation of 3-arylaUyl acetates or hahdes, most typically cinnamyl acetate, involving intramolecular acylpalladation with arenes results in the construction of 1-naphthol, which is a hiding member of cyclic aromatic ketones. The outline of the conversion is sketched in Scheme 1. In fact, this type of carbonylation-cyclization reaction (cyclocarbonylation) can be applied to the synthesis of a variety of fused aromatics, which is summarized in the following subsection. 

The high-yielding and highly enantioselective synthesis of carba[10]paracyclophanes has been achieved by the cationic rhodium(I)/(S,S)-BDPP complex-catalyzed [2+2+2] cycloaddition of cyclic diynes with terminal monoynes (Scheme 21.22) [26]. 

The combination of reactions of rhodium carbenoids with polyether-macrocycle synthesis offered interesting procednres for the synthesis of this important class of compounds. One elegant example is the Rh-catalyzed four-component reaction of two a-diazo- 3-keto esters and two cyclic ethers, such as tetrahydrofuran or 1,4-dioxane, to yield functionalized 16- to 18-membered macrocycles 65 (Scheme 5.44) [42]. The process involves the generation of electrophilic rhodium carbenoid A, the addition of cyclic ether to this intermediate, as well as the formation and dimerization of the oxonium ylide intermediate B. Another example is the Rh-catalyzed macrocyclization of oxetanes with a-diazocarbonyls (Scheme 5.45) [43]. In this case, three oxetanes and one rhodium carbenoid intermediate condense in a one-step process. It is noteworthy that these macrocyclizations could proceed under high-concentration conditions (1M). 

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