Chiral aldehydes, reaction with

Many of the chiral allylboron reagents discussed in Section 1.3.3.3.3.1.4. have been utilized in double asymmetric reactions with chiral aldehydes. Chiral 2-(2-butenyl)-3.5-dioxa-4-boratri-cyclo[5.2.1.02-6]decanes were among the first chiral reagents of any type to be used in double asymmetric reactions52a,b. 

Results of the asymmetric 2-propenylborations of several chiral a- and /i-alkoxy aldehydes are presented in Table 11 74a-82 84. These data show that diisopinocampheyl(2-propenyl)borane A and l,3-bis(4-methylphenylsulfonyl)-4,5-diphenyl-2-propenyl-l,3,2-diazaborolidine C exhibit excellent diastereoselectivity in reactions with chiral aldehydes. These results are in complete agreement with the enantioselectivity of these reagents in reactions with achiral aldehydes (Section 1.3.3.3.3.1.4.). In contrast, however, the enantioselectivity of reactions of the tartrate 2-propenylboronate B (and to a lesser extent the tartrate (/i)-2-butenylhoronate)53b is highly... 

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.). 

P-Allyl-to-(isopinocampheyl)borane exhibits high stereoselectivity in reactions with chiral a-substituted aldehydes.40 The stereoselectivity is reagent controlled, in that there is no change in stereoselectivity between the two enantiomeric boranes in reaction with a chiral aldehyde. Rather, the configuration of the product is determined by the borane. Both enantiomers of (Ipc)2BH are available, so either enantiomer can be prepared from a given aldehyde. 

Pentadienyltrimethylstannanes undergo regioselective conjugate additions to aldehydes, catalysed by Lewis acids. The dominant product obtained depends on the catalyst used, as shown in reaction 46. In the case of titanium tetrachloride catalysis the reaction is also stereoselective and only one diasteroisomer is obtained297. Reaction with chiral aldehydes leads to asymmetric induction with similar organotin compounds298. 

Now, we examine the interaction of chiral aldehyde (-)-96 with chiral enolate (S )-lOOb. This aldol reaction gives 104 and 105 in a ratio of 104 105 > 100 1. Changing the chirality of the enolate reverses the result Compound 104 and 105 are synthesized in a ratio of 1 30 (Scheme 3-38).66 The two reactions (—)-96 + (S )-lOOb and (—)-96 + (7 )-100b are referred to as the matched and mismatched pairs, respectively. Even in the mismatched pair, stereoselectivity is still acceptable for synthetic purposes. Not only is the stereochemical course of the aldol reaction fully under control, but also the power of double asymmetric induction is clearly illustrated. 

The cycloaddition of aldehydes and ketones with ketene under the influence of quinine or quinidine produce chiral 2-oxetanones [46,47]. Solvolytic cleavage of the oxetanone, derived from chloral, and further solvolysis of the trichloromethyl group leads to (5)- and (R)-malic acids with a 98% ee [46] (the chirality of the product depends on the configuration of the catalyst at C-8 and, unlike other alkaloid-induced reactions, it is apparently independent of the presence of the hydroxyl group). No attempts have been made to catalyse the reaction with chiral ammonium salts. 

For applications in total synthesis this method was also thought to be applicable to chiral aldehydes, leading to matched and mismatched situations. Therefore, vinylogous ketene acetal 40 was put to reaction with chiral aldehyde 44 and both enantiomers of Carreira s catalyst. Reaction of aldehyde 44 with the (S)-Tol-BINAL-CuF catalyst (matched case) produced only one diastereomeric... 

Scheme 18 Vinylogous aldol reactions with chiral aldehyde 44...

Solutions to problems (i) and (ii) were already available as a result of studies by Hoffmann and Wuts on the reactions of 7-alkoxyaIlyl-boronates with achiral aldehydes (Figure 6). 3 Relatively little information was available, however, regarding the stereochemistry of such reactions with chiral aldehydes. Hoffman had published several examples of reactions of (E)- and (Z)-crotylboronates (methyl replacing OMe in Figure 6) with chiral aldehydes such as 2-methylbutanal, but the best diastereofacial selectivity that had been reported was only 83 17.14 Thus, it was by no means certain that the chemistry summarized in Figure 7 would be successful.3a... 

The poor diastereoselectivity of the reactions of chiral aldehydes and achiral allylboronates appeared to be a problem that could be solved by recourse to the strategy of double asymmetric synthesis.f Our studies thus moved into this new arena of asymmetric synthesis, our objective being the development of a chiral allylboron reagent capable of controlling the stereochemical outcome of reactions with chiral aldehydes independent of any diastereofacial preference on the part of the carbonyl reaction partner. 

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. 

Allyl-bis(isopinocampheyl)borane exhibits high stereoselectivity in reactions with chiral a-substituted aldehydes.39... 

A. Dondoni and P. Merino, Chemistry of the enolates of 2-acetylthiazole Aldol reactions with chiral aldehydes to give 3-deoxy aldos-2-uloses and 3-deoxy-2-ulosonic acids. A short total synthesis of 3-deoxy-D-manno-2-octulosonic acid (KDO), J. Org. Chem. 56 5294 (1991). 

Boron enolates bearing menthol-derived chiral ligands have been found to exhibit excellent diastereo- and enantio-control on reaction with aldehydes34 and imines.35 Highly diastereo- and enantio-selective aldol additions of geometrically defined trichlorosilyl ketone enolates (31) and (32) have been achieved by promoting the reactions with chiral Lewis bases, of which (,S., S )-(33) proved to be the most effective.36 Moderate enantiomeric excesses have been achieved by using chiral ammo alcohols as catalysts for the Baylis-Hillman condensation of aldehydes with methyl vinyl ketone the unexpected pressure effect on the reaction has been rationalized.37... 

Scheme 5.6. Diastereoselective domino-Knoevenagel-hetero-Diels—Alder reaction with chiral aliphatic aldehydes.

By NMR, Hoffmann determined the configurational stability of a simple lithiated benzylamine 192 to be 9.0 kcal mol"1.2 However, an attempted Hoffmann test on 193 was inconclusive due to the low level of kinetic resolution observed in its reaction with chiral aldehydes.6... 

Related Allylboronate Reagents. A stereoselective synthesis of anti 1,2-diols has been achieved by using a DIPT-modified ( )-y-[(cyclohexyloxy)dimethylsilyl]allylboronate reagent. This reagent is best applied in double asymmetric reactions with chiral aldehydes such as o-glyceraldehyde acetonide (eq 9). 

An aldol reaction with chiral /3-benzyloxy aldehyde provides a method for the stereodivergent synthesis of both syn and anti diastereomers [97] with high diastereo-selectivity dictated primarily by the chirality of the BINOL-Ti catalyst (1) rather than the /1-benzyloxy aldehyde (Sch. 37) [98]. The aldol products can be used as useful key intermediates for /1-lactone synthesis [99]. 

In recent years the synthetic potential and mechanistic aspects of asymmetric catalysis with chiral Lewis base have been investigated. Aldol addition reactions between trichlorosilyl enolates with aldehydes have been also intensively studied. Now, full investigations of the trichlorosilyl enolates derived from achiral and chiral methyl ketones, in both uncatalysed and catalysed reactions with chiral and achiral aldehyde acceptors have been reported. The aldol addition is dramatically accelerated by the addition of chiral phosphoramides, particularly (137) and proceed with good to high enantioselectivity with achiral enolates and aldehydes (Scheme 34). ... 

The tartrate-derived crotylboronate reagents are most useful in the context of double asymmetric reactions with chiral aldehydes [118, 203]. Equations (11.16)-(11.19) demonstrate the utility of ( )-219 and (Z)-213 in the synthesis of dipropionate adducts 105-108. 

Marshall s chiral allenylmetal reagents have been utilized in double asymmetric reactions with chiral aldehydes for the synthesis of polypropionate natural products. All four dipropionate diastereomers are accessible from the reactions of chiral allenylmetal reagents with a-chiraI-y5-alkoxy aldehydes 97 (153, 158, 276, 277]. The BF3-OEt2-catalyzed addition of allylstannane (l )-218a to aldehyde 97a occurs in high yield and diastereoselectivity to give the xyn.syn-dipropionate 395, presumably through either the synclinal or antiperiplanar Felkin transition states 396 and 397 (Eq. (11.31)). 

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