Camphorsultam acylated

For a related V-acyl camphorsultam see G. Bernardinelli, W. Oppolzer, D. Dupuis, Acta Crystallogr., Sect. C 42, 1460 (1986). 

Introduction. The toluene-2,a-sultams are recently introduced relatives of the well established 10,2-Camphorsultam chiral auxiliary and have been designed to provide similar high levels of face discrimination in reactions of pendent prochiral functionality. Feamres that distinguish them include high crystallinity and facile NMR and HPLC analysis of derivatives, favorable acylation and aldolization characteristics of derived Al-acyl enolates, and improved cleavage characteristics. 

Preparation of Derivatives. IV-EnoyP and IV-acyl sultam derivatives are readily prepared using either Sodium Hydride-acid chloride or Triethylamine-add chloride single-step protocols. Various alternative derivatization procedures that work for the 10,2-camphorsultam auxiliary would also be expected to be effective. 

Syn-aldol derivatives may also be obtained directly from bo-ryl enolates of the same M-acyl-a-methyltoluene-2,a-sultams by condensation with aliphatic and aromatic aldehydes (eq 4). The high C(a)-it topicity of these reactions parallels but exceeds that when using the 10,2-camphorsultam auxiliary and is the result of an analogous transition state. It is noteworthy, however, that al-dolizations of a-methyltoluene-2,a-sultam derivatives generally proceed to completion with just a small excess of aldehyde (1-1.2 equiv, cf. 2-3 equiv when 10,2-camphorsultam mediated). This may be ascribed to the lack of acidic protons a to the SO2 group in the Saccharine-derived auxiliary. 

Nondestructive Auxiliary Cleavage. The toluene-2,a-sultam auxiliaries are even more readily cleaved from derivatives than the 10,2-camphorsultam auxiliary. Following iV-acyl bond cleavage, simple extraction and crystallization usually effect almost quantitative recovery of enantiomerically pure auxiliary which may be re-used if desired. 

N-Arylated 1,3-propanesultams 236 (R =Ar, R = H) are efficiently prepared from a Pd-catalyzed cross-coupling reaction with different aryl bromides in the presence of Xantphos <2004TL3305>. N-Fluorinated (-l-)-camphorsultams 237 (X = H, Cl, OMe R = F) have been prepared the corresponding imine 16 and difluoro derivative 238 were formed as by-products. The use of 237 is reported in Section 4.05.12.1 <1998JOC9604>. The syntheses of Ar-(l-alkynyl)-Oppolzer s sultams are reported in Section 4.05.6.3.4. Many examples of acylated Oppolzer s sultams are reported in Section 4.05.12.1. 

Oppolzer s acylated camphorsultams (147, Equation 12) remain a classic among chiral auxiliaries for asymmetric synthesis and have been successfully applied in a variety of mechanistically distinct chemical transformations [88, 91]. The corresponding enolates can readily be prepared with a variety of strong bases and have been shown to undergo diastereoselective alkylation with a range of activated and non-activated electrophilic reagents. An illustrative example is the formation of 149 in dr >99 1 [91]. The sense... 

Carreira has reported that N-acylated camphorsultams such as 85 undergo stereoselective cycloaddition with TMSCHN2 (Scheme 18.18) [81-83]. Treatment of the initial cycloadduct 86 with acid provided the corresponding A -pyrazoline 87 (dr=90 10) [81]. In general, the isolated pyrazolines serve as versatile synthetic intermediates for further elaboration. In the depicted example, N-acetylation and subsequent diastereoselective addition of the silyl ketene acetal 88 furnish methyl ester 89 as a single diastereomer [82]. 

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