Acyl transfer, catalyzed asymmetric

The mechanism by which chiral nucleophiles catalyze asymmetric acyl transfer in the KR of, yec-alcohols can be seen as a three-step process (Scheme 1) [2]. 

Scheme 2 Classification of catalyzed asymmetric acyl transfer process [2]...

It should be noted that asymmetric acyl transfer can also be catalyzed by chiral nucleophilic A-heterocyclic carbenes [27-32] and by certain chiral Lewis acid complexes [33-37] but these methods are outside the scope of this review. Additionally, although Type I and Type II tr-face selective acyl transfer processes have been reported to be catalyzed by some of the catalysts described in this review, these also lie outside the scope of this review. 

Of the numerous examples of asymmetric reactions catalyzed by Lewis bases, this chapter focuses mainly on the activation of silicon reagents and related processes. Various other types of Lewis basic (nucleophilic) activation, namely the Morita-Baylis-Hillman (MBH) reaction, acyl transfer, nucleophilic carbenes, and carbonyl reduction, are described in the other chapters of this book. 

Asymmetric Acyl Transfer Reactions Table 8.13 Deng s (DHQD)2AQN-catalyzed KR of 1,3-dioxolane-2,4-diones [194]. 

Prochiral Compounds. The enantiodifferentiation of prochi-ral compounds by lipase-catalyzed hydrolysis and transesterification reactions is fairly common, with prochiral 1,3-diols most frequently employed as substrates. Recent reports of asymmetric hydrolysis include diesters of 2-substituted 1,3-propanediols and 2-0-protected glycerol derivatives. The asymmetric transesterification of prochiral diols such as 2-0-benzylglycerol and various other 2-substituted 1,3-propanediol derivatives is also fairly common, most frequently with Vinyl Acetate as an irreversible acyl transfer agent. 

Acylation of 3,4,7,8-tetramethylglycoluril by the method of Sun and Harrison [34] leads to the monoacyl derivatives, which can be further selectively acylated with lithium diisopropylamide (LDA) and acyl chlorides. The resulting symmetrical or asymmetrical diacyl compounds undergo a base-catalyzed acyl transfer reaction. Consequently, the glycoluril acts as a temporary template that facilitates a condensation between acyl units. The absence of O-acylation products is explained by chelation of the lithium by the intermediate enolate. 

The manufacture of optically active trans-2-bromoindan-l-ol (106) and its esters starting from racemic tmns-2-bromo-l-(acyloxy)indan (rac-105) has been conducted by Ichikawa Gosei Kagaku Co., Japan (Scheme 32) [97]. Compound 106 is a useful intermediate for the synthesis of c/s-l-aminoindan-2-ol (107), which can be used for the preparation of anti-HIV drugs. An asymmetric hydrolysis of rac-105 could be performed through enzyme-catalyzed acyl transfer onto methanol. Thus, alcohol 106 was produced by applying Novozyme 435 in diisopropyl ether/methanol in 45% yield besides acetate (l, 2i )-105 in 52% yield. 

The same catalyst system works well in hetero-allylic asymmetric alkylations (h-AAA Scheme 1-16). Substrates such as enol esters 163 provide entry to nonracemic esters of allylic alcohols. Remarkably, competing 1,2-addition and/or acyl transfer were not issues yields are good (80-99%). In these cases, catalyst loading can go as low as 0.8%, and ee s are mostly >95%. Additional chemoselectivity has been noted in the case of cinnamyl ester 163, where the desired Sn2 AAA takes place without competing Cu-catalyzed 1,4-addition to the enoate. This sets the stage for a subsequent metathesis (GH-2 = Grubbs-Hoveyda second-generation catalyst) en route to butenolide 164. 

While an array of 0- and iV-acylation processes catalyzed by Lewis bases have been developed, C-acylation or C-carboxylation processes are relatively unexplored. However, one C-carboxylation protocol, the O- to C-carboxyl transfer of oxazolyl carbonate derivatives to give the corresponding 4- or 2-carboxyazlactones, initially demonstrated in 1970 by Steglich and HOfle, is often used as the benchmark standard for assessing asymmetric Lewis... 

Mechanisms of Asymmetric Epoxidation Reactions 558 Nature s Hydride Reducing Agent 566 The Captodative Effect 573 Stereoelectronics in an Acyl Transfer Model 579 The Swern Oxidation 580 Gas Phase Eliminations 588 Using the Curtin-Hammett Principle 593 Aconitase—An Enzyme that Catalyzes Dehydration and Rehydration 595... 

Although the process of direct phosphoryl transfer shares some mechanistic similarities to acyl transfer in so far as it can be catalyzed by some of the same small-molecule nucleophiles (e.g., N-methylimidazole, 4-DMAP, pyridine-N-ox-ides) [77], it presents some distinct challenges with regard to asymmetric catalysis as the result of the tetrahedral nature of the transferred phosphorus(V) center as compared to the trigonal planar carbonyl carbon. Additionally, achiral alcohol... 

Fig. 8.33 DYKAT of 1,3-diols via lipase-catalyzed acyl-transfer in combination with Ru-catalyzed epimerization of hydroxyl groups. G=chiral carbon, convertible for equilibration and acyl migration, but not for the irreversible step H=chiral carbon, convertible for equilibration, acyl migration and the irreversible step l=chiral carbon, convertible for acyl migration, stable chirality. (From J. Steinreiber, K. Faber, H. Griengl, De-racemization of enantiomers versus de-epimerization of diastereomers-chssification of dynamic kinetic asymmetric transformations (DYKAT), Chemistry 14 (2(X)8), 8060. Copyright 2008 Wiley).

The sense of asymmetric induction in chiral Sc(III)-catalyzed reactions can be rationalized by assuming an intermediate octahedral Sc(IIl)-dienophile complex (Sch. 7). The axial chirality of (/ )-BINOL is transferred to the amine, the re face of the acyl-1,3-oxazolidin-2-one is effectively shielded by the amine part, and a diene approaches the dienophile from the si face to afford the adduct with a high enantio-selectivity. 

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