Diastereoselection substrate-induced

Simple Diastereoselectivity Substrate-Induced Diastereoselectivity Reagent-Induced Stereoselectivity... 

Highly diastereoselective, substrate-induced lithiation and substitution in the 4-position is possible when the l-Cby group is exchanged for a non-com-plexing Ugand and the amino group [Eq. (34)] is turned into a N,N-dimethyl-amino group [77]. CarboxyHc ester 122 was obtained from the 4-carbamate 121, albeit in modest yield [Eq. (34)]. 

A combination of substrate-induced and auxiliary-induced stereoselectivity is provided by the diisopinocampheylborinates 11a and lib derived from the chiral ketone (S)-l-benzyloxy-2-mcthyl-3-pentanone52. Whereas this ketone provides no significant diastereoselectivity when converted into the dibutylboron enolate and, subsequently, added to aldehydes, use of the diisopinocampheyl reagents 11a and lib leads to the jS-hydroxy ketones 12 and 13 in a stereoselective manner. The chiral information which is located in the carbon chain of the starting ketone 10 is incorporated into the products ... 

Substrate-induced diastereoselectivity is provided by the chlorotitanium enolate of 14a,b47b and the boron enolate of ketone 15S3 to give predominantly. wt-aldols. 

In a pioneering investigation on the addition of the following chiral lithium enolate to propanal, only poor substrate-induced diastereoselectivity (57 43) was obtained54-35. 

However, if the isopinocampheyl residue is used instead of achiral ligands (such as butyl or cyclohexyl) in the enolborinate, the diastereoselectivity is slightly improved (93 7). Thus, the combination of substrate-induced and auxiliary-induced stereoselectivity has only a marginal effect in this case56. 

Acyclic Imines 1.4.1.1.1.1. Substrate-Induced Diastereoselection Stereogenic Center at Carbon... 

I.4.I.5.2. Cyclic Oxime Ethers 1.4.1.5.2.1. Substrate-Induced Diastereoselection... 

Substrate-Induced Diastereoselection Stereogenic Center at Carbon... 

Scheme 30 Substrate-induced diastereoselective reductions of a-aminooximes and a-amino imines...

Other functional groups which have a heteroatom rather than a hydroxyl group capable of directing the hydrogenation include alkoxyl, alkoxycarbonyl, carboxylate, amide, carbamate, and sulfoxide. The alkoxy unit efficiently coordinates to cationic iridium or rhodium complexes, and high diastereoselectivity is induced in the reactions of cyclic substrates (Table 21.3, entries 11-13) [25, 28]. An acetal affords much lower selectivity than the corresponding unsaturated ketone (Table 21.3, entries 14 and 15) [25]. 

The introduction of the allylic silane moiety required for the intermolec-ular Hosomi-Sakurai reaction is depicted in Scheme 16. Following the formation of the enol triflate 97, a Stille coupling provided excess to the allylic alcohol 98 [51]. The allylic alcohol (98) was endowed with a phosphate leaving group for the subsequent allylic substitution. Utilizing a trimethylsilyl cuprate as nucleophile for the 5 2 reaction, the allylic phosphate was converted into the allylic silane 89. A useful substrate-induced diastereoselectivity in favour of (14i )-89 was encountered at small scale but decreased significantly upon up-scaling. 

The synthesis of the non-natural ( )-7,14-epz-l(15),8-dolastadien-7,14-ol (rac-7yl4-epi-l09) was published by Paquette in 1986 and is highlighted by a photochemical rearrangement of the 6,6,6-tricyclic a,yS-epoxy ketone 148 into the 5,7,6-tricyclic dolastane skeleton (149) (Scheme 23) [84]. The succeeding hydroxylation of carbon atom by photo oxygenation with singlet oxygen as well as a DIBAH reduction of a keto function proceeded with an undesired substrate-induced diastereoselectivity to provide the racemic 7,14-epimer of the natural dolastane 109. 

The introduction of umpoled synthons 177 into aldehydes or prochiral ketones leads to the formation of a new stereogenic center. In contrast to the pendant of a-bromo-a-lithio alkenes, an efficient chiral a-lithiated vinyl ether has not been developed so far. Nevertheless, substantial diastereoselectivity is observed in the addition of lithiated vinyl ethers to several chiral carbonyl compounds, in particular cyclic ketones. In these cases, stereocontrol is exhibited by the chirality of the aldehyde or ketone in the sense of substrate-induced stereoselectivity. This is illustrated by the reaction of 1-methoxy-l-lithio ethene 56 with estrone methyl ether, which is attacked by the nucleophilic carbenoid exclusively from the a-face —the typical stereochemical outcome of the nucleophilic addition to H-ketosteroids . Representative examples of various acyclic and cyclic a-lithiated vinyl ethers, generated by deprotonation, and their reactions with electrophiles are given in Table 6. 

Substrate-induced diastereoselection is the most common principle in alkylations of enolates derived from ketones. There are numerous successful applications reported in the literature (for extensive reviews, see refs 1, 3, and 79). The following account does not cover this extensive field with all its applications in detail, but rather presents representative examples which provide a general overview of the different synthetic methods available for alkylations of ketone enolates of various structural types, as well as demonstrating that remote asymmetric induction can be efficient and predictable. 

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