Cyclization reagent

The acyl residue controls the formation and stability of the carbonium ion. If the carbonium ion is destabilized (by electron withdrawing groups), then cyclization to the phenanthridine nucleus will be sluggish. The slower the rate of cyclization, the greater the chance of side reactions with the cyclization reagent. Therefore, the yield of the phenanthridine will depend on the relative rates of cyclization and side reactions, which is controlled by the stability of the carbonium ion. 

A recent report describes the conversion of A-formyl- and N-acetyl-L-leucine into optically active azlactones with dicyclohexyl-carbodiimide (DCC) [Eq. (29)]. Other cyclization reagents, e.g. acetic anhydride, POCI3, SOCI2, and polyphosphoric acid, cause racemiza-tion. These azlactones react with optically active amino acid esters to give esters of dipeptides with retention of activity. 

For the synthesis of various 2-substituted benzotellurazoles 12, PCI3 instead of POCI3 was used as the cyclizing reagent (88MI1). The yields of 12 are in the range of 30-50%. 

A number of simple reactions are now known which form 2-oxo-tetrahydro-1,3-oxazine (18). Here, also, 3-aminopropanol and some of its derivatives are frequently used, Cyclizing reagents are carbonic acid esters in strongly basic medium, " ethyl chloropropionate, trichloracetic esters, or phenyl isocyanate. An example of the first of these methods is ... 

Hydrazine 835 underwent ring closure with one carbon cyclizing reagents to afford 837 and/or /V-acyl derivatives 836. The N-acyl derivatives underwent cyclization on treatment with phosphorus oxychloride. They were also prepared by the reaction of hydrazones 838 with thionyl chloride (84JHC1565). Compound 835 underwent ring closure with carbon disulfide and ethyl chloroformate to give 839 (Scheme 169). 

Fig. 26 Solid-phase synthesis of indol-2-ones by microwave-assisted radical cyclization. Reagents and conditions a NaH, DMF b BusSnH, AIBN, DMF, MW 170 °C, 45 min, sealed vessel c 10% TFA in CH2CI2. R = H, F, Me, OCF3 R = Phe, 3-OMe - Phe, 4-Me - Phe, 3,4-0CH20-Ph, (CH2)4, diMe R" = H, Me R " = H, Me...

Scheme 92. Synthesis of cu-alpinigenine (445) and alpinigenine (441) by photochemical double cyclization. Reagents a, Mel b, IRA-400 c, A d, NBS, 1 N HO e, HI04, H2S04 f, Av, /-BuOH.

Mode of Cyclization2 Resinb (Final Deprotection) Peptide Cyclization Reagent(s) Detection Method Preferred Reagent Ref... 

An alternative to A-aryl derivatives described above is the use of A-aryl thioureas as the cyclization reagent. In this case, a microwave-assisted reaction gave significantly higher yields of 379o-q from 378o-q <2003BKC1038>. Only a few representative examples are provided here. 

These compounds ( 1) are synthesized from primary o-amino-phenylphosphine and various cyclization reagents, from secondary o-aminophenylphosphines under elimination of an ether and by oxidation or thermal treatment of 1,3-benzazaphospholenes (Scheme 1). In these cyclizations the NH-benzazaphospholes are formed exclusively. This underlines the C=P double bond system in these special cases to be favored over the C=N bond. A PH isomer was never observed. 

The o-phenylendiphosphine which is easily available by reduction of the appropriate benzene phosphonates give similar results on reaction with amide acetales or other cyclization reagents. 

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