Face-selective additives

The above interesting approach to the asymmetric allyltitanation reaction does, however, have a limitation. Thus, L-glucose is much more expensive that the D-form and, consequently, homoallylic alcohols of the opposite configuration cannot easily be obtained by this method. In an attempt to induce the opposite si face selectivity, other acetonide derivatives of monosaccharides from the xylose, idose, and allose series were tested [42b,42c], The enantiofacial discrimination was, however, much lower than that with DAGOH and both re and si face selective additions to aldehydes were observed. 

Ab initio calculations at the HF/6-31G level have been used to explore energy changes, structural variation, and electron density shifts during jr-face selective addition of substituted acetylide ions to cyclohexanone and cyclohexanethione. Charge polarization of the jr-bond on approach of the nucleophile is such that the carbonyl carbon becomes considerably electron deficient for most of the reaction path (and may... 

Hence, a reaction of Type I will involve a racemic or achiral/me,t(9 nncleophile which will react enantioselectively with an achiral acyl donor in the presence of a chiral catalyst, while on the other hand, a reaction of Type II will associate an achiral nncleophile and a racemic or udm lmeso acyl donor in the presence of a chiral catalyst. In both cases, when a racemic component is implicated the process constitntes a KR and the maximum theoretical yield of enantiomerically pure product, given perfect enantioselectivity, is 50%. When an achiral/mera component is involved, then the process constitutes either a site-selective asymmetric desymmetrisation (ASD) or, in the case of tt-nucleophiles and reactions involving ketenes, a face-selective addition process, and the maximum theoretical yield of enantiomerically pure product, given perfect enantioselectivity, is 100%. 

Karl Anker Jorgensen of Aarhus University, Denmark has found (J. Am. Chem. Soc. 2005, /27, 3670) that face-selective addition can also be carried out on an activated aromatic ring. In this work, the chirality is delivered by a quinine-derived organocatalyst. 

Addition (n-Nu, face selective) Addition (n-E, face selective) ... 

Chiral aryl acetic acids constitute a privileged class of target structures due to their prevalence in bioactive natural products and pharmaceuticals and so, unsurprisingly, they constitute attractive targets for asymmetric synthesis [198]. The face-selective addition of a nucleophile to an aryl alkyl ketene provides a very direct entry for the preparation of such compounds. Although this can be achieved by the use of a chiral nucleophile or acid (cf. Scheme 8.1) [199], catalysis of the addition of an achiral nucleophile is clearly attractive from the standpoint of efficiency. 

Enantioselective copper phosphoramidite-catalyzed conjugate addition of dialkylzinc reagents to several 4,4-disubstituted cyclohexadienones is achieved with diastereomeric ratios ranging from 1/1 to 99/1 with 85% to 99% ee. When the two substituents are equal (eq 2), selective Re versus Si face-selective addition of the zinc reagent affords a single isomer. Sequential catalytic 1,4-addition to the prochiral dienones gave cis or trans bis-adducts with high enantio and diastereoselectivity. ... 

The addition of HCN to aldehydes has been a well-known reaction since the 19th century, especially in the context of the Kiliani-Fischer synthesis of sugars. Even older is the Strecker synthesis of amino acids by simultaneous reaction of aldehydes with ammonia and HCN followed by hydrolysis. The challenge in recent years has been to achieve face-selectivity in the addition to chiral aldehydes. These face-selective additions, known as nonchelation-controlled processes, refer to the original formulation of Cram s for the reaction of nucleophiles with acyclic chi carbonyl compounds. The chelation-controlled reactions refer also to a formulaticxi of Cram s, but whose stereochemical consequences sometimes differ. 2... 

Pyrimidine cyclization based on 3-amino derivatives of thiophene 03MI47. Studies on 7t-face selective additions with 3,4-di-Art-butyl thiophene 1-oxide and 1-imide 03YGK1106. 

Figure 5.11. Models for face-selective addition of enolates to i -sulfoxides, (a) Chelate model predicts nucleophilic attack on Si face, (b) Nonchelate model, which has the C=0 and S-O bonds antiperiplanar, predicts Re face attack.

There are two (limiting) possibilities that could explain the enantioselectivity a group-selective metal insertion distinguishing the enantiotopic allylic protons, or a face-selective addition that distinguishes the enantiotopic double bond faces. Figure... 

This work demonstrates the first case where both a non face-selective and a face-selective addition to the tri-substituted olefinic portion of DMAPP has occurred within the same molecule. A related observation with respect to the loss of stereochemistry in the reverse prenylated indole alkaloids echinulin and roquefortine have been reported and are discussed elsewhere in this article. 

Yamada S, Morita C (2002) Face-selective addition to a cation-K complex of a pyridinium salt synthesis of chiral 1,4-dihydropyridines. J Am Chem Soc 124 8184—8185... 

Face-selective additives can today be designed to fit into the structures of single crystal faces. Their effectiveness is determined by the energy of interaction between the additive and the crystal face. In simple cases, this energy can be calculated for different positions of the additive on the crystal face. 

Another way to incorporate an enantiomerically-pure oxygenated stereogenic center into a molecule is the enantio face-selective addition of hydride to a ketone such as 6. Alain Burgos and his team at PPG-SIPSY in France have described Tetrahedron Lett. 2007, 48, 2123) a NaBH -based protocol for taking the Itstmo-Corey reduction to industrial scale. 

Chiral amines are commonly prepared by face-selective addition to imine derivatives or by enantioselective... 

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