Enantioselectivity 1,2 -Wittig rearrangements

The enantioselective [1,2]-Wittig rearrangement of various ethers using this protocol [t-BuLi (2.0 equiv.)/5 (2.0 equiv.)] is summarised in Table 2. 

A single report on enantioselective [1,2]-Wittig rearrangements was published by Tomooka and Nakai in 1999. A chiral bis-oxazoline ligand was employed to facilitate asymmetric lithiation/rearrangement of dibenzyl ether and benzyI(propargyl) ether derivatives with enantioselectivities ranging from 40-65% ee. In a representative transformation, treatment of 61 with -BuLi and bis-oxazoline 62 led to the formation of 63 in 86% yield and 60% ee. 

Transient enantioenriched 1-lithio-l-alkoxyalkynides have been generated via lithiodestannylation by Nakai for enantioselective Wittig rearrangements [247] (s. a. Hodgson et al, in this volume). 

The pioneering work on enantioselective [2,3]-Wittig rearrangement was carried out by Marshall and Lebreton in the ring-contracting rearrangement of a 13-membered cyclic ether using lithium bis(l-phenylethyl) amide (63) as a chiral base (equation 34). Upon treatment with a (S,S)-63 (3 equivalents) in THF at —70 to —15 °C, ether 64 afforded the enantioenriched [2,3]-product 65 in 82% yield with 69% ee. The reaction was applied in the synthesis of (+)-aristolactone (66). 

A high level of enantioselectivity in an acyclic system has been reported in the rearrangement of tricarbonylchromium(O) complexes of allyl benzyl ethers using chiral lithium amide base 73 (equation 38) . Upon treatment with 1.1 equivalents of lithium amide 73 and 1 equivalent of LiCl at —78 to —50°C, ether 74 afforded the rearrangement product R)-75 in 80% yield with 96% ee. The effect of substituents on the chemical yields and enantioselectivity of the [2,3]-Wittig rearrangement was also studied (see Table 3). 

Norpseudoephedrine-derived amino ether 81 was also used as a chiral coordinating agent for the enantioselective [2,3]-Wittig rearrangement. The rearrangement of propargyl ether 82 induced by n-BuLi/81 provided allenyl alcohol (5 )-83 in 62% ee (equation 45). In contrast, a similar reaction with (-)-24 provided only 9% ee of (S)-S3. 

Chiral bis(oxazoline) 27 is an effective chiral coordinating agent for enantiocontrol in the [2,3]-Wittig rearrangement. The rearrangement of (Z)-crotyl benzyl ether 84 with f-BuLi/(5, 5)-27 (1.5 equivalents each) in hexane provided [2,3]-shift product (l/ ,25 )-85 in 40% ee (equation 46The feasibility of the asymmetric catalytic version was also examined. In this case, the rearrangement with 20 mol% of 27 in ether was found to provide the same level of enantioselectivity (34% ee). 

The enantioselective [2,3]-Wittig rearrangements are grouped according to the structure of substrate in Table 3. 

Enantioselective deprotonation to yield a configurationally defined organolithium offers great potential for future asymmetric [2,3]-Wittig rearrangements. The first steps in this area were taken by Nakai and Tomooka, who treated 182 with r-BuLi in the presence of the bis-oxazoline ligand 114. The product 183 is formed in 89% ee.133... 

Treatment of the (.V)-( A )-[(.svr-allylo y )dimcsitylsilyl]stannanc with -BuLi provides a (R)-(.E)-allylsilane with high enantioselectivity, in which 1,3-chirality transfer occurs during the [2,3]-sila-Wittig rearrangement (Equation (118)).290... 

Chiral lithium bases have been used for enantioselective deprotonation to yield configurationally stable a-oxy carbanions. This holds potential for asymmetric [2,3]-Wittig rearrangement in stereoselective synthesis. Thus, treatment of propargylic ether 72 with (S,S)-3 in THF at — 70 °C to —15 °C afforded propargylic alcohol 73 in 82% yield and in 69% ee of the shown enantiomer96,97. This product was successfully employed as a precursor of (-l-)-Aristolactone (Scheme 55). 

Other Enantioselective Reactions. Enantioselective epoxide elimination by chiral bases has been demonstrated. More recently, the enantioselective [2,3]-Wittig rearrangement of a 13-membered propargylic ally lie ether has been performed using the lithium amide of (f ,f )-(l) as the base for deprotonation (eq 15). For this particular substrate, THF is a better solvent than ether, although pentane produces better results in a related transformation (eq 16). In fact, a change in solvent in this type of reaction has been shown to lead to a reversal of the stereoselectivity of the transformation. ... 

More recently, bisoxazolines were studied as ligands in [2,3]-Wittig rearrangements (up to 89% ee) [46] these ligands were also effective in a catalytic maimer [47]. Bisoxazoline 30 provides remarkably high enantioselectivity in the benzyhc lithiation-electrophile trapping reactions of benzyl methyl ether, iso-chroman and phthalan (up to 97% ee) (e.g.,Scheme 15) [48]. 

This type of carbanion rearrangement is recognised to proceed by means of a radical dissociation-recombination mechanism. In 1983, Mazaleyrat and Wel-vart reported the kinetic resolution of a racemic binaphthyl ether, which involves an enantioselective variant of the [1,2]-Wittig rearrangement [Eq.(2)j [3]. 

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