TADDOL diols

A chiral titanium complex with 3-cinnamoyl-l,3-oxazolidin-2-one was isolated by Jagensen et al. from a mixture of TiCl 2(0-i-Pr)2 with (2R,31 )-2,3-0-isopropyli-dene-l,l,4,4-tetraphenyl-l,2,3,4-butanetetrol, which is an isopropylidene acetal analog of Narasaka s TADDOL [48]. The structure of this complex was determined by X-ray structure analysis. It has the isopropylidene diol and the cinnamoyloxazolidi-none in the equatorial plane, with the two chloride ligands in apical (trans) position as depicted in the structure A, It seems from this structure that a pseudo-axial phenyl group of the chiral ligand seems to block one face of the coordinated cinnamoyloxazolidinone. On the other hand, after an NMR study of the complex in solution, Di Mare et al, and Seebach et al, reported that the above trans di-chloro complex A is a major component in the solution but went on to propose another minor complex B, with the two chlorides cis to each other, as the most reactive intermediate in this chiral titanium-catalyzed reaction [41b, 49], It has not yet been clearly confirmed whether or not the trans and/or the cis complex are real reactive intermediates (Scheme 1.60). 

Phosphoramidite ligands based on TADDOL (36) and on D-mannitol (37) [74] have also been used (Scheme 28.11). However, the enantioselectivities reported for the hydrogenation of a-dehydroamino acids and itaconates were generally lower compared to the ligands based on BINOL. A different strategy is the use of ligands 38a-g based on the achiral diol catechol, and chiral amines [75]. 

Ito et al.120 reported TADDOL 126 as a new type of chiral ligand in place of amino alcohol and examined the catalytic ligand effect of using various chiral diols in the presence of Ti(OPr )4. 

The self-assembly of a chiral Ti catalyst can be achieved by using the achiral precursor Ti(OPr )4 and two different chiral diol components, (R)-BINOL and (R,R)-TADDOL, in a molar ratio of 1 1 1. The components of less basic (R)-BINOL and the relatively more basic (R,R)-TADDOL assemble with Ti(OPr )4 in a molar ratio of 1 1 1, yielding chiral titanium catalyst 118 in the reaction system. In the asymmetric catalysis of the carbonyl-ene reaction, 118 is not only the most enantioselective catalyst but also the most stable and the exclusively formed species in the reaction system. 

Bidentate chiral auxiliaries have since been examined. While camphane-2,3-diol and (5-binaphthol gave disappointing results, tartrate-derived (TADDOL) ligands were found to be very promising as chiral inductors [44]. Particularly interesting results were obtained by using complex 21, readily available from natural (P,J )-(+)-tartaric acid (Scheme 13.21). 

Seebach et al. (154) showed that a 0-isopropylidene-2,3-dihydroxy-l, 1,4,4-tetraphenyl-l,4-diol (TADDOL)-derived aminothiolate serves as a moderately effective ligand for the catalyzed conjugate addition of Grignard reagents to cyclic enones. The catalyst, synthesized from the lithiothiolate and CuCl, exhibits optimal selectivities under a slow addition protocol (2 h), Eq. 124. 

The role of multicomponent ligand assembly into a highly enantioselective catalyst is shown in the enantioselective catalysis for the carbonyl-ene reaction (Table 8.9). The catalyst is prepared from an achiral precatalyst, Ti(0 Pr)4 and a combination of BINOL with various chiral diols such as TADDOL and 5-Cl-BIPOL in a molar ratio of 1 1 1 (10mol% with respect to the olefin and glyoxylate) in... 

A simple, commercially available chiral alcohol, a,a,a a -tetraaryl-l,3-dioxo-lane-4,5-dimethanol (TADDOL, 7a), catalyzes the hetero- and carbo-Diels-Alder reactions of aminosiloxydienes with aldehydes and a-substituted acroleins to afford the dihydropyrones and cyclohexenones, respectively, in good yields and high enan-tioselectivities. More recently, it was reported that axially chiral biaryl diols 7b and 7c were more highly effective catalysts for enantioselective hetero-Diels-Alder reactions (Scheme 12.5). ... 

The enantioselective hetero-Diels-Alder (HDA) reaction of carbonyl compounds with 1,3-dienes represents an elegant access to optically active six-membered oxo-heterocycles. Since the pioneering work of Rawal et al. in 2003 [55], the enantioselective HDA reaction catalyzed by diols (such as TADDOLs) has become a flourishing field of research [56]. 

In the catalytic system shown in Scheme 9, a hydrogen bond between one hydroxy function of the diol catalyst and the carbonyl group of the substrate is regarded as the driving force of catalysis. Here, the spatial orientation of the bulky a-1-naphthyl substituents of the TADDOL (a,a,a, a -tetraaryl-l,3-dioxolan-4,5-dimethanol) scaffold generates the chiral environment controlling the enantioselectivity of the reaction. 

The Rawal group next applied diol catalysis to the enantioselective vinylogous Mukaiyama aldol (VMA) reaction of electron-deficient aldehydes [105]. Screening of various known chiral diol derivatives, including VANOL, VAPOL, BINOL, BAMOL, and TADDOL, revealed that 38a was the only catalyst capable of providing products in acceptable levels ofenantioselection (Scheme 5.55). Subsequent to this work, Scettri reported a similar study of TADDOL-promoted VMA reactions with Chan s diene [106]. 

Lewis acid-promoted asymmetric addition of dialkylzincs to aldehydes is also an acceptable procedure for the preparation of chiral secondary alcohol. Various chiral titanium complexes are highly enantioselective catalysts [4]. C2-Symmet-ric disulfonamide, chiral diol (TADDOL) derived from tartaric acid, and chiral thiophosphoramidate are efficient chiral ligands. C2-Symmetric chiral diol 10, readily prepared from 1-indene by Brown s asymmetric hydroboration, is also a good chiral source (Scheme 2) [17], Even a simple a-hydroxycarboxylic acid 11 can achieve a good enantioselectivity [18]. 

Another useful procedure for the synthesis of dioxepins, oxathiepins, as well as dithiepins under basic conditions involves deprotonation of a diol or dithiol precursor and treatment of the resulting anion with a gdihalo compound, as demonstrated with the synthesis of the TADDOL-derived oxathiepin 64 <1991SL844> and biaryl derivative 132 <2005TL7291> (Scheme 62) ... 

Oxidative homo-coupling of enolates from acyl oxazolidinones to give the corresponding dimers can be achieved in the presence of oxidants. Titanium and ytterbium enolates of 252 were coupled in the presence of a chiral diol or chiral bisoxazoline in the presence of ferrocenium cation 254 (Scheme 63) [166]. The amount of the meso dimer varied with the chiral ligand with a maximum of 5 1. TADDOL 172 performed best providing a 76% ee for the meso product. Ytterbium enolate gave a low ee of 34% with the same ligand. 

A related approach has recently been reported by Belokon and Kagan et al. These workers used chiral TADDOL-type diols, derived from tartaric acid and 2-amino-2 -hydroxy-1,1 -binaphthyl (NOBIN), as catalysts to obtain yields of up to 95% and enantioselectivity up to 93% ee [59-61], The catalytically active species seem to be the sodium salts of the diols. 

Romo et al. have used Lewis acids to catalyze the formation of a-silyl-/ -lactones in their synthesis of potential inhibitors of yeast 3-hydroxy-3-methyl glutaryl-coenzyme A (HMG-CoA) synthase <1998BMC1255>. In addition to various Lewis acid catalysts, a chiral promoter based on the chiral diol (l/ ,2R)-2-[(diphenyl)hydroxymethyl]cyclo-hexan-l-ol was introduced to the reaction in an attempt to improve the stereoselectivity. A variety of chiral 2-oxetanones were formed, with enantioselectivities ranging from 22% to 85%. Dichlorotitanium-TADDOL catalysts 113 and 114 have also been used in an attempt to encourage the stereoselective [2+2] cycloaddition of silyl ketenes and aldehydes (TADDOL = (—)-/ra r-4,5-bis(diphenyl-hydroxymethyl)-2,2-dimethyl-l,3-dioxolane), although this method only afforded 2-oxetanones in moderate yields and optical purity (Equation 41) <1998TL2877>. 

Narasaka has demonstrated that TADDOL-Ti dichloride prepared from TADDOL and Cl2Ti(OPr )2 in the presence of MS 4A acts as an efficient catalyst in asymmetric catalytic Diels-Alder reactions with oxazolidinone derivatives of acrylates, a results in extremely high enantioselectivity (Sch. 45) [112]. Narasaka reported an intramolecular version of the Diels-Alder reaction, the product of which can be transformed into key intermediates for the syntheses of dihydrocompactin and dihydromevinolin (Sch. 46) [113]. Seebach and Chapuis/Jurczak [114] independently reported asymmetric Diels-Alder reactions promoted by chiral TADDOL- and 3,3 -diphenyl BINOL-derived titanium alkoxides. Other types of chiral diol ligands were also explored by Hermann [115] and Oh [116]. 

During the past two decades the homogeneous and heterogeneous catalytic enan-hoselective addition of organozinc compounds to aldehydes has attracted much attention because of its potential in the preparation of optically active secondary alcohols [69]. Chiral amino alcohols (such as prolinol) and titanium complexes of chiral diols (such as TADDOL and BINOL) have proved to be very effective chiral catalysts for such reactions. The important early examples included Bolm s flexible chiral pyridyl alcohol-cored dendrimers [70], Seebach s chiral TADDOL-cored Frechet-type dendrimers [28], Yoshida s BINOL-cored Frechet-type dendrimers [71] and Pu s structurally rigid and optically active BlNOL-functionalized dendrimers [72]. All of these dendrimers were used successfully in the asymmetric addition of diethylzinc (or allyltributylstannane) to aldehydes. 

We prepared and purified the air- and moisture-sensitive complex 43 to carry out these studies. We have also found that it is possible to generate this complex in situ, with the starting ArOH (two equivalents) and two equivalents of BuLi, followed, at it, by TiCU, and then at -18° by the diene and two more equivalents of BuLi. The cyclization results are the same as with the preprepared complex 43. We will use this latter approach to quickly screen a variety of other alcohols and diols, including enantiomerically pure diols such as BINOL (1,1 -bi-2-naphthol) and Taddol (a,a,a, a -tetraaryl-l,3-dioxolane-4,5-dimethanol), in this cyclization. 

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