Addition substrate controlled diastereoselective

The substrate-controlled diastereoselective addition of lithiated alkoxyallenes to chiral nitrones such as 123, 125 and 126 (Scheme 8.32) furnish allenylhydroxyl-amines as unstable products, which immediately cydize to give enantiopure mono-orbicyclic 1,2-oxazines (Eqs 8.25 and 8.26) [72, 76]. Starting with (R)-glyceraldehyde-derived nitrone 123, cydization products 124 were formed with excellent syn selectivity in tetrahydrofuran as solvent, whereas precomplexation of nitrone 123 with... 

There appears to exist only one single example of substrate-controlled diastereoselection in the conjugate addition to allenoates7 Base-catalyzed addition of methanol to the steroid allene 11 afforded only one of the two possible diastereomeric products in 95% yield. Unfortunately, the configuration around the exocyclic C —C double bond [( )/(Z)] of 12 was not established7. 

Substrate-Controlled Diastereoselective Conjugate Addition to Chiral a,/MJnsaturated Compounds... 

Substrate-controlled diastereoselectivity is also apparent in the intermolecular addition of carbon-centered radicals to the double bond of chiral nonracemic a,/J-unsaturated esters derived from glyceraldehyde acetonide28, Different levels of selectivity arc observed starting from the (Z)- or the ( )-isomer. respectively,... 

The preparation of an allyl intermediate from iodooxa-zoline 95 en route to (—)-allosamizoline was achieved though a substrate-controlled diastereoselective Keck allyl addition to give 96 (Scheme 25.45). Allosamizoline is the aglycon of allosamidin, which was isolated from mycelial extracts of Streptomyces sp. No 1731 and inhibits all characterized family 18 chitinases. 

Boland applied this methodology to Garner s aldehyde, and found the addition to be substrate-controlled rather than reagent-controlled (Scheme 9.13b) [68]. Viny-lepoxide 15 could thus also be obtained with high diastereoselectivity with achiral 9-MeO-9-BBN. 

Substrate control This refers to the addition of an achiral enolate (or allyl metal reagent) to a chiral aldehyde (generally bearing a chiral center at the a-position). In this case, diastereoselectivity is determined by transition state preference according to Cram-Felkin-Ahn considerations.2... 

O-Benzyllactaldehyde dimethylhydrazone 230 allows a substrate control in the addition reaction of organomagnesium halides, leading almost exclusively to the 5yn-isomer 231 (equation 155) . The resulting hydrazide can be reduced on Raney Ni to the corresponding iyw-aminoalcohol 232. The stereoselective Grignard addition to a similar A-formyl hydrazone 233 proceeds with 92% diastereoselectivity (equation 156). The silylation of the amide nitrogen by TMSCl provides the pure iyw-adduct . 

Towards this goal, the potential of the o-DPPB group to control diastereoselectivity in a carbon carbon bond forming reaction, following the hydroformylation step was explored [IS]. Enoates 17, were chosen as the test substrates since the stereoselective 1,4-addition of a methyl would provide a structural building block found in biologically important natural products of the polyketide class (e.g. antitumor agent dictyostatin 1 and the ionophore calci-mycin). 

The stereochemical result is no longer characterized solely by the fact that the newly formed stereocenters have a uniform configuration relative to each other. This was the only type of stereocontrol possible in the reference reaction 9-BBN + 1-methylcyclohexene (Figure 3.25). In the hydroborations of the cited chiral alkenes with 9-BBN, an additional question arises. What is the relationship between the new stereocenters and the stereocenter(s) already present in the alkene When a uniform relationship between the old and the new stereocenters arises, a type of diastereoselectivity not mentioned previously is present. It is called induced or relative diastereoselectivity. It is based on the fact that the substituents on the stereocenter(s) of the chiral alkene hinder one face of the chiral alkene more than the other. This is an example of what is called substrate control of stereoselectivity. Accordingly, in the hydroborations/oxidations of Figures 3.26 and 3.27, 9-BBN does not add to the top and the bottom sides of the alkenes with the same reaction rate. The transition states of the two modes of addition are not equivalent with respect to energy. The reason for this inequality is that the associated transition states are diastereotopic. They thus have different energies—just diastereomers. 

Conversely, the addition of enantiomerically pure chiral dialkylboranes to enantiomerically pure chiral alkenes can also take place in such a way that substrate control and reagent control of diastereoselectivity act in the same direction. Then we have a matched pair. It reacts faster than the corresponding mismatched pair and with especially high diastereoselectivity. This approach to stereoselective synthesis is also referred to as double stereodifferentiation. 

Another example of substrate-induced diastereoselection in the intermolecular addition of an O-nucleophile to a cyclic acceptor has been reported16. Thus, treatment of the norbornene derivative 9 with sodium phenylmethoxide resulted in the formation of the exo-benzyl ether 11 as the major stereoisomer in 88 % yield. As judged from control experiments, dehydrobromi-nation to the 2-norbornadiene carboxylate 10 is the initial step, followed by conjugate addition of the O-nucleophile. 

The majority of the reported examples are diastereoselective conjugate additions (Section 7.3.1.). This section has been organized into reactions where the chiral information is located on the nucleophile (Section 7.3.1.1.), on the electrophile (Section 7.3.1.2.), or on both the nucleophile and the electrophile (Section 7.3.1.3.). Further division has then been made, i.e., substrate-controlled vs. auxiliary-controlled diastereoselective reactions, and subdivision according to whether the reactions are inter- or intramolecular in nature. 

The diastereoselective hydride addition of a chiral metal hydride reagent to a ketone substrate bearing a stereogenic center is called a substrate-controlled process, and it leads to 1,2-asymmetric induction. Enantioselective hydride addition to a prochiral ketone by metal... 

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