Chirality transfer reagents

Studies of the transfer of Br+ and I+ from amine-coordinated halonium ions to acceptor l-co-alkenols have been undertaken to determine the mechanism in an effort to assist in the development of chiral transfer reagents. Transfer of Br+ and I+ from two commercially available dimeric hydroquinine and hydroquinidine ligands ((DHQ)2PHAL and (DHQD)2PHAL) to various 1, (o-alkenols and l,co-alkenoic acids is shown to provide enantiomeric excesses of 4-47% depending on the acceptor alkene. 

As a second example, we recently used the readily available (W)-phenylglycine amide as a Chirality Transfer reagent (see Chapter 25).43 In this case, a Strecker reaction is performed on pivaldehyde under equilibrium conditions resulting in two covalent diastereoisomeric products (Scheme 7.9). The lower solubility of the (.S. /H-diastereoisomer results in transformation of the (R,/H-diastereoisomer into the (.S. /H-diastereoisomer in 93% yield and >99% diastereoselectivity. 

I.3.3.1.4, With Reagent-Induced Stereoselectivity I.3.3.I.4.I. 1,3-Chirality Transfer... 

Enantiomerically enriched l-(diisopropylaminocarbonyloxy)allyllithium derivatives (Section 1.3.3.3.1.2.) add to carbonyl compounds with syn-l,3-chirality transfer21, giving good evidence for a pericyclic transition state in the main reaction path (Section 1.3.3.1.). However, since the simple diastereoselectivity and the degree of chirality transfer are low, for synthetic purposes a metal exchange with titanium reagents or trialkyltin halides (Section D.1.3.3.3.8.2.3.) is recommended. 

The enantiomeric excess which is achieved for a given ally carbamate is independent of the carbonyl compound used it reflects the skill of the operator in the crystallization procedure. The high degree of reagent-controlled chirality transfer is also obvious from the reaction with either enantiomer of 2-benzyloxypropanal103a 107a. 

The employment of silver(i) complexes having a chiral carbene ligand L (Figure 19) and the empirical formula [AgBrL] has been reported for use as both carbene-transfer reagents to the corresponding dichloropalladium(n)... 

Scheme 9.9. Chirality transfer from chiral allenyltitanium reagents.

The intramolecular cyclization of l,2-dien-7-ynes and l,2-dien-6-ynes regiospecifically affords the corresponding titanacycles, which react with protons, carbon monoxide, aldehydes, or imines to give single products, as shown in Eqs. 9.56 and 9.57 [102], As the formation of titanacycles and their subsequent reaction with externally added reagents such as carbon monoxide (Eq. 9.56) or an aldehyde (or imine) (Eq. 9.57) proceeds with excellent chirality transfer, this represents a new method for synthesizing optically active cyclopentane derivatives from optically active allenes [102]. 

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. 

There can be two kinds of chiral tin reagents tin chiral and C-chiral. Early reports of chiral tin hydride involved transfer of chirality via a chiral tin center [45-47]. These tin hydrides were prone to racemization. Thus, chiral carbon-based ligands attached to the tin center were synthesized to minimize racemization. The first chiral tin hydride containing a C2-symmetric binaphthyl substituent was reported by Nanni and Curran (Scheme 16) [48]. a-Bromoketone 58 was reduced by chiral tin hydride 59 (R3 = Me), where the reactivity and selectivity was dependent on the reaction conditions (entry 4). 

Efficient chirality transfer was reported for the reactions of enantiomerically enriched 75 with Grignard reagents [85], Using 10mol% of CuBr or CuCN-2LiBr, the axially chiral allenes 76 are obtained from the centrally chiral 75 with nearly complete chirality transfer (Scheme 3.39). 

The titanium reagents are configurationally stable and react from the 1-endo-conformation with a high degree of iyw-1,3-chirality transfer. As a result the reaction... 

Dimesityldioxirane, a crystalline derivative, has been isolated by Sander and colleagues and subjected to X-ray analysis. The microwave and X-ray data both suggest that dioxiranes have an atypically long 0—0 bond in excess of 1.5 A. Those factors that determine the stability of dioxiranes are not yet completely understood but what is known today will be addressed in this review. A series of achiral, and more recently chiral oxygen atom transfer reagents, have been adapted to very selective applications in the preparation of complex epoxides and related products of oxidation. A detailed history and survey of the rather remarkable evolution of dioxirane chemistry and their numerous synthetic applications is presented in Chapter 14 of this volume by Adam and Cong-Gui Zhao. Our objective in this part of the review is to first provide a detailed theoretical description of the electronic nature of dioxiranes and then to describe the nuances of the mechanism of oxygen atom transfer to a variety of nucleophilic substrates. 

It has recently been shown that when the tetrahedral intermediate of the reaction is cyclic, it is a better donor of nucleophilic CF3. These cyclic intermediates can be generated intramolecularly from trifluoroacetamides or trifluorosulfmamides derived from (9-silylated ephedrine. These reagents are able to trifluoromethylate aldehydes and ketones, even in the case of enolizable substrates, as a strong base is not required (Figure 2.34). However, while the source of CF3 is chiral, there is no chirality transfer to the addition product, and the replacement of ephedrine by other chiral amino alcohols did not show any improvement. " Similar to asymmetric trifluoromethylation with the Ruppert reagent, only the use of a fluoride salt of cinchonine can increase the enantioselectivity. " " ... 

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