Ethers, propargylic Wittig rearrangement

The bis(oxazoline) S, 5)-(115) has been used as an external chiral ligand to induce asymmetric diastereoselective lithiation by r-BuLi during [2,3]-Wittig rearrangement of achiral substrates, (fj-crotyl propargylic ethers.It is believed that the enantios-electivity is determined predominantly at the lithiation step. 

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. 

TABLE 4. [1,4]-Wittig rearrangement of propargyl ether systems... 

Attempts to isolate 1,3-dilithiated propargylic ethers with two equivalents of BuLi at temperatures above -20 give unsatisfactory results, because the dilithio compounds are unstable. In the case of HCsCCH2Or-Bu, HCsCCH(-f-Bu)OH is found after aqueous hydrolysis, possibly as a result of a Wittig-rearrangement [2]. At temperatures below -20 C the dilithiation is too sluggish to be of practical interest. With the super-basic reagent BuLi.t-BuOK in a THF-hexane mixture dipotassiation can be effected in a relatively short time at low temperatures. 

Ether was a better solvent in cases where the propargylic position was unsubstituted (methylene group) since, in THF, a competitive [1,2] -Wittig rearrangement took place and led to diminished yields. When applied to the secondary homoallylic propargyl ethers 388, the zinc-ene-allene cyclization afforded the c -2,3,5-trisubstituted tetrahydrofurans 389 with moderate to satisfactory levels of diastereoselectivity, which could be rationalized by the preferential pseudo-equatorial positioning of the homoallylic substituent in the cyclic... 

Wittig Rearrangements of propargyl ethers can afford allenic alcohols, but the scope is relatively limited and the process is not general. 

Sigmatropic Wittig rearrangement of macrocyclic allyl propargyl ethers to carbocycles 91TA1. 

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. ... 

Still-Wittig rearrangement of the nonracemic (/ )-propargylic ethers (100a) and (100b) has been found to give the (/ )-allenes (100c) and (lOOd) with complete asymmetric transfer (equation 25a). The stereochemistry is consistent with a five-membered cyclic transition state. 

Table 5 2,3-Wittig Rearrangement of Allyl Propargyl Ethers...

Scheme 6 Envelope transition states for 2,3-Wittig rearrangements of propargyl allyl ethers...

Table 7a 2,3-Wittig Rearrangement of Nonracemic Allylic Propargylic Ethers Derived fiom (5)-Lactaldehyde. OSiBu Me2...

In connection with studies on chirality transfer in 2,3-Wittig rearrangements, Tsai and Midland examined the ( )- and (Z)-( )-l-isopropyl-2-butenyl benzyl ethers (131 equation 32) and (135 equation 33). Both ethers rearranged with essentially complete suprafaciality, but the (Z)-isomer (135) showed considerably higher ( )/(Z) and synlanti selectivity in accord with transition state considerations previously discussed for the analogous propargylic ethers (Scheme 7). 

Wittig rearrangement of a-allyloxycarboxylic acid dianions and allyl propargylic dianions (Section 3.11.3.3) might be expected to proceed analogously. In fact, the same high preference for ( )-pro-ducts is observed, but the diastereoselectivity is reversed (Table 17, entries 5 versus 6). A chelated bicyclo [3.3.0] transition state readily explains the anti selectivity of (Z)-allylic ethers [Scheme 12, compare (R) with (T)]. The basis for syn selectivity observed with ( )-allylic ethers (Q) versus (S) is less clear. 

Allyl propargyl ethers are also good substrates for the Wittig rearrangement. Deprotonation of the propargyl position is relatively facile. 

Wittig rearrangements of alkynyl ethers follow the stereochemical trends demonstrated by other w-donor-stabilized substrates, and simple diastereoselection is typically excellent for both E- and Z-substrates 37 " 39. Propargyl-stabilized anions of E- and Z-crotyl ethers 27 exhibit high levels of simple diastereoselection. 

Entry 1 was the first example, reported in 1970 [40], of a highly stereoselective [2,3]-Wittig rearrangement, but comparison with entry 5 shows that only the Z isomer is selective. Entries 2-4 illustrate substituted propargyl Z allyl ethers. 

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