Chiral rhodium catalysts, intramolecular

Mechanistic study revealed that the reaction proceeds through intramolecular 1,3-hydrogen migration, and the chiral rhodium catalyst differentiates the enantiotopic C-l hydrogens of allylic alcohols (Scheme 29).53... 

As shown in the previous two sections, rhodium(n) dimers are superior catalysts for metal carbene C-H insertion reactions. For nitrene C-H insertion reactions, many catalysts found to be effective for carbene transfer are also effective for these reactions. Particularly, Rh2(OAc)4 has demonstrated great effectiveness in the inter- and intramolecular nitrene C-H insertions. The exploration of enantioselective C-H amination using chiral rhodium catalysts has been reported by several groups.225,244,253-255 Hashimoto s dirhodium tetrakis[A-tetrachlorophthaloyl-(A)-/ r/-leuci-nate], Rh2(derived rhodium complex, Rh2(i -BNP)4 48,244 afforded moderate enantiomeric excess for amidation of benzylic C-H bonds with NsN=IPh. 

Che has reported that both achiral and chiral rhodium catalysts function competently for intramolecular aziridination reactions of alkyl- and arylsulfonamides (Scheme 17.29) [59, 97]. Cyclized products 87 are isolated in 90% yield using 2 mol% catalyst, PhI(OAc)2, and AI2O3. Notably, reactions of this type can be performed with catalyst loadings as low as 0.02 mol% and display turnover numbers in excess of 1300. In addition, a number of chiral dimeric rhodium systems have been examined for this process, with some encouraging results. To date, the best data are obtained using Doyle s Rh2(MEOX)4 complex. At 10 mol% catalyst and with a slight excess of Phl=0, the iso-... 

It is worthy of note that this reaction is still the subject of solid and productive interest, as shown by the following recent examples. Chiu has exploited a rhodium carbene-promoted intramolecular formation of a carbonyl ylid - cycloaddition cascade as the key reaction in the synthesis of the nucleus of the cytotoxic diterpenoids pseudolaric acids A and B [54]. Although the diastereoselectivity was preferential for the undesired isomer 64, use of Hashimoto s chiral rhodium catalyst Rh2(SBPTV)4 reversed the selectivity in favor of 65 (64 65, 1 1.4) [55] (Scheme 29). 

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>. 

This collection begins with a series of three procedures illustrating important new methods for preparation of enantiomerically pure substances via asymmetric catalysis. The preparation of 3-[(1S)-1,2-DIHYDROXYETHYL]-1,5-DIHYDRO-3H-2.4-BENZODIOXEPINE describes, in detail, the use of dihydroquinidine 9-0-(9 -phenanthryl) ether as a chiral ligand in the asymmetric dihydroxylation reaction which is broadly applicable for the preparation of chiral dlols from monosubstituted olefins. The product, an acetal of (S)-glyceralcfehyde, is itself a potentially valuable synthetic intermediate. The assembly of a chiral rhodium catalyst from methyl 2-pyrrolidone 5(R)-carboxylate and its use in the intramolecular asymmetric cyclopropanation of an allyl diazoacetate is illustrated in the preparation of (1R.5S)-()-6,6-DIMETHYL-3-OXABICYCLO[3.1. OJHEXAN-2-ONE. Another important general method for asymmetric synthesis involves the desymmetrization of bifunctional meso compounds as is described for the enantioselective enzymatic hydrolysis of cis-3,5-diacetoxycyclopentene to (1R,4S)-(+)-4-HYDROXY-2-CYCLOPENTENYL ACETATE. This intermediate is especially valuable as a precursor of both antipodes (4R) (+)- and (4S)-(-)-tert-BUTYLDIMETHYLSILOXY-2-CYCLOPENTEN-1-ONE, important intermediates in the synthesis of enantiomerically pure prostanoid derivatives and other classes of natural substances, whose preparation is detailed in accompanying procedures. 

Early efforts in enantioselective intramolecular cyclopropanation using chiral rhodium catalysts focused on the use of carboxylates as hgands and although these catalysts were highly efficient kinetically in diazo decomposition, the enantiomeric excesses in the products were very hmited. For example, Rh2(S-mande-late)4, (2) in Fig. 3, achieved an ee of 12% in the cychzation in Eq. (18) [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. 

Addition of dicarboethoxycarbene to cycloocta-1,3-diene yields a mixture of cis-and fran -cyclopropane adducts, probably by addition of the singlet carbene on the partially isomerized diene (due to the irradiation). Diastereoselective cyclopropan-ation of a ,/3-unsaturated acetals has been described using a camphor-derived chiral auxiliary. Intramolecular cyclopropenation of a diazo ester, tethered through a naphthalene, to an alkyne was catalysed by rhodium acetate and reported as a efficient method unfortunately, the use of chiral rhodium catalysts gave a less efficient reaction and did not provide high asymmetric induction. ... 

Additionally, enantioselective C-H insertions using chiral rhodium catalysts have been used to forge dihydrobenzofurans. The following examples describe intramolecular C-H insertion as a strategy to create natural products containing dihydrobenzofuran units (Figure 16.2) [46]. 

The development of catalytic, enantioselective C-H insertion reactions has been relatively slow in comparison with the diastereoselective variants described in Section 15.7. It was only in 1990 that McKervey reported the first such example in the context of an intramolecular ring closure (Equation 28) [51]. Exposure of 169 to chiral rhodium catalyst 170 thus afforded 171 in 12% ee. 

Our initial objective, in this investigation, had been to design a useful chiral auxihary. We were pleased to find that naphthylborneol 31, upon optimization of the catalyst and the reaction temperature, served effectively. Until useful chiral catalysts are developed, naphthylborneol 31 will be of significant practical value for directing the absolute course of cyclopentane construction by rhodium-mediated intramolecular C-H insertion. 

Rhodium(II) acetate catalyzes C—H insertion, olefin addition, heteroatom-H insertion, and ylide formation of a-diazocarbonyls via a rhodium carbenoid species (144—147). Intramolecular cyclopentane formation via C—H insertion occurs with retention of stereochemistry (143). Chiral rhodium (TT) carboxamides catalyze enantioselective cyclopropanation and intramolecular C—N insertions of CC-diazoketones (148). Other reactions catalyzed by rhodium complexes include double-bond migration (140), hydrogenation of aromatic aldehydes and ketones to hydrocarbons (150), homologation of esters (151), carbonylation of formaldehyde (152) and amines (140), reductive carbonylation of dimethyl ether or methyl acetate to 1,1-diacetoxy ethane (153), decarbonylation of aldehydes (140), water gas shift reaction (69,154), C—C skeletal rearrangements (132,140), oxidation of olefins to ketones (155) and aldehydes (156), and oxidation of substituted anthracenes to anthraquinones (157). Rhodium-catalyzed hydrosilation of olefins, alkynes, carbonyls, alcohols, and imines is facile and may also be accomplished enantioselectively (140). Rhodium complexes are moderately active alkene and alkyne polymerization catalysts (140). In some cases polymer-supported versions of homogeneous rhodium catalysts have improved activity, compared to their homogenous counterparts. This is the case for the conversion of alkenes direcdy to alcohols under oxo conditions by rhodium—amine polymer catalysts... 

Intramolecular Cyclopropanation with Chiral Rhodium(II) 2-Pyrroli-done-5-carboxylates. Applications of chiral copper and cobalt catalysts, including... 

Several iodonium ylides, thermally or photochemically, transferred their carbene moiety to alkenes which were converted into cyclopropane derivatives. The thermal decomposition of ylides was usually catalysed by copper or rhodium salts and was most efficient in intramolecular cyclopropanation. Reactions of PhI=C(C02Me)2 with styrenes, allylbenzene and phenylacetylene have established the intermediacy of carbenes in the presence of a chiral catalyst, intramolecular cyclopropanation resulted in the preparation of a product in 67% enantiomeric excess [12]. 

The use of chiral additives with a rhodium complex also leads to cyclopropanes enantioselectively. An important chiral rhodium species is Rh2(5-DOSP)4, which leads to cyclopropanes with excellent enantioselectivity in carbene cyclopro-panation reactions. Asymmetric, intramolecular cyclopropanation reactions have been reported. The copper catalyzed diazoester cyclopropanation was reported in an ionic liquid. ° It is noted that the reaction of a diazoester with a chiral dirhodium catalyst leads to p-lactones with modest enantioselectivity Phosphonate esters have been incorporated into the diazo compound... 

Application of this cyclization reaction to a large variety of 4-pentenals with the aid of the rhodium complex has been reported. The first example of an asymmetric cyclization of 4-pentenals via hydro acylation using a chiral rhodium diphosphine catalyst was published by Sakaki et al. in 1989 [ 104]. The diphosphine ligand ((lS,2S)-rraws-l,2-bis(diphenylphosphinomethyl)cyclohexane) having a cyclohexane backbone in the chiral center shows the better asymmetric induction than DIOP ligand. Various types of enals are applicable to this asymmetric intramolecular hydro acylation reaction [105,106]. The use of BINAP ligand as the chiral auxiliary improves the optical yield to >99% ee when 4-substituted 4-pentenals are used as the substrate (Eq. 49) [106]. Steric repulsion between the substituent at the 4-position and the substituent on the phosphine atom controls the enantiofacial selection. 

The most significant breakthrough in this area was Doyle s introduction of chiral rhodium (II) carboxamidates (Fig. 4). These catalysts show an exceptional ability to direct highly enantioselective intramolecular cyclopropanation of al-lylic and homoallylic diazoesters, Eq. (19), and diazoamides, Eq. (20). 

In a useful extension of this methodology for enantioselection in intramolecular cyclopropanation, Doyle s group have used chiral rhodium (II) carbox-amidates to effect enantiomer differentiation in reactions of racemic secondary allylic diazoacetates [47]. The catalyst-enantiomer matching approach has also been applied very successfully to intramolecular C-H insertion reactions vide infra). The (R)- and (S)-enantiomers, (10) and (11), respectively, of cyclohex-2-en-1 -yl diazoacetate are displayed in Scheme 7. On exposure to Rh2(4i -MEOX)4 the (R)-enantiomer (10) undergoes cyclopropanation to form tricyclic ketone... 

Major advances have been made in enantioselective intramolecular C-H insertion in a relatively short space of time. Because of the superiority of rhodium catalysts over copper catalysts for C-H insertion, the focus has been very much on development of chiral versions of the former. Both the structure of the diazo precursors and the ligands on the catalyst can have a profound influence on di-astereoselectivity and enantioselectivity, two important determinants on the efficacy of C-H insertion in stereoselective synthesis. Chemoselectivity is another control feature on which catalyst design can have a major influence. 

Doyle s chiral rhodium (II) carboxamidates have proved to be exceptionally successful for asymmetric C-H insertion reactions of diazoacetates and some diazoacetamides leading to lactones and lactams, respectively. With 2-alkoxyethyl diazoacetates and the Rh2(5S- and 5R-MEPY)4 catalysts, for example, highly enantioselective intramolecular C-H insertion reactions occur, the 5S-catalyst, Eq. (40), and 5R-catalyst furnishing the S- and R-lactone, respectively [58]. A polymer-bound version of Rh2(5S-MEPY)4 has also been applied to the cycliza-tion in Eq. (40) to yield the lactone with 69% ee (R=Me) the catalyst could be recovered by filtration and reused several times, but with decreasing enantiose-lection [59]. 

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