Titanium complexes silyls

A combination of diethylzinc with sulfonamides 18 or 19 offers another possibility for the enantioselective acetate aldol reaction39,41. The addition of silyl enol ethers to glyoxylates can be directed in a highly enantioselective manner when mediated by the binaphthol derived titanium complex 2040. 

Addition of the (l-silylalkyne)titanium complex to carbonyl compounds and imines occurs at the (3-position to the silyl group, as shown in Fig. 9.2. However, the reaction with sBuOH takes place exclusively at the carbon—titanium bond a to the silyl group to give the (P-silylalkenyl)titanium species, as in Eq. 9.5 (values in square brackets denote the regioselectivity) [24], where the vinyl—titanium bond is visualized by the outcome of the iodi-nolysis. The overall reaction can therefore be regarded as the hydrotitanation of silylace-... 

Bernadi and Scolastico, and later Evans in a more effective manner, indicated that the enantioselective addition reaction using silyl enol ethers can be catalyzed by Lewis acidic copper(II) cation complexes derived from bisoxazolines [38-40]. In the presence of the copper complex (S,S)-14 (10 mol %), silyl enol ethers derived from thioesters add to alkylidenemalonates or 2-alkenoyloxazo-lidone in high ees (Scheme 12). Bernadi, Scolastico, and Seebach employed a titanium complex derived from TADDOL for the addition of silyl enol ethers to nitroalkenes or 2-cyclopentenone [41-43], although these are stoichiometric reactions. 

BINOL-derived titanium complex was found to serve as an efficient catalyst for the Mukaiyama-type aldol reaction of ketone silyl enol ethers with good control of both absolute and relative stereochemistry (Scheme 8C.24) [57]. It is surprising, however, that the aldol products were obtained in the silyl enol ether (ene product) form, with high syn-diastereoselec-tivity from either geometrical isomer of the starting silyl enol ethers. 

Carreira et al. used a chiral BlNOL-derived Schiff base-titanium complex as the catalyst for the aldol reactions of acetate-derived ketene silyl acetals (Scheme 8C.29) [64a]. The catalyst was prepared in toluene in the presence of salicylic acid, which was reported to be crucial to attain a high enantioselectivity. A similar Schiff base-titanium complex is also applicable to the carbonyl-ene type reaction with 2-methoxypropene [64b], Although the reaction, when con-... 

A few dinuclear complexes are known, in which the a-CH bond of a metal-bonded alkyl group is tj2 coordinated to another metal moiety, similar to the previously discussed dinuclear silyl complexes. In the iron complex 22 (75) both metal moieties are the same, and therefore the Fe—C distances [202.5(3) and 211.3(3) pm] can be directly compared without correction. The relative lengthening of the M—C distance of the Fe—H—C three-center bond (4.5%) is comparable to that in the silane-bridged titanium complex 13 (6.5%), corresponding to a similar stage of the oxidative addition. 

Examples of the asymmetric functionalization of isoquinoline derivatives were reported in 2002. One example illustrated the enantioselective addition of ketene silyl acetal (82) to cyclic nitrone (81) catalyzed by a chiral titanium complex to prepare 1,2,3,4-tetrahydroisoquinoline (83) in 84% yield with 83% ee <02JA2888>. 

Now the aldol reaction can occur the positive charge on the titanium-complexed carbonyl oxygen atom makes the aldehyde reactive enough to be attacked even by the not very nucleophilic silyl enol ether. Chloride ion removes the silyl group and the titanium alkoxide captures it again. This last step should not surprise you as any alkoxide (MeOLi for example) will react with Me3SiCl to form a silyl ether. 

Transformations involving chiral catalysts most efficiently lead to optically active products. The degree of enantioselectivity rather than the efficiency of the catalytic cycle has up to now been in the center of interest. Compared to hydrogenations, catalytic oxidations or C-C bond formations are much more complex processes and still under development. In the case of catalytic additions of dialkyl zinc compounds[l], allylstan-nanes [2], allyl silanes [3], and silyl enolethers [4] to aldehydes, the degree of asymmetric induction is less of a problem than the turnover number and substrate tolerance. Chiral Lewis acids for the enantioselective Mukaiyama reaction have been known for some time [4a - 4c], and recently the binaphthol-titanium complexes 1 [2c - 2e, 2jl and 2 [2b, 2i] have been found to catalyze the addition of allyl stannanes to aldehydes quite efficiently. It has been reported recently that a more active catalyst results upon addition of Me SiSfi-Pr) [2k] or Et2BS( -Pr) [21, 2m] to bi-naphthol-Ti(IV) preparations. 

As in the case of the related titanium complexes, the oxidation of the unshielded silyl enolates affords the related 1,4-diketones (Table 6). 

Mukaiyama Aldol Condensation. The BINOL-derived titanium complex BINOL-T1CI2 is an efficient catalyst for the Mukaiyama-type aldol reaction. Not only ketone silyl enol ether (eq 25), but also ketene silyl acetals (eq 26) can be used to give the aldol-type products with control of absolute and relative stereochemistry. 

Mukaiyama Aldol Condensation. As expected, the chiral titanium complex is also effective for a variety of carbon-carbon bond forming processes such as the aldol and the Diels-Alder reactions. The aldol process constitutes one of the most fundamental bond constructions in organic synthesis. Therefore the development of chiral catalysts that promote asymmetic aldol reactions in a highly stereocontrolled and truly catalytic fashion has attracted much attention, for which the silyl enol ethers of ketones or esters have been used as a storable enolate component (Mukaiyama aldol condensation). The BINOL-derived titanium complex BINOL-TiCl2 can be used as an efficient catalyst for the Mukaiyama-ty pe aldol reaction of not only ketone si ly 1 enol ethers but also ester silyl enol ethers with control of absolute and relative stereochemistry (eq 11). ... 

Keck also investigated asymmetric catalysis with a BINOL-derived titanium complex [102,103] for the Mukaiyama aldol reaction. The reaction of a-benzyloxyalde-hyde with Danishefsky s dienes as functionalized silyl enol ethers gave aldol products instead of hetero Diels-Alder cycloadducts (Sch. 40) [103], The aldol product can be transformed into hetero Diels-Alder type adducts by acid-catalyzed cyclization. The catalyst was prepared from BINOL and Ti(OPr )4, in 1 1 or 2 1 stoichiometry, and oven-dried MS 4A, in ether under reflux. They reported the catalyst to be of BINOL-Ti(OPr% structure. 

Trimethylsilyloxy)furan can also be used as a functionalized silyl enol ether for the asymmetric catalytic aldol-type reaction. Figadere has reported that the reaction of aliphatic aldehydes with the siloxyfuran catalyzed by BINOL-derived titanium complex provides the diastereomeric mixtures with high enantioselectivity (Sch. 42) [107], The addition reaction proceeds at the y position of the siloxyfuran to give butenolides of biological and synthetic importance. 

The Lewis acid-catalyzed conjugate addition of silyl enol ethers to a,y3-unsaturated carbonyl derivatives, the Mukaiyaraa Michael reaction, is known to be a mild, versatile method for carbon-cabon bond formation. Although the development of catalytic asymmetric variants of this process provides access to optically active 1,5-dicarbonyl synthons, few such applications have yet been reported [108], Mukiyama demonstrated asymmetric catalysis with BINOL-Ti oxide prepared from (/-Pr0)2Ti=0 and BINOL and obtained a 1,4-adduct in high % ee (Sch. 43) [109]. The enantioselectiv-ity was highly dependent on the ester substituent of the silyl enol ether employed. Thus the reaction of cyclopentenone with the sterically hindered silyl enol ether derived from 5-diphenylmethyl ethanethioate proceeds highly enantioselectively. Sco-lastico also reported that reactions promoted by TADDOL-derived titanium complexes gave the syn product exclusively, although with only moderate enantioselectiv-ity (Sch. 44) [110]. 

Allyltrichlorosilane reacts with benzaldehyde in the presence of BU4NF to give l-phenylbut-3-en-lol7 and with a chiral additive the reaction proceeds with good enantioselectivity. When chiral titanium complexes are used in the reaction, allylic alcohols are produced with good asymmetric induction/ Other chiral additives have been used, as well as chiral catalysts,and chiral complexes of allyl silanes 7 Chiral allylic silyl derivatives add to aldehydes to give the chiral homo-allylic alcoholJ ... 

The use of chiral diamine 60 with Sn(OTf)2/Bu2Sn(OAc)2 promotes Mukaiya-ma aldol reactions, and such an example was used in a recent synthesis of Tax-ol , in which adduct 61 was obtained with 99% ds and 96% ee (Scheme 9-20) [42J. Other notable contributions to this field have been made using dienolate chemistry. For example, the titanium complex 62 promotes aldol reactions of silyl dienol ethers (Scheme 9-21). Products 63 and ent-63 were then used in the synthesis of macrolactin A (64) [43],... 

The binuclear titanium complex Cp2TiCl(/x-0)TiCl(acac)2 is formed by the reaction of Gp2TiCl2 with 2 equiv. of 2,4-pentanedione in the presence of NEt3 in CH3CN at room temperature. Its molecular structure has been determined by X-ray diffraction. On activation with LiBu11, the compound catalyzes the reaction of phenylsilane with aldehydes to give O-silylation products.1531... 

Doubly bridged ansa-titanium complexes are considered as a new class of stereorigid catalysts for stereospecific a-olefin polymerization. Doubly silyl bridged -complexes are considerably more strained than their singly bridged analogs. 

A different, possibly more productive, research direction has been the development of less syndioselective catalysts, based on modifications of the silyl-bridged cyclopentadienyl-amido titanium complex. 

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