Diastereoselective 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. 

It has been shown that the tri-n-butyltin group can control the diastereoselection of an aza-[2,3]-Wittig rearrangement, and the silicon-assisted aza-[2,3]-Wittig rearrangement of crotyl-type amines has been used to furnish each diastereoisomer of the... 

As an extention of these studies, Maleczka and Geng have investigated a chelation effect in the diastereoselective [1,2]-Wittig rearrangement where a lithium-bearing terminus is enantiomerically defined. ... 

The acetal [1,2]-Wittig rearrangement protocol is also applicable to the synthesis of medium-sized cyclic ethers. For example, a reaction of the 9-membered cyclic acetal 37 with lithium piperidide provides the 8-membered ring ether 38 in good yield along with high diastereoselectivity (equation 20) . 

This [1,4]-Wittig rearrangement system is applicable to the sequential [l,4]-rearrange-ment/aldol reaction which provides -hydroxy ketones with moderate diastereoselectivity (Table 4). 

Chiral Substrates with Other Achiral Reagents Diastereoselective Claisen Rearrangement and Wittig Reactions... 

Diastereoselective [2,3] Wittig rearrangement of propynyloxyacetic acids and esters has recently been reported95 and leads to allenic esters with d.r. in excess of 90 10 [(S,M)/(7t,Af)] for the examples shown. 

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... 

As described above, the desired compound 17 with high degree of anti selectivity could be obtained from the starting materials, propargylic alcohols in only three steps. Thus,ester-enolate [2,3]-Wittig rearrangement can be considered as one of the most attractive synthetic methods for new types of trifluoromethyla-ted intermediates. However, switching of ( )- and (Z)-substrates did not lead to the diastereoselective construction of the different stereoisomers. The next... 

Hoffmann, R. Ruckert, T. Bruckner, R. [1,2]-Wittig rearrangement of a lifhioalkyl benzyl ether with inversion of configuration at the carbanion C atom. Diastereoselective reductions of cydohexyl radicals with Li arerie. Tetrahedron Lett. 1993, 34, 297-300. 

A diastereoselective imino [1,2]-Wittig rearrangement of allyl hydroximates provides for the preparation of optically active a-hydroxy oxime ethers when R3 is designed (g) as shown to participate in the reaction (Scheme 5).8... 

Wittig rearrangement has been used in a diastereoselective total synthesis of the triester of viridiofungin.10 The Wittig rearrangement of 17(20)-ethylidene-16- (g) furfuryloxy steroids (8) has provided natural and unnatural 22-hydroxy steroids (9), (10), and (ll).11... 

Sin, N and Kallmerten, J, Diastereoselective [2,3] Wittig rearrangement of carbohydrate-derived tertiary aUylic ethers. 2. Synthesis of an advanced rapamycin intermediate from D-glucose, Tetrahedron Lett., 34, 753-756, 1993. 

Scheme 11 Transition states rationalizing the diastereoselectivity of Wittig rearrangements with EWG = acyl...

A thia-Wittig rearrangement in the methylenecyclopentane (154) proceeded to (155) without formation of the epimer (equation 45). Obviously, the reaction proceeds on the less hindered (convex) face of the bicyclic framework. Equally high diastereoselectivity — unassigned, but presumably also on the less hindered (exo) face — is recorded for the 2,3-rearrangement of a methylenecyclopentane-derived sulfur ylide. ... 

Hauser noted that diallyl ether (8) also undergoes Wittig rearrangement upon base treatment and suggested that product formation could involve either a 1,2-shift or a cyclic mechanism (equation 3). Later studies by Schdllkopf and Makisumi with substituted allylic ethers (10,11 and 14-16 equations 4 and 5) pointed to a cyclic (SnO mechanism a process allowed by the Woodward-Hoffmann rules. The diastereoselectivity of the reaction was not determined in these cases, but Schollkopf subsequently found that benzyl rrans-crotyl ether (20 equation 6) affords mainly the anti products upon rearrangement of ether (20) with BuLi in THF. Rautenstrauch observed a 1 1 mixture of syn and anti products upon rearrangement of ether (20) in the presence of TMEDA, whereas the cis isomer (23) gave only the syn product (22 equation 7). ... 

In the first purely synthetic application of the reaction, Schreiber employed the 1,2-Wittig rearrangement to synthesize 1,3-diol monoethers (equation 15). The syn products (56) were obtained in 14—32% yield with 90-95% diastereoselectivity (Table 3). The 1,4-product (57) was found to predominate at low temperature, whereas at 0 °C the 1,2-product was favored but the absolute yield did not increase. 

A novel approach to stereocontrol in 2,3-Wittig rearrangements involves the use of chiral chromium tricarbonyl complexes (Table 8a). The reactions, which were carried out with racemic ethers, show excellent diastereoselectivity as a consequence of a preferred transition state in which the benzylic oxygen and the R -substituent and the vinylic grouping and Cr(CO)3 grouping adopt anti orientations (Lc). 

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. 

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