Azetidines, carbonylation

The most informative feature of the IR spectra of azetidin-2-ones is generally the /3-lactam carbonyl absorption, the frequency of which is affected by substitution and by fusion of the ring (c/. Table 3). Thus, IR spectra of simple monocyclic /3-lactams generally have absorption maxima in the region 1730-1760 cm while the fused 2- and 3-cephem systems (60) and (61) show IR maxima in the regions 1772-1784 and 1782-1792 cm S respectively (b-72MI50900 p. 318). 

IR spectra of systems related to /3-lactams show the expected trends in the frequency of the carbonyl absorption, where present. For example, the presence of an exocyclic double bond at C-4 in an azetidin-2-one raises the value of vc=o considerably. Thus the 4-thioxoazetidin-2-one (62 Z=S) and the derived 4-alkylidene systems (62 Z = CR R ) exhibit /3-lactam carbonyl absorptions at 1835 and 1800-1810 cm respectively (80JOC1477, 80JOC1481), while the 4-iminoazetidin-2-ones (63) have vc=o at 1800-1825 cm (81CC41). Additional spectral data for these and similar systems may be found in the references in Table 5. 

There appear to be few examples of the formation of azetidin-2-ones by closure of the C(2) —C(3) bond. One reaction which fits into this category involves reaction of the iron carbonyl lactone complexes (144) with an amine to give the allyl complexes (145) which on oxidation are converted in high yield to 3-vinyl-/3-lactams (146) (80CC297). 

Metal-mediated carbonyl allylation, allenylation, and propargylation of optically pure azetidine-2,3-diones were investigated in aqueous environments.208 Different metal promoters showed varied regioselec-tivities on the product formation during allenylation/propargylation reactions of the kcto-fi-lactams. The stereochemistry of the new C3-substituted C3-hydroxy quaternary center was controlled by placing a chiral substituent at C4. The process led to a convenient entry to densely functionalized hydroxy-ji-lactams (Eq. 8.82). 

As mentioned in chapter 4.2.3, aliphatic imines are photochemically rather unreactive. When the C—N double bond is conjugated to an electron withdrawing group (e.g. carbonyl group), as in O-alkyl derivatives of succinimide and phthalimide, the reactivity increases and azetidines are obtained in cycloadditions to olefins486). A somehow similar example is the photoaddition of a 6-azauracil derivative to 2,3-dimethyl-2-butene... 

Hydroxyazetidin-2-ones can be oxidised efficiently to azetidine-2,3-diones by P205 in DMSO <00JPR585>, and then the 3-carbonyl group can be alkylated stereoselectively by application of the Baylis-Hillman reaction <99TL7537> or by use of substituted propargyl bromides to provide densely functionalized 3-hydroxy-P-lactams . 

The only example known for the formation of azetidine 82 by direct intramolecular aza-Wittig reaction is the reaction of the /3-azidoketone 81 with triphenylphosphane (Scheme 41). Attempts to transfer this reaction to 83 and 84 were not successful (87NKK1250). This failure can be attributed to the formation of intermediates with highly energetic transition states, where the rate of intramolecular attack on the carbonyl function is so slow that oligo- and polymeric compounds are preferentially formed. 

Chlor-ethyl)-l,4-diaryl-2-oxo-azetidine reagieren mit Natriumcyanid in Methanol unter Umlagcrung und Bildung von Pyrrolidinen, z.B. trans-1,2-Diphenyl-3-methoxy-carbonyl-pyrrolidin (65%) bzw. trans-3-Methoxycarbonyl-l-(4-methoxy-phenyl)-2-(3-py-ridinyl)-pyrrolidin (52%)3 ... 

In 2000, the metal-mediated carbonyl propargylation or allenylation of enantio-merically pure azetidine-2,3-diones [211] has been reported to afford stereoselec-tively functionalized 3-substituted 3-hydroxy-(3-lactams (Scheme 95), [212],... 

Scheme 95 Metal-mediated carbonyl propargylation or allenylation of pure azetidine-2,3-diones...

The reaction of 2-/-butyldiphenylsilylmethyl-substituted aziridines and the corresponding azetidine with nitriles and carbonyl substrates have been reported (Scheme 1)... 

Diphenylsilane is compatible with the ester group at C-4 in azetidin-2-ones 203 and reduces only the amide carbonyl group affording azetidin-2-carboxylates 204 (Equation 55) <2004TL2193>. Removal of the />-methoxy-benzyl group from azetidin-2-carboxylates 204 allowed the preparation of conformationally strained amino ester hydrochlorides. 

The /3-lactam carbonyl group transformations have been utilized successfully in the synthesis of azetidine derivatives. The reduction of the carbonyl group in azetidin-2-ones yielding azetidine derivatives is described in Section 2.01.2.8.10. Treatment of jV-BOC-protected 4-(trifluoromethyl)azetidin-2-one 229 with a stabilized Wittig reagent yielded the azetidines 28 and 230 (Equation 61) <20030L4101>. 

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