Enantioselective Ru-catalyzed

Finally, Katsuki and coworkers [271] described an enantioselective Ru-catalyzed domino reaction, which includes a sulfamidation of an aryl allyl sulfide 6/3-111 using the chiral Ru(salen)-complex 6/3-115, followed by a 2,3-sigmatropic rearrangement of the formed 6/3-112 to give N-allyl-N-arylthiotoluenesulfonamides 6/3-113. On hydrolysis, 6/3-113 yielded N-allyltoluenesulfonamides 6/3-114 (Scheme 6/3.33). The enantioselectivity ranged from 78 to 83% ee. 

S R ratio = 5 1) [22]. Yanada and Yoneda constructed the deazaflavinophane 26, which exhibits complete facial selectivity in its oxidation and reduction reactions, e.g. the reduction with NaBD to afford 27 [23], Belokon and Rozen-berg used scalemic 4-formyl-5-hydroxy[2.2]para-cyclophane (FHPC) 28 in the synthesis of a-ami-no acids (ee 45-98 %) [24], An alternative approach to FHPC was more recently reported by Hopf [25]. Other interesting advances in the area of chiral cyclophanes include the homochir-al [2.2]paracyclophane-derived amino acids 29 and 30 [26], as well as (5)-PHANEPHOS (31) [27], which has been shown to be an effective ligand for highly enantioselective Ru-catalyzed asymmetric hydrogenations of -ketoesters and... 

Merck s anthraxlethal factor inhibitor(LFI) has potent preexposure efficacy against the Bacillus anthracis challenge in both mouse and rabbit infection models. Shultz and Dreher for the synthesis of Merck s anthrax LF-inhibitor 225 attempted an enantioselective Ru-catalyzed hydrogenation of the A -sulfonylated-a-dehydroamino acids, in order to avoid the extra steps of exchanging the acetyl group for the desired sulfonyl side chain (Scheme 29.28). ... 

Scheme 12.5 Total synthesis of baconipyrone C by an enantioselective Ru-catalyzed ring-opening/cross-metathesis (ROCM) reaction. PMB = p-methoxybenzyl Mes = 2,4,6-Me3C6H2.

Although sulfur is unHkely to chelate the metal in this case, it is worth mentioning the axially chiral diphosphine Hgands, based on hz-thienyl systems which increase the electronic density at phosphorus such as 159 (used in Ru-catalyzed reduction of /1-keto esters with 99% ee) [llla],BITIANP 160,andTMBTP 161 (in a Pd-catalyzed Heck reaction, the regio- and enantioselectivity are high with 160 but low with 161) [mb]. 

Davies [30] studied the PyBOx-induced conformational effects by testing several ligands sterically hindered on the oxazoUne moieties (Scheme 11, structures 18 and 19). However, these new ligands gave poorer results in terms of yields and enantioselectivities than ligand 16 for the Ru-catalyzed cyclopropanation reaction, indicating unfavorable steric interactions between styrene and the carbene complex. 

The results clearly show that these novel ligands are able to form a suitable asymmetric enviromnent around the metal resulting in high asymmetric induction. Their catalytic potential has been demonstrated in the highly enantioselective Rh-catalyzed hydrogenation of itaconates and a-enamides and Ru-catalyzed hydrogenation of p-functionalized ketone. 

Scheme 2. Ru-catalyzed RCM efficiently provides substrates required for the Zr-catalyzed enantioselective alkylation...

Chan has discovered a completely atropdiasteroselective synthesis of a biaryl diphosphine based on an enantioselective intramolecular Ullmann coupling or a Fe(III)-promoted oxidative coupling. A chiral atropisomeric biaryl bisphosphine ligand 2 was synthesized through this central-to-axial chirality transfer [30]. Recently, a xylyl-biaryl bisphosphine ligand, Xyl-TetraPHEMP was introduced by Moran, and found to be effective for the Ru-catalyzed hydrogenation of aryl ketones [31]. 

The synthetic versatility and significance of the Zr-catalyzed kinetic resolution of exocyc-lic allylic ethers is demonstrated by the example provided in Scheme 6.9. The optically pure starting allylic ether, obtained by the aforementioned catalytic kinetic resolution, undergoes a facile Ru-catalyzed rearrangement to afford the desired chromene in >99% ee [20], Unlike the unsaturated pyrans discussed above, chiral 2-substituted chromenes are not readily resolved by the Zr-catalyzed protocol. Optically pure styrenyl ethers, such as that shown in Scheme 6.9, are obtained by means of the Zr-catalyzed kinetic resolution, allowing for the efficient and enantioselective preparation of these important chromene heterocycles by a sequential catalytic protocol. 

Scheme 6.11. Tandem Zr-catalyzed kinetic resolution and Ru-catalyzed conversion of the resulting optically pure ethers in the enantioselective synthesis of dihydrofurans. The efficiency of the catalytic resolution requires the presence of the pendant acyclic alkene and depends on its substitution.

Related catalytic enantioselective processes It is worthy of note that the powerful Ti-catalyzed asymmetric epoxidation procedure of Sharpless [27] is often used in the preparation of optically pure acyclic allylic alcohols through the catalytic kinetic resolution of easily accessible racemic mixtures [28]. When the catalytic epoxidation is applied to cyclic allylic substrates, reaction rates are retarded and lower levels of enantioselectivity are observed. Ru-catalyzed asymmetric hydrogenation has been employed by Noyori to effect the resolution of five- and six-membered allylic carbinols [29] in this instance, as with the Ti-catalyzed procedure, the presence of an unprotected hydroxyl function is required. Perhaps the most efficient general procedure for the enantioselective synthesis of this class of cyclic allylic ethers is that recently developed by Trost and co-workers, involving Pd-catalyzed asymmetric additions of alkoxides to allylic esters [30]. 

Asymmetric hydrogenation of prochiral ketones,s Ketones substituted in the a- or (3-position by diverse polar groups, particularly OH,OR,NR2,COOR, can undergo highly enantioselective hydrogenation catalyzed by BINAP-Ru complexes. A key factor of asymmetric induction is undoubtedly chelation of the carbonyl group and the hetero atom to the Ru atom. 

A further enantioselective synthesis of (+)-T-4 (125), T-6 (128), T-7 (129) and T-8 (126) has been reported by Stragies and Blechert [198]. Key steps are a Pd-catalyzed domino allylation and a Ru-catalyzed metathesis ring rearrangement. Their strategy represents a general approach towards all naturally occurring tetraponerines and will be illustrated here by the description of the syntheses of (+)-T-4 (125) and (+)-T-8 (126) (Scheme 9). 

For a review of asymmetric Mo-catalyzed metathesis, see Catalytic Asymmetric Olefin Metathesis, A. H. Hoveyda, R. R. ScHROCK, Chem. Eur. J. 2001, 7, 945-950 for reports on chiral Ru-based complexes, see (b) Enantioselective Ruthenium-Catalyzed Ring-Qosing Metathesis, T.J. Sei-DERS, D.W. Ward, R.H. Grubbs, Org. Lett. 2001, 3, 3225-3228 (c) A Recyclable Chiral Ru Catalyst for Enantioselective Olefin Metathesis. Efficient Catalytic Asymmetric Ring-Opening/Cross Metathesis In Air, J. J. Van Veldhuizen, S. B. 

For examples of Ru-catalyzed hydrogenation of N-(3.4-dihydro-2-naphthalenyl)-acetamide see (a) Renaud. J.L., Dupau, P., Hay. A.-E.. Guingouain. M., Dixneuf P.H. and Brtmeau. C. (2003) Ruthenium-catalysed enantioselective hydrogenation of trisubstituted enamides derived from 2-tetralone and 3-chromanone Influence of substitution on the amide ai m and the aromatic ring. Adv. Synth. Catal.. 345. 230-238. 

SCHEME 48. BINAP-Ru-catalyzed enantioselective hydrogenation substrates and product ee s. 

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