1.2- Oxazine derivatives, asymmetric synthesis

Asymmetric synthesis of a,a-disubstituted a-amino acids via an intramolecular Strecker synthesis using l,4-oxazin-3-one derivatives as key intermediates 97YGK982. 

With the increasing demand for chiral nonracemic compounds, stereoselective methods for the synthesis of 1,3-oxazine derivatives and applications of enantiopure 1,3-oxazines in asymmetric transformations have gained in importance in the past decade, as reflected by the increasing trend in the number of publications on this topic, and accordingly by the share of this topic in the present compilation. The limited size of this survey and the scope of this chapter do not allow a discussion here of the applications of 1,3-oxazines in polymer chemistry and the synthesis and properties of 1,3-benzoxazine-containing hetero-calixarenes. 

N-Acylimines which may react as l-oxa-3-aza-l,3-butadienes represent a class of heterodienes which exhibit a close relationship to l-thia-3-aza-l,3-butadienes [13]. A very impressive application of such an l-oxa-3-aza-l,3-butadiene has been worked out by Swindell et al.[445]. The asymmetric hetero Diels-Alder reaction described therein opens a very elegant approach to the A-ring side chain of taxol. This synthesis takes advantage of the bulky chiral auxiliary attached to the dienophile 6-5 which upon cycloaddition with the l-oxa-3-aza-1,3-butadiene 6-4 yielded the 1,3-oxazine derivative 6-6. Subsequent hydrolysis, hydrogenolysis and transesterification gave the methyl ester of the taxol A-ring side chain 6-7 in good endo and excellent zr-facial selectivity (Fig. 6-2). 

Alder reaction [524, 525]. Danishefsky et al. have used nitroso dienophiles for the synthesis of mitomycin K and antibiotics of the FR 900482 family, the latter ones are structurally unique aziridino-l,2-oxazine derivatives [526-529]. An approach directed to the cephalotaxus alkaloids has been worked out by Fuchs et al. [530], and several indolizidine alkaloids have been prepared by Keck s [531] and Kibayashi s groups [532,533]. Kibayashi et al. also synthesised Nuphar piperidine alkaloids in enantiomerically pure form by means of an asymmetric nitroso Diels-Alder reaction [534]. 

An intramolecular cycloaddition reaction results in the simultaneous formation of two new rings. Examples include the formation of a tetrahydroquinoline derivative (Section 4.4.2.3.4), the asymmetric synthesis of 1,2-oxazine derivatives (Section 4.3.2.4.2), and the preparation of a hcxahydrothiazino 2,3vz]quinolinc (Section 4.6.3.4) by intramolecular... 

Chiral nitroso dienophiles (e.g., 136) useful for asymmetric synthesis of 1,2-oxazine derivatives via the intramolecular DielsAlder reaction have been developed (Scheme 70) <1994S1107>. 

Betti later reported that ammonia was also a suitable reaction component when 2 equiv of benzaldehyde are used (followed by HCl treatment to hydrolyze the initial product—the imine/oxazine derivative of the Betti base, see 7.1.5)/ In addition to his work on the reaction that now bears his name, Betti also studied the relationship between molecular constitution and optical rotatory power and is thus considered a pioneer in the field of asymmetric synthesis. In 1939 he was appointed as the senator of the Kingdom of Italy. 

Azomethine ylides derived from (55,6/ )-2,3,5,6-tetrahydro-5,6-diphenyl-1,4-oxazin-2-one (53) and various aldehydes have been prepared by Williams and co-workers (87,88) (Scheme 12.19). In a recent communication they reported the application of the azomethine ylide 54 in the asymmetric total synthesis of spirotryprostatin B 56 (88). The azomethine ylide 54 is preferentially formed with ( )-geometry due to the buLkiness of the aldehyde substituent. The in situ formed azomethine ylide 54 reacted with ethyl oxindolylidene acetate to give the 1,3-dipolar cycloaddition adduct 55 in 82% yield as the sole isomer. This reaction, which sets four contiguous stereogenic centers, constmcts the entire prenylated tryprophyl moiety of spirotryprostatin B (56), in a single step. 

---