Cyclic derivatives, cyclization tables

Table 1.5 summarizes the studies on cyclics of poly(di-methyl siloxane) and derivatives, and Table 1.6, those of other polymers. In these tables, refers to the molar cyclization equilibrium constant and RIS, to the rotational isomeric state scheme to analyze chain conformations. 

Because of the chelate control of the process, allylamides such as 129 react under hydroformylation conditions to give mainly the branched aldehyde 131, together with cyclic derivatives 132 and 133 (Table 5) [82, 83]. Products 132 and 133 are formed from the linear aldehyde through a sequence of reactions involving cyclization to give the enamide 134, followed by hydrogenation or hydroformylation, respectively [84]. 

Vinylpyrrole 27a is treated with alcohol solutions of secondary amines (refluxing, 4 h) to give the corresponding aminopyrrolizines (56%-89% yields. Scheme 2.99, Table 2.11) [573,574]. It is shown [574] that the first stage of reaction involves cyclization of pyrrole 27a into iminopyrrolizine 28a followed by the substitution of the ethylthio group in cyclic derivative. Such reaction route is supported by direct synthesis of aminopyrrolizines from pyrrolizine 28a and secondary amines. 

Table 6 O-Cyclization of Derivatives of Cyclic Allylic Alcohols and Amines Entry Ref.

Cyclizations of chloral hemiacetal derivatives of cyclic allyl alcohols were regio- and stereo-selective (Table 6, entry 1), but a mixture of regioisomers was obtained from analogous derivatives of acyclic allyl alcohols with a nonterminal double bond.93 Hemiacetal derivatives of allyl alcohols with a terminal vinyl group have been cyclized with mercury(II) acetate to give acetal derivatives of threo 1,2-diols with moderate selectivities (equation 54 and Table 15, entries 1 and 2).147 Moderate to excellent stereoselectivity has been observed in the iodocyclizations of carbonate derivatives of allyl alcohols (entries 3-5).94a The currently available results do not provide a rationale for the variation in observed stereoselectivity. 

The cholates 8.117-8.119 were designed for the preparation of dynamic hbraries with different binding affinities for alkah metal ions. The presence of a polyether chain in position 7 of 8.117 provided a recognition element for metal binding that was absent from the disubstituted p-methoxybenzyl substitution pattern of 8.118, while the 7-deoxy derivative 8.119 was even less prone to metal coordination. The three monomers were submitted to transesterification/cyclization protocols, either without metal templates or using different alkali metal salts as templates. The relative abundances of cyclic dimers, trimers, tetramers, and pentamers for each experiment are reported in Table 8.7. 

Both cyclic and acyclic enone systems participate in the (trimethylsilyl)cyclopentene annelation (Table 6). a-Methylene ketones react to form spiro-fiised systems and the intermediates derived from ace-tylcyclohexanone, cyclohexenone and cyclopentanone cyclize to yield S,S- and 6,3-fiised ring systems. ... 

Simonet and coworkers described the formation of (i,/-hydrodimers and cyclic enam-ines when 3-(2-furyl)propenenitriles were electrochemically reduced at a Hg cathode in aqueous EtOH or DMF, under controlled potential (Table 15). The stereoselective formation of the cw-cyclopentene derivative by exclusive cyclization of the me o-hydrodimer and the lack of reactivity toward cyclization of the (i,/-hydrodimer were best explained by a preferential adsorption on the cathode of the former. It is worth mentioning that the trans-enamine was obtained when the /-hydrodimer was treated with sodium r-butoxide in t-butanol. 

Further, we cyclized the methyl group on the nitrogen with the CH2 of the ethoxy linker to form a hve- or six-membered ring (Scheme 19.4) to obtain compounds that showed activity superior to that of their parent molecules. The synthesis of these molecules is outlined in Scheme 19.5. The activity of these compounds to reduce blood glucose and triglyceride in db/db mice is shown in Table 19.2. It is observed that the cyclic linker moiety improved the antidiabetic activity of the compounds compared to the N— Me ethoxy linker. The unsaturated analogs showed better activity than that of their saturated counterparts. Benzyl-protected compounds have been found to be better than free OH compounds, despite losing antioxidant activity. Further, the benzopyran moiety in these molecules were shrunk to dihydrobenzofuran and benzofuran derivatives, which showed modest antidiabetic activities. 

The intramolecular cyclization of ureas derived from 3-hydroxy-4-pentenylamines and 4-hydroxy-5-hexenylamines was also investigated (Table 5)3 From these (chiral) substrates two different products can arise because the intermediate Pd-acyl species can either react with the hydroxy group to form a lactone or with the nitrogen function to form a cyclic urea derivative. The selectivity was found to depend both on the substrate and on the acidity of the solvent (MeOH or AcOH). 

Resin 23 was first swollen in CH2CI2 and, in a manner that parallels the route employed in the solution-phase synthesis, was reacted with a selected benzylsulfonyl chloride and t-BuOLi as a base to afford the corresponding sulfonamide resin 28, containing the first diversity element R. The sulfonamide resin 28 was then reacted under Mitsunobu conditions (PPha (triphenyl phosphine), DIAD (diisopropyl azodicarboxylate), THE, room temperature) with the appropriate alcohols. This process efficiently produced resin 29 and introduced the second diversity element R. Cyclization reaction of resin 29 was promoted by sodium hydride in DMF and led to the formation of the desired thiazolo[4,5-c] [l,2]thiazine resin 30. Treatment of resin 30 with mCPBA in CH2CI2 generated the resin-bound cyclic sulfonamide 31. Finally, the thiazolo[4,5-c][l,2]thiazine derivatives 5 were formed and cleaved from the resin (in a traceless manner" ) by treatment of resin 31 with the corresponding amines (R R" N diversity elements) in respectable yields (34 examples, from 11% to 29% for seven linear steps starting with Merrifield resin 1, Table 10.4). 

---