Lactams from furans

Grigg s group synthesized a unique bicyclic P-lactam 108 via an intramolecular Heck reaction from 107 [87, 88]. The 7-membered ring was formed via an unusual insertion at C(3) of furan, an aromatic rc-system. 

A concise synthesis of highly substituted furans, pyrroles, butenolides, and 2-butene-4-lactam esters starts from alkynyl adducts of a Fischer carbene complex 21 (Scheme 27) < 1998JOC3164>. Incorporation of an aldehyde yields a reactive vinyl tungstencarbonyl complex 22 that can be oxidatively transformed to an ester group, furnishing the furan carboxylic ester 23. 

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]. 

Furans. The reagent activates thioacetal function by methylthiolation. It induces cyclization of thioacetals derived from carbonyl compounds (including lactones and lactams) and bis(methylthio)acetaldehyde via aldol reaction and acetylation. 

Intramolecular reaction of the vinyl triflate with benzo[ ]furan in 7 is a key step in the preparation of the synthetic intermediate 8 of (—)-frondosin A [5], Intramolecular reaction of the iodide with furan in 9 gave the tetracyclic jS-lactam 10 containing furan ring in the presence of TI2CO3 as a base. The rather unusual C-3 substitution occurs in the reactions of 7 and 9, because the C-2 positions are blocked [6], If the cyclizations of 7 and 9 proceed similar to Heck-type carbopalladation and f-H elimination, direct syn y3-H elimination is not possible, and isomerization from anti to syn, followed by syn y3-H elimination should occur. Therefore, direct electrophilic substitution may be a better explanation. 

Ozonolysis causes usually in other furan containing natural compounds the loss of C H 0 unit from the molecule and a carboxylic group is formed. It can be assumed that in the NTBN molecule the positively charged nitrogen atom withdraws the electrons from the furan ring so the C4 - Cll bond bears some olefinic character. This bond could be attacked by ozone molecule in the subsequent reaction step and quinolizidone derivatives are formed. X-ray analysis of NTBN bromohydride shows that C4 - Cll bond is really shortened. In the next reaction step lactam rings could be cleaved by acid in ethanol and corresponding esters are formed. The C-15 compounds are presumably formed via sulfenic acid intermediate. 

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