Asymmetric synthesis carbocations

In continuation of our investigations on asymmetric nucleophilic acylations with lithiated a-aminonitriles [40], we envisaged the asymmetric synthesis of 3-substituted 5-amino-4-oxo esters A, bearing both a-amino ketone and 5-amino ester functionalities (Scheme 1.1.14) [41]. Since a-amino ketones are precursors of chiral p-amino alcohols [42, 43] and chiral amines [43], their asymmetric synthesis has the potential to provide valuable intermediates for the synthesis of biologically active compounds, including peptidomimetics [44]. The retrosynthetic analysis of A leads to the a-aminoacyl carbanion B and p-ester carbocation... 

Arenechromiumtricarbonyl-stabilized benzyl carbocations in asymmetric synthesis of tetrahydroisoquinolines 93SL323. 

As resolution procedures are often tedious, and asymmetric synthesis provides chiral products with only limited enantiomeric excess, it seems an obvious strategy to use an enantiomerically pure material from the chiral pool to construct chiral ferrocenes by incorporating these compounds in the final product. As such chiral materials, cheap terpenes (menthone, a- and -pinene, and camphor) were chosen. The reaction of ferrocene with carbonyl compounds under acidic conditions is a very convenient way to obtain directly a-ferrocenylalkyl carbocations. The starting materials were therefore converted to aldehydes or their enol ethers (menthone and camphor are too sterically hindered and do not react with ferrocene). Joint dissolution of the aldehydes and ferrocene in trifluoroacetic acid or in the trichloroacetic acid/ fluorosulfonic acid system gives a-ferrocenylalkyl carbocations, which can either... 

New modifications of the traditional approach to isoquinoline synthesis via carbocation intermediates continue to be reported. Abnormal products of the Bischler-Napieralski reaction were observed <97JCS(P1)2217>. A stereoselective introduction of a quaternary carbon center in the A-acyliminium cyclization (Scheme 14) of the chiral enamide 46 affords an asymmetric synthesis of tetrahydroisoquinolines <97T2449,3045>. An asymmetric Pictet-Spengler reaction has been developed mediated by the chiral urethane 47 <97T16327>. A Pummerer reaction of A-acyl-A-(aryl)methyl-2-(phenylsulfinyl)ethylamine allows cyclization to the 4-phenylthio-... 

Both chiral Brpnsted and Lewis acids have been useful in asymmetric Friedel-Crafts reactions. For example, the chiral Brpnsted acid 40 was used in the asymmetric synthesis of chiral fluorenes from an achiral indole and the biarylaldehyde 39 (Scheme 1.11) [32]. Initial steps in the conversion lead to the ion pair 42. Through ion pairing with the electrophilic carbocation, the chiral anion... 

According to this strategy, a-lithium alkyl sulfoxides I (Scheme 2) have been used as chiral a-hydroxyalkyl carbanion equivalents A, with fluorinated A-protected imines 2, synthetic equivalents of a-amino fluoroalkyl/aryl carbocations B (path 1), to give the target P-fluoroalkyl p-amino alcohols 3. This represents an unprecedented application of lithium alkyl sulfoxides in asymmetric synthesis, which have been... 

A synthesis of the Inhoffen-Lythgoe diol (46.7, Scheme 2.46), a useful intermediate in the synthesis of Vitamin D derivatives, demonstrates the use of a chiral acetal in an asymmetric tandem cyclisation reaction.102 Once again, Lewis acid co-ordination to the less hindered oxygen of the acetal 46.1 initiated a Prins-like cyclisation that terminated by attack of the propargylsilane on an incipient tertiary carbocation. After removal of the chiral auxiliary, the allene function in the alcohol 46.4 was transformed into the side chain of 46.7 with the creation of two new stereogenic centres. 

The use of carbocations in asymmetric synthetic methods is of increasing importance and mechanistic understanding has played a critical role in such development. The use of carbocations in stereoselective synthesis has been reviewed. ... 

A similar type of chiraUty transfer was exploited by Tius in the total synthesis of roseophilin (69) (Scheme 3.15) [18]. A key intermediate in the synthetic pathway consisted of a substituted cyclopentanone, constructed via a Nazarov-type cyclization. The asymmetric cyclopentannulation reaction was initiated by generating the cyclopentenyl intermediate in situ using the lithioallene 64 and the amide 65. The chiral substituent on the delocahzed carbocation 66 induced... 

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