Stereochemical induction

Since FORTRAN (unlike LISP) cannot easily accept ASCII representations of rules and use them directly, they must be read, parsed, analyzed and translated to the form QED can interpret. The general flow of the compiler is shown in Figure 4. As an example, lets follow the processing of the rule ALPHA-TO-SC that defines sites where stereochemical induction may occur ... 

While the chirality of perezone (552) has been known for some time that of the a- (555) and p-pipitzols (554) which are derivable from 552 by thermolysis was rigorously proven only recently by chemical transformation to cedrene and x-ray diffraction The cycliration of 552 has been shown to involve a ncerted [4+2] cycloaddition which lacks stereochemical induction by the chiral center already present, since 555 and 554 are obtained in equimolar amounts However, a stepwise mechanism having higher stereoselectivity is followed by 552 in the presence... 

The appreciable levels of asymmetric induction observed in the catalytic ARCM reactions mentioned above suggest a high degree of enantiodifferentiation in the association of olefinic substrates and chiral complexes. This stereochemical induction may also be exploited in asymmetric ring-opening metathesis (AROM). Catalytic ROM transformations [20] offer unique and powerful methods for the preparation of complex molecules [2d, 2g]. The chiral Mo-alkyli-denes that are products of AROM reactions can be trapped either intramolecu-larly (RCM) or intermolecularly (cross metathesis, CM) to afford a range of optically enriched adducts. 

On alkylation of 2-(aminomethyl)oxazolines (42) and (43), stereochemical induction is evident for the tertiary carbamates (43), but not the tertiary amines (42) this is apparently a consequence of prior complexation of the carbamate carbonyl group to the base and kinetic preference for ( )-enolate formation on deprotonation 47 4-Alkenylamides (44) having a /1-cliiral centre have been found to undergo syn-selective a-iodination with iodine to give syn-a-iodoalkcnamidcs, via an intermediate... 

There are some interesting features related to these aminosugars compound 30 possesses very high stereochemical inductivity, but cleavage conditions are still too... 

Several studies have tackled the structure of the diketopiperazine 1 in the solid state by spectroscopic and computational methods [38, 41, 42]. De Vries et al. studied the conformation of the diketopiperazine 1 by NMR in a mixture of benzene and mandelonitrile, thus mimicking reaction conditions [43]. North et al. observed that the diketopiperazine 1 catalyzes the air oxidation of benzaldehyde to benzoic acid in the presence of light [44]. In the latter study oxidation catalysis was interpreted to arise via a His-aldehyde aminol intermediate, common to both hydrocyanation and oxidation catalysis. It seems that the preferred conformation of 1 in the solid state resembles that of 1 in homogeneous solution, i.e. the phenyl substituent of Phe is folded over the diketopiperazine ring (H, Scheme 6.4). Several transition state models have been proposed. To date, it seems that the proposal by Hua et al. [45], modified by North [2a] (J, Scheme 6.4) best combines all the experimentally determined features. In this model, catalysis is effected by a diketopiperazine dimer and depends on the proton-relay properties of histidine (imidazole). R -OH represents the alcohol functionality of either a product cyanohydrin molecule or other hydroxylic components/additives. The close proximity of both R1-OH and the substrate aldehyde R2-CHO accounts for the stereochemical induction exerted by RfOH, and thus effects the asymmetric autocatalysis mentioned earlier. 

The addition of diorganozinc reagents to a-alkoxyaldehydes furnishes selectively protected 1,2-diols.19 Applications toward the synthesis of pheromones like (-)-exo- and (-)-endo-brevicomin 2 and 3 exploits the catalytic nature of the stereochemical induction, e.g. the newly formed chiral centre depends only on the configuration of the chiral catalyst 1. 

The applications described below outline the effectiveness of cyclic chiral sulfoxides as stereocontrol elements, and highlight the ready removal of the sulfoxide group after its contribution to the synthetic scheme. In all cases, the sense of stereochemical induction can be rationalized and predicted on the basis of steric, stereoelectronic, and/or chelation control factors. 

From these and other studies we have developed a rule of thumb for prediction of stereochemical induction during enolate derivatization for both syn and anti substrates, the relative stereochemistry at the newly created asymmetric center is opposite to that of the sulfoxide moiety when the structure is drawn as shown above. 

The nature of the group attached to the 9-0 position of dihy-droquinidine was found to have a profound impact on the level of stereochemical induction in these reactions and a variety of new ligands have been developed (see 1-5). ... 

Stereochemical induction by a stereogenic center on the excited state enone, particularly cyclohexe-nones, has been rationalized by Wiesner as resulting from attack of the ground-state alkene on the most... 

A synthetic procedure has been developed which enables the (Rp)-diastereoisomer of dinucleoside methanephosphonates to be prepared in up to 79% diastereomeric excess.Reaction of dichloromethylphosphine with the 3 -hydroxy function of an otherwise protected nucleoside at -80 C gives the chloromethylphosphlne (81) as a 1 1 mixture of dlastereoisomers as determined by n.m.r. Stereochemical induction therefore occurs in the subsequent... 

Although the previous reaction involved the use of an unactivated olefin, this was apparently not the source of the lack of stereochemical induction. This is illustrated by work reported by Herscovici et al. [70,71], shown in Scheme 7.13, where several unactivated olefins were successfully used to produce a-C-glycosides in good to excellent yields. Additional work in this area resulted in a facile route to fused-ring C-glycosides [72] similar to the core structures of natural products including the halichrondrins [73], the herbicidins [74-76], and octosyl acid [77]. 

Therefore, stereochemical induction leads almost exclusively to the SAS-configured products. A combination of this consideration with the open transition states given above indicates that mainly the (5S,6S)-isomer of 13 is formed via transition state A when the iS-configured silane 12 is employed. 

During the total synthesis of rhizoxin D by J.D. White et al., an asymmetric aldol reaction was utilized to achieve the coupling of two key fragments. " The aldol reaction of the aldehyde and the chiral enolate derived from (+)-chlorodiisopinocampheylborane afforded the product with a diastereomeric ratio of 17-20 1 at the CIS stereocenter. During their studies. White and co-workers also showed that the stereochemical induction of the chirai boron substituent and the stereocenters present in the enolate reinforce each other thus representing a matched aldol reaction. 

The use of relatively rigid, chiral alkenes, e.g. cycloalk-2-enones, leads to a significant stereochemical induction, i.e. face selectivity of the attack. Interestingly, 4-methylcyclopent-2-enone stereospecifically reacts to provide ejco,c -3-methyl-4-methylenehexahydropentalen-l(2//)-one (22), " a product of formal proximal ring cleavage, in the presence of a phosphane-modified nickel catalyst. 

On thermolysis, perezone (192) undergoes a [4+2] cycloaddition to produce equal amounts of the two pipitzols (193) and (194) i.e. there is no stereochemical induction by the chiral centre in (192). If, however, the reaction is carried at 0 °C in the presence of boron trifluoride etherate the cyclization becomes highly stereoselective producing largely a-pipitzol (193) and it has been shown that a stepwise mechanism (195)—K196)->(193) is operative in this case.108... 

As already mentioned, there has been significant progress in the development of chiral catalysts for asymmetric hydroamination reactions over the last decade. However, significant challenges remain, such as asymmetric intermolecular hydro aminations of simple nonactivated alkenes and the development of a chiral catalyst, which is applicable to a wide variety of substrates with consistent high stereochemical induction and tolerance of a multitude of functional groups as well as air and moisture. Certainly, late transition metal based catalysts show promising leads that could fill this void, but to date, early transition metal based catalysts (in particular, rare earth metals) remain the most active and most versatile catalyst systems. 

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