Allyltitanium chiral

The preparation of chiral allyltitanium reagents having a stereogenic center and their utilization in asymmetric synthesis have been pursued. As shown in Eq. 9.27, chiral allyl-... 

Scheme 13.31. Regiocontrolled addition of chiral allyltitanium derivatives to aldehydes.

Based on the Kulinkovich reagent (Ti(OiPr)4/iPrMgCl), a new route to allyltita-niums has been devised by Sato and coworkers and this has allowed the synthesis of chiral allylTi reagents which, by reaction with aldehydes and imines provide diverse polyfunctional chiral building blocks. Thus, while a number of versatile and dependable Ti-based allyl-transfer reagents are now available, the development and employment of chiral allyltitaniums appears to be poised for new application. 

Homoaldol Addition with Chiral A-Allylimidazolidinone Derived from Ephedrine. The chiral allyltitanium compound derived from ephedrine reacts with carbonyl compounds with very high (>200 1) de. Subsequent hydrolysis and oxidation affords optically pure 4-substituted y-lactones (eq 9). 4-Substituted -y-lactones with 92% ee can also be synthesized by catalytic enan-tioselective alkylation of 3-formyl esters. ... 

This strategy was devised to enable the chiral center of the reagent to be closer to the carbonyl group during the addition. Ligand systems based on cyclopentadienyls lead to unsatisfactory enantiomeric excesses," as is reported for the reaction of benzaldehyde with the chiral allyltitanium(IV) reagent (148) derived from (147) by in situ treatment with allylmagnesium chloride (Scheme 20). 

Variable enantioselectivities are obserx presence of ligand 35. - P-Hydroxyaldehydi with a chiral allyltitanium species 36. " wh pared from 37 by various organometallic n mercially available and inexpensive, are mediated allylation, even though they iiv Allylation such as that effected by 38 affon lation. ... 

The chiral allyltitanium reagents prepared from the reaction of allyl Grignard or lithium reagents with chiral titanium complexes have been used stoichiomet-rically for the allylic addition to aldehydes with excellent enantioselectivities [71] (Scheme 14.16). Various applications of this methodology in the synthesis of natural products have been reviewed in several articles [72]. 

Only few allyltitanium reagents bearing a removable chiral auxiliary at the allylic residue are known. The outstanding example is a metalated 1-alkyl-2-imidazolinone14, derived from (—)-ephedrine, representing a valuable homoenolate reagent. After deprotonation by butyllithium, metal exchange with chlorotris(diethylamino)titanium, and aldehyde or ketone addition, the homoaldol adducts are formed with 94 to 98% diastereoselectivity. 

Table 9. Enantioselective Alkenylations with Chiral 3-Substituted Allyltitanium Complexes...

Gais and co-workers recently reported the preparation and use of chiral sulfoximine-substituted allyltitanium(iv) complexes of type 78 for the asymmetric synthesis of 3-substituted unsaturated proline derivatives 79 (Scheme 31).108... 

Asymmetric carboxylation was also achieved by use of 7r-allyltitanium complexes bearing chiral ligands (Scheme 13).26 The enantiomeric selectivity was significantly influenced by the chiral auxiliary ligands used. In the case of 45, the chiral /3,7-unsaturated carboxylic acid 46 was obtained with excellent ee.27,28... 

The synthesis of optically active compounds by the diastereoselective reaction of allyltitanium reagents with chiral electrophiles has also been reported. The reaction of allyltitanium reagents with chiral imines proceeds with excellent diastereoselectivity, as shown in Eq. 9.28, thus providing a new method for synthesizing optically active homoallylic amines with or without a P-substituent [51,52],... 

In contrast to the allyltitaniums derived from acrolein cyclic acetals, such as 1,2-dicyclo-hexylethylene acetal shown in Scheme 9.8, those derived from acrolein acyclic acetals react with ketones and imines exclusively at the y-position. As shown in Eq. 9.29, the reaction with chiral imines having an optically active 1-phenylethylamine moiety proceeds with high diastereoselectivity, thus providing a new method for preparing optically active 1-vinyl-2-amino alcohol derivatives with syn stereochemistry [53], The intermediate allyltita-nium species has also found use as a starting material for a carbozincation reaction [54],... 

Efforts have been made to apply r 3-allyltitanium chemistry to the asymmetric synthesis of homoallylic alcohols and carboxylic acids. The synthesis and reactions of chiral r 3 -allyl-titanocenes with planar chirality, or containing Cp ligands with chiral substituents, have been reported [6c,15,30—32]. The enantiofacial selectivity in the allyltitanation reactions has been examined for the complexes 12 [15], 13 [30], 14 [31], 15, 16, and 17 [32] depicted in Figure 13.2. 

Asymmetric reactions have also been developed. The reactions of allyltitaniums with chiral aldimines derived from optically active 1-phenylethylamine afford optically active homoallylic amines with excellent diastereofacial selectivities. Thus, the Cram syn addition products are obtained highly predominantly when using crotyltitanium reagent 33, as exemplified in Scheme 13.30 [61]. 

Allyltitanium complexes derived from a chiral acetal have been reacted with carbonyl compounds and imines [63], While the chiral induction proved to be low with carbonyl compounds, high induction was observed with imines. This complex represents the first chiral homoenolate equivalent that reacts efficiently with imines. Finally, the reactions with electrophiles other than carbonyl compounds and imines, namely a proton source, NCS, and I2, furnished the corresponding alkene, chloro, and iodo derivatives in good yields [64]. 

Enantioselective ally lotion.1 The reaction of 2 with allylmagnesium chloride in ether affords a chiral orange allyltitanium complex 3. This complex reacts with an aldehyde at —78° to afford homoallyl alcohols in 55-88% yield and in 86-94% ee and with release of 1 and a titanate that can be reconverted to CpTiCl3 (equation I). Reaction of 3 with aryl ketones requires a temperature of 0°, and the enantioselectiv-ity is only about 50%. 

Allyltitanium compounds and Ti enolates derived from mono-Gp chloro titanium complexes with two chiral alkoxo ligands add to aldehydes with high enantioface discrimination.973... 

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