Benzyl derivatives Davis

The first total synthesis of (-)-fumiquinazoline A and B was accomplished by B.B. Snider and co-workers using a Buchwald-Hartwig Pd-catalyzed cyclization of an iodoindole carbamate to construct the imidazoindolone moiety. In order to set up the stereochemistry at the benzylic position of the indole fragment, the double bond was oxidized with the saccharine-derived Davis oxaziridine in the presence of methanol to give the major diastereomer in 65% yield. 

Alternatively, to avoid difficult separation of diastereomers 18a and epi-18a, the Fmoc-y9 -amino acid of unlike configuration 26 can be obtained as a single dia-stereoisomer in a three-step reaction sequence via conjugate addition of the Li-amide derived from (S)-N-benzyl-l-phenylethylamine (Davies methodology [113]) to tert-butyl tiglate [105] (Scheme 2.3). 

In 2005, the Davies group discovered that the generally reliable catalyst Rh2(DOSP)4 failed to induce high levels of chiral control when benzyl silyl ether derivatives 37 were employed as reaction components. Fortunately, Hashimoto s Rh2(iS-PTTL)4 catalyst showed a superb performance, delivering C—H bond functionalization products 38 in prominent levels of diastereo-and enantioselectivity (up to >95% de and 98% ee) (Scheme 1.11). 

Davies and co-workers also applied a ring-closing metathesis strategy in their preparation of constrained p-amino acid derivatives. Their work employed a chiral auxiliary, S -(l-phenyl-ethyl)-carbamic acid benzyl ester, to achieve the desired P-amino acid derivatives in a stereoselective fashion. Treatment of diene precursors 46 and 48 with 4 mol % of 3 in refluxing dichloromethane provided the corresponding carbocyclic P-amino acid derivatives 47 and 49 in 85 and 35% yield, respectively, with greater than 95% diastereoselectivity in both cases. The diminished yield in the case of 49 is presumably due to sterics effects. 

Phenylsulfonyl)-3-phenyloxaziridine (1S6. Davis reagent. Figure 11.61) has been shown to react with sodium enolates of chiral carboximides of the Evans-Oppolzer type, providing a-hydroxyacyl derivatives with diastereoselectivities of 90-98% d. g 92,133 Subsequent titanium(IV) isopropoxide-mediated transesterification with benzyl alcohol and hydrogenolytic debenzylation releases the free a-hydroxy acids in enantiomerically pure form and in yields of 65-75%. This procedure was applied... 

Davies pioneered a versatile method to prepare chiral /S-amino ester derivatives through diastereoselective conjugate additions of chiral amines onto unsaturated esters [33, 101]. Conjugate addition of lithium amide 103 to acceptor 102 thus afforded an adduct in 82 % yield, and after hydrogenolytic cleavage of the N-benzyl group this provided -amino ester 104 in >98% ee [102]. Such asymmetric amide additions have been demonstrated to have wide substrate scope with respect to the substituents that may be employed on the a,y5-unsaturated esters [33]. 

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