Diastereoselectivity organometallic compound addition

As with the reduction of aldehydes and ketones (16-23), the addition of organometallic compounds to these substrates can be carried out enantioselectively and diastereoselectively. Chiral secondary alcohols have been obtained with high ee values by addition to aromatic aldehydes of Grignard and organolithium compounds in the presence of optically active amino alcohols as ligands. ... 

Diastereoselective addition of a wide range of Grignard reagents to C -alkyl and C-aryl-A-[a.-phenyl- or u-methyl-j3-(benzyloxy)ethyl nitrones is determined by the presence of a stereogenic A -substituent (136, 137). High diastereoselectiv-ity in the addition of organometalic compounds to A-(( i-methoxyalkyl) nitrones can be explained by a simple chelation model (Scheme 2.132) (136). 

Fig. 10.16. The three transition state models for the occurrence of diastereoselectivity in the addition of hydride donors (Nu = H ), organometallic compounds (Nu = R ) to a-chiral carbonyl compounds (R[ar e refers to the large substituent, R...

Diastereoselective Addition of Organometallic Compounds to Carbonyl Compounds... 

Further detailed investigations of the solvation of carbonyl compounds as the predominant factor influencing the diastereoselectivity of nucleophilic additions of various organometallics (n-BuLi, t-BuLi, n-BuMgBr) to a-RsSiO-substituted aldehydes can be found in reference [853]. 

As with the Michael reaction (15-24) the 1,4-addition of organometallic compounds has been performed diastereoselectively and enantioselectively. ... 

The diastereoselectivities of addition of organometallic compounds to ketones and aldehydes are often quite poor (2 1), and there are numerous cases in which anti-Felkin-Anh selectivity is observed, but the rule is widely invoked anyway. 

A base-induced ring-opening imine isomerization/diastereoselective organometallic addition sequence on 4-substituted-2-perfluoroalkyl-l,3-oxazolidines 205 was developed for the asymmetric synthesis of perfluoroalkyl amino alcohols 207 via intermediates 206. Chiral compounds were obtained in good yields and high diastereoselectivity <04OL641>. 

Concerning reversal of diastereoselectivity in the BF promoted addition of crotyl-organometallic compounds to aldehydes, Y. Yamamoto and K. Maruhama,... 

In most cases of diastereoselective nucleophilic addition reactions where achiral organometallic reagents are added to chiral carbonyl compounds, the chirulity inducing asymmetric center is in close vicinity to the newly created center and cannot be removed without the loss of chirality of either the inducing center or the newly formed center. This type of reaction is very useful in propagating chirality in a molecule from one center to an adjacent one, or in immolative processes. 

Increasing interest is expressed in diastereoselective addition of organometallic reagents to the ON bond of chiral imines or their derivatives, as well as chiral catalyst-facilitated enantioselective addition of nucleophiles to pro-chiral imines.98 The imines frequently selected for investigation include N-masked imines such as oxime ethers, sulfenimines, and /V-trimcthylsilylimines (150-153). A variety of chiral modifiers, including chiral boron compounds, chiral diols, chiral hydroxy acids, A-sull onyl amino acids, and /V-sulfonyl amido alcohols 141-149, have been evaluated for their efficiency in enantioselective allylboration reactions.680... 

Amino aldehydes provide useful starting materials for the sequence of Scheme 11.3 because they can easily be prepared from a-amino acids in enantiomerically pure forms and are, therefore, useful chiral building blocks.18 The addition of organometallic allylic reagents (including Zn, used in the reaction described) to such compounds can produce homoallylic alcohols 13 with a high anh-diastereoselectivity. 

The synthesis of enantiopure amino-functionalized compounds such as a- and (3-amino acids or nonfunctionalized amines can be envisaged by the use of aldehydes, ketones, a- or (3-keto acids, or derivatives thereof as substrates for imine formation followed by, for example, diastereoselective Strecker reactions, reductions, or organometallic addition reactions. In the literature, diastereoselective syntheses based on a large variety of chiral auxiliaries, such as a-arylethylamines,4... 

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