Diastereoselectivity substrate-induced

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

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. 

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...

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. 

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. 

Combining substrate-induced diastereoselection and mutual diastereoselectivity, as illustrated for the crotylzincation of the alkenyllithium derived from 209, led to excellent results as the gewt-dimetallic species 217 was obtained in a highly stereoselective fashion. The stereochemical outcome was explained by the addition of the kinetically reactive cisoid metallotropic form of the crotylzinc reagent anti to the propyl group in the chelated allyl alkenylzinc intermediate. After hydrolysis, compound 218 was obtained as a single diastereomer (equation 106)148,149. 

The slow carbozincation, attributed to the presence of TMEDA, was more problematic when substrate-induced diastereoselection was also involved. Thus, addition of zincated allyl ethyl ether to the alkenyllithium derived from the secondary y-iodo allylic ether 209 afforded a 65/35 mixture of the diastereomers 228 and 229 in low yield after hydrolysis. The erosion of diastereoselectivity was not a consequence of a less efficient substrate-induced diastereoselection but rather of the fact that both the (E) and (Z) isomers of the zincated allyl ethyl ether had reacted. Although the use of a catalytic amount of TMEDA (10 mol%) in the metallation step substantially improved the yield, the diastereoselectivity remained low (equation 111)151. 

Substrate-induced diastereoselection has also been achieved in the case of alkenyllithium reagents derived from (Z)-5-iodo homoallylic ethers152,153. Thus, the allylzincation of the alkenyllithium derived from 230 proceeded efficiently in ether at — 20 °C and led after hydrolysis to 231 as a single diastereomer (equation 112). 

Although substrate-induced diastereoselection can be conveniently achieved when the alkenylmetal was coordinated by an oxygen atom, other heteroatoms such as sulfur and nitrogen resulted in high inductions as illustrated by the crotylzincation of the organolithium reagents derived from the allylic sulfide 238 or the tertiary amine 239 (equation 117)154. 

Substrate-induced diastereoselective allylzincations essentially rely on coordination of the alkenylmetal by an appropriately located heteroatom, but a zinc-alkene -interaction23 27 can also exert a remarkable stereodirecting effect. Indeed, the alkenyllithium derived from 248, bearing an appropriately located carbon—carbon double bond, underwent highly diastereoselective allyl- and crotylzincations which led after hydrolysis to the corresponding 1,6-dienes 249 and 250. The stereochemical outcome... 

If two different external electrophiles are to be added to the dimetallic species, diastere-oselectivity can only be achieved if the two carbon-metal bonds are properly discriminated against the reaction with a first electrophile. Moreover, the resulting monometallic species has to exhibit significant configurational stability. Coordination by a heteroatom, which turned out to be essential for achieving substrate-induced diastereoselection, also nicely served these purposes. 

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