Borane enantioselective allylation with

The first comes from Jacques Lebreton, and comprises as a key step an enantioselective allylation with (IS)-B-allyldiisopinocamphenylborane, which is readily accessible from allylmagnesium chloride and (IS)-B-chlorodiisopino-camphenylborane. [561] Since the pyridine nitrogen complexes to the borane, at least two equivalents are necessary to obtain good yields and high enantio-selectivity. After mesylation, the azide moiety is introduced with highly selective... 

Catalytic enantioselective allylation with allylsilanes has also been achieved with chiral Lewis acid catalysts such as Ti/binol " and chiral (acyloxy)borane complexes (Scheme 3-89). 

In parallel with the search for catalytic systems, an impressive amount of results in the field of enantioselective allylation has emerged (equation 8). The pioneering work of Marshall and Tang, using a chiral (acyloxy)borane 6 (CAB) system57, was followed by titanium-based catalysts 758 and 859-62 leading to various homoallylic alcohols with enantiomeric excess up to 98%. 

To accelerate aUylation with aUylstaimanes, addition of a Lewis acid is often required, because coordination of the Lewis acid to the carbonyl can enhance the electrophilicity of the substrate and facilitate the couphng reaction. Since Yamamoto showed that a nonracemic Lewis acid, chiral (acyloxy)borane (CAB), catalyzed enantioselective allylation [73], chiral Lewis acid catalysts have been extensively developed. Above all, easily available chiral compounds such as BINOL and BINAP have been most frequently used as chiral auxiliaries [74], and enantioselective allylations of C-N double bonds and of carbonyl groups have been achieved [48a, 75]. 

Stereoselective Allylation Reaction. The enantioselective allylation of aldehydes with allyltrimethylsilane is now possible with good control. One example is the use of a chiral acyloxy borane (CAB) catalyst. Besides that, chiral Ti(OiPr)2X2-BINOL and TiFa-BINOL catalysts are effective for the enantioselective allylation of glyoxylates and aldehydes, respectively (eq 35). Chiral homoallylamines can be prepared from the reaction of imines and allyltrimethylsilane using chiral tt-allylpalladium complexes with TBAF (eq 36) or an (5)-Tol-BINAP-CuPFe system. Free radical allyl transfers from allyltrimethylsilane provides another method for this enantioselective C-C bond formation. Promoted by chiral Lewis acids, both... 

Another breakthrough came from Antilla et al., who employed a chiral phosphoric acid as an efficient catalyst for the reduction of prochiral ketones (83). As an extension of their success in the enantioselective allylation of aldehydes with allyl borate [84], they hypothesized that a chiral phosphoric could activate and direct the borane reduction of ketones. Initial studies showed that the asymmetric reduction truly works and, after screening various chiral phosphoric acids, found that 6 stands out as the most suitable catalyst. The enantioselectivity is further improved by using 4-(dimethylamino)pyridine (DMAP) as an additive (ee up to 95%) (Scheme 32.30). To gain mechanistic insight into this reduction, the authors performed several parallel B NMR experiments the results suggest that the complex formed between 6, catechol borate, and DMAP might be the real catalyst for the asymmetric reduction. 

In 1978, Hoffmann reported enantioselective allylation reactions of aldehydes with a camphor-derived chiral boronate 13 (Equation 1) [55]. Three classes of chiral boron reagents that furnish allylation products with very high levels of enantioselectivity have emerged Brown s diisopinocampheyl or diisocaranyl allyl boranes [35-41], Roush s tartrate-derived boronates [33, 42-48], and Hoffmann s "a-chiral boronates [56-61],... 

In parallel with the search for catalytic systems, has emerged an impressive amount of results in the field of enantioselective allylation. The pioneering work of Marshall using a chiral (acyloxy)borane (CAB) system [216] was readily followed by titanium/BINOL catalysts [217], leading to homoallylic alcohols with enantiomeric excess up to 98%. An extension of this work in fluorous phase was also developed with 6,6 -perfluoroalkylated BINOLs [218]. Replacing the titanium by zirconium (IV) salts, led to more reactive catalyst for the allylation of aromatic and aliphatic aldehydes [219]. One of the more active catalyst is the zirconium-BINOL system associated with 4-tert-butylcalix [4]arene, which remains active with only 2% of the chiral inductor [220]. The use of activators, such as iPrSSiMe3, iPrSBEt2,... 

The tartrate ester modified allylboronates, the diisopropyl 2-allyl-l,3,2-dioxaborolane-4,5-di-carboxylates, are attractive reagents for organic synthesis owing to their ease of preparation and stability to storage71. In the best cases these reagents are about as enantioselective as the allyl(diisopinocampheyl)boranes (82-88% ee with unhindered aliphatic aldehydes), but with hindered aliphatic, aromatic, a,/l-unsaturated and many a- and /5-alkoxy-substituted aldehydes the enantioselectivity falls to 55-75% ee71a-b... 

Optically active TV-sulfonylamino alcohols derived from D-camphor or norephedrine were found to be efficient chiral ligands for the enantioselective allylboration of iV-silylimines (Equation (170)) 646-648 B-Allyl(diisopinocampheyl)borane allylated iV-diisobutylaluminum imines with 87% ee (Equation (171)).649,650... 

As mentioned in Section 9.12.2.1.1, the boron-zinc exchange can be performed stereoselectively if diisopropyl-zinc instead of diethylzinc is used. For example, hydroboration of the chiral, racemic endocyclic olefin 134 with diethylzinc, followed by twofold transmetallation and electrophilic capture of the resulting copper intermediate with allyl bromide was used for the highly diastereoselective formation of the stereotriad in product 136 (Scheme 35).35,35a 103 QorreSp0nding enantioselective transformations were carried out with chiral boranes and catalytic amounts of copper salts (see Section 9.12.2.2.2).36... 

Several arylboronic acids have been examined in place of borane-THF to improve the Lewis acidity of 2 and the stereoselectivity [49b]. The boron substituent of 2 has a large effect on the chemical yield and the enantiomeric excess of the allylation adduct, and 3,5-bistrifluoromethylbenzeneboronic acid results in the greatest reactivity— when a complex which is easily prepared from a tartaric acid derivative and 3,5-bistri-fluoromethylbenzeneboronic acid in propionitrile at room temperature is used, the reactivity is improved without reducing the enantioselectivity. For instance, the reaction of l-trimethylsilyl-2-methyl-2-propene with benzaldehyde in the presence of only 10 mol % 2 proceeds to give 99 % yield and 88 % ee (Fig. 19). 

Asymmetric allylation of aldehyde 66, available in two steps from 3-hydroxypropionitrile, with allyl borane 67 gave the expected homoallylic alcohol 68 in good yield and with acceptable enantioselectivity. This material was converted uneventfully to a doubly protected dihydroxy aldehyde 69 and thence to 70 along lines similar to our synthesis of 56 from 34 (see Scheme 8). The aldol reaction employed within this five step sequence provided the means to remove vestiges of the minor enantiomer of 69 introduced from the allylation of 66. In an... 

Both carenes 40 and 41 are readily hydroborated by borane dimethyl sulfide complex to give the diisocaranylboranes (Icr.BH) which can be isolated in pure form. Treatment w ith methanol gives the S-methoxy derivatives, which readily react with allylic carbanions to give the corresponding allyldiisocaranylboranes 42-45. These compounds have been used for asymmetric allyl additions to carbonyl compounds (Sections D. 1.3.3.3. and D.2.5.2.). The reagents 44 and 45, derived from 2-carene39, are more enantioselective than those from 3-carene(1. 

C3-quatemised 3-prenyl indolenines are accessible in an enantioselective manner by Pd-catalysed 3-allylation of 3-prenylindoles, as reported by Trost and Quancard in 2006 (Scheme 28) [122]. In addition to the Pd-source and the anthracene-derived chiral ligand 139, an optimised bulky tertiary borane (9-BBN-CgHi3) is added, which coordinates to the indole nitrogen, prevents N-allylation and also enhances the enantioselectivity of the reaction. The reaction from 138 to 140 is especially suitable for electron-rich indoles and could be tried with prenol as allylic alcohol. 

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