Ketenes catalytic enantioselective cycloaddition

Catalytic enantioselective cycloaddition reactions of ketenes have been intensively explored over the past several decades. Various chiral catalysts have been developed for these cycloadditions, such as cinchona alkaloids, N-heterocyclic carbene (NHC) catalysis (2013SL1614), planar-chiral 4-(JV,JV-dimethylamino)pyridine (DMAP)-derived catalysts, and Lewis acid-based catalysts (2009T6771, 2004ACR542). 

Dochnahl M, Fu GC (2009) Catalytic asymmetric cycloaddition of ketenes and nitroso compounds enantioselective synthesis of a-hydroxycarboxylic acid derivatives. Angew Chem Int Ed 48 2391-2393... 

Drawing from their success with catalytic [4 + 2] cycloaddition, Lectka group developed another highly enantioselective cycloaddition of o-quinone methide (o-QM) with silyl ketene acetals, using a chiral cinchona alkaloid derived ammonium, N-(3-nitrobenzyl)quinidinium fluoride Is, as a precatalyst. The free hydroxyl group of the cinchona alkaloid moiety was crucial to high optical induction. A variety of silyl ketene acetals had been screened to afford the cycloadducts 22 with good ee (72-90%) and excellent yield (84—91%) (Scheme 10.26) [35]. 

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. 

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. 

Following the same strategy, further improvements in similar catalytic asymmetric [4 + 2] cycloaddition reaction have been made by Lectka group. The cyclic 1,4-benzoxazinones 3 (Scheme 10.4) that rely on the highly enantioselective [4 + 2] cycloaddition of o-benzoquinone imides with chiral ketene enolates were efficiently constructed, which can be derivatized in situ to provide a-amino acid derivatives in good to excellent yields and with virtual enantiopurity [9]. 

Another catalytic application of chiral ketene enolates to [4 + 2]-type cydizations was the discovery of their use in the diastereoselective and enantioselective syntheses of disubstituted thiazinone. Nelson and coworkers described the cyclocondensations of acid chlorides and a-amido sulfones as effective surrogates for asymmetric Mannich addition reactions in the presence of catalytic system composed of O-TM S quinine lc or O-TMS quinidine Id (20mol%), LiC104, and DIPEA. These reactions provided chiral Mannich adducts masked as cis-4,5 -disubstituted thiazinone heterocycles S. It was noteworthy that the in situ formation of enolizable N-thioacyl imine electrophiles, which could be trapped by the nucleophilic ketene enolates, was crucial to the success of this reaction. As summarized in Table 10.2, the cinchona-catalyzed ketene-N-thioacyl-imine cycloadditions were generally effective for a variety of alkyl-substituted ketenes and aliphatic imine electrophiles (>95%ee, >95%cis trans) [12]. 

In 2010, the group developed the cycloaddition of atyl(allqrl)ketenes and a nitroso compound under the catalytic effect of precatalyst C6. Various allqrlatylketenes were tolerated to provide the corresponding cycloadducts 172 in moderate to high 5deld and with good to excellent enantioselectivity (up to 95% enantiomeric excess) (Scheme 20.72). ... 

The first catalytic asymmetric version of [2 + 2] cycloaddition reaction was realized by Narasaka in 1989 using chiral titanium catalyst derived from TADDOL. It was found that the reaction of ketene dithioacetal with acryloyloxazolidinone derivatives proceeded smoothly in the presence of 10 mol% of TADDOL-TiCl2 to give the cyclobutane derivatives in high yields (64-96%) and good to excellent enantioselectivities (80-98%) [183]. The reaction is presumed to proceed via a carbonyl substrate chelated TADDOL-TiCb intermediate although the exact reaction mechanism is unclear. Moreover, alkynyl, alkenyl, and 1,2-propadienyl... 

Ye applied his catalytic system to enantioselective p-lactam and p-lactone formations via Staudinger-like reactions with imines or ketones (Scheme 14.22). Furthermore, the reaction with benzoyldiazenes gave the corresponding oxadiazin-6-ones issue of a [4+2] cycloaddition reaction, instead of the reported [2+2] DMAP derivatives, as nucleophilic catalysts. The postulated formation of an azolium enolate upon reaction of the NHC with the ketene in these reactions was evidenced experimentally by the isolation and full characterization of such zwitterionic adducts in model reactions. ... 

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