Cyclization enantioselectivity

Use of chiral acetal groups can result in enantioselective cyclization.1... 

Doyle s rhodium(n) carboxamidate complexes are undisputedly the best catalysts for enantioselective cyclizations of acceptor-substituted carbenoids derived from diazo esters and diazoacetamides, displaying outstanding regio- and stereocontrol.4 These carboxamidate catalysts consist of four classes of complexes pyrrolidinones... 

With the advent of enantioselective zirconocene-catalyzed alkene carbomagnesiation,27 27a 27c 28 28a chirally modified zirconocenes soon were applied to asymmetric reductive diene carbocyclization.2 a c As demonstrated by the reductive cyclization of 5a,29 highly enantioselective cyclization is enabled through the use Brintzinger s chiral, mszz-zirconocene.30 30a (For the preparation and resolution of chiral tf .szz-zirconocene 6, see Refs 30,30a.) However, moderate diastereoselectivities and yields are generally observed (Scheme 5). 

Attempts at enantioselective cyclization have met with only limited success, but provide further insight into the catalytic mechanism. a Silane-mediated reductive cyclization of dienyl aldehyde 74a in the presence of... 

While the notion that the alkoxides derived from aliphatic alcohols are poor nucleophiles toward 7r-allylmetal complexes has prevailed over the years, much progress made in the recent past has rendered the transition metal-catalyzed allylic alkylation a powerful method for the O-allylation of aliphatic alcohols. In particular, owing to the facility of five- and six-membered ring formation, this process has found extensive utility in the synthesis of tetrahydrofurans (THFs) (Equation (29))150-156 and tetrahydropyrans (THPs).157-159 Of note was the simultaneous formation of two THP rings with high diastereoselectivity via a Pd-catalyzed double allylic etherification using 35 in a bidirectional synthetic approach to halichondrin B (Equation (30)).157 The related ligand 36 was used in the enantioselective cyclization of a Baylis-Hillman adduct with a primary alcohol (Equation (31)).159... 

Scheme 42 Enantioselective cyclization in tandem processes leading to bicydic systems...

When the nucleophile bears an appropriately unsaturated chain, these enantioselective cyclizations can be used to advantage in tandem processes leading to bicyclic systems (Scheme 42) [131,141,142], The greater enantios-electivity observed with the mesylate group in this example may be due to the lower degree of stabilization of the alkene radical cation in the looser ion pair, which leads to more rapid cyclization. 

Another report by Rychnovsky et al. explored the potential of chirality transfer in the transannular cyclization of cyclodecene 45 [42], They proposed a radical deoxygenation of 45, which produces an intermediate cyclodecenyl radical that can cyclize in a 5-exo fashion to yield 5,7-fused bicycle 48 (Scheme 13). The potential for the optically enriched radical precursor 45 to undergo enantioselective cyclization is dependent on the rate of transannular cyclization. That is, if the radical generated from optically pure... 

Highly enantioselective atom transfer radical cydization reactions catalyzed by chiral Lewis acids have been reported by Yang et al. [80]. Two main advantages of these enantioselective cyclizations include installing multiple chiral centers and retaining a halogen atom in the product, which allows for further functionalization. 

SnCl4 is also superior to 22 SnCl4, and is effective for the enantioselective cyclization of 2-(polyprenyl)phenol derivatives to give polycyclic terpenoids bearing a chroman skeleton.The synthetic utility of 26 SnCl4 is demonstrated by very... 

Along these lines, Jacobsen and co-workers <99AG(E)2012> published an interesting enantioselective cyclization of meso epoxy alcohols which were catalyzed by the cobalt(UI)salen complex 69. Thus, epoxy alcohol 70 was converted to the chiral bicyclic hydroxy ether 71 in 96% yield and 98% ee. 

In a similar fashion, ( + )-(7 )-2-hydroxy-2 -(3.7,ll-trimethyl-2,6,10-dodecatrienyloxy)-l,l-bi-naphthylyl undergoes enantioselective cyclization to give 2-methyl-6-(4-methyl-3-cyclohex-enyl)-2,5-heptadiene (/ -bisabolene) in 76% ee1 18. 

Gunter Helmchen of the Universitat Heidelberg took advantage (Chem. Comm. 2004, 896) of the substitutional flexibility of It-allyl indium complexes to develop enantioselective cyclizations such as 3 to 4. Six-membered rings are also formed efficiently (88% ). 

Certain unsaturated aldehydes may be converted to cyclic ketones by a related mechanism. The formyl group reacts with Rh(I) complexes to form an acyl-Rh hydride species, which undergoes intramolecular reaction with the olefinic linkage present in the same molecule (117a). Asymmetric induction is observed with a chiral diphosphine ligand (Scheme 53) (117b-d). Enantioselective cyclization of 4-substituted 4-pentanals into 3-substituted cyclopentanones in greater than 99% ee is achieved with a cationic BINAP-Rh complex. 

Scheme 126 shows the enantioselective cyclization of 1,3-dichloro-2-propanol to form partially resolved epichlorohydrin, which is achieved by combining small amounts of a chiral Schiff-base Co(II) complex and potassium carbonate (305). The same chiral Co(II) catalyst allows enantiomer-selective carbonation of propylene bromohydrin to afford propylene carbonate in fair chemical and optical yields (306). 

TABLE 4.6. Zr-Catalyzed Enantioselective Cyclization of Dienes Containing Allylamine Moieties Induced by n-BuMgCl... 

Transition metal complexes other than Co2(CO)8 catalyse the Pauson Khand reaction. The complex [RhCl(CO)2]2 catalyses the reaction of 224 [97], and Ru3(CO)12 [98] also catalyses these reactions at somewhat high temperatures. Highly enantioselective cyclization of 225 is catalysed by the chiral Ti(ebthi) complex to give 226 with 94% ee [99]. 

Problem 1 focuses on reagents for the synthesis of carbocyclic systems. Problems 2-4 address selectivity issues associated with carbocyclic systems. The syntheses of TMs in Problems 5 and 6 require the selection of specific reagents to achieve chemo-, stereo-, or enantioselective cyclizations. 

Sakamoto et al. have provided an example of absolute asymmetric synthesis involving [i-hydrogen abstraction by thiocarbony] sulfur (Scheme 4.68) [102]. The achiral benzothioamides 126 crystallize in chiral space group P212121. When the chiral crystals were irradiated in the solid state at —45 °C, followed by acetylation with AcCl at —78 °C, the aziridines 127 were obtained as a main product in a highly enantioselective cyclization. 

Acylcyclohexanes have received considerable study and, especially as solids, undergo highly stereoselective cyclization, since H-abstraction occurs with the phenyl twisted away from the a-methyl, where it stays until the biradical cyclizes [56]. Addition of a chiral ammonium salt to the benzene ring fosters enantioselective cyclization, presumably by inducing a tilt of the benzoyl group that leads to preferred abstraction from one of the two y carbons [57],... 

The enantioselective cyclization of prochiral substrates of type 22 to bicyclic products 23 was examined by Shibasaki and co-workers [11 -14]. In the presence of BINAP as a chiral ligand the two enantiotopic double bonds of 22 are differen-... 

Enantioselective cyclization of 4-substituted 4-pentenals to 3-substituted cyclopentanones in >99% ee is achieved with a cationic BINAP-Rh complex (eq 18). ... 

Enantioselective Polyene Cyclization Catalyzed SnCU-BINOL Derivatives. Non-enzymatic enantioselective polyene cyclizations are very attractive alternatives to the multistep synthesis from naturally occurring chiral synthons. The authors have succeeded in the first enantioselective biomimetic cyclization of polyprenoids catalyzed by LBA. (—)-Ambrox is the most important commercial substitute for ambergris, due to its unique olfactory and fixative properties. The successful preparation of (—)-ambrox has been achieved by the enantioselective cyclization of homofamesol promoted by (/ )-BINOL-Me-SnCl4, although the enantioselectivity and diastereoselectivity is moderate (eq 10). 

Tetracyclic terpene from Eocene Messel shale (Germany) can be also synthesized by using the LBA-induced enantioselective cyclization of 3-homofarnesyltoluene as a key step (eq 16). 

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