Azlactones O-acylated

Since amines react more readily than alcohols in noncatalyzed reactions with anhydrides, the reaction is more difficult and initially required stoichiometric catalyst loadings [107], but could be performed in a catalytic sense with an O-acylated azlactone as acylating agent, which does not react with a benzylic amine at —50°C, but is capable of acylating the catalyst [108, 109]. Depending on the buUdness of the substrate, selectivities ranged from S = 11 to 27 (s = [ enantiomer l]/[ enantiomer 2])-... 

Scheme 12 Fu s, Vedejs , Johannsen s and Richards chiral DMAP-catalyzed rearrangements of O-acyl azlactones [103-107]...

Catalytic kinetic resolution of amines has been a typical domain of enzymatic transformations. Attempts to use low-molecular-weight catalysts have notoriously been frustrated by the rapid uncatalyzed background reaction of the amine substrate with the acyl donor [40]. The first solution to this problem was recently developed by Fu, who used the planar chiral catalyst 21d and O-acyl azlactone 40 as the acyl donor (Scheme 12.19) [41]. In this process, the acyl transfer from the azlactone 40 to the nucleophilic catalyst 21d is rapid relative to both direct transfer to the substrate and to the transfer from the acylated catalyst to the substrate amine. Under these conditions, which implies use of low reaction temperatures, selectivity factors as high as 27 were achieved (Scheme 12.19) [41]. 

Rearrangement of O-Acyl Azlactones, O-Acyl Oxindoles, and O-Acyl Benzofuranones... 

In 1970 Steglich and Hofle reported that 4-dimethylaminopyridine (DMAP) and 4-(pyrrolidino)pyridine (PPY) are excellent catalysts for isomerization of O-acyl azlactones E to their C-acylated isomers F [79-81], In this rearrangement, a new quaternary stereocenter is generated (Scheme 13.41). Clearly, DMAP or PPY afford the rearrangement products F in the racemic form. 

In 1998 Fu and Ruble reported that the planar chiral 4-(diakylamino)pyridine derivatives 79a and 79b (Scheme 13.42) induce high enantiomeric excesses in the catalytic O-acyl azlactone rearrangement [85, 86]. In particular with the PPY-derivative 79b, O-acyl azlactones 80 were smoothly rearranged to the products 81 in almost quantitative yields and enantiomeric excesses up to 92% (Scheme 13.42) [85]. 

This chapter summarizes three related and highly effective approaches to the catalytic asymmetric generation of quaternary stereocenters - organocatalytic rearrangements of O-acyl azlactones to their C-acylated isomers and analogous isomer-izations of O-acyl oxindoles and O-acyl benzofuranones. All three processes hold great promise for application in, e.g., natural product synthesis [91-93],... 

Additions to prochiral ketenes [13.2] Desymmetrization of meso-diols [13.3] Dynamic kinetic resolution of azlactones rearrangement of O-acyl azlactones, O-acyl oxindoles, O-acyl benzofuranones [13.6]... 

In 1970, Steglich reported that DMAP catalyzed the rearrangement of O-acylated azlactones to their C-acylated isomers (the Steglich rearrangement) [166, 167]. This process effects C-C bond formation and concomitant construction of a qua-... 

Chromatography) (equation 82). These complexes are used as enantioselective nucleophilic catalysts for reactions such as the rearrangements of O-acylated azlactones, oxindoles, and benzofuranones, and the kinetic resolution of secondary alcohols via acylation. X-ray crystal structures have been obtained for iV-acylated derivatives of (366), allowing for characterization of a likely intermediate along the catalytic pathway. 

Tertiary phosphines are known to behave as Lewis bases in acylation reactions that proceed through a nucleophilic activation mechanism (see Section 4.06.7 for possible mechanisms operating in organocatalyzed polymerization). Their use as nucleophilic catalysts in enantioselective processes, which include the addition of alcohols to ketenes, the rearrangement of O-acylated azlactones, and the kinetic resolution of alcohols, is also well documented. " ... 

Fu et al. were the first to develop an efficient catalytic system for the KR of primary amines [120], Their method relied on the use of a stoichiometric amount of the O-acylated azlactone 111 as the achiral acyl donor in conjunction with a catalytic amount of a planar chiral DMAP derivative 112. Hence, after optimizing the reaction conditions, they were able to resolve various racemic primary aryl alkyl amines with moderate to good selectivities ranging from s = 11 to 27 independently of the substitution pattern on the aromatic ring or on the alkyl chain (Scheme 41.43). 

Ruble, J.C. and Fu, G.C. (1998) Enantioselective construction of quaternary stereocenters rearrangements of O-acylated azlactones catalyzed by a planar-chiral derivative of 4-(pyrrolidino) pyridine. J. Am. Chem. Soc., 120, 11532-11533. 

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