Stereocontrol methods

CARBOETHOXY-2,3-DIMETHYL-1-OXA-8-AZASPIRO[4-5]DECANE, a procedure that exemplifies a new stereocontrolled method for constructing substituted tetrahydrofurans. 

The Baylis-Hillman reaction of TV-protected 3-substituted 4-formylazetidin-2-ones with methyl vinyl ketone has been used to prepare intermediates from which highly functionalised P-lactams fused to medium rings were obtained by radical, stereocontrolled methods <99CC1913>. 

For the total synthesis of aminodeoxy sugars from nonsugar precursors, it is logical to turn to amino acids as primary sources of chiral templates. The challenge is to find innovative and stereocontrolled methods of chain extension reactions that lead to higher-carbon aminodeoxy sugars. 

The first stereocontrolled method for the preparation of 3-alkylideneoxepanes was demonstrated using this cyclization strategy. Thus, Lewis acid promoted cyclizations of vinylsilane acetals (37a) and (37b) yield the seven-membered ring alkylideneoxacycles (38a) and (38b), as illustrated in Scheme 16. 

Straightforward stereocontrolled methods for synthesizing both geometric isomers of a-alkylidene-y-butyrolactones have been reported. Following successive treatment with LDA and the readily available bis[methoxy(thiocarbonyl)] disulphide, y-butyrolactone reacts with aldehydes to give predominantly E-a-alkylidene-y-butyrolactones. The presence of a metal salt [e.g. copper(l) iodide or zinc chloride] dramatically alters the stereochemical outcome of the reaction (e.g. Scheme 56). 

Erythronolide B, the biosynthetic progenitor of the erythromycin antibiotics, was synthesized for the first time, using as a key step a new method for macrolactone ring closure (double activation) which had been devised specifically for this problem. Retrosynthetic simplification included the clearance of the stereocenters at carbons 10 and 11 and the disconnection of the 9,10-bond, leading to precursors A and B. Cyclic stereocontrol and especially the Baeyer-Villiger and halolactonization transforms played a major role in the retrosynthetic simplification of B which was synthesized starting from 2,4,6-trimethylphenol. 

Recently, Charette et al. have also demonstrated this behavior in the stereoselective cyciopropanations of a number of enantiopure acyclic allylic ethers [47]. The high degree of acyclic stereocontrol in the Simmons-Smith cyclopropanation has been extended to synthesis several times, most notably in the synthesis of small biomolecules. Schollkopf et al. utilized this method in their syntheses of cyclopropane-containing amino acids [48 a, b]. The synthesis of a cyclopropane-containing nucleoside was also preformed using acyclic stereocontrol [48c]. 

A salient structural feature of intermediate 18 (Scheme 2b), the retrosynthetic precursor of aldehyde 13, is its y,r5-unsaturated ester moiety. As it turns out, the Johnson ortho ester variant of the Clai-sen rearrangement is an excellent method for the synthesis of y,<5-unsaturated esters.11 In fact, the Claisen rearrangement, its many variants included, is particularly valuable in organic synthesis as a method for the stereocontrolled construction of trans di- and tri-substituted carbon-carbon double bonds.12,13 Thus, it is conceivable that intermediate 18 could be fashioned in one step from allylic alcohol 20 through a Johnson ortho ester Claisen rearrangement. In... 

These reactions imply an aldol condensation following the initial Michael addition. Two examples in which absolute stereocontrol over three or four new stereogenic centers is achieved in a single operation illustrate the potential of these methods. 

CM has, in most cases, a good to excellent ii-selectivity. This is primarily due to steric reasons in the metallacycle intermediate of the metathesis. The high ii-selectivity of the CM makes it an ideal method for the stereocontrolled synthesis of stilbenes [152], while there is still no highly Z-selective Ru-based catalyst known [153]. 

The overall transformation of this sequence corresponds to the aldol addition of an aldehyde with a cyclic ketone. The actual aldol addition frequently proceeds with low stereocontrol, so this sequence constitutes a method for stereoselective synthesis of the aldol adducts. The reaction has been done with several Lewis acids, including SnCl4, BF3, and Ti(0-/-Pr)3Cl. 

Backvall et al. (240) have described a method which permits the stereocontrol-led preparation of 3a- and 3/ -hydroxytropane derivatives at will. The approach is related to the Kibayashi synthesis (92,93). 

Diastereoselective conjugate addition of nucleophiles to enones, enals, and enoates occurs with high stereocontrol and constitutes a powerful method in stereoselective synthesis.185... 

Dipolar addition to nitroalkenes provides a useful strategy for synthesis of various heterocycles. The [3+2] reaction of azomethine ylides and alkenes is one of the most useful methods for the preparation of pyrolines. Stereocontrolled synthesis of highly substituted proline esters via [3+2] cycloaddition between IV-methylated azomethine ylides and nitroalkenes has been reported.147 The stereochemistry of 1,3-dipolar cycloaddition of azomethine ylides derived from aromatic aldehydes and L-proline alkyl esters with various nitroalkenes has been reported. Cyclic and acyclic nitroalkenes add to the anti form of the ylide in a highly regioselective manner to give pyrrolizidine derivatives.148... 

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