Enantioselective oxidative cyclization

An enantioselective oxidative cyclization of 4-alkenoic acids to give y-lactone derivatives via palladium-catalyzed allylic C-H activation was also disclosed by Sasai in 2011 (Scheme 3.42) [76]. In the presence of 10mol% Pd(OAc)2 and 15mol% spiro bis(isoxazoline) ligand, a variety of five-membered ring lactones could be constructed in moderate to excellent yields. However, the enantioselectivity is highly depended on the structures of substrates. 

The structure of glabrescol was subsequently revised, and the new structure was synthesized enantioselectively through sequential hydroxy-directed anti-oxidative cyclization of acyclic y-alkenols with VO(acac)2/TBHP to construct the adjacent THF rings via epoxides under acid conditions [35b],... 

Parker has outlined an elegant, enantioselective synthesis of L-vancosamine derivatives commencing from noncarbohydrate precursors (Scheme 17.38) [116]. This approach features a diastereoselective allenylstannane addition and W(CO)5-catalyzed cycloisomerization to construct the pyranose core. Oxidative cyclization of the C4-carba-mate 128 is performed with 10 mol% Rh2(OAc)4 and proceeds stereospecifically to give the crystalline oxazolidinone 129 (86%). All told, synthesis of this useful L-vancosa-mine glycal equivalent covers seven steps from (S)-(-)-ethyl lactate 127 and is accomplished in 44% overall yield. 

Palladium(II)-promoted oxidative cyclization of alkenes bearing tethered nucleophiles represents an intramolecular variant of the Wacker reaction. These reactions, which typically generate five- and six-membered heterocycles, have been the subject of considerable interest in organic chemistry [89-96]. Contemporary interest centers on the development of enantioselective examples [95,97] and reactions that employ dioxygen as the sole oxidant for the Pd catalyst [92-96]. 

Aerobic oxidative cyclization of 2,2-dihydroxystilbenes via oxygen cation radical leading to the formation of c -4b,9b-dihydrobenzofuro[3,2-h]benzofurans was carried out in an enantioselective manner by using (nitrosyl)Ru(salen) as a catalyst under irradiation conditions <02CL36>. 

Sasai s group [13] developed a series of bisnitrogen ligands with fused hetero spiro cyclic backbones, including spiro bis(isoxazoline) 11 and 12, spiro isoxazole-isoxazoline 13, spiro bis(oxazoline) 14, spiro bis(pyrazole) 15, and spiro bis(isoxazole) 16 (Figure 3). Ligands 11 [14] and 13 [15] exhibited excellent reactivity and enantioselectivity in the Pd-catalyzed oxidative cyclization reactions. 

Scheme 11.37 Pd(ll)-catalyzed enantioselective oxidative domino cyclization [55],...

An oxidative cyclization of 4-alkenoic acids (37) has been developed. The reaction occurs in the presence of p-benzoquinone as oxidant and is believed to proceed via the TT-allyl Pd intermediate (38), generated by an allylic C—H activation. Moderate to good enantioselectivity was observed when the spiro bis(isoxazoline) ligand (SPRIX) (39) was employed. ... 

Rovis and coworkers reported the first enantioselective rhodium-catalyzed [4-I-2-I-2] cycloaddition of terminal alkynes 131 with ( i-dienyl isocyanates 132 to construct the bicyclo[6.3.0]azocines [48]. Heating a toluene solution (110 °C) of 131 and 132 in the presence of a catalytic amount of [Rh(C2H4)2Cl]2 and chiral phosphoramidite afforded the [4-I-2-I-2] cycloadducts 133 in good yields with excellent enantiomeric excesses [49], Initial oxidative cyclization between the diene and the isocyanate moiety of 132 afforded rhodacycle 134. Coordination and insertion of alkyne 131 to 134 followed by reductive elimination of the resulting rhodacycle 135 provided the [4-I-2-I-2] adduct 133 (Scheme 4.27). 

Desymmetrization of a meso-intermediate also held the key to enantio-selectivity in the approach to (—)-swainsonine (378) by Katsuki and his colleagues (Scheme 70). In this case, the (R,R)-(salen)manganese complex 524 mediated the enantioselective oxidation of the meso-pyrrolidine 525 with iodosylbenzene to the (2S)-hydroxypyrrolidine 526, which was further oxidized with pyridinium chlorochromate to yield lactam (—)-527 in an overall yield of 56% and an ee of 71%. Reaction with 4-chlorobutylmagne-sium bromide opened the lactam ring to give the chloroketone (+)-528, which underwent spontaneous cyclization to the cyclic imine 529 upon... 

In 2007, Gagne s group succeeded in a regio- and diastereoselective oxidative polycyclization of di- and trienols catalyzed achiral [(dppe)Pt] dications, wherein turnover was achieved by the trityl cation abstracting a hydride from a putative [(dppe)Pt-H] intermediate [32i]. One year later, Gagne s group developed the catalytic enantioselective polyene cyclization induced by [(S)-(xylyl-PHANEPHOS) Pt][(BF )j] catalyst, which was prepared from (S)-(xylyl-PHANEPHOS)PtIj and AgBF in situ (Scheme 9.21) [32j]. This asymmetric catalysis enables the oxidative cascade cyclization of polyalkene substrates [32k] (Scheme 9.15). 

Excellent chemoselectivity in the enantioselective dihydroxylation of dienes has been observed with substrates such as 324 (Equation 51) and 326 (Equation 52) [218], An interesting expansion of this methodology was recently reported by Donohoe, who discovered that 1,5-dienes participated smoothly in highly diastereoselective osmium-catalyzed oxidative cyclization reactions [219]. This mild oxidation method was combined with an initial asymmetric catalytic dihydroxylation reaction to give optically active tetrahydrofurans, as illustrated by the conversion of 328 into 330 (95 % ee. Scheme 9.42) [220]. 

Catalytic enantioselective crossed aldehyde-ketone benzoin cyclizations of ketoaldehydes, such as 13, readily obtained from an aryl nitrile oxide and a 1,3-diketone, were studied in order to perform the synthesis of complex molecules. Significant asymmetric induction was observed with chiral triazolium salts such as 14, in the presence of DBU as base, leading to compound 15 in high yield and with 99% ee in favor of the R enantiomer <06AG(E)3492>. 

The enantioenriched sulfoxide intermediate 72 (R = CH2OH), obtained by asymmetric 5-oxidation with a chiral oxaziridine (89 11 enantiomeric ratio), has provided a highly enantioselective synthesis of the benzothiepin derivative 71 (4R, 5R). The aldehyde intermediate 72 (R = CHO) was cyclized asymmetrically to 71 (4R, 5R) with >98 2 enantiomeric ratio. Base treatment (f-BuOK, -10°C, THF) of the racemic benzothiepin 73... 

Trost et al.59 were the first to report enantioselectivity in the transition metal-catalyzed Alder-ene reaction. Several different acids were surveyed for the degree of efficacy in oxidizing the Pd(0) precursor to the active Pd(n) species and for compatibility with the catalyst, substrate, and product. Among acids surveyed were several chiral carboxylic acids products of reactions using these optically active acids were formed with modest enantioselectivity. (A)-binaphthoic acid gave the most promising result, with the cyclized product 83 obtained with 33% ee (Equation (52)). 

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