Matching mismatch

With nonracemic chiral diazoacetates the insertion process occurs with evident match/mismatch characteristics. This has been demonstrated in reactions of optically pure 2-methylcyclohexyl diazoacetates (Eq. 9) [85] and in carbon-hydrogen insertion reactions of steroidal diazoacetates (Eq. 10) [86], as well as with the synthesis of pyrrolizidines 36 and 37 [84]. The mechanistic preference for formation of a /J-lactone in Eq. 10 over insertion into the 4-position is not clear,but there are other examples of /J-lactone formation [87]. In these and related examples, selectivities in match/mismatch examples are high, and future investigations are anticipated to show even greater applicability. 

When the allene moiety of 2,3-allenylamines was substituted with Br, an intramolecular nucleophilic substitution reaction led to a chiral 2,3-ds-ethynylaziridine 323. The diastereoselectivity depends on the absolute configuration of the allene moiety, i.e. typically for a matched-mismatched pair the S,aR-isomer afforded the product with much higher stereoselectivity [155, 156],... 

Diastereoselective hydrogenations of this type have been reported by Burgess and coworkers [54—59] using chiral-protected and -unprotected allylic and homo allylic alcohols as substrates with their carbene catalyst lr(9). Catalyst control was found to be dominant, but depending on the position and nature of the oxygen substituents, moderate to strong match/ mismatch effects were observed. 

By contrast, lithium enolates derived from tertiary amides do react with oxiranes The diastereoselectivity in the reaction of simple amide enolates with terminal oxiranes has been addressed and found to be low (Scheme 45). The chiral bicyclic amide enolate 99 reacts with a good diastereoselectivity with ethylene oxide . The reaction of the chiral amide enolate 100 with the chiral oxiranes 101 and 102 occurs with a good diastereoselectivity (in the matched case ) interestingly, the stereochemical course is opposite to the one observed with alkyl iodides. The same reversal is found in the reaction of the amide enolate 103. By contrast, this reversal in diastereoselectivity compared to alkyl iodides was not found in the reaction of the hthium enolate 104 with the chiral oxiranes 105 and 106 °. It should be noted that a strong matched/mismatched effect occurs for enolates 100 and 103 with chiral oxiranes, and excellent diastereoselec-tivities can be achieved. 

Configurational match/mismatch governs these reactions so that different products may be produced in high yield and selectivity when enantiomeric catalysts are apphed to the same substrate [61, 62], as illustrated by the reaction processes in Scheme 15.8 [61]. Additional examples in the steroidal field have also been reported [66]. In these cases the formation of four-membered ring y9-lactones is common. 

List later applied this strategy to the 1,4 reduction of various acyclic and cyclic a,P-unsaturated ketones using the diasteriomeric salt 15 (Scheme 5.37) [66]. Notably, use of the opposite (S) phosphate counterion resulted in a matched/ mismatched ion pair combination, forming the same enantiomer of the product but in significantly diminished ee. 

Since a-branched aldehydes gave rather higher asymmetric induction (Scheme 6.166), Nagasawa et al. extended the biphasic strategy to the diastereoselective Henry reaction of nitromethane with enantiomerically pure (S)-configured N,N -dibenzyl protected a-amino aldehydes and a-hydroxy aldehydes protected as silyl ethers. The screening reaction (Scheme 6.169) demonstrated a match/mismatch... 

Scheme 6.170 Suggested transitions states for the anti-diastereoselective Henry (nitroaldol) reaction promoted by (R,R)-catalyst 186 (TS 1) and its (S,S)-isomer 183 (TS 2) to demonstrate the match/mismatch relationship between guanidine-thiourea catalyst and (S)-a-aldehyde.

Cycloadditions to racemic mixmres of chiral alkenes also show that there is virtually no induction from the nitrile oxide part, meaning that there is no effect of matching-mismatching of the partners in the transition state. In the reaction with glyceraldehyde, and threose- and glucose-derived nitrile oxides, only the usual ... 

Depending on the substrate, matched/mismatched combinations between the stereogenic elements at BINOL and the sulfoximine were observed. In the conver-... 

Consequently, matched/mismatched cases [25] can result, and indeed our investigations on cooperative effects of stereogenic elements in such systems revealed 9 be the matched case and 23 (which is also easily prepared by following a directed deprotonation-silylation-deprotonation-trapping-desilylation sequence [11]) to be the mismatched case in diethylzinc additions to aldehydes [26]. Later, these investigations were extended to more complex systems such as 24 [27], but ferrocene 9 still remains superior to all other compounds. 

Later, the oxazolines 25 were examined to study the effects of matched/mismatched combinations of stereogenic centers on catalyzed aryl transfer reactions to aldehydes. Of these mandelic acid-derived catalysts, 25b gave the best results in terms of enantioselectivity (up to 35% ee), while diastereomer (l ,S)-25b proved to be superior to (S,S)-25b with respect to catalyst activity [29]. With both compounds, the absolute configuration of the product was determined by the oxazo-line moiety. 

Both the selectivity and the activity of the diastereomeric ligands, (Rp,S)-5a and (Sp,S)-5a, were nearly identical and both showed positive chiral cooperativity (there was no observation of a mismatched pair). Through introduction of a phenyl residue in the a-position of the side-chain as shown in ligand pair 6a, there was again a small matched/mismatched effect, which was not as strong as in the unsubstituted case in ligand pair 4a. Overall, we could derive a simple rule for the ligands ... 

The first example synthesized was based on the AHPC structure with (S)-cy-clohexylethylamine in the side-chain. The use of the more sterically hindered (S)-cyclohexylethylamine in the side-chain increased the enantiomeric excess from 83% ee (with (Sp,S)-5a to 90% ee with (Sp,S)-5b (complete conversion). The other diastereomer, (Pp,S)-5b, resulted in 94% yield and 87% ee. The ligand pair 6b, which is based on BHPC with (S)-t-butylethylamine in the side-chain, resulted in a matched/mismatched pair. The (Rp,S) diastereomer gave a 98% yield and an excellent 89% ee, but the (Sp,S) diastereomer produced only a 25% yield with a moderate 42% ee. The diastereomeric pair 6c, also based on BHPC 3 with (S)-naphthalen-l-ylethylamine in the side-chain, resulted similarly in a matched/mismatched pair with high activity, but only moderate enantiomeric excess. 

Additions to the anti,anti and anti,syn aldehydes exhibited a more typical matched/mismatched profile (equations 28 and 29). It was concluded that dipole effects of the /S-OTBS group must play an important role in the mismatching observed with these latter two aldehydes. 

The score/penalty assigned to a match/mismatch is dependent on the likelihood that this match/mismatch occurred by chance alone. If an event occurs randomly with a high frequency the score will be small, while very rare events will receive very large scores. For example, a conservative amino-acid substitution will receive a very small penalty, while the introduction of a stop codon will be penalized heavily. A variety of scoring schemes have been generated based on factors such as the bio-physical character, evolutionary distance, and the subcellular localization of the sequences being compared. 

A remarkable match-mismatch effect is observed. The difference in reactivity of the matched catalyst—for example, Ru(R-BINAP)(S,S-DPEN)Cl2—can be 120 times more reactive than the mismatched catalyst, Ru(S-BINAP)(S,S-DPEN)Cl2.196 197... 

Thought Experiments II and III on the Hydroboration of Chiral Alkenes with Chiral Boranes Reagent Control of Diastereoselec-tivity, Matched/Mismatched Pairs, Double Stereodifferentiation... 

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