3- Oxazolin-2-ones reduction

Thioacetyl derivatives (155) are obtained by direct heterocyclization reactions (365. 378, 563) and by a sulfur-oxygen exchange" reaction involving thioacetic acid and A-2-oxazoline-5-one (154) or A-2-thiazoline-5-one (156) (Scheme 81) (365, 378, 379). Ra-Ni reduction of 155 affords the 5-unsubstituted thiazole (379). 

Ring fission occurs readily in many of these compounds. For example, azlactones, i.e. 4JT-oxazolin-5-ones containing an exocyclic C=C bond at the 4-position (508), are hydrolyzed to a-benzamido-a,/3-unsaturated acids (509), further hydrolysis of which gives a-keto acids (510). Reduction and subsequent hydrolysis in situ of azlactones is used in the synthesis of a-amino acids e.g. 508 -> 507). 

The aziridine-2-carboxaldehyde 56 can also serve as synthon for the synthesis of sphingosines, which are important biomembrane constituents [64]. One possible route involves the addition of an alanate to the aldehyde. In a later stage of this synthetic plan the aziridine can be opened, either via the intermediacy of an oxazoline or directly with dilute acid. Unfortunately, the reaction of aldehyde 56 with a vinylalanate has a poor diastereoselectivity of 3 2. Therefore, an alternative approach was considered, namely one involving the addition of a vinylzinc reagent to the aldehyde thereby employing our N-tritylaziridinediphenyl-methanol 51 as the chiral catalyst. Gratifyingly, only one diastereomer was obtained. Reductive removal of the trityl function, acetylation of the hydroxy... 

P,y-Unsaturated ketones. The last step in a synthesis of /J.y-enones involves hydrolysis of a 2-allyl-3-oxazoline-5-one, previously conducted with Ba(OH)2 in variable yield. Recent investigations reveal that treatment with CrfOAclj-HjPOj or reduction with NaBIl4 in TlIE -CIljOH followed by a treatment with citric acid is superior. 

Cyclization of an allyl A-acyl-1 -phenylglycinate (398) with triphenylphosphine, hexa-chloroethane and triethylamine affords a 2-allyl-3-oxazolin-4-one (400) (81AG(E)395, 77AG(E)394). Reductive cleavage of the oxazolinone with chromium(II) acetate and aqueous hypophosphorous acid furnishes a j3,y-unsaturated ketone (Scheme 88). 

Chiral sulfoxides are useful both as intermediates and target molecules of synthetic elaboration. The /J-amino-y-hydroxysulfoxidc moiety is one type of chiral sulfoxide which is the intermediate target in the synthesis of (5 )-(+)-sparsomycin. In the key step in this synthesis, the sought after moiety was produced by asymmetric reduction of an oxazoline using DIBAL, in the presence of zinc chloride and at — 78 °C (equation 79)326. 

The first example of an enantioselective thiadiene cycloaddition involved the reaction of 2,-4-diphenyl- 1-thiabuta-1,3-diene with l-propenoyl-l,3-oxazolidin-2-one. Stoichiometric quantities of a copper triflate bis-imine complex catalyst 428 and 4 A molecular sieves are necessary to achieve the highest enantioselectivity and the best endojexo ratio. The absolute configuration of the major endo isomer was determined by reduction of the acyloxazolidine side chain to the known (3/ ,4/ )-5-hydroxymethyl derivative (Scheme 137) <1997J(P1)2957>. The process is improved using a homochiral Cu triflate or Ni perchlorate bis(oxazoline) complex when catalytic amounts are adequate for a range of thiabutadienes <1999CC1001>. 

With oxazolin-2-one 43 in hand, simple functional group transformations ensued. Thus, mesylation of 43 using methylsufonyl chloride gave mesylate 44, which was followed by an Sn2 displacement with NaN3 to produce azide 45. Reduction of the... 

Pyrazines have been prepared by heating 1,2-dicarbonyl compounds with a-amino acids. Thus Rizzi (308) observed that under the conditions of the Strecker degradation, equimolar amounts of DL-valine (44) and butane-2,3-dione in refluxing bis(2-methoxyethyl) ether, diglyme, gave isobutyraldehyde, tetra-methylpyrazine (9%), and a mixture of cis- and trans-2-isopropyl-4,5-dimethyl-3-oxazoline (4%). He proposed a reductive amination mechanism in which butane-23-dione was converted to 2-aminobutan-3-one which underwent self-condensation to the pyrazine. Tetramethylpyrazine was also prepared when the same reactants were heated in dimethylformamide at 123° for 5 hours (and other pyrazines prepared similarly) (308a). 

Reaction of lithiodithianes with acyl chlorides, esters or nitriles leads to the fOTination 1,2-dicarbonyl compounds in which one of the carbonyl groups is protected as the thioacetal. d76043j44 Optically active amino ketones of type (69) are inepared via acylation of dithiane with an oxazoline-protected (5)-serine methyl ester (Scheme 41). Optically active (5)-2-alkoxy-l-(l,3-dithian-2-yl)-l-propanones were prepaid by the reaction of the corresponding methyl (5)-lactate with 2-lithio-l,3-enantioselective synthesis of (-)-trachelanthic acid. Enantioselective synthesis of L-glyceraldehyde involves the acylation of a dithiane glycolic acid derivative followed by bikers yeast mediated reduction. ... 

The reduction of 2-oxazolin-5-ones (228) with excess NBH results in the cleavage of a C—O bond to afford the amides 229. ° By contrast, the oxazoline moiety itself (230) is stable to reduction by LAH and serves as a protecting group for the carboxylic acid function. However, 2,2 -bis(oxa-zolines) (232) have been recorded in the patent literature as precursors to the amino alcohols 233. ... 

To decrease the number of operations, an obvious remedy is to redefine the route by using different starting materials that require fewer steps to produce the product. Another similar time-saving approach is to carry out more than one synthetic transformation in one step. For example, three double reactions were developed for the benzazepine 7 (Figure 2.9) hydrolysis of a nitrile and an oxazoline, reduction of an amide and an ester/lactone, and cyclization-demethylation [12], Such double reactions save considerable operating time and expenses on scale. 

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