Mismatched reaction

The matched double asymmetric reactions with (7 )-l and (a.R,S,S)-2 provide the (S,Z)-diastereomer with 94% and 96% selectivity, while in the mismatched reactions [(S)-l and (aS,R,R)-2] the (S.Z)-diastereomer is obtained with 77% and 92% selectivity, respectively. Interestingly, the selectivity of the reactions of (/ )-2,3-[isopropylidenebis(oxy)]propanal and 2 is comparable to that obtained in reactions of (7 )-2,3-[isopropylidenebis(oxy)]propanal and the much more easily prepared tartrate ester modified allylboronates (see Table 7 in Section 1.3.3.3.3.1.5.)41. However, 2 significantly outperforms the tartrate ester allylboronates in reactions with (5)-2-benzyloxypropanal (Section 1.3.3.3.3.1.5.), but not the chiral reagents developed by Brown and Corey42-43. 

Total RNA is isolated from the lymphocytes according to standard procedures and used as a template for radioactive labeled cDNA synthesis. The purified cDNA is used as probe for cDNA expression arrays. The advantages of this method as compared to other array systems are as follows (1) Radioactive-labeled probes are more sensitive than fluorescent-labeled probes and therefore need less sample RNA. (2) The primers used in the cDNA synthesis match the genes represented on the array. (3) The primer sequences are longer compared to other array systems, which increases the hybridization fidelity of RNA to the matching correct set of genes and therefore reduces mismatch reactions. 

The stereoselective construction of nitrogen heterocycles remains a topic of intense synthetic interest [39]. Evans and Robinson described the combination of the stereospecific aUylic amination with ring-closing metathesis as a strategy for the constmction of mono- and disubstituted azacycles, which they demonstrated with the stereospecific construction of cis- and tra s-2,5-disubstituted pyrrolines [40]. Furthermore, this approach provided an ideal system for the determination of whether the enantiospecific rhodium-catalyzed aUyhc amination with an enantiomerically enriched nucleophile experiences a matched and a mismatched reaction manifold. 

The origin of the third diastereomer produced, complex 12, is of particular mechanistic interest. The configuration at Ca of 12 is opposite to that of the other two products 10 and 11 indicating that the opposite face of the enolate 6 has been approached by the epoxide. Two possible alterations of the geometry of enolate 6 inay be invoked to account for this, adoption of the 5yn- -conformer or adoption of the anti-Z-conformer. Examination of the different structures shown reveals that the observed minor product 12 could arise from a matched reaction pair of the ivn-E-enolate and epoxide (Newman Projection G) or from a mismatched reaction pair of the anti-Z-enolate and epoxide (Newman projection I). The absence of diastereomer 13 strongly suggests that the minor product 12 arises from reaction of the. ryn- -enolate, underscoring the extreme reluctance of iron-acyl complexes to form Z-enolates on deprotonation (see scheme on p 955). 

In the mismatched reaction of the chiral substrate A with the chiral Ti-(-i-)-DET catalyst, the two preferences are opposed. Since the reagent preference [Ti-(-i-)-DET] is much stronger than the substrate preference [alcohol A], the reagent preference prevails and the epoxide H is formed with good diastereose-lectivity (22 1). 

With protected ketone 85 in hand, the next aldol coupling required its syn-selective reaction with aldehyde 74 to install the C15-C16 stereocenters in 86 (Scheme 9-28). A boron triflate reagent would be expected to generate the desired (Z)-enolate. However, studies earned out on the separate components indicated that this was a mismatched reaction, and it did not prove possible to overturn the aldehyde facial bias by use of a chiral reagent. 

The completion of the synthesis of ebelactone A required an anti aldol reaction of a suitable three-carbon unit to proceed with and-Felkin selectivity, i.e. a mismatched reaction. Conversion of thioester 280 into its ( )-enol borinate and reaction with aldehyde 279 gave two anti aldol adducts, unfortunately with little stereochemical preference. The minor isomer 281 from this reaction was used in the successful synthesis of ebelactone A (274), and the same chemistry, now using thioester 282, was employed to complete the first synthesis of ebelactone B (275). 

In reactions of a-methyl chiral aldehydes with achiral (Z)-crotylboronates, the anti-Felkin adduct (cf. 107b) is favored (for further discussion see Section 11.2) [3, 65]. In the double asymmetric reaction of 97b and (S,S)-213, the anti,syn-di-propionate 107b is obtained with high selectivity (selectivity=95 5). The stereochemistry of 107b is consistent with product formation via the matched anti-Felkin transition state 247. Finally, the, vyn,5y -dipropionate 106c is obtained as the major product from the mismatched reaction of the TBDPS-protected aldehyde 97c with (f ,R)-(Z)-213 this reaction, however, is not sufficiently stereoselective to be synthetically useful (selectivity = 64 36). The mismatched transition state... 

In their synthesis of (-i-)-damavaricin D (Fig. 11-24), Ronsh and co-workers used crotylboronate methodology three times in the assembly of the C(I)-C(13) polypropionate segment 250 [178, 204, 205]. The synthesis of 250 was designed so that chain growth occurs from C(13) to C(l) and such that the mismatched reaction necessary to install the C(10)-C(12) anp. anfl-dipropionate stereotriad could be dealt with early in the synthetic sequence, when the aldehyde substrate had a relatively modest diastereofacial bias (Scheme 11-9). 

In their synthesis of the cA-octahydronaphthalene nucleus 471 of superstolide A (Fig. 11 -39), Roush and co-workers demonstrated the use of Keck s original catalytic allylation procedure to effect the diastereoselective conversion of aldehyde 472 to the 1,3-vyn diol 473 (79% yield, selectivity=94 6) (Scheme 11-37) [313]. This transformation constitutes a mismatched reaction since the 3-anti diol is favored under substrate-controlled allylation (see Section 11.3 for a discussion of 1,3-stereo-induction) [93]. 

Scheme 51 illustrate this point.First, the mismatched double asymmetric reaction of (274) and (5,5)-(18) provides the 3A-anti-4,5-anti diastereomer (276) (cf., 137) with only 73% selectivity. This is a substantial drop in stereoselectivity compared to the mismatched reaction of (5,5)-(18) and (254) that provides (137) with 84% selectivity (Table 8, entry 26). Substrate (277) is even more problematic diastereomer (278) predominates with >95 5 selectivity from the reaction with (/ ,/ )-(18), while (279) was the expected product based on the stereochemical preferences of (/ , )-(18). Thus, the intrinsic dia-stereofacial selectivity of (277) totally overwhelmed that of (/ , )-(18) in this attempted mismatched double asymmetric reaction. 

A comparison between single and double induction in the photochemical [2 + 2] cycloadditions of 3-oxo-l-cyclohexen-l-carboxylates with the ketene acetals was investigated89 90. Single induction using (-)-menthol as chiral auxiliary [R1 or R2 = (-)-menthyl] gave low selectivities only. A combination of these single inductions [R1 = R2 = (-)-menthyl] leads to the intermediacy of a matched reaction pair which gave an increased diastereoselectivity (d.r. 27.5 72.5) whereas a mismatched" reaction pair [R1 = ( + )-menthyl, R2 = (-)-menthyl] resulted in a decrease (d.r. 41.5 58.5). A more pronounced contrast in double induction results when the two chiral auxiliaries arc not equivalent [R1 = (—)-8-phenylmenthyl, R2 = (—)-menthyl]. 

This complex aldol coupling requires the use of reagent control to reverse the intrinsic substrate selectivity, i.e., it is a mismatched reaction. ... 

As can be seen from reaction C in Fig. 6, this is indeed the case and the expected product is obtained virtually as a single isomer (d.r. 40 1).The control experiment (reaction D) carried out with an (S)-dienophile and the (R)-diene confirms that in this case the two reactants contrast each other s intrinsic stereoselectivity, leading to poor stereocontrol. Reactions C and D are defined to occur between matched and mismatched reaction partners, respectively [33],... 

In several examples, such as the (S)-valinol derivative [68], (-)-sparteine prevents the mismatched reaction path completely no deprotonation occurs. This is an ideal situation for the kinetic resolution of a racemic sample such as rac-184 [Eq.(48)j [119]. 

Dipropionates are available through the reaction of the (. -and (2)-crotylboronates 2 and 3 with a-methyl-P-hydroxy aldehydes. The syn,anti-dipropionate 43a emerges as the major product with 97 3 selectivity from the matched crotylation reaction of aldehyde 40a with (R,R)-2. This is the intrinsically favored adduct, and its formation can be rationalized via the Felkin transition state F. The antAanh-dipropionate 44b is the major adduct (selectivity = 90 10) of the mismatched reaction of aldehyde 40b and 2. Its formation can be rationalized via anti-Felkin transition state G and is an example of a reagent-controlled reaction. 

In reactions of a-methyl chiral aldehydes with (.. -enolates and Type (2)-crotylmetal reagents like 3, the anti-Felkin addition product is favored due to unfavorable syn-pentane interactions in the Felkin transition state. Thus, in the matched reaction, the (S,5)-3 reagent reacts with aldehyde 40a to provide the anh, syn-dipropionate 45 with 95 5 selectivity. The stereochemical outcome of the reaction can be rationalized by anti-Felkin transition state H, where the nucleophile must approach near the methyl substituent. The mismatched reaction between aldehyde 40b and (R,R)-3 provides a mixture of dipropionates where the syn,syn-dipropionate 46 is only modestly favored (64 36 = sum of all other diastereomers). Transition state I, that rationalizes the formation of the major product, is less favorable as the nucleophile must approach the carbonyl carbon past the larger R substituent. 

As a general rule, the success of reagents 1-3 in overcoming the intrinsic selectivity of an aldehyde in mismatched reactions becomes increasingly more difficult as the size of the aldehyde s large a-substitutent increases, thus, mismatched reactions should be planned early in a synthetic sequence, when the aldehyde is still relatively small. ... 

Radiations from nuclear source/electromagnetic source Noise and vibration Material mismatch Reactions Exothermic/endothermic Corrosive and toxic material exposure Loss of containment for liquids and gases Fire and explosion Biological... 

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