Evans asymmetric aldol

Scheme 5 details the asymmetric synthesis of dimethylhydrazone 14. The synthesis of this fragment commences with an Evans asymmetric aldol condensation between the boron enolate derived from 21 and trans-2-pentenal (20). Syn aldol adduct 29 is obtained in diastereomerically pure form through a process which defines both the relative and absolute stereochemistry of the newly generated stereogenic centers at carbons 29 and 30 (92 % yield). After reductive removal of the chiral auxiliary, selective silylation of the primary alcohol furnishes 30 in 71 % overall yield. The method employed to achieve the reduction of the C-28 carbonyl is interesting and worthy of comment. The reaction between tri-n-butylbor-... 

A key step in the synthesis of the spiroketal subunit is the convergent union of intermediates 8 and 9 through an Evans asymmetric aldol reaction (see Scheme 2). Coupling of aldehyde 9 with the boron enolate derived from imide 8 through an asymmetric aldol condensation is followed by transamination with an excess of aluminum amide reagent to afford intermediate 38 in an overall yield of 85 % (see Scheme 7). During the course of the asymmetric aldol condensation... 

A similar Evans asymmetric aldol/reduction sequence could also serve well in a synthesis of fragment 158. Compounds 161 and 162 thus emerge as potential precursors to 158. In theory, building blocks 161 and 162 could be procured in optically active form from commercially available and enantiomerically pure (+)-/ -citro-nellene (163) and D-mannitol (164), respectively (see Scheme 42). 

We now tum our attention to the C21-C28 fragment 158. Our retrosynthetic analysis of 158 (see Scheme 42) identifies an expedient synthetic pathway that features the union of two chiral pool derived building blocks (161+162) through an Evans asymmetric aldol reaction. Aldehyde 162, the projected electrophile for the aldol reaction, can be crafted in enantiomerically pure form from commercially available 1,3,4,6-di-O-benzylidene-D-mannitol (183) (see Scheme 45). As anticipated, the two free hydroxyls in the latter substance are methylated smoothly upon exposure to several equivalents each of sodium hydride and methyl iodide. Tetraol 184 can then be revealed after hydrogenolysis of both benzylidene acetals. With four free hydroxyl groups, compound 184 could conceivably present differentiation problems nevertheless, it is possible to selectively protect the two primary hydroxyl groups in 184 in... 

The approach for the enantioselective aldol reaction based on oxazolidinones like 22 and 23 is called Evans asymmetric aldol reaction.14 Conversion of an oxazolidinone amide into the corresponding lithium or boron enolates yields the Z-stereoisomers exclusively. Reaction of the Z-enolate 24 and the carbonyl compound 6 proceeds via the cyclic transition state 25, in which the oxazolidinone carbonyl oxygen and both ring oxygens have an anti conformation because of dipole interactions. The back of the enolate is shielded by the benzyl group thus the aldehyde forms the six-membered transition state 25 by approaching from the front with the larger carbonyl substituent in pseudoequatorial position. The... 

A stereocontrolled synthesis of the biologically active neolignan (+)-dehydrodiconiferyl alcohol, which was isolated from several Taxus species, was achieved via Evans asymmetric aldol condensation [58] using ferulic acid amide derived from D-phenylalanine. The reaction steps are shown in Fig. 9. This stereocontrolled reaction is also useful for preparing the enantiomer of (+)-dehydroconiferyl alcohol using chiral auxiliary oxazolidinone prepared from L-phenylalanine. This reaction also enables the syntheses of other natural products that possess the same phenylcoumaran framework. 

If one now considers what would probably be needed in the synthetic direction once aldehyde 5 had been reached, a -selective Evans asymmetric aldol reaction11 with boron enolate 6 could potentially set the C(21) and C(22) stereocentres in 3. All that would be required subsequently would be product liberation from the auxiliary by reduction, and oxidation at C(20). With compound 3 in hand the stage would then be set for implementation of the second Julia olefination tactic. 

T. Nakata et al. developed a simple and efficient synthetic approach to prepare (+)-methyl-7-benzoylpederate, a key intermediate toward the synthesis of mycalamides. The key steps were the Evans asymmetric aldol reaction, stereoselective Claisen condensation and the Takai-Nozaki olefination. The diastereoselective Claisen condensation took place between a 5-lactone and the lithium enolate of a glycolate ester. 

There are also stereochemical considerations here and Holmes used the Evans asymmetric aldol reaction (chapter 27) to make the starting material 174 R=Bn. The formation of any allyl vinyl ether reagent involves no change in the stereochemistry of the allyl alcohol - this is acetal exchange at the vinyl ether or acetal centre. The enol ether was added in masked form as a selenium compound 175 (chapter 32) as selenoxides eliminate at room temperature. The stereochemistry is developed directly from that in 177 as it transforms during the [3,3] shift. 

For their second approach [84], Gurjar et al. have explored an Evans asymmetric aldol reaction, and a regiospecific ring opening of epoxides. They started their synthesis from (2S,3i )-epoxy-alcohol 121, which was prepared from propargyl alcohol 120 in six high yielding steps... 

Since its discovery in 1974, more than 180 papers have been published on the use of the Overmann rearrangement to prepare allylic amines and their analogs from their allylic alcohols. For example, a recent synthesis of the fluoroalkene peptidomimetic precursor of A -acetyl-Z,-glutamyI-Z.-alanine involves the Overman rearrangement of the imidate derived from the allylic alcohol 60. ° This alcohol is readily prepared through Evans asymmetric aldol reaction of oxozolidinone with an aldehyde. 

Further examples of Evans asymmetric aldol method are seen in section 7.2.1. 

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