Cram type chelation

The stereochemical outcome of allylation reaction is very satisfying due to predominant creation of threo isomer. This selectivity has been interpreted on the basis of the Cram type chelation [113,114]. It consists in formation of the five membered chelate between the allyl, indium and a-OH group of aldose, followed by the attack of the allylic nucleophile at the aldehyde from the less hindered side, thus favoring the syn product [111-114], Similarly, the other sugars i.e. D-ribose, D-xylose and D-arabinose have been reacted to achieve the appropriate ulosonic acids [112]. 

A variety of Lewis acids have been used to promote the addition of an allylsilane or allylstannane to an aldehyde (or ketone or imine). The Lewis acid BF3-OEt2 is effective and promotes Cram (Felkin-Anh)-type addition (see Section 1.1.5.1). However, Lewis acids such as TiCU, SnCU or MgBr2 can co-ordinate to a neighbouring (normally a-) heteroatom and promote chelation-controlled addition. For example, allylation of the aldehyde 161 gave either the Cram-type product or the chelation-controlled product depending upon the nature of the Lewis acid (1.153). 

Of related interest is the diastereoselective addition of Grignard reagents to 2-acyl-l,3-dithiane 5-oxides [75], which gave results in accordance with chelated Cram-type transition states [76] involving equatorial sulfoxides (Scheme 3.46). 

The Lewis acid mediated addition of silyl enol ethers or silylketcne acetals to oc-alkoxyaldehydcs is the most versatile and reliable method of providing chelation control in aldol-type additions3. The stereochemical outcome is as predicted by Cram s cyclic model11 ... 

The stereochemical outcome of the Mukaiyama reaction can be controlled by the type of Lewis acid used. With bidentate Lewis acids the aldol reaction led to the anti products through a Cram chelate control [366]. Alternatively, the use of a monoden-tate Lewis acid in this reaction led to the syn product through an open Felkin-Anh... 

Product stereochemistries can be greatly influenced by these chelation control effects. This was first observed by Cram.10 There are many controversies about this topic, and the issue remains a topic of investigative interest.11 Without kinetic data, it has been suggested that it is impossible to distinguish the following two mechanistic types 12... 

As a Stereochemical Prohe in Nucleophilic Additions. Historically, the more synthetically available enantiomer, (4R)-2,2-dimethyl-l,3-dioxolane-4-carhoxaldehyde, has been the compound of choice to probe stereochemistry in nucleophilic additions. Nevertheless, several studies have employed the (45)-aldeh-yde as a substrate. In analogy to its enantiomer, the reagent exhibits a moderate si enantiofacial preference for the addition of nucleophiles at the carbonyl, affording anti products. This preference for addition is predicted by Felkin-Ahn transition-state analysis, and stands in contrast to that predicted by the Cram chelate model. Thus addition of the lithium (Z)-enolate shown (eq 1) to the reagent affords an 81 19 ratio of products with the 3,4-anti relationship predominating as a result of preferential si-face addition, while the 2,3-syn relationship in each of the diastere-omers is ascribed to a Zimmerman-Traxler-type chair transition state in the aldol reaction. ... 

A high degree of stereoselectivity can be realized under chelation control, where an oxygen atom of an ether function (or more generally a Lewis base) in the a-, P- or possibly y-position of carbonyl compounds can serve as an anchor for the metal center of a Lewis acid. Since Cram s pioneering work on chelation control in Grignard-type addition to chiral alkoxy carbonyl substrates [30], a number of studies on related subjects have appeared [31], and related transition state structures have been calculated [32], Chelation control involves Cram s cyclic model and requires a Lewis acid bearing two coordination sites (usually transition metal-centered Lewis acids). 

An example should make this clear. The aldehyde (64) carries.a chelating group, suggesting that, in the presence of magnesium bromide, the facial selectivity is of the chelated Cram-rule type.l22] Note the syn selectivity due to the Z-enolate (65). 

The stereochemical outcome in these additions can be understood by invoking Cram chelate [48] and Felkin-Anh-type [49] transition states for N-benzyl and N-sulfonyl aldimines, respectively (Figure 11.2 see also Chapter 2). The consequences of these results and their applications are noteworthy. Thus, selection of the appropriate N-protecting group can lead to preferential formation of either syn or anti 1,2-diamines at will [46]. 

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