Aldehydes allylboration

In a second set of examples, it was shown that the stereoselectivity of the aldehyde allylborations of 9-[( T)-l-trimethylsilyl- or l-trimethylstannyl-2-butenyl]-9-borabicyclo[3.3.1]nonane is controlled to a significant extent by conversion to an ate complex by treatment with butyllithium, MT-butyllithium or pyridine19. 

It is well accepted that the high diastereospecificify of aldehyde allylboration reactions is a consequence of the compact cyclic transition structure. Theoretical calculations have shown that the chairlike transition structure shown in Scheme 1 and Fig. 1 is the lowest in energy relative to other possibilities such as the twist-boat conformation. With boronate reagents, it has also been suggested that a weak hydrogen bond between the axial boronate oxygen and the hydrogen of the polarized formyl unit contribntes to the preference for the transition structme with the aldehyde substituent in the psendo-eqnatorial position. ... 

Computational studies of the formation of ( )-5-stannyl homoallylic alcohols by an allene hydroboration-aldehyde allylboration sequence show that the kinetic allene hydroboration product is less stable and isomerizes to the more sterically congested a-stannylallylborane with the C—Sn to boron a—n hyperconjugation interaction sufficiently stabilizing to override the steric congestion (Scheme 77). " ... 

If the presence of sensitive functional groups poses problems of chemoselectivity in the use of hard allylmetal reagents, allylboronate derivatives can also be accessed by transmetallation of allyltin species with boron halides [29], This approach was used by Corey in the synthesis of chiral bis(sulfonamido)boron reagents (Section 6.3.1.3) [30]. Recently, Williams and co-workers employed this mild approach to synthesize the highly functionalized allylboron reagent 9, which was employed in a key aldehyde allylboration reaction en route to the total synthesis of leucasdandrolide A (Equation 5) [31]. 

Vaultier and co-workers were the first to demonstrate the utility of 1-borono-l,3-butadienes in [4+2] cycloadditions with electron-poor dienophiles such as maleic anhydride and maleimides (Equation 32) [78]. As exemplified with diene 56, the [4+2] cycloaddition unmasks an allylboronate, 57, which at that time was isolated prior to its use in aldehyde allylboration. Lallemand and Six later showed that this sequence can be performed easily as a one-pot, three-component process [79], and the same group used this chemistry as an approach to the synthesis of clerodin [80]. Since then, the one-pot tandem [4+2] cycloaddition/allylboration strategy has been extended to the construction of highly functionalized heterocycles (Section 6.4.1.1). 

The data reported in Table 3 for the 2-butenylborations of 2-(dibenzylamino)propanal shed additional light on this transition state model. The ( )-2-butenylboration of 2-(dibenzyl-amino)propanal evidently proceeds preferentially (90%) by way of transition state 9, suggesting that the bulky dibenzylamino substituent destabilizes transition state 8 (X = NBn2 > CH3). On the other hand, the (Z)-2-butenylboration of 2-(dibenzylamino)propanal is relatively non-selective, compared to the excellent selectivity realized in the (Z)-allylborations of a-chloro- or x-alkoxy-substituted chiral aldehydes. This result suggests that an increase in the steric requirement of X destabilizes transition state 11 such that significantly greater amounts of product are obtained from transition state 10. 

The cyclohexyloxy(dimethyl)silyl unit in 8 serves as a hydroxy surrogate and is converted into an alcohol via the Tamao oxidation after the allylboration reaction. The allylsilane products of asymmetric allylboration reactions of the dimethylphenylsilyl reagent 7 are readily converted into optically active 2-butene-l, 4-diols via epoxidation with dimethyl dioxirane followed by acid-catalyzed Peterson elimination of the intermediate epoxysilane. Although several chiral (Z)-y-alkoxyallylboron reagents were described in Section 1.3.3.3.3.1.4., relatively few applications in double asymmetric reactions with chiral aldehydes have been reported. One notable example involves the matched double asymmetric reaction of the diisopinocampheyl [(Z)-methoxy-2-propenyl]boron reagent with a chiral x/ -dialkoxyaldehyde87. 

Chiral, nonracemic allylboron reagents 1-7 with stereocenters at Cl of the allyl or 2-butenyl unit have been described. Although these optically active a-substituted allylboron reagents are generally less convenient to synthesize than those with conventional auxiliaries (Section 1.3.3.3.3.1.4.), this disadvantage is compensated for by the fact that their reactions with aldehydes often occur with almost 100% asymmetric induction. Thus, the enantiomeric purity as well as the ease of preparation of these chiral a-substituted allylboron reagents are important variables that determine their utility in enantioselective allylboration reactions with achiral aldehydes, and in double asymmetric reactions with chiral aldehydes (Section 1.3.3.3.3.2.4.). 

Allyl tetrafluoroborates are also useful allylboration reagents. They can be made from allylic boronic acids and are stable solids.63 The reaction with aldehydes is mediated by BF3, which is believed to provide the difluoroborane by removing a fluoride. The addition reactions occur with high stereoselectivity, indicating a cyclic TS. 

The Hall group [52] has developed a new three-component domino reaction of 1-aza-4-borono-1,3-butadiene 4-152, a dienophile and an aldehyde to give a-hydroxy-methylpiperidine derivatives. In the first step, a hetero-Diels-Alder reaction takes place, which is followed by allylboration. As an example, reaction of 4-152 with the maleimide 4-153 in the presence of benzaldehyde furnished 4-154 in yields of up to 80% using the three substrates in a 1 2 1 ratio (Scheme 4.32). 

As demonstrated by Hoffmann and coworkers, hydroformylation can also be combined with an allylboration and a second hydroformylation, which allows the formation of carbocycles and also heterocycles [213]. A good regioselectivity in favor of the linear aldehyde was obtained by use of the biphephos ligand [214]. Reaction of the allylboronate 6/2-76 having an B-configuration with CO/H2 in the presence of catalytic amounts of Rh(CO)2(acac) and biphephos led to the lactol 6/2-80 via 6/2-77-79 (Scheme 6/2.17). In a separate operation, 6/2-80 was oxidized to give the lactone 6/2-81 using tetrabutyl ammonium perruthenate/N-methylmorpholine N-oxide. 

In a similar fashion, allylboronates can be used as allylation reagents under hydroformylation conditions. Thus condensed 1,5-oxazadecalin systems are achieved via tandem hydroformylation/allylboration/hydroformylation sequences starting from an N-allyl-y-amidoallylboronate (Scheme 23) [77,78]. The aldehyde obtained from a regioselective hydroformylation undergoes diastereoselective intramolecular allylboration to give an intermediate al-lylic alcohol derivative. The reaction does not stop at this stage, since this... 

A theoretical study of allylboration of aldehydes shows that (i) an initial complex may form, but if so, it is weak, and predicted reactivity trends are unchanged whether it is taken into account or not, and (ii) electron delocalization from the aldehyde oxygen to the boron p atomic orbital governs the reaction. ... 

The increased enantioselectivity of 88 is also apparent in reactions with chiral aldehydes (Figure 28). p-Alkoxypropionaldehydes 90 were relatively poor substrates when 36 was used.3 The best selectivity ever obtained for syn diastereomer 91 in the matched double asymmetric reactions was 89 11 [(S,S)-36 and 90a], whereas the best selectivity for anti diastereomer 92 was 87 13 [reaction of 90b and (R,R)-36. In contrast, the allylborations of 90a,b with the new reagent 88 now proceed with up to 97 3 selectivity for either product diastereomer. Even more impressive results were obtained with glyceraldehyde acetonide (23) the matched double asymmetric reaction leading to 29 now proceeds with 300 1 diastereoselectivity, while the mismatched combination leading to 30 proceeds with 50 1 selectivity. 

Hydroformylation reactions have been shown to be amenable to use in tandem or domino reaction sequences. In one elegant example, alkene 36 was subjected to rho-dium(I)-catalyzed hydroformylation, and the resulting aldehyde underwent smooth intramolecular allylboration (Scheme 5.14) [19]. This produced a new terminal alkene which underwent a second hydroformylation to provide, after workup,lactols 37 in 80% yield and with excellent diastereoselectivity. 

Additions of allylic boron reagents have been reported on a very wide range of classes of functionalized aldehydes. Some types of aldehydes, however, are very reactive and may lead to side-reactions. For example, p,Y-unsaturated aldehydes are notoriously difficult substrates but an indirect procedure for their in situ generation leads to clean products of allylboration. Although most examples... 

The presence of a stereogenic center on the aldehyde can strongly inlinence the diastereoselectivity in allylboration reactions, especially if this center is in the a-position. Predictive rules for nucleophilic addition on snch a-snbstitnted carbonyl substrates such as the Felkin model are not always snitable for closed transition structures.For a-substituted aldehydes devoid of a polar substituent, Roush has established that the minimization of ganche-ganche ( syn-pentane ) interactions can overrule the influence of stereoelectronic effects. This model is valid for any 3-monosubstituted allylic boron reagent. For example, althongh crotylboronate (E)-7 adds to aldehyde 39 to afford as the major prodnct the diastereomer predicted by the Felkin model (Scheme 2), " it is proposed that the dominant factor is rather the minimization of syn-pentane interactions between the Y-snbstitnents of the allyl unit and the a-carbon of the aldehyde. With this... 

Recently, the first examples of catalytic enantioselective preparations of chiral a-substituted allylic boronates have appeared. Cyclic dihydropyranylboronate 76 (Fig. 6) is prepared in very high enantiomeric purity by an inverse electron-demand hetero-Diels-Alder reaction between 3-boronoacrolein pinacolate (87) and ethyl vinyl ether catalyzed by chiral Cr(lll) complex 88 (Eq. 64). The resulting boronate 76 adds stereoselectively to aldehydes to give 2-hydroxyalkyl dihydropyran products 90 in a one-pot process.The diastereoselectiv-ity of the addition is explained by invoking transition structure 89. Key to this process is the fact that the possible self-allylboration between 76 and 87 does not take place at room temperature. Several applications of this three-component reaction to the synthesis of complex natural products have been described (see section on Applications to the Synthesis of Natural Products ). 

The real promise of this catalytic reaction is the eventual development of an efficient enantioselective allylboration catalyzed by chiral Lewis acids. A stereoselective reaction using a substoichiometric amount of a chiral director has been reported, but only modest levels of stereo-induction were achieved with an aluminum-BINOL catalyst system (Eq. 19)P Recently, a chiral Brpnsted acid catalyzed system has been devised based on a diol-tin(IV) complex (Eq. 80). In this approach, aliphatic aldehydes provide enantioselectivities (up to 80% ee) higher than those of aromatic aldehydes when using the optimal complex 114. Although the levels of absolute stereoselectivity of this method remain too low for practical uses, promising applications are possible in double diastereoselection (see section on Double Diastereoselection ). 

Intramolecular Allylboration. In one rare but impressive example involving a masked aldehyde, a domino hydroformylation/allylboration/hydroformyla-tion reaction cascade has been designed to generate bicyclic annulated... 

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