Diastereoselectivity inherent

The diastereoselectivity inherent to the Diels-Alder reaction can be seen in most of the examples in preceding reactions. The reaction is not, however, enantioselective since there is no facial control for intermolecular reactions (some facial control is available for intramolecular reactions). The ortho rule, the endo rule (secondary orbital interactions), and steric interactions provide some orientational control but facial control is also required for enantioselectivity. When ethyl acrylate reacts with 2-methyl-1,3-pentadiene, it can approach from the bottom as in 247A or from the top as in 247B. Clearly, the two products (248A and 248B) are mirror images and enantiomers. This lack of facial selectivity leads to racemic mixtures in all Diels-Alder cyclizations discussed to this point. 

Due to the inherent unsymmetric arene substitution pattern the benzannulation reaction creates a plane of chirality in the resulting tricarbonyl chromium complex, and - under achiral conditions - produces a racemic mixture of arene Cr(CO)3 complexes. Since the resolution of planar chiral arene chromium complexes can be rather tedious, diastereoselective benzannulation approaches towards optically pure planar chiral products appear highly attractive. This strategy requires the incorporation of chiral information into the starting materials which may be based on one of three options a stereogenic element can be introduced in the alkyne side chain, in the carbene carbon side chain or - most general and most attractive - in the heteroatom carbene side chain (Scheme 20). 

Asymmetric allylic C-H activation of more complex substrates reveals some intrinsic features of the Rh2(S-DOSP)4 donor/acceptor carbenoids [135, 136]. Cyclopropanation of trans-disubstituted or highly substituted alkenes is rarely observed, due to the steric demands of these carbenoids [16]. Therefore, the C-H activation pathway is inherently enhanced at substituted allylic sites and the bulky rhodium carbenoid discriminates between accessible secondary sites for diastereoselective C-H insertion. As a result, the asymmetric allylic C-H activation provides alternative methods for the preparation of chiral molecules traditionally derived from classic C-C bond-forming reactions such as the Michael reaction and the Claisen rearrangement [135, 136]. 

With meso-conflgured dialdehyde precursors, the enantiotopic nature of the termini must give rise to a conflgurational terminus differentiation upon twofold chain extension because the catalyst-controlled diastereoselective aldol additions will break the inherent o symmetry. While the two enantiotopic termini cannot... 

Despite its inherent difficulties, carbometallation has, in fact, played important roles in catalytic asymmetric carbon-carbonal bond formation. Isotactic and syndiotactic alkene polymerization involving both heterogeneous and homogeneous Ti and Zr catalysts must involve a series of face-selective carbometallation processes, although the main stereochemical concern in poly(alkene) formation is diastereoselectivity rather than enantioselectivity. This fascinating topic, however, is outside the scope of this chapter, and the readers are referred to Chapter 11 and other previous reviews [6]. 

R,R,R,R, A)-20 (Figure 1.14), each as a diastereoisomeric pair in which the (R,R)-configured side groups are combined with inherently chiral addition patterns of opposite configuration (fC or fA) ,( After the separation of all isomers, they found that the formation of the bis-adducts 13-16 was only weakly diastereoselective (d.e. <10%). Furthermore the CD spectra of the diastereoisomeric pairs 13/14,15/16, and 17/18 are nearly mirror-image shaped which clearly proves the opposite configuration of the addition patterns in each pair and also the predominant chiroptical contribution of the distorted residual fullerene n-chromophorcs in comparison to that of the addends. 

An equally high diastereoselectivity (d.e. >96%) was observed in the generation of the inherently chiral cis-3 addition pattern when (R,R,fA)-32 and (S,S, C)-32 (Scheme 1.4) were prepared (next to the corresponding cis-2... 

The inherent planar chirality of substituted phosphaferrocenes can be exploited for the diastereoselective deriva-tization of the heterometallocenes themselves. This is nicely illustrated by the preparation of the alcohol derivative 323 as a single diastereomer (cf. LiAlH4 reduction of 307, which affords a 1 1 mixture of diastereomers Scheme 107) <1998CEJ2148>. Alcohol 323 was then used to prepare the enantiomerically pure P,P-diphosphoms ligand 324. 

Two major mechanisms have to be taken into consideration for the alkylation of Co -corrins. The classical mechanism of a bimolecular nucleophilic substitution reaction at carbon (the Co -corrin acts as a nucleophile) leads to /3-aUcylated Co -corrins with high diastereoselectivity. Secondly, an electron transfer-induced radical process (where the Co -corrin acts as a one-electron reducing agent) may also lead to cobalt alkylation. The observed formation of incomplete a-aUcylated Co -corrins under kinetically controlled conditions has been proposed to occur via this path. The high nucleophilic reactivity of Co -corrins and their diastereoselective nucleophilic reaction on the ( upper ) /3-face are not increased by the nucleotide function on the ( lower ) a-face rather they appear to be an inherent reactivity of the corrin-bound tetracoordinate Co -center. Among the organometallic B12 derivatives prepared to date, neopentylcobalamin, benzylcobalamin, and... 

There is a large amount of published material available on the diastereoselectivity of epoxidation with common peroxy compounds61 64, particularly peracids. Extended systematic studies of inherent diastereoselectivity, including less common reagent systems, are, as yet, absent. 

A new epoxidation method has been reported involving the use of a polyleucine catalyst in the epoxidation of 133. The use of the immobilized D- or L-polyleucine can overcome the inherent substrate-directed diastereoselectivity in the reaction <1999TL1779>. 

The chelation between zinc and heteroatoms allows a diastereoselective allyl- or crotylzincation of secondary y-heterosubstituted vinyl metals. However, the intramolecular interaction between the metal center and an olefinic site was also described in the case of di(4-pentenyl)zinc [114]. This weak dipolar chelation is the result of the inherent polarity of the Zn - C " bond and the polarity of the double bond (having a partial negative charge on the terminal carbon). Such interactions were evidenced by NMR investigations and the spiro structure of di(4-pentenyl)zinc was postulated to interpret this phenomenon (Fig. 7-1). The oxygen chelation described in Scheme 7-95 is now replaced by a jr-chelation between a vinyl organozinc and an cu-olefinic residue. 

Table 10 summarizes the data for the addition of various achiral tetraalkylaluminates (23) to chiral keto esters as oudined in equation (9). Presumably, the observed diastereoselectivities will reflect the inherent facial bias of the controlling chiral element, namely menthol (R in Table 10). In this case the diastereoselectivities are moderate (67 to 75%), but, since Corey, Oppolzer and WhiteselP have observed superior inherent facial selectivity for the 8-substituted menthol chiral auxiliary, it would be interesting to attempt the alkyl aluminate additions on substrates incorporating this auxiliary.

What is an ideal or viable synthesis, and how does one approach a synthetic project The overriding concern in a synthesis is the yield, including the inherent concepts of simplicity (fewest steps) and selectivity (chemoselectivity, regioselectivity, diastereoselectivity, and enantioselectivity). Furthermore, the experimental ease of the transformations and whether they are environmentally acceptable must be considered. 

The stereochemical outcome of an aldol reaction involving more than one chiral component is consistent with the rule of approximate multiplicativity of diastereofacial selectivities intrinsic to the chiral reactants. For a matched case, the diastereoselectivity approximates (substrate DS) X (reagent DS). For a mismatched case, the diastereoselectivity is (substrate DS) (reagent DS). Double asymmetric induction also can be used to enforce the inherent facial selectivity of a chiral aldehyde, as shown below. 

On the other hand the inherent a-selectivity of allylsulfur carbanions can sometimes be transformed to a y-reactivity by a sigmatropic rearrangement, earning in addition the stereoselectivity typical for such reactions (see Section 4.S.2.3). Due to their significance in synthesis a lot of work has been done on reactions of heteroatom-substituted allyl anions with special emphasis on their use as homoenolate anion equivalents. The more recent developments, with the possibility of introducing diastereoselectivity, will be discussed later in Section 4.S.3.2.I. 

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