Heteroatom stereogenic centers

The Diels-Alder cycloaddition is the best-known organic reaction that is widely used to construct, in a regio- and stereo-controlled way, a six-membered ring with up to four stereogenic centers. With the potential of forming carbon-carbon, carbon-heteroatom and heteroatom-heteroatom bonds, the reaction is a versatile synthetic tool for constructing simple and complex molecules [1], Scheme 1.1 illustrates two examples the synthesis of a small molecule such as the tricyclic compound 1 by intermolecular Diels-Alder reaction [2] and the construction of a complex compound, like 2, which is the key intermediate in the synthesis of (-)chlorothricolide 3, by a combination of an intermolecular and an intramolecular Diels-Alder cycloaddition [3]. 

Conjugate addition reactions of acyclic Michael acceptors possessing heteroatom-substituted stereogenic centers in their y-positions may provide useful levels of diastereoselectivity. A typical example is given with the y-alkoxy-substituted enoate 49 in Scheme 6.8 [17]. High levels of diastereoselectivity in favor of the anti addition product 50 were found in the course of dimethylcuprate addition. 

Most of the reactions which will be discussed lead to carbonyl compounds with a stereogenic center in the 3-position. This is illustrated in Scheme 1 a substrate molecule (1 X = heteroatom or heteroatom-based functional group), having an electron-deficient double bond, is attacked by a nucleophilic reagent (possibly in the presence of a coordinating ligand or a catalyst) to form an anionic intermediate (2), which is then converted to the product (3) on hydrolytic work-up. 

A functionalized amino acid derivative has been synthesized by alkylation of a heteroatom-substituted Jt-allyl intermediate (Scheme 8E.27) [146], The alkylation of a Schiif base, which forms a 2-aza-7t-allyl intermediate, furnishes the malonate adduct with 85% ee despite the epimerizable nature of the newly generated stereogenic center. 

Oxidations of carbon-heteroatom species often results in the destruction of a stereogenic center, as in the oxidation of a secondary alcohol to a ketone. In some instances, this reaction can be coupled with another to provide a chiral product (see Chapter 21). One example is the enzymatic acetylation of one enantiomer of a secondary alcohol, where a redox reaction with a transition metal catalyst equilibrates the unreactive isomer of the alcohol (Scheme 9.1).10 12 The redox reaction can also be performed by an enzyme.13... 

The oxidation of a heteroatom such as sulfur can generate a new stereogenic center. This type of oxidation has presented special problems (see Section 9.7). 

Induction in the chirality transfer from C-l to C-3 overrides that of the chirality transfer from the sulfur atom to C-3. Therefore, the chirality at the heteroatom only has an impact on systems lacking a stereogenic center at C-l. The two diastereomeric transition states for the rearrangement of such chiral sulfoxides are designated as exo and endo"1. These lead to the different enantiomers of the allylic alcohol. Their energy difference, which depends mainly on the substitution of the double bond, determines the enantioselectivity of the process. 

The influence of a stereogenic center at C-l seems to override that of the stereogenic heteroatom. In selenoxides monosubstituted at C-1, the R1 substituent will occupy the equatorial position. One of the diastereoniers will rearrange via the exo, the other via the endo, transition state to give the same allylic alcohol, e.g., for the (C)-alkene as shown overleaf. 

Heteroatoms surrounded by four different groups are also stereogenic centers. Stereogenic N atoms are discussed in Chapter 25. 

This chapter focuses on [2,3] sigmatropic reactions which result in the formation of a new carbon-carbon tr-bond for examples of [2,3] rearrangements which result in the formation of heteroatom-bearing stereogenic centers see Sections D.4.11 and D.7.6. For the purpose of this discussion, [2,3] rearrangements which result in carbon-carbon c-bond formation arc divided into two major subgroups ... 

For the purposes of asymmetric synthesis, the initial alkene must be prochiral i.e., either 1,1-disubstituted or trisubstituted), so that the rearrangement produces a new stereogenic center. As shown in Figure 6.1, this is often contrathermodynamic, but not in the case of compounds with allylic heteroatoms. 

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