1.2- Oxazine ring, tetrahydro- from

Hydrolytic reactions can also be applied in the synthesis of aldehydes or ketones via the corresponding 1,3-oxazine derivatives. The anion formed from 3-methyl-2-(4-pyridyl)tetrahydro-l,3-oxazine 155 on treatment with BuLi proved to react with various electrophiles (alkyl halides, carboxylic esters, acid chlorides, or aldehydes) exclusively at position 2 of the 1,3-oxazine ring and not at the pyridine nitrogen atom. The readily formed 2,2-disubstituted-l,3-oxazine... 

Tetrahydro-l,2-oxazine ring from ethylene derivs. and a-diloronitrones... 

The stereodynamics of /V-siloxy-ene- nitroso acetals related to 3-alkylen-substituted 4//-tetrahydro-1,2-oxazines (e.g., see (416 d)) differs from that of BENA in that free rotation about the C,N bond in oxazines cannot occur, but the ring inversion should take place (process Ir) (see Scheme 3.228). 

Enantiomerically pure tetrahydro-l//-pyrrolo[2, l -acrylamides derived from proline (see Section 11.11.7.4), are versatile intermediates for the synthesis of natural products or drugs. Compound 86a was submitted to debromination with Bu3SnH followed by ring opening in KOH and further reduction with BHj to give diol 89 that was then easily transformed into (A)-4-(2,2,4-trimethyl-l,3-dioxolan-4-yl)-lT>utanol 90, a key intermediate for )-frontalin, <2002TA155>,... 

The simplest and most commonly used method for the synthesis of tetrahydro-l,3-oxazines is the ring closure of the corresponding 1,3-amino alcohols with oxo compounds [80H(14)1333]. The parent ring system is known merely in the case of 3,1-perhydrobenzoxazines 18 cis or trans R = H, Ph) it was prepared from cis- and rrans-2-hydroxymethyl-l-cyclohex-... 

To increase the yields of the ring closure reactions, a new method was developed that was successfully applied for the synthesis of alicyclic fused systems of both the parent oxazolidine-2-thione and tetrahydro-1,3-oxazine-2-thione (85S1149). As an example, the synthesis of 2-thioxoperhydro-l,3-benzoxazine 103 is described. The dithiocarbamate 101, prepared from the amino alcohol 100, carbon disulfide and triethylamine, was treated with ethyl chloroformate in the presence of triethylamine, to give the thioxo derivative 103 via the transition state 102 (85S1149). In this way, the fused-skeleton thioxooxazines (91, X = S, 92) can be prepared with considerably higher yields (50-70%) than by the earlier methods (85S1149). 

The acetic anhydride-induced cyclodehydration of the symmetrical diamide 411, derived from the tetrahydro-benzothiophene / -amino ester 410 and diethyl malonate, afforded the thieno[2,3-r7 [h3]oxazine derivative 413 rather than the expected bis-oxazine 412 (Scheme 78). The reaction probably takes place through sequential cyclizations, in which the pyridine ring of 413 is produced by condensation of the exocyclic double bond of the enamine tautomeric form of the 1,3-oxazine moiety and the mixed anhydride formed by the carboxylic group and acetic anhydride <2003PS245>. 

H-NMR variable-temperature studies of 2,5-dimethyltetrahydro-l,2,5-oxadiazine351-354 established a high energy barrier process (AG 14.4 + 0.1 kcal mol-1 and AS —1.2 + 0.4 kcal mol-1) comparable to that in N-methyltetrahydro-l,2-oxazine. From studies of a deuterated tetrahydro-1,2-oxazine, it was concluded that this should be attributed to slowing of 2-AT-Me inversion rather than ring reversal.353... 

The ring opening of tetrahydro-l,3-oxazines to aldehydes has recently found wide application through the work of Meyers.2-3 2-Alkylidene-tetrahydro-l,3-oxazines, prepared from the readily available 5,6-dihydro-4//-1,3-oxazines, possess strong nucleophilic properties and can react with alkyl halides and carbonyl compounds. The derivatives so obtained can be reduced to tetrahydro-l,3-oxazines, and through ring opening the latter can furnish acyclic, alicyclic, and a,jS-unsaturated aldehydes and their C-l deuterated derivatives.221-223 228... 

Preparative details for passing from dihydro- to tetrahydro-1,3-oxazines followed by ring opening have been given.241,242 The methods have been used to synthesize systems related to natural products243 including those with a pyrrole ring.244-248... 

Photolytic or thermolytic cleavage of the N-0 bond of tetrahydro-1,2-oxazine-3,6-diones (407), followed by decarboxylation, gives intermediate 1,4-diradicals (408) which close to form 3-lactams (409), albeit in poor yields. Diradical intermediates analogous to (408) may be formed in the biosynthesis of isopenicillin N from trlpeptide precursors. In a similar vein, Easton has published full details of the synthesis of 3-lactams by ring contraction of isothiazolidinones, a reaction which may also be relevant to... 

Conventional methods have been used to prepare ribonucleoside analogues from 2-(l//)pyrazinone, 3,5-disubstituted pyridines (including a-anomers), 6-methyl-l,3-oxazine-2,4-dione and 6-methyluracil, 2-alkyl-4,5-dicarboxamido-imidazoles, 7-membered ring analogues (4) and (5) of uracil and tetrahydro-uracil [one diastereomer of (4) being the most potent inhibitor of cytidine deaminase yet discovered], 2-alkylthioadenine, 8-aza-3-deaza-guanine/ ... 

Functionalization of methyl groups Tetrahydro-l,3-oxazin-2-one ring from azidoformic acid esters... 

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