Lewis acids with aryl esters

Sulfur tetrafluoride [7783-60-0] SF, replaces halogen in haloalkanes, haloalkenes, and aryl chlorides, but is only effective (even at elevated temperatures) in the presence of a Lewis acid catalyst. The reagent is most often used in the replacement of carbonyl oxygen with fluorine (15,16). Aldehydes and ketones react readily, particularly if no alpha-hydrogen atoms are present (eg, benzal fluoride [455-31-2] from benzaldehyde), but acids, esters, acid chlorides, and anhydrides are very sluggish. However, these reactions can be catalyzed by Lewis acids (HP, BF, etc). 

Another synthesis of the cortisol side chain from a C17-keto-steroid is shown in Figure 20. Treatment of a C3-protected steroid 3,3-ethanedyidimercapto-androst-4-ene-ll,17-dione [112743-82-5] (144) with a tnhaloacetate, 2inc, and a Lewis acid produces (145). Addition of a phenol and potassium carbonate to (145) in refluxing butanone yields the aryl vinyl ether (146). Concomitant reduction of the C20-ester and the Cll-ketone of (146) with lithium aluminum hydride forms (147). Deprotection of the C3-thioketal, followed by treatment of (148) with y /(7-chlotopetben2oic acid, produces epoxide (149). Hydrolysis of (149) under acidic conditions yields cortisol (29) (181). 

A great advantage of catalyst 24b compared with other chiral Lewis acids is that it tolerates the presence of ester, amine, and thioether functionalities. Dienes substituted at the 1-position by alkyl, aryl, oxygen, nitrogen, or sulfur all participate effectively in the present asymmetric Diels-Alder reaction, giving adducts in over 90% ee. The reaction of l-acetoxy-3-methylbutadiene and acryloyloxazolidinone catalyzed by copper reagent 24b, affords the cycloadduct in 98% ee. The first total synthesis of ewt-J -tetrahydrocannabinol was achieved using the functionalized cycloadduct obtained [23, 33e] (Scheme 1.39). 

For the preparation of aryl esters from phosphorus oxychloride, a Lewis acid is generally added as a catalyst. Commonly, aluminum chloride with an excess of phosphorus oxychloride added to the phenol provides excellent yields (Equation 4.2).4... 

It has been shown that the lead tetraacetate-mediated 1,2-aryl shift of various meta-substituted / -cyclohexyl aryl ketones, e.g. (10), results in excellent yields of the corresponding rearranged esters (11). A unique reaction, providing 3-hydroxy-2-arylacrylic acid ethyl esters (14), has been observed between aryl aldehydes and ethyl diazoacetate in the presence of the iron Lewis acid [rj — (C5H5)Fe(CO)2(THF)BF4], It appears that the enol esters are formed by an unusual 1,2-aryl shift from a possible intermediate (13), which in turn is formed from the reaction of the iron aldehyde complex (12) with ethyl diazoacetate (see Scheme 4). 

Aryl cyanates (cyanic esters), which can be prepared in situ (67AG(E)206), form 1,3,5-triazines under either acid or base catalysis (Scheme 83) (77RCR278, 78RCR975). The acid-catalyzed reactions are not properly understood, but it seems that the mechanism is dependent on the precise nature of the Lewis acid used. Yields are usually good (Table 14). The reaction of aryl cyanates with ketoximines yields 1,3,5-triazines (146) via the intermediate (145) (Scheme 84) (66CB2361). Alkyl cyanates are very reactive, and isomerize readily therefore they are unsuitable starting materials for 1,3,5-triazine synthesis. 

Because of the special structural requirements of the resin-bound substrate, this type of cleavage reaction lacks general applicability. Some of the few examples that have been reported are listed in Table 3.19. Lactones have also been obtained by acid-catalyzed lactonization of resin-bound 4-hydroxy or 3-oxiranyl carboxylic acids [399]. Treatment of polystyrene-bound cyclic acetals with Jones reagent also leads to the release of lactones into solution (Entry 5, Table 3.19). Resin-bound benzylic aryl or alkyl carbonates have been converted into esters by treatment with acyl halides and Lewis acids (Entry 6, Table 3.19). Similarly, alcohols bound to insoluble supports as benzyl ethers can be cleaved from the support and simultaneously converted into esters by treatment with acyl halides [400]. Esters have also been prepared by treatment of carboxylic acids with an excess of polystyrene-bound triazenes here, diazo-nium salts are released into solution, which serve to O-alkylate the acid (Entry 7, Table 3.19). This strategy can also be used to prepare sulfonates [401]. 

Reaction of aldehydes with ethyl diazoacetate normally results in the formation of [5-oxo esters. When a cationic Fe(II) Lewis acid is used as the catalyst, an unexpected 1,2-aryl shift results in the formation of a-formyl arylacetic acid ester 23, which is isolated as its enol tautomer (Scheme 8.6) [28]. The catalyst of this reaction,... 

Simple /V-a Iky I a ted imines, e.g. V-methylaldimine (18, R1 = aryl, alkyl), undergo nucleophilic addition using a masked acyl cyanide reagent [19, where the masked group = —C(CN)2—O—] with C-C bond formation to give an a-amido ester (20).78 This mild conversion does not require pre-activation (i.e. incorporation of an activating group in the substrate) or post-activation (i.e. Brpnsted or Lewis acid, or metallic species). 

The allylation of a-iV-tosylimino esters, highly activated imines, proceeds by catalytic use of a Lewis acid. Tol-BINAP-Cu(l) complexes are effective catalysts of asymmetric allylation of these imines with allylsilanes (Equation (28)).124 125 The presence of an aryl group at the position j3 to silicon improves the enantioselectivity. 

Attempts to apply the thermal decarboxylation reaction in the liquid phase to aromatic halofor-mic acid esters have shown that their reaction is different from that ol the aliphatic haloformates. It was found that evolution of carbon dioxide occurs, but only high boiling products could be isolated.136 On heating in the presence of aromatics and Lewis acids, aryl chloroformates do not react to give chlorinated aromatics with concomitant decarboxylation, but undergo a Friedel-Crafts reaction to give phenyl benzoates.137 Under similar conditions phenyl fluoroformate undergoes only polymerization and carbonate formation.137... 

In a mechanistic study on the Lewis acid catalyzed addition of ethyl diazoacetate to ketones a similar profile of rearrangement to the 3-keto esters was observed (Scheme 9). In the same reaction with acetophenones, substitution on the benzene ring was found to only slightly affect the otherwise 90 10 preference for migration of aryl versus methyl. ... 

Metal thiolates or benzenethiols in the presence of triethylamine also react very smoothly with di-ketene to yield S-alkyl (35) or S-aryl acetothioacetates (36). The p-keto thioesters (35) can be used in exceptionally mild preparations of P-keto amides (37), whereas (36) can be cyclized by Lewis acids to form thiocumarins (38). The S-f-butyl thiol ester (35) is also a suitable substrate for C-alkylation in the P-position or, after double deprotonation, in the 8-position (Scheme 3). ... 

The rearrangement of acetals of 2-haloalkyl aryl ketones is a well-documented process yielding esters of 2-arylalkanoic acids by 1,2-aryl shift (equation 7). The mechanism of this rearrangement is reminiscent of other semipinacol rearrangements. Loss of the halogen (usually assisted by Lewis acid), yields a carbocation (4), which then undergoes a 1,2-aryl shift with carbonyl group formation. 

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