Allylic matched/mismatched reaction

The AE reaction has been applied to a large number of diverse allylic alcohols. Illustration of the synthetic utility of substrates with a primary alcohol is presented by substitution pattern on the olefin and will follow the format used in previous reviews by Sharpless but with more current examples. Epoxidation of substrates bearing a chiral secondary alcohol is presented in the context of a kinetic resolution or a match versus mismatch with the chiral ligand. Epoxidation of substrates bearing a tertiary alcohol is not presented, as this class of substrate reacts extremely slowly. 

Stoichiometric reaction with matched S-carbamate having the D atom in the Z-position 733) in the presence of S,S-ligand 64 without a nucleophile solely formed (no other isomer was observed by NMR) the Mo-complex 74 without transposition of the label. The structure of 74 was probed based on NMR studies by comparison with NMR studies and the X-ray structure of the protio complex 71. Nucleophilic attack of sodium malonate on the Mo complex 74 provided the S-product 75, where the D atom remained at the Z-position. On the other hand, stoichiometric reaction with mismatched R-carbamate having the D atom in the Z-position 76 without a nucleophile generated the Mo complex 80 as sole product, based on NMR studies. The structure of the complex 80 was elucidated by NMR. In 80, Mo is located on the same face as in 74 but the D atom is transposed from the Z to the E position. The transposition could be explained as follows. Initially the n-allyl Mo-complex 77 (unobserved) must form with retention. Mo complex 77 is equilibrated into the more stable Mo complex 80, where the D atom is moved... 

The reactions of titanated 133 and 134 with (R) and (5) TBDMS-protected lactaldehyde [MeCH(OTBDMS)CHO] are also highly diastereoselective. Very high levels of diastereoselectivity (> 98%) were observed when the facial selectivity of the allylic sulfoximine anion matched that of the chiral aldehyde (the matched case).86,87 In the mismatched cases the diastereoselectivities were less but still... 

Several other allylic alcohols with primary C-2 substituents have been epoxidized with good results (Table 3, entries 7-10 and 14). Epoxy alcohols have been obtained with 93-96% ee and when the catalytic version of the reaction is used, as in Table 3, entry 10, the yield is excellent. When the C-2 substituent is more highly branched, as in entries 11-13, there may be some interference to high enantiofacial selectivity by the bulky group, since the ee in two cases (entries 11 and 12) is 86%. Another example which supports this possibility of steric interference to selective epoxidation is summarized in equation (3). In this case, the optically active allylic alcohol (12) was subjected to epoxidation with bo antipodes of the titanium tartrate catalyst. With (+)-DIPT enantiofacial selectivity was 96 4 ( matched pair ), but with (-)-DIPT selectivity fell to only 1 3 ( mismatched pair ), a further indication that a secondary C-2 substituent can perturb the fit of the substrate to the active catalyst species. In the epoxidation of the allylic alcohol shown in elation (4), the epoxy alcohol is obtained in 96% yield and with a 14 1 ratio of enantiofacial selectivity. An interesting alternate route to the epoxide of entry 12 (Table 3) has been described, in which 2-r-butylpropene is first converted to an allylic hydroperoxide via photooxygenation and then, in the presence of the titanium tartrate catalyst, undergoes asymmetric epoxidation (79%... 

Double asymmetric reactions between [7-(alkoxy)allyl]stannanes 230 and the a-benzyloxy aldehyde 55 exhibited clear matched and mismatched behavior [168]. With BF3 OEt2 catalysis, the matched double asymmetric reaction between (R)-230a and aldehyde (S)-55 generates exclusively the syn,anti adduct 425 (Eq. (11.40)). Formation of 425 can be rationalized through either the antiperipla-nar, Felkin transition state 426 (as proposed by Marshall) or the synclinal Felkin transition state 427. 

Matched and mismatched characteristics have been observed in reactions with non-racemic a-benzyloxypropionaldehyde. The matched asymmetric allylation of (E)-stannane 278 with (S)-aldehyde, initiated by complexation with BFs OEta, exclusively provides the E-4.5-syn-5,6-anti compound 279 as the expected Felkin-Anh adduct (Scheme 5.2.61, top). On the other hand, the Q -chelation-controlled process can also be achieved via a matched case of double diastereoselection using the (S)-stannane 280 and pre-complexation with MgBr2 OEt2. The syn product 281 is rationalized via the antiperiplanar transition state 282 (Scheme 5.2.61, bottom). 

Scheme 8.8. Reactions of a chiral allylic alcohol under Sharpless epoxidation conditions (Ti(0-i-Pr)4, /-BuOOH) using the chiral tartrates given (DIPT = diisopropyltartrate). (a) The matched case, in which the preferred approach of the asymmetric catalyst and the diastereoselectivity of the substrate are the same, (b) The mismatched case, (cj An example of a Sharpless kinetic resolution (KR).

Like the vanadium-based catalysts, the Sharpless AE system intrinsically favors 1,2-anti products this is because the cyclohexyl group in Scheme 8.8a occupies the position denoted by group Ra in Figure 8.2, away from the catalyst. In fact, this diastereoselectivity is somewhat amplified relative to achiral titanium catalysts. When the S allylic alcohol is used with (-f)-DIPT, a matched pair results (Scheme 8.8a). The strong enantiofacial selectivity of the L-(-f-)-DIPT catalyst clashes with the R substrate s resident chirality (this is the case shown in Figure 8.2 with Rb = cyclohexyl). In this mismatched pair, the preference of the chiral catalyst for a attack moderately exceeds that of the allylic alcohol for 1,2-anti product (Scheme 8.8b). The most important consequence is that the latter reaction is 140 times slower than the former. 

This is further illustrated in Figure 3.2 1 for DET, which shows the propensity for (+)-DET to give the anti-product from the re-si face and for (-)-DET to give the syn-product from the si-re face. Figure 3.2 illustrates consonance when the chirality of natural (-t)-DET leads to faster reaction from the si face to give the anti-product. Conversely, the chirality of (-)-DET is mismatched to the si face making that reaction slower, although it is matched to the re face and that epoxidation is faster. Allylic alcohol (214), for example, reacts... 

The chromium(II)-mediated addition (Hiyama reaction) of chiral allylic bromide 835 to lactaldehyde 831 proceeds with high Felkin—Anh selectivity to furnish exclusively adduct 836 [230]. In addition to the Felkin model, the high stereoselectivity is also explained by the effect of matched pairing of the two reaction partners. If the corresponding R-enantiomer of THP-lactaldehyde 831 is employed ( mismatched pair ), a mixture of three diastereomers (3 1 1) is produced. The THP group of 836 can be removed in the presence of the TBPS protecting group by treatment with PPTS in methanol (54% yield). 

Researchers fundamentally interested in C-C bond-forming methods for polyketide synthesis have at times viewed allylation methods as alternatives, and maybe even competitors, to aldol addition reactions. Both areas have dealt with similar stereochemical problems simple versus absolute stereocontrol, matched versus mismatched reactants. There are mechanistic similarities between both reaction classes open and closed transition states, and Lewis acid and base catalysis. Moreover, there is considerable overlap in the prominent players in each area boron, titanium, tin, silicon, to name but a few, and the evolution of advances in both areas have paralleled each other closely. However, this holds for an analysis that views the allylation products (C=C) merely as surrogates of or synthetic equivalents to aldol products (C=0). The recent advances in alkene chemistry, such as olefin metathesis and metal-catalyzed coupling reactions, underscore the synthetic utility and versatility of alkenes in their own right. In reality, allylation and aldol methods are complementary The examples included throughout the chapter highlight the versatility and rich opportunities that allylation chemistry has to offer in synthetic design. 

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