Lactams, preparation from hydroxy-esters

Another synthetic route to ( )-retronecine (27) has been developed by Vedejs and Martinez.11 The protected hydroxy-lactam (22) was prepared from 2-methoxy-1-pyrroline by known methods. The key ylide intermediate (24) was then generated from the salt (23) by desilylation with caesium fluoride (Scheme 6). This ylide (24) reacted with methyl acrylate in a 1,3-dipolar cycloaddition to afford the unsaturated pyrrolizidine (25) in 57% yield from the lactam (22). Catalytic hydrogenation of the ester (25) gave an unstable endo-product, which epimerized to the exo-form (26). Introduction of the 1,2-double-bond into (26) was carried out by insertion and thermal elimination of a phenylseleno-group.12 Reduction then yielded ( )-retronecine (27). 

Indium enolates, prepared conveniently by transmetalation of hfhium enolates with IriCl j, react wifh aldehydes to give fhe corresponding -hydroxy esters [80]. Ultrasound irradiation promotes fhe Reformatsky reaction of aldehydes and ethyl bromoacetate wifh indium [81]. Indium-mediated Reformatsky reaction of phenyl a-bromoalkanoates wifh ketones or aldehydes gives di-, tri-, and tetrasubstituted -lactones (Scheme 8.57) [82]. Indium-mediated reaction of imines with ethyl bromoacetate gives 3-unsubstituted -lactams (Scheme 8.58) [83]. An indium-Refor-matsky reagent prepared from 2-(chlorodifluoroacetyl)furan couples with aldehydes (Scheme 8.59) [84]. 

Several other interesting synthetic procedures have recently been reported. Thus, j9,y-unsaturated ketones were synthesized from aqueous aUylation of acy-loyl pyrazoles, whereas tertiary alcohols were obtained with acyloyl imidazoles [153]. A variety of j9-hydroxy esters were prepared efficiently by indium-mediated aUylation of aldehydes using 3-bromo-2-chloro-l-propene followed by ozo-nolysis [154]. Highly functionalized )8-lactams were prepared by aUylation of... 

A number of heterocyclic amines has been prepared. The lactam (68), which possesses the pyrrolizidine alkaloid skeleton, was synthesized from Boc-L-prolinal via conversion of an epimeric mixture of N-protected hydroxy esters into a single crystalline amine salt (67) (Scheme 104). Protected pyrrole-2-carboxylic... 

A different approach to the synthesis of the protected hydroxy amino acid moiety was also described by Broady et al (ref.127) (see Scheme 7). Construction was from the IJ-lactam aldehyde (78) prepared from L-aspartic acid. Condensation of (78) with benzyl bis (2, 2,2-trifluoroethyl)phosphonoacetate (79) afforded the (Z)-ester (80) along with a small amount (11%) of (E)-isomer. The hydroxyl substituents were introduced by cis-hydroxylation using catalytic osmylation in the presence of NMO. This reaction was found to be moderately stereoselective and gave a mixture of diastereomers in the ratio ca. 80 20 with the major product being the correct diastereomer (81). The diol group was protected as the... 

Spirofused (3-lactams related to 64 were prepared from 3-hydroxy-3-arylpropanamides after activation of the hydroxyl group by formation of a phosphate ester <97JOC6412>. A similarly easy cyclization occurred when the A-aryl amide 66 was treated with potassium carbonate <97TA739>. Radical induced 4-e.w-trig cyclizations of yV-vinyl-2-bromobutan-... 

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