BINOLs

Secondary butyl alcohol, methylethyl car-binol, 2-butanol, CH3CH2CH(Me)OH. B.p. I00°C. Manufactured from the butane-butene fraction of the gas from the cracking of petroleum. Used to prepare butanone. 

The first substance examined in the steroid field was 3j6-hydroxycholest-4-ene (1) and the epimeric 3a-alcohol (3). These compounds react stereospecifically in dry ether with the Simmons-Smith reagent to yield the isomeric cyclopropyl carbinols (2) and (4) in 90 % and 67 % yields, respectively. The rate of this reaction is about one fifth of that observed with simple cyclic car-binols. ... 

The inverse electron-demand Diels-Alder reaction is also accelerated by Lewis acids, but the successful application of chiral Lewis acids to this kind of Diels-Alder reaction is very rare. Marko and coworkers applied Kobayashi s catalyst system (Yb(OTf)3-BINOL-amine) to the Diels-Alder reaction of 3-methoxycarbonyl-2-py-rone with vinyl ether or sulfide [58] (Scheme 1.72, Table 1.29). A bulky ether or... 

Yamamoto et al. were probably the first to report that chiral aluminum(III) catalysts are effective in the cycloaddition reactions of aldehydes [11]. The use of chiral BINOL-AlMe complexes (R)-S was found to be highly effective in the cycloaddition reaction of a variety of aldehydes with activated Danishefsky-type dienes. The reaction of benzaldehyde la with Danishefsky s diene 2a and traws-l-methoxy-2-methyl-3-(trimethylsilyloxy)-l,3-pentadiene 2b affords cis dihydropyrones, cis-3, as the major product in high yield with up to 97% ee (Scheme 4.6). The choice of the bulky triarylsilyl moiety in catalyst (J )-8b is crucial for high yield and the en-antioselectivity of the reaction in contrast with this the catalysts derived from AlMe3 and (J )-3,3 -disubstituted binaphthol (substituent = H, Me, Ph) were effective in stoichiometric amounts only and were less satisfactory with regard to reactivity and enantioselectivity. 

Keck et al. reported that a catalyst generated from (S)- or (l )-BINOL 12 and Ti(0-i-Pr)4 in a 2 1 ratio is more selective than the catalyst formed from a 1 1 mixture [19fj. The former catalyst was shown to catalyze the cycloaddition reaction of aldehydes 1 with Danishefsky s diene 2a affording the dihydropyrones 3 with moderate to excellent enantioselectivity (Scheme 4.12). The reaction proceeds well for different aldehydes with up to 97% ee and good yield of the cycloaddition products. 

The dihydropyrones are not produced directly in the initial BINOL-titanium(IV)-cat-alyzed reaction. The major product at this stage is the Mukaiyama aldol product which is subsequently cyclized by treatment with TFA [19fj. The formal cycloaddition product 3d (97% ee) obtained from a-(benzyloxy)acetaldehyde is an important intermediate for compactin and mevinolin. Scheme 4.13 outlines how the structural subunit 13 is available in three steps via this cycloaddition approach [19 fj. 

The interest in chiral titanium(IV) complexes as catalysts for reactions of carbonyl compounds has, e.g., been the application of BINOL-titanium(IV) complexes for ene reactions [8, 19]. In the field of catalytic enantioselective cycloaddition reactions, methyl glyoxylate 4b reacts with isoprene 5b catalyzed by BINOL-TiX2 20 to give the cycloaddition product 6c and the ene product 7b in 1 4 ratio enantio-selectivity is excellent - 97% ee for the cycloaddition product (Scheme 4.19) [28]. 

It has also been shown by Mikami et al. that a BINOL-titanium(IV) complex in which the 6,6 position of the BINOL ligand is substituted with bromine catalyzes... 

A remarkable change in reaction course is notable when changing the metal from aluminum to titanium for cydoaddition reactions using BINOL as the chiral ligand. When the chiral aluminum(III) catalyst is applied the cydoaddition product is the major product, whereas for the chiral titanium(IV) catalyst, the ene product is the major product. The reason for this significant change in reaction course is not fully understood. Maybe the glyoxylate coordinates to the former Le-... 

The major developments of catalytic enantioselective cycloaddition reactions of carbonyl compounds with conjugated dienes have been presented. A variety of chiral catalysts is available for the different types of carbonyl compound. For unactivated aldehydes chiral catalysts such as BINOL-aluminum(III), BINOL-tita-nium(IV), acyloxylborane(III), and tridentate Schiff base chromium(III) complexes can catalyze highly diastereo- and enantioselective cycloaddition reactions. The mechanism of these reactions can be a stepwise pathway via a Mukaiyama aldol intermediate or a concerted mechanism. For a-dicarbonyl compounds, which can coordinate to the chiral catalyst in a bidentate fashion, the chiral BOX-copper(II)... 

The assumed transition state of this reaction is shown in Scheme 5.3. Yb(OTf)3, (J )-(-h)-BINOL, and DBU form a complex with two hydrogen bonds, and the axial chirality of (J )-(-h)-BINOL is transferred via the hydrogen bonds to the amine parts. The additive would interact with the phenolic hydrogen of the imine, which is fixed by bidentate coordination to Yb(III). Because the top face of the imine is shielded by the amine, the dienophiles approach from the bottom face to achieve high levels of selectivity. 

Polymer-supported BINOLs thus prepared were treated with Zr(Ot-Bu)4 to form polymer-supported zirconium 20. In the presence of 20 mol% of various zirconium 20, the model aza Diels-Alder reactions of imine Id with Danishefsky s diene (7a) were performed results from selected examples are shown in Table 5.8. Whereas the 4-t-butylphenyl group resulted in lower enantiomeric excess (ee), higher ee were obtained when 3,5-xylyl, 4-biphenyl, 4-fluorophenyl, and 3-tri-... 

A model for the mechanism of the highly enantioselective AlMe-BINOL-cata-lyzed 1,3-dipolar cycloaddition reaction was proposed as illustrated in Scheme 6.13. In the first step nitrone la coordinates to the catalyst 11b to form intermediate 12. In intermediate 13, which is proposed to account for the absolute stereoselectivity of this reaction, it is apparent that one of the faces of the nitrone, the si face, is shielded by the ligand whereas the re face remains available... 

The above described reaction has been extended to the application of the AlMe-BINOL catalyst to reactions of acyclic nitrones. A series chiral AlMe-3,3 -diaryl-BINOL complexes llb-f was investigated as catalysts for the 1,3-dipolar cycloaddition reaction between the cyclic nitrone 14a and ethyl vinyl ether 8a [34], Surprisingly, these catalysts were not sufficiently selective for the reactions of cyclic nitrones with ethyl vinyl ether. Use of the tetramethoxy-substituted derivative llg as the catalyst for the reaction significantly improved the results (Scheme 6.14). In the presence of 10 mol% llg the reaction proceeded in a mixture of CH2CI2 and petroleum ether to give the product 15a in 79% isolated yield. The diastereoselectiv-ity was the same as in the acyclic case giving an excellent ratio of exo-15a and endo-15a of >95 <5, and exo-15a was obtained with up to 82% ee. 

Whereas there are numerous examples of the application of the products from diastereoselective 1,3-dipolar cycloaddition reaction in synthesis [7, 8], there are only very few examples on the application of the products from metal-catalyzed asymmetric 1,3-dipolar cycloaddition reaction in the synthesis of potential target molecules. The reason for this may be due to the fact that most metal-catalyzed asymmetric 1,3-dipolar cycloaddition reaction have been carried out on model systems that have not been optimized for further derivatization. One exception of this is the synthesis of a / -lactam by Kobayashi and Kawamura [84]. The isoxazoli-dine endo-21h, which was obtained in 96% ee from the Yb(OTf)3-BINOL-catalyzed... 

The reactions of nitrones constitute the absolute majority of metal-catalyzed asymmetric 1,3-dipolar cycloaddition reactions. Boron, aluminum, titanium, copper and palladium catalysts have been tested for the inverse electron-demand 1,3-dipolar cycloaddition reaction of nitrones with electron-rich alkenes. Fair enantioselectivities of up to 79% ee were obtained with oxazaborolidinone catalysts. However, the AlMe-3,3 -Ar-BINOL complexes proved to be superior for reactions of both acyclic and cyclic nitrones and more than >99% ee was obtained in some reactions. The Cu(OTf)2-BOX catalyst was efficient for reactions of the glyoxylate-derived nitrones with vinyl ethers and enantioselectivities of up to 93% ee were obtained. 

The reaction was studied in the absence, and presence, of (MeO)2AlMe as a model catalyst for the BINOL-AlMe system. The change in relative energy for the concerted hetero-Diels-Alder reaction, and formation of the hetero-Diels-Alder adduct 11 via a Mukaiyama aldol reaction, is shown in Fig. 8.13. The conclusion of the study was that in the absence of a catalyst the concerted reaction is the most... 

BINOL-AlMe 316 BINOL-aluminum(III) 155 BINOL-titanium(IV) 155, 161 bis(oxazolines) 26f. 

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