Davis oxaziridines

Stojanovic, M. N. (1995). Chemistry of Bioluminescence and Chemiluminescence Dinoflagellate, Fungal and Davis Oxaziridine Systems, Ph.D. Dissertation, Department of Chemistry, Harvard University. 

The next phase of the synthesis was construction of the C-ring. An aldol addition was used to introduce a 3-butenyl group at C(8) and the product was trapped as a carbonate ester. The Davis oxaziridine was then used to introduce an oxygen at C(2). After reduction of the C(3) oxygen, a cyclic carbonate was formed, and C(2) was converted... 

The hydroxyl group in alcohol 122 is then oxidized. Deprotonation of this ketone with KHMDS (1 eq.), followed by the addition of Davis oxaziridine (see Chapter 4 for a-hydroxylation of ketones)28 (2 eq.) allows the stereo-controlled introduction of the C-10 oxygen from the less hindered enolate face, providing only the (i )-hydroxyketone 123. Subsequent reduction of 123 with excess LAH provides the tetra-ol 124. Treatment of this compound with imidazole and TBSC1 followed by PPTS and 2-methoxypropene provides in one operation the acetonide 125 with 91% yield (Scheme 7-37). 

Hydroxylation of 4-oxo-substituted 1,2-thiazine 99 via the racemic Davis oxaziridine reagent 100 afforded alcohol 101 in good yields. Efforts to produce 101 as a single enantiomer with chiral oxaziridine reagents afforded products with only a modest 46% ee (Equation 9) <2002EJP221>. 

Chiral Davis oxaziridines allow the oxidation of phosphonates to a-hydroxy-phosphonates in good ee with apparently wide generality and with a sense of induction that is well controlled by the chirality of the reagent used.109 mCPBA oxidation of a bi-cyclic e do-camphorylsulfonylimine surprisingly resulted in an exo-camphorylsulfonyl-oxaziridine, whereas all other camphorylsulfonylimines resulted only in endo-oxaziiidines.110 Asymmetric oxidation of sulfides to sulfoxides and the a-hydroxylation of enolates were predicted by models in which steric interactions are minimized. 

Enders and coworicers have shown that deprotonation of chiral SAMP/RAMP hydrazones (or their substituted analogs) derived from ketones or aldehydes, followed by reaction with Davis oxaziridine reagent provides the a-hydroxy hydrazones in moderate yield but with high diastereoselectivity. Direct unmasking or protection followed by unmasking provides the corresponding a-hydroxy ketones or aldehydes respectively (Scheme 24). Both antipodes of the hydroxylated compounds are available by appropriate choice of (5)- or (R)-proline-deiived auxiliaries. The direction of induction is predictable, if not wholly uniform (R substitution alters the a-stereochemistry for aldehyde hydrazones). The process clearly provides a valuable approach to both systems. 

Enolate Hydroxylation. Treatment of the sodium enolates with the Davis oxaziridine reagent affords the hydroxylated products with the same sense of induction as the alkylation products (eq 23). Although high diastereoselectivity may be achieved with Oxodiperoxymolybdenum(pyridine)(hexamethylphosphoric triamide) (MoOPH), such reactions proceed in lower yields. 

Davis oxaziridine c) MOMCI, f-Pr2NEt, CH2CI2 d) DIBAL-H e) Swern oxidation, f) PhjP-CHC02Me, CH2CI2 g) NaBH4, THF/ H2O h) TrCl, DMAP, CH2Cb i) NaH, Mel, DMF )) TBAF,THF k) CuBr SMe2, MeLi LiBr,... 

During the highly stereoselective total synthesis of epothilone B by J.D. White and co-workers, the stereochemistry of the alcohol portion of the macrolactone was established by applying Davis oxaziridine oxidation of a sodium enolate. The sodium enolate was generated from the corresponding chiral oxazolidinone derivative, which upon oxidation gave 71% yield of a-hydroxylated compound. 

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. 

Davis oxaziridine oxidation Oxidation of electron-rich substrates (e.g. alkenes, enolates, enol ethers etc.) with oxaziridines. 130... 

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