Catalytic Asymmetric Synthesis of

Scheme 5. The Sumitomo Chemical Company s catalytic asymmetric synthesis of ethyl (+)-(1 S)-2,2-dimethylcyclopropanecarboxylate (18), an intermediate in Merck s commercial synthesis of cilastatin (19).

Of course, the key limitation of the ylide-mediated methods discussed so far is the use of stoichiometric amounts of the chiral reagent. Building on their success with catalytic asymmetric ylide-mediated epoxidation (see Section 1.2.1.2), Aggarwal and co-workers have reported an aza version that provides a highly efficient catalytic asymmetric synthesis of trans-aziridines from imines and diazo compounds or the corresponding tosylhydrazone salts (Scheme 1.43) [68-70]. 

Following Uskokovic s seminal quinine synthesis [40], Jacobsen has very recently reported the first catalytic asymmetric synthesis of quinine and quinidine. The stereospecific construction of the bicyclic framework, introducing the relative and absolute stereochemistry at the Cg- and expositions, was achieved by way of the enantiomerically enriched trans epoxide 87, prepared from olefin 86 by SAD (AD-mix (3) and subsequent one-pot cyclization of the corresponding diol [2b], The key intramolecular SN2 reaction between the Ni- and the Cg-positions was accomplished by removal of the benzyl carbamate with Et2AlCl/thioanisole and subsequent thermal cyclization to give the desired quinudidine skeleton (Scheme 8.22) [41],... 

Anderson CE, Donde Y, Douglas CJ, Overman LE (2005) Catalytic asymmetric synthesis of chiral allylic amines. Evaluation of ferrocenyloxazoline palladacycle catalysts and imidate motifs. J Org Chem 70 648-657... 

Wiskur SL, Fu GC (2005) Catalytic asymmetric synthesis of esters from ketenes. J Am Chem Soc 127 6176-6177... 

Hodous BL, Ruble JC, Fu GC (1999) Enantioselective addition of alcohols to ketenes catalyzed by a planar-chiral azaferrocene catalytic asymmetric synthesis of arylpropionic acids. J Am Chem Soc 121 2637-2638... 

Lee EC, McCauley KM, Fu GC (2007) Catalytic asymmetric synthesis of tertiary alkyl... 

Taggi AE, Hafez AM, Wack H, Young B, Ferraris D, Lectka T (2002) The development of the first catalyzed reaction of ketenes and imines catalytic, asymmetric synthesis of P-lactams. J Am Chem Soc 124 6626-6635... 

Zajac M, Peters R (2009) Catalytic asymmetric synthesis of P-Sultams as precursors for taurine derivatives. Chem Eur J 15 8204-8222... 

Matsuura, T, Overman, L.E., Poon, D.J. (1998) Catalytic Asymmetric Synthesis of Either Enantiomer of the Calabar Alkaloids Physostigmine and Physovenine. Journal of the American Chemical Society, 120, 6500-6503. 

Another microwave-mediated intramolecular SN2 reaction forms one of the key steps in a recent catalytic asymmetric synthesis of the cinchona alkaloid quinine by Jacobsen and coworkers [209]. The strategy to construct the crucial quinudidine core of the natural product relies on an intramolecular SN2 reaction/epoxide ringopening (Scheme 6.103). After removal of the benzyl carbamate (Cbz) protecting group with diethylaluminum chloride/thioanisole, microwave heating of the acetonitrile solution at 200 °C for 2 min provided a 68% isolated yield of the natural product as the final transformation in a 16-step total synthesis. 

Arai, T., Bougauchi, M., Sasai, H., and Shibasaki, M., Catalytic asymmetric synthesis of a-hydroxy phosphonates using the Al-Li-BINOL complex, /. Org. Chem., 61, 2926, 1996. 

The palladium-catalyzed asymmetric hydrosilylation of styrenes has been applied to the catalytic asymmetric synthesis of l-aryl-l,2-diols from arylacetylenes (Scheme 6).46 Thus, ( )-l-aryl-2-(trichlorosilyl)ethenes, which are readily generated by platinum-catalyzed hydrosilylation of arylacetylenes, were treated with trichlorosilane and the palladium catalyst coordinated with MOP ligand 12f to give 1 -aryl-1,2-bis(silyl)ethanes, oxidation of which produced the enantiomerically enriched (95-98% ee) 1,2-diols. 

Scheme 3. Catalytic asymmetric synthesis of threo-dihydrosphingosine.

H. Sasai, T. Suzuki, N. Itoh, M. Shibasaki, Catalytic Asymmetric Synthesis of Propranolol and Metoprolol Using La-Li-BINOL Complex, Appl. Organomet. Chem... 

K. Yamada, T. Arai, H. Sasai, M. Shibasaki, A Catalytic Asymmetric Synthesis of U-Deoxy-PGFla Using ALB, a Heterobimetallic Multifunctional Asymmetric Complex, J. Org. Chem 1998, 63, 3666-3672. 

In addition to its utility in the enantioselective formation of C-0 bonds (cf. Scheme 15), Trost s chiral ligand 102 has been used in the catalytic asymmetric synthesis of C-N bonds. An impressive application of this protocol is in the enantioselective total synthesis of pancrastatin by Trost (Scheme 17) H9i Thus, Pd-catalyzed desymmetrization of 112 leads to the formation of 113 efficiently and in > 95 % ee. The follow-up use of the N3 group to fabricate the requisite cyclic amide via isocyanate 117 demonstrates the impressive versatility of this asymmetric technology. 

T. Takemoto, M. Sodeoka, H. Sasai, M. Shibasaki Catalytic Asymmetric Synthesis of Benzylic Quaternary Carbon Centers. An Efficient Synthesis of (-)-Eptazocine , J. Am. Chem. Soc 1993,115, 8477-8478. 

Shioiri and co-workers developed a catalytic asymmetric synthesis of allenes by isomerization of the alkyne 240 to allene 242 under the control of a chiral phase-transfer catalyst 241 (Scheme 4.62) [98], Although the enantiomeric excess is not high (35% ee), this is the first example of the asymmetric isomerization of alkynes under phase-transfer catalyzed conditions. 

The catalytic asymmetric synthesis of allenes was first achieved by Elsevier and co-workers in 1989 [104]. A palladium-catalyzed cross-coupling reaction of an allenyl-metal compound 250 (M = ZnCl, MgCl or Cu) with iodobenzene in the presence of DIOP 251 gave 252 in 25% ee (Scheme 4.65). The synthesis of 252 by the reaction of 250 (M = Br) with phenylzinc chloride in the presence of a chiral palladium catalyst gave a quantitative conversion but very low enantiomeric excesses (3-9% ee). 

Scheme 4.65 First catalytic asymmetric synthesis of allene 252 with a chiral palladium catalyst.

In 1993, Hayashi and co-workers reported a catalytic asymmetric synthesis of alle-nylboranes 256 by palladium-catalyzed hydroboration of conjugated enynes 253 (Scheme 4.66) [105]. Reaction of but-l-en-3-ynes 253 with catecholborane 254 in the presence of a catalyst, prepared from Pd2(dba)3 CHC13 (1 mol%) and a chiral mono-dentate phosphine ligand (S)-MeO-MOP 255 (1 mol%), gave an allenylborane 256. The ee of 256 was determined by the reaction with benzaldehyde affording the corresponding optically active homopropargyl alcohols 257 with up to 61% ee (syn anti= 1 1—3 1). 

Scheme 4.66 Catalytic asymmetric synthesis of allenylboranes by a chiral palladium catalyst.

Catalytic Asymmetric Synthesis of Nitroaldols Using a Lanthanum-Lithium-BINOL Complex. 

The initial work on the asymmetric [4-1-2] cycloaddition reactions of A -sulfinyl compounds and dienes was performed with chiral titanium catalysts, but low ee s were observed <2002TA2407, 2001TA2937, 2000TL3743>. A great improvement in the enantioselectivity for the reaction of AT-sulfinyl dienophiles 249 or 250 and acyclic diene 251 or 1,3-cyclohexadiene 252 was observed in the processes involving catalysis with Cu(ll) and Zn(ii) complexes of Evans bis(oxazolidinone) (BOX) ligands 253 and 254 <2004JOC7198> (Scheme 34). While the preparation of enantio-merically enriched hetero-Diels-Alder adduct 255 requires a stoichometric amount of chiral Lewis acid complex, a catalytic asymmetric synthesis of 44 is achieved upon the addition of TMSOTf. 

The utility and efficiency of this methodology is demonstrated by the first catalytic asymmetric synthesis of (—)-phaseolinic acid , a natural product displaying useful antifungal, antitumor and antibacterial properties, as illustrated in equation 110. 

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