Catalytic asymmetric cyclization

Synthesis of a m-decalin system by the asymmetric cyclization[38] has been carried out with high enantioselectivity[142,143,147,148], Using BINAP as a chiral ligand, 91% ee was achieved in the asymmetric cyclization of 177 to give 178. In order to achieve an efficient asymmetric cyclization, selection of the reaction conditions is crucial, and sometimes added Ag salts play an important role[148], A catalytic asymmetric cyclization of 179 to prepare the key intermediate enone 180 for vernolepin synthesis has been carried out[149]. Highly efficient asymmetric cyclization of 181 to give the tetralin system 182 has been applied to the synthesis of (-)-eptazocine (183)[150], Hydrindans are synthesized in 86% ee[151]. 

A phenolic oxygen participates in facile oxypalladation. 2-Allylphenol (55) undergoes clean cyclization to 2H-l-benzopyran (56) in DMSO under air with a catalytic amount of Pd(OAc)2 without a reoxidant. 2-Methylbenzofuran (57) is obtained when PdCl2 is used [50]. But different chemoselectivity with the Pd(II) salts was also reported [51]. Catalytic asymmetric cyclization of the tetrasubstituted 2-allylic phenol 58 using the binaphthyl-type chiral ligand 60, called (.S, .S )-ip-borax, afforded the furan 59 with 96% ee. Use of Pd(CF3 002)2 as a catalyst is essential in the presence of benzoquinone [52]. Formation of the benzofuran 62 from 61 has been utilized in the synthesis of aklavinione [53]. The intramolecular reaction of 2-hydroxychalcone (63) produces the flavone 64 [54]. 

While virtually all of the research described above has focused on the inter-molecular cycloaddition of azomethine ylides, the intramolecular process holds considerable promise for the synthesis of polycyclic natural products. The Pfaltz group reported an intramolecular catalytic asymmetric cyclization of aryl iminoesters 112 using a complex of silver acetate with PHOX type ligand 100 (Scheme 2.29,... 

Pd(0Ac)2, but the benzofuran 67 was obtained by exo cyclizadon with PdCb [34], Catalytic asymmetric cyclization of 2-(2,3-dimethyl-2-butenyl)phenol (68) using the binaphthyl-based chiral ligand 70, called (5,5)-ip-boxax afforded the furan 69 with high ee (97%) [35],... 

Catalytic asymmetric intramolecular Mizoroki-Heck reactions have been employed to synthesize several polyaromatic polyketide natural products. In one such endeavour, the catalytic asymmetric cyclization of alkenyl naphthyl triflate 84 was a central step in total syntheses of halenaquinone (88) and halenaquinol (89) recorded in the Shibasaki group laboratory (Scheme 16.19) [52]. Naphthyl triflate 84, which arose from Suzuki coupling of triflate 81 with alkylborane 82, was cyclized using the conditions that had become nearly... 

In an extension of this work, the Shibasaki group developed the novel transformation 48—>51 shown in Scheme 10.25c To rationalize this interesting structural change, it was proposed that oxidative addition of the vinyl triflate moiety in 48 to an asymmetric palladium ) catalyst generated under the indicated conditions affords the 16-electron Pd+ complex 49. Since the weakly bound triflate ligand can easily dissociate from the metal center, a silver salt is not needed. Insertion of the coordinated alkene into the vinyl C-Pd bond then affords a transitory 7t-allylpalladium complex 50 which is captured in a regio- and stereocontrolled fashion by acetate ion to give the optically active bicyclic diene 51 in 80% ee (89% yield). This catalytic asymmetric synthesis by a Heck cyclization/ anion capture process is the first of its kind. 

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],... 

Asymmetric cyclization was also successful in the rhodium-catalyzed hydrosilylation of silyl ethers 81 derived from allyl alcohols. High enantioselectivity (up to 97% ee) was observed in the reaction of silyl ethers containing a bulky group on the silicon atom in the presence of a rhodium-BINAP catalyst (Scheme 23).78 The cyclization products 82 were readily converted into 1,3-diols 83 by the oxidation. During studies on this asymmetric hydrosilylation, silylrhodation pathway in the catalytic cycle was demonstrated by a deuterium-labeling experiment.79... 

The Pictet-Spengler reaction is the method of choice for the preparation of tetrahydro-P-carbolines, which represent structural elements of several natural products such as biologically active alkaloids. It proceeds via a condensation of a carbonyl compound with a tryptamine followed by a Friedel-Crafts-type cyclization. In 2004, Jacobsen et al. reported the first catalytic asymmetric variant [25]. This acyl-Pictet-Spengler reaction involves an N-acyliminium ion as intermediate and is promoted by a chiral thiourea (general Brpnsted acid catalysis). 

In 2007, Hiemstra et al. established a catalytic asymmetric Pictet-Spengler reaction that proceeds via (V-sulfenyliminium ions (Scheme 15) [27], Treatment of iV-sulfenylated tryptamines 42 with aldehydes 40 and BINOL phosphate (R)-3f (5 mol%, R = 3,5-(CF3)2-CgH3) afforded tetrahydro-P-carbohnes. After completion of the cyclization the sulfenyl group was cleaved by the use of HCl. This one-pot... 

Alkyl- or 3-aryl-2,4-oxazolidinediones via photochemical cyclization, ° organonickel-mediated carbonylation, ° cyclization of A-alkenyl-a-acet-amides, ° carboxylation and cyclization of 2-propynamides, °" cyclization of (9-carbamates of a-hydroxy acetic acids and esters,cyclization of a-hydroxy acetamides,and catalytic asymmetric dihydroxylation (ADH) of A-alkenoyl-2-oxazolidinones. ... 

Widenhoefer and co-workers have developed an effective protocol for the asymmetric cyclization/hydrosilylation of functionalized 1,6-enynes catalyzed by enantiomerically enriched cationic rhodium bis(phosphine) complexes. For example, treatment of dimethyl allyl(2-butynyl)malonate with triethylsilane (5 equiv.) and a catalytic 1 1 mixture of [Rh(GOD)2] SbF6 and (i )-BIPHEMP (5 mol%) at 70 °G for 90 min gave the silylated alkylidene cyclopentane 12 in 81% yield with 98% de and 92% ee (Table 4, entry 1). A number of tertiary silanes were effective for the rhodium-catalyzed asymmetric cyclization/hydrosilylation of dimethyl allyl(2-butynyl)malonate with yields ranging from 71% to 81% and with 77-92% ee (Table 4, entries 1-5). Although the scope of the protocol was limited, a small number of functionalized 1,6-enynes including A-allyl-A-(2-butynyl)-4-methylbenzenesulfonamide underwent reaction in moderate yield with >80% ee (Table 4, entries 6-8). 

Suisse and co-workers have studied the asymmetric cyclization/silylformylation of enynes employing catalytic mixtures of a rhodium(i) carbonyl complex and a chiral, non-racemic phosphine ligand. Unfortunately, only modest enantioselectivities were realized.For example, reaction of diethyl allylpropargylmalonate with dimethylphenyl-silane (1.2 equiv.) catalyzed by a 1 1 mixture of Rh(acac)(GO)2 and (i )-BINAP in toluene at 70 °G for 15 h under GO (20 bar) led to 90% conversion to form a 15 1 mixture of cyclization/silylformylation product 67 and cyclization/ hydrosilylation product 68. Aldehyde 67 was formed with 27% ee (Equation (46)). 

Until 1968, not a single nonenzymic catalytic asymmetric synthesis had been achieved with a yield above 50%. Now, barely 15 years later, no fewer than six types of reactions can be carried out with yields of 75-100% using amino acid catalysts, i.e., catalytic hydrogenation, intramolecular aldol cyclizations, cyanhydrin synthesis, alkylation of carbonyl compounds, hydrosilylation, and epoxidations. 

Mikami et al. reported the first examples of catalytic asymmetric intramolecular carbonyl-ene reactions of types (3,4) and (2,4), using the BINOL-derived titanium complex (1) [46,49], The catalytic 7-(2,4) carbonyl-ene cyclization gives the corresponding oxepane with high enantiopurity, and the gem-dimethyl groups are not required (Scheme 8C.I8). In a similar catalytic 6-(3,4) ene cyclization, tran.v-tetrahydropyran is preferentially obtained with high enantiopurity (Scheme 8C. 19), The sense of asymmetric induction is the same as that observed for the glyoxylate-ene reaction, that is, (R)-BINOL-Ti catalyst provides (R)-alcohol. Therefore, the... 

Keck [63] and Carreira [64] have independently reported catalytic asymmetric Mukaiyama aldol reactions. Keck et al. also reported the aldol reaction of an a-benzyloxy aldehyde with a Danishefsky s diene. The aldol product was transformed to the corresponding HDA-type product through acid-catalyzed cyclization. In these reactions, the catalyst that is claimed to... 

Figure 50. Proposed mechanism for catalytic asymmetric hydroamination/cyclization.

The Pictet-Spengler reaction, the cyclization of an electron-rich aryl or heteroaryl group onto an imine electrophile, is the established method for the synthesis of tetrahydroisoquinoline and tetrahydro-/ -carboline ring systems. Catalytic asymmetric approaches to these synthetically important structures are mostly restricted to asymmetric hydrogenations of cyclic imines [77, 78]. In a noteworthy... 

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