The Mukaiyama aldol reaction is one of the most versatile synthetic methods for stereoselective carbon-carbon bond formation. Asymmetric catalysis of this category utilizing chiral complexes derived from B, Al, Sn(II), Ti(IV), Cu(II), Pd(II), and Ln(III) has been explored in the past 10 years with significant breakthroughs. 1 Mukaiyama and co-workers have documented novel uses of various trityl salts serving as efficient catalysts in various aldol type transformations, 2 highlighting their potential in asymmetric variations. Nevertheless, several intrinsic and pending problems still hinder their practical design in that context. First, the reacting carbenium ion center is sp 2hybridized. Placement of the three flanking aryl groups in a chiral environment is so far impossible due to the extremely low barrier to racemization of chiral carbenium ions. 3 Second, in sharp contrast to most existing chiral Lewis acids generated from chiral natural sources (e.g., diols, diamines, amino acids, and tartrates), 1,4 no natural skeleton has been found that is relevant to the triarylmethyl scaffold. Third, the precise nature of the catalytic species in these transformations remains elusive in view of the recent elegant mechanistic study by Bosnich. 5 Apparently, development of new types of chiral Lewis acids with reactive carbenium-based centers are essential in view of their potential impact on both mechanistic and synthetic utility aspects. We describe herein our preliminary findings toward this end.Platzek and Snatzke have reported the synthesis of C 2symmetric diol 1, a common skeleton in various anti-inflammatory drugs, in scalemic form. 6 This resolved (10R,11R)-1, was utilized as a conceivable trityl ion precursor, whose enantiomeric purity was determined to be >99% enantiomeric excess (ee) by HPLC analysis on a chiral support (Chiralcel OJ). We have so far accessed two different 10,11-dialkyl (dimethyl and diethyl) substituted C 2 -symmetric trityl salts. To convert the alcohol moieties into methyl appendages, the diol-1 was mesylated with methanesulfonyl chloride (MsCl) in CH 2 -Cl 2 in the presence of Et 3 N (6 equiv). Reduction of the resultant dimesylate with LiEt 3 BH (3 equiv) in anhydrous THF provided 10,11-dimethyldibenzosuberane (2) in essentially quantitative yield (Scheme 1). In a similar manner, the scalemic diol 1 was transformed in 96% yield to the corresponding ditosylate by treatment with TsCl in the presence of Et 3 N and catalytic 4-(dimethylamino)pyridine (DMAP). Double S N 2 displacement of the ditosylate with (CH 3 ) 2 CuLi at -10°C provided the diethyl analog 3 quantitatively. 7 These two dialkyldibenzosuberanes were readily oxidized at ambient temperature to the respective ketones, 4 and 5, by KMnO 4 (2.5 equiv) in benzene using dicyclohexano-18-crown-6 as a phase transfer catalyst. 8 Both ketones were obtained in 91% yields.To probe the stereoelectronic influence of the 5-aryl group on the structure, reactivity, and selectivity of triarylcarbenium ions in the aldol process, two representative ...
Stereochemical studies have indicated that functionalized Tr + SbCl 6 -may serve as efficient aldol reaction catalysts by judicious choice of a silyl component. The aldol addition between TMS ketene acetal derived from γ-butyrolactone and benzaldehyde provided the silyl aldolates with high syn diastereoselectivities.Triphenylcarbenium ions (trityl salts) constitute a unique mode of carbon-centered Lewis acids for the Mukaiyama-type aldol addition. 1 So far, the precise nature of the catalytic species in this system remains elusive in view of several documented facile silyl-mediated pathways. 2 Recently, a cogent mechanistic study by Bosnich strongly suggests that Me 3 Si-X species is the real catalyst in the trityl perchlorate and triflatemediated reactions. 3 Their results disagree with our previous mechanistic findings by the employment of trityl ions based on a dibenzosuberane scaffold. 4 One reasonable hypothesis for this discrepancy is that our trityl ions are more catalytically active due to the peculiar confinements of two of the three aryl groups in a sevenmembered ring. An alternative explanation is that the operation of silyl catalysis requires a matched use of silyl group and counter ion (e.g., TMS and triflate). To support the conjectures, we have conducted a more thorough stereochemical study of this catalyzed process with functionalized triarylcarbenium ions.To gain insights into the effects of substituents and counter ions on the reactivity of trityl ions and extent of silyl catalysis, triarylcarbinols with 5 different aryl appendages of varying electronic and/or steric demands were synthesized by treatment of dibenzosuberone with the respective aryllithium. The trityl alcohols were all delivered in good yields ranging from 71 to 91% even in the 2,6-disubstituted cases (1d-f), Scheme 1. 5 Their structural identities (1d-f) were further proven by X-ray crystallographic analysis. Scheme 1We have recently developed a novel way of accessing carbenium ions with functionalized aryl groups, which involves Meerwein saltpromoted ionization of the corresponding trityl methyl ethers 2. The requisite ethers can be produced in good to excellent yield (70-97%) by the standard Williamson etherification procedure (NaH/CH 3 I). Three commercial Meerwein salts (Et 3 O + BF 4 -, Et 3 O + PF 6 -, and Me 3 O + SbCl 6 -) have been examined to transform the respective trityl methyl ethers into the corresponding triarylcarbenium ions. The efficiency of this process was assessed by the recovery yield of trityl alcohols on column chromatography and on HPLC analysis after buffered, aqueous quenching of the resulting trityl salts. In marked contrast to triethyloxonium salts, clean delivery of all trityl hexachloroantimonates except 3d was achieved by the employment of Me 3 O + SbC1 6 -. The optimal procedure involved treatment of the individual trityl methyl ether with Me 3 O + SbCl 6 -(1.0 equiv.) in a mixed solvent of EtNO 2 /CH 2 Cl 2 (1/3). The reaction proceeded with full strength in less than 4 hours. In all cases but...
stereochemistry stereochemistry (general, optical resolution) O 0030 -048Chiral Triarylcarbenium Ions in Asymmetric Mukaiyama Aldol Additions.-Title compounds such as (I) and (II), are used as new chiral Lewis acids in asymmetric Mukaiyama aldol additions. Enantiomerically enriched esters (V) are obtained with up to 38% e.
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