Applications with chiral aldehydes

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. 

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... 

From these examples it is clear that the principles of acyclic stereocontrol that govern the allylation reactions of achiral Type II allyl- and crotylmetal reagents with chiral aldehydes can be used to excellent advantage in the stereoselective synthesis of natural products. In the following section, the factors that influence the stereoselective formation of cyclic compounds in the ring-closing allylation reaction are discussed and selected synthetic applications are reviewed. 

The [ 2 + 4]-cycloaddition reaction of aldehydes and ketones with 1,3-dienes is a well-established synthetic procedure for the preparation of dihydropyrans which are attractive substrates for the synthesis of carbohydrates and other natural products [2]. Carbonyl compounds are usually of limited reactivity in cycloaddition reactions with dienes, because only electron-deficient carbonyl groups, as in glyoxy-lates, chloral, ketomalonate, 1,2,3-triketones, and related compounds, react with dienes which have electron-donating groups. The use of Lewis acids as catalysts for cycloaddition reactions of carbonyl compounds has, however, led to a new era for this class of reactions in synthetic organic chemistry. In particular, the application of chiral Lewis acid catalysts has provided new opportunities for enantioselec-tive cycloadditions of carbonyl compounds. 

Ooi has recently reported application of chiral P-spiro tetraaminophosphonium salt 37 as a catalyst for the highly enantio- and diasterioselective direct Henry reaction of a variety of aliphatic and aromatic aldehydes with nitroalkanes (Scheme 5.51) [92]. Addihon of the strong base KO Bu generates in situ the corresponding catalyhcally active triaminoiminophosphorane base A. Ensuing formation of a doubly hydrogen-bonded ion pair B positions the nitronate for stereoselective addition to the aldehyde. This catalyst system bears many similarities to guanidine base catalysis. 

Unlike the 13C-NMR method, H-NMR spectra are not applicable to 3-alkylaldehydes. For 3-arylaldehydes, the chemical shifts of 2-H, 3 -H, and 5-H appear deshielded in oxazolidines derived from chiral aldehydes with configuration A, where Rz is the aryl group. 

A review describing the major advances in the field of asymmetric reduction of achiral ketones using borohydrides, exemplified by oxazaborolidines and /9-chlorodiisopino- camphenylborane, has appeared. Use of sodium borohydride in combination with chiral Lewis acids has been discussed.298 The usefulness of sodium triacetoxyboro-hydride in the reductive amination of aldehydes and ketones has been reviewed. The wide scope of the reagent, its diverse and numerous applications, and high tolerance for many functional groups have been discussed.299 The preparation, properties, and synthetic application of lithium aminoborohydrides (LABs) have been reviewed. 

Similar to the reaction of allylamines, allyl alcohols also undergo enantioselective isomerization in the presence of [Rh(BINAP)(COD)]+ [10]. Yields and enantio-selectivity are usually moderate, however. Considerable improvement was recently achieved by application of Rh(I) catalysts bearing phosphaferrocenes, 27, as chiral ligands (Scheme 7) [11]. These air-stable complexes, which can be recovered after the reaction, afford chiral aldehydes with up to 93 % ee. 

The asymmetric synthesis of (—)-denticulatin A (30) shows an interesting application of the boron aldol chemistry (Scheme 6) [23]. In a group-selective aldol reaction between the weso-aldehyde 27 and (5)-28, the hydroxyalde-hyde 29 was formed with > 90 % de, which spontaneously cyclized to the lactol 31. The configuration at the stereocenters of C-2 and C-3 in 29 is in accordance with the induction through the sultam auxiliary as well as with preference of an a-chiral aldehyde to react to the ant/-Felkin diastereomer in an aldol reaction which is controlled by the Zimmermann-Traxler model [24, 25]. 

The Danishefsky group has investigated the mechanism of this process in some detail. It has also been found that the cycloadditions show excellent diastereofacial selectivity with many chiral aldehydes. - Moreover, chiral catalysts have proven effective in controlling the enantioselectivity of the cycloaddition.These features of the reaction, along with applications to natural product total syntheses, are discussed in detail in Volume 2, Chapter 2.5. 

In the alkylation of a-chiral aldehydes with no ability to chelate with organometal-lic compounds such as Grignard reagents, erythro alcohols are usually obtained preferentially according to the Cram s rule [127], and high Cram selectivity can be achieved with alkyltitanium reagents developed by Reetz [128]. In contrast, application of amphiphilic alkylation to a-chiral aldehydes enables one to achieve the hitherto difficult anti-Cram selectivity, affording threo alcohols selectively as shown in Sch. 91 [125]. 

Catalytic reactions have the advantage over the methods discussed so far in that the chiral catalyst need not be added in stoichiometric amounts, but only in very small quantities, which is important if not only the metal (very often a precious one) but also the chiral ligand are expensive. Among the ferrocenes, phosphines are by far the most important catalysts for stereoselective reactions, and are covered in Chapter 2 of this book. We will therefore focus here mainly on the catalytic applications of chiral ferrocenes not containing phosphine groups. Only recently, some progress has been made with such compounds, mainly with sulfides and selenides, and with amino alcohols in the side chain (for this topic, see Chapter 3 on the addition of dialkyl zinc to aldehydes). 

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