BINOL-Ti complexe

Scheme 8C.3. Asymmetric carbonyl-ene reaction catalyzed by BINOL-Ti complex.

In an effort to develop new chiral BINOL-Ti complexes, chemical modifications of the chiral complex (f )-BINOL-Ti(OPr )2 (R-2) that can easily be prepared by simply mixing ( PrO)4Ti and (/ )-BINOL in the absence ofMS4A have been studied [37c-e]. A dimeric form has been reported for the single-crystal X-ray structure of complex R-2 [38], (I )-BINOL-Ti-p3-oxo complex, prepared via hydrolysis of complex R-2 has been shown to serve as an efficient and moisture-tolerable asymmetric catalyst [37d,e]. It is noteworthy that the (/ )-BINOL-Ti-)i3-oxo catalyst [37e] shows a remarkable level of (+)-NLE (asymmetric amplification), thereby attaining the maximum enantioselectivity for this system by using (/ )-BINOL with only 55-60% ee as the chiral source (consult Scheme 8C. 14). 

BINOL-Ti complexes (1) has been shown to serve as efficient asymmetric catalysts for the carbonyl addition reaction of allylic stannanes and silanes 152,53]. The addition reactions to glyoxylates of ( )-2-butenylsilane and -stannane proceed smoothly to afford the corresponding syn-product with high enantiomeric excess (Scheme 8C.21) [52]. 

It has also been shown that the Sakurai-Hosomi reaction of methallylsilanes with glyoxylates is catalyzed by the BINOL-Ti complex (1) to give the products, surprisingly, in an allylic silane (ene product) form with high enantioselecdvity (Scheme 8C.22) [53],... 

Asymmetric catalysis of BINOL-Ti complexes in the reaction of aliphatic and aromatic aldehydes with an allylstannane has also been reported independently by Umani-Ronchi [54] and Keck [55]. The former group has suggested that a new complex generated by the reaction of the BINOL-Ti complex with allylstannane is the catalytic species that provides remarkably high enantioselectivity (Scheme 8C.23). It is interesting that no reaction occurs if dry MS 4A... 

In our research on the asymmetric catalysis of the carbonyl-ene reaction, we found that the BINOL-Ti complexes (1) [30], prepared in situ, in the presence of 4-A molecular sieves, from diisopropoxytitanium dihalides (X2Ti(OPr )2 X = Br [31] or Cl [32]) and optically pure BiSfOL (vide infra), catalyze [33], rather than promote stoichiome-trically, the carbonyl addition reaction of allylic silanes and stannanes [34]. The addition to glyoxylate of ( )-2-butenylsilane and -stannane proceed smoothly to afford the syn product in high enantiomeric excess (Sch. 5). The s yn-product thus obtained could be readily converted to the iaetone portion of verrucaline A [35]. 

The BINOL-Ti complex-catalyzed addition of allylsilane to aliphatic and aromatic aldehydes has been reported by Carreira [43], The catalyst is prepared from BINOL and polymeric Tip4 (Sch. 9). The presence of a small amount of CH3CN is crucial to achieving not only high catalytic activity but also high enantioselectivity. 

Faller demonstrated the enantiomer-selective deactivation of racemic BINOL-Ti complex by using DIPT-derived titanium complex as a chiral poison (vide infra) (Sch. 10) [44], The enantiomeric excess (ee) of the allylation product increased as the amount of DIPT employed was increased. 

Reactions were conducted with 1.0 mmol methyl glyoxylate, 2.0 mmol olefin, and the indicated amount of BINOL-Ti complex at -30 °C. 

The synthetic utility of the vinylic sulfide and selenide approach is exemplified by the synthesis of enantio-pure (i )-(-)-ipsdienol, an insect aggregation pheromone (Sch. 13) [54], Kabat and Uskokovic have demonstrated the asymmetric catalytic synthesis of la,25-dihydroxyvitamin D3 (la,25(OH)2D3) A-ring synthon by means of a glyoxylate-ene reaction catalyzed by BINOL-Ti complex (1) (Sch. 14) [55]. 

Figure 1. (+)-NLE in the asymmetric glyoxalate-ene reaction catalyzed by the BINOL-Ti complex.

We have previously reported that the hetero Diels-Alder reactions of glyoxylates with 1-methoxy-l,3-butadienes proceed smoothly under catalysis by BINOL-Ti complex to give the cis product with high ee (Sch. 48) [128]. The hetero Diels-Alder products thus obtained can be transformed into monosaccharides [129], The hetero Diels-Alder product can, furthermore, readily be converted into the lactone portion of HMG-Co A inhibitors such as mevinolin or compactin [106] in few steps. 

The Diels-Alder reaction of methacrolein with 1,3-dienol derivatives can also be catalyzed by the BINOL-derived titanium complex, although the catalyst must be freed from molecular sieves (MS) to give the endo adduct with high enantioselectivity (Sch. 50) [131], because MS act as achiral catalysts in the Diels-Alder reaction. The asymmetric Diels-Alder reaction catalyzed by the MS-free (MS-(-)) BINOL-Ti complex (L) can be applied naphthoquinone derivatives as dienophiles to provide entry to the asymmetric synthesis of tetra- and anthracyclinone [132] aglycones (Sch. 51). The sense of asymmetric induction is exactly the same as that observed in the presence of MS in the asymmetric catalytic reactions described above. 

Alkylations. The effect of subjoined Lewis acid (e.g., trimethyl borate) on the catalytic ally lation of aldehydes with allylstannanes promoted by a BINOL-Ti complex has been examined. With allenyltributylstannane the products are homopropargyl alcohols.. Allylation in a Sn(II)-mediated Barbier reaction exhibits much lower ee, although jllenylation with (terminally substituted) propargyltributylstannanes shows good results. 4-Trimethylsilylbut-2-ynyl)tributylstannane undergoes destannylative addition to... 

The reaction of methallyltri-n-butylstannane 117 with achiral aldehydes is also effectively promoted by the binol-Ti complex [89 c]. In all but one case (cyclo-hexanecarboxaldehyde), the yields and enantioselectivities observed with the methallylstannane are identical or higher than those obtained in the reactions with allyltributylstannane with only 10 mol% of the binol-Ti complex (Scheme 10-50). Insight into the nature of the titanium catalyst is provided by the observation of asymmetric amplification [89 b] and chiral poisoning [89 g]. An intruiging hypothesis on the origin of enantioselection in allylation and related reactions [89 h]. 

Similarly, Keck et al. have demonstrated the utility of chiral BINOL-Ti complex 60, prepared by heating enantiomerically pure BINOL, Ti(Oi-Pr)4, (BINOL-Ti 1 1) and 4-A MS in CH2CI2 under reflux for 1 h [150]. In the 60-catalyzed aldol reaction of benzaldehyde wifh S-t-butyl thioacetate TMS enolate, a high isolated yield and the optimum enantiomeric excess (90%, 97% ee) are obtained when fhe reaction is performed wifh 20 mol% 60 in Et2O at -20 °C. Under these conditions the aldol reactions of aromatic and aliphatic aldehydes proceed in good to high yields with high enantioselectivity (70-90%, 89 to >98% ee). 

The BINOL-Ti complex 59 can achieve good enantioselectivity in the crotylation of methyl glyoxylate although the catalytic activity and diastereoselectivity are not so high (48%, 66% de (syn), 80% ee) [399]. 

The carbonyl ene reaction is between a similarly reactive aldehyde and an alkene rather than aketene. Glyoxalate esters and chloral are typical of the carbonyl compounds involved. Asymmetric versions rely on Lewis acid catalysts similar to those used in Diels-Alder reactions based on Ti and A1 among other metals.43 A simple example is the formation of 190 from methyl glyoxalate and an alkene 189 catalysed by 0.5mol% of a BINOL-Ti complex 191. Other alkenes that react well are 192 -195. 

Yu and co-workers reported that PrSSiMej accelerates the catalytic asymmetric allylation of aldehydes with BINOL-Ti complex ent-6B [17]. For example, the... 

Tagliavini and Umani-Ronchi found that chiral BINOL-Zr complex 9 as well as the BINOL-Ti complexes can catalyze the asymmetric allylation of aldehydes with allylic stannanes (Scheme 9) [27]. The chiral Zr catalyst 9 is prepared from (S)-BINOL and commercially available Zr(0 Pr)4 Pr0H. The reaction rate of the catalytic system is high in comparison with that of the BINOL-Ti catalyst 4, however, the Zr-catalyzed allylation reaction is sometimes accompanied by an undesired Meerwein-Ponndorf-Verley type reduction of aldehydes. The Zr complex 9 is appropriate for aromatic aldehydes to obtain high enantiomeric excess, while the Ti complex 4 is favored for aUphatic aldehydes. A chiral amplification phenomenon has, to a small extent, been observed for the chiral Zr complex-catalyzed allylation reaction of benzaldehyde. 

Scheme 8. Ene vs hetero Diels-Alder reaction catalyzed by BINOL-Ti complex Table 2. The reaction of glyoxylate with isoprene ...

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