Enantioselectivity 2+2 cycloadditions

Enantioselective [2 + 2 cycloaddition.2 The chiral allylic ether (1), prepared from (lS,2R)-( + )-2-phenylcyclohexanol, undergoes enantioselective cycloaddition with dichloroketene to furnish, after one crystallization, optically pure (-)-2. This cyclobutanone after ring expansion and exposure to chromium(II) perchlorate gives... 

A Ti-catalyzed enantioselective [2 + 2]-cycloaddition between allenyl sulfide 30 and 31 afforded the adduct with a high optical purity [27]. 

The diastereoselective and enantioselective [2+2] cycloaddition of a 7-oxanorbornene with a chiral alkynyl acyl sultam was effected by using a ruthenium catalyst to provide the . 

Table 4.6 D ual Lewis acid-Lewis base activation in the enantioselective [2 + 2] cycloaddition of TMS-ketene and ethyl glyoxalate.

Attempts at asymmetric, enantioselective [2 + 2] cycloadditions, using chirally modified nickel catalysts, have been reported, but without positive results27. 

Quinidine [3, (9S)-6 -methoxy-9-cinchonanol] is mostly applied for the same purposes as quinine, such as the addition of zinc alkyls to carbonyl compounds (Section D 1.3.1.4.), or addition of thiophenol to acrylic derivatives (Section D.2.I.). An important technical synthesis of malic acid is based on the quinidine catalyzed enantioselective [2 + 2] cycloaddition of ketene to chloral (see Section D. 1.6.1.3.). Esters and ethers of dihydroquinidine (4) (just like the corresponding derivatives of dihydroquinine) have been used as chiral ligands in osmium tetroxide catalyzed dihydroxylations of alkenes (Section D.4.4.). 

Ishihara, K. et al. reported an enantioselective [2+2] cycloaddition of unactivated alkenes (e.g., 161) with a-acyloxyacroleins 162, catalyzed by chiral organoammo-nium salts, catalyst 163, Scheme 3.52 [68], A possible stepwise mechanism was proposed by authors to account for the stereoselectivity, which includes initial Michael addition of alkene to (Z)-iminium enal intermediate and intramolecular cyclization to afford the cycloadducts. The proposed transition states were stabilized by aromatic n-n stacking and intramolecular hydrogen-bonding interaction. 

The formal [2+2] cycloaddition also provides an interesting approach for stereoselective synthesis of chiral cyclobutane derivatives. Ishihara and co-workers [70] reported the enantioselective [2 + 2] cycloaddition of unactivated alkenes 113 with a-acyloxyacroleins (Scheme 6.26). The reaction is catalyzed by chiral anunonium salt 114 and gives highly functionalized cyclobuten derivatives 115 with high... 

Enantioselective [2 + 2] cycloaddition ofketenes with N-sulfmylaniUnes catalyzed by N-heterocyclic carbene 156 generated from 155 leads to stereoselective 3-oxo-P-sultam (l,2-thiazetidin-3-one 1,1-dioxide) formation (Eqn (4.95)). ... 

In the field of metal-catalyzed asymmetric cycloadditions, [2+2] cycloaddition seems to be relatively rare due to the ring strain force of the products. In 2010, Studer and co-workers presented the first Cu(I)/Walphos-catalyzed enantioselective [2+2] cycloaddition of 2-nitrosopyridine with various ketenes to afford synthetically valuable 1,2-oxazetidine-3-ones with good enantioselectivity (Scheme 33) [58]. Density function theory (DPT) calculations give evidence that the reaction occurs via a concerted pathway. 

Also, reaction of ketene with 4-nitrophenyl trichloroacetophenone at —25°C in the presence of a quinidine catalyst gives the corresponding /3-lactone in 95 % yield (89 % e,e). Ketene reacts with aldehydes in the presence of oxazaborolidine catalysts to give the j3-lactones in an enantioselective manner The enantioselective [2+2] cycloaddition of silylketenes 221 with a-ketoesters affords the cycloadducts 222 in 86-99 % yield (high e,es) . 

Likewise, chiral Af-heterocyclic carbenes are efficient catalysts for the enantioselective [2+2] cycloaddition reaction of disubstituted ketenes with oxoaldehydes, and yields of up to 99 % are achieved with enantioselectivities of up to 99 %... 

Reaction under these conditions led to the enantioselective 2+2 cycloaddition of some 2-quinolones, both 4-alkenylo3qr (2) and (less satisfactory) 3-alkenyloxy (3), as illustrated in Scheme 3 by using either stereoisomer of the photocatalyst (see Scheme 3). ... 

In the [2 + 2]cycloaddition chemistry, enantioselective carbo[2 + 2]cycloaddition catalyzed by chiral Al(III) Lewis acids has not been reported. On the other hand, catalytic enantioselective [2 + 2]cycloaddition of ketenes and aldehydes is well known. As the pioneering work, Miyano and coworkers reported that substoichiometric amount of chiral Lewis acid (S)-(46a) prepared from (S)-BINOL derivative and Me3Al promotes [2 + 2]cycloaddition of aldehydes and ketene to give P-lactones in moderate optical yield (Scheme 6.106) [125]. The same research group also reported (R,R)-(116a) as a more effective Lewis acid catalyst. 

Asymmetric Catalytic [2+2] Cycloaddition Reaction Using a Chiral Aluminum Complex In 2007, Canales and Corey provided the first enantioselective [2+2] cycloadditions of sUyl enol ethers with a, 3-unsaturated esters by catalytic amounts of aluminum bromide complex [21]. Aluminum catalyst 18 is conveniently generated in situ by the addition of a commercially available solution of aluminum bromide in CH2Br2 to a solution of the known oxazaborohdine component [22,23]. The results of enantioselective [2+2] cycloaddition reaction catalyzed by aluminum complex are summarized in Table 4.6. 

TABLE 4.6 Enantioselective [2+2] Cycloaddition of Silyl Enol Ethers with a, l-Unsatnrated Esters... 

Chateijee I, Jana CK, Steinmetz M, Grimme S, Studer A. Copper-catalyzed enantioselective [2+2] cycloadditions of 2-nitrosopyridine with ketenes. Adv. Synth. Catal. 2010 352 945-948. 

Some innovative approaches using chiral Lewis acids to promote catalytic enantioselective [2 + 2]-cycloadditions have been documented [36, 148-150]. The earliest example appears to have been reported by Narasaka (Equation 19) [148]. In these cycloaddition reactions, a titanium complex of TADDOL ligand 239 catalyzes the reactions between ketene dithioacetal 237 and acceptors. With fumarate derivative 238, adduct 240 was obtained in 96% yield and 98% ee. 

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