Urethanes vinylogous

Ultraviolet absorptions ofvinylogous lactams were found by MOLCAO calculations and compared with experimental values (663). Infrared spectroscopic studies of vinylogous amides (664) and some fifty vinylogous urethanes (665) allowed configurational and structural assignments. The effect of enamine-imine equilibrium in a series of benzophenone derivatives was established (666) and the effect of structure on enamine basicity studied (667). 

The acylation of enamines derived from cyclic ketones, which can lead to the acyl ketone or ring expansion (692-694), was studied by NMR and mass spectroscopic analysis of the products (695,696). In a comparative study of the rates of diphenylketene addition to olefins, a pronounced activation was observed in enamines (697). Enamine N- and C-acylation products were obtained from reactions of Schiff s bases (698), vinylogous urethanes (699), cyanamides (699), amides (670,700), and 2-benzylidene-3-methylbenzothiazoline (672) with acid chlorides, anhydrides, and dithio-esters (699). 

The reactions of vinylogous amides and vinylogous urethanes with excess ketene were found to give a-pyrones (421), which could also be obtained from further reactions of acylated enamines with ketene (383,421). 

Rearrangements of vinylogous urethanes to vinylogous carbonic acids and decarboxylation are other interesting enamine rearrangements which may be synthetically useful in the formation of cyclic enamines (623,624). 

Reaction of aniline derivatives with 4-chlorobutyroyl chloride followed by cyclization with sodium ethoxide and subsequent thionation promoted by sonication gave the corresponding A -arylpyrrolidine-2-thiones 126. Zinc-mediated condensation of diethyl bromomalonate with 126 using iodine as activator gave the vinylogous urethanes 127 whose cyclization with PPA gave the tricyclic compound 128 which upon hydrolysis afforded the acid 129 (96TL9403). 

When the enolate of an ,) - or a /j,y-unsatunited amide is used, it can react in an a or in a y fashion with a,/i-unsaturated esters, however, in most cases only a-selectivity is observed. Using l-(l-oxo-2-butenyl)pyrrolidine and lithium diisopropylamide at — 78 °C in a THF/HM-I A mixture (1 1), high. syn-selective formation of 3-alkyl-5-oxo-5-(l-pyrrolidinyl)-4-vinylpen-tanoates is achieved78,381 382. Related syn- or anti-selective additions of a vinylogous urethane also are known79. 

Bicyclic 2-pyridones fused over the nitrogen is another important heterocyclic scaffold. In the quest towards the total synthesis of Camptothecin, Danishefsky and co-workers developed a method where a vinylogous urethane was reacted with 1,3-dicarboxymethoxyallene generated in situ from dimethyl 3-chloroglutaconate to a bicyclic 2-pyridone intermediate [31-34]. This method has later been successfully applied in the synthesis of other... 

Diastereoselective synthesis of lactones.1 Acylation of the enolate (LDA) of the vinylogous urethane (1) results in a product (2) that on reduction with LiBH[CH(CH3)C2H5]3 (3) forms the anft-lactone (4) exclusively (equation I). This two-step synthesis of lactones is the equilvalent of an aldol condensation between... 

Selective reduction of esters.1 Sodium borohydride does not usually reduce esters, but it can reduce normal esters slowly in CH3OH. This reaction has been used to reduce a normal ester selectively in the presence of a vinylogous urethane. Thus the methylene group of the enamine (E)-l, formed from dimethyl acetone-... 

Interesting rearrangements proceed upon refluxing the azido diene 105 in benzene solution and form 61% of the vinylaziridine 106 as a mixture of diastereoisomers and the vinylogous urethane 108 (28%) (equation 37)53. It was shown that the process 106 - 108 occurs entirely at elevated temperature (refluxing xylene, ca 140 °C). However, treatment of the aziridine 106 with p-toluenesulfonic acid in THF at room temperature gives rise to trans,trans-, 3-butadiene carboxylic ester 107 in 98%53. 

Chlorination of these vinylogous urethanes 152 with r rt-butylhypochlo-rite, followed by reaction with silver tetrafluoroborate and protonated vindoline, at or below room temperature, provided almost exclusively coupling products 157 and 158 with the desired C-16 -C-14 PARF rela-... 

Heterocyclic secondary 183-type enamines (exocyclic vinylogous urethanes) show ambident bisnucleophilicity their nucleophilic reaction... 

An example of an intriguing ring-size dependency of the reaction pathway is that of the cyclization of vinylogous urethanes 328a-c with cinnamaldehyde (08T883). Pyrrolidine- and azepane-based esters 328a and c, respectively, give via aza-[3+3] annulation the expected... 

At low temperatures, the Zn enolate derived from dimethyl 3-methylpent-2-endioate 39 reacts with aldehydes in a one-pot aldolisation and cyclisation to yield the syn-dihydropyran-2-one 40. At the higher temperatures necessary to achieve reaction with a-aminoaldehydes, the anri-products predominate indicating thermodynamic control (Scheme 22) <99T7847>. An aldol condensation features in the asymmetric synthesis of phomalactone. The key step is the reaction of the enolate of the vinylogous urethane 41 with crotonaldehyde which occurs with 99% syn-diastereoselectivity and in 99% ee (Scheme 23) <99TL1257>. 

Rearrangement of vinylogous urethanes to give cyclic enamines [193, 194]. 

Other examples of deuterium incorporation at the epimeric centre have also been reported. When treated with a deuterated acid (DCl/MeOD and TFA-d, respectively), both P-carboline derivative 18 [20] and vinylogous urethane 19 [21] resulted in deuterium incorporation at C-l and C-12b (both correspond to C-3), respectively, Fig. (2). Mechanisms similar to that of Mechanism 1 were suggested to explain the epimerization. It should be noted, however, that, as pointed out above, mere deuterium incorporation is not sufficient evidence for Mechanism 1. Were Mechanism 1 alone responsible for the epimerization, both deuterium incorporation and epimerization would have to happen at the same rate. 

The mechanistic studies of the epimerization reaction still cause confusion. For the first time, direct evidence for Mechanism 1 has been presented based on the incapability of the C-12b methyl substituted vinylogous urethanes to epimerize. Further evidence for Mechanism 1 was provided by deuterium incorporation at the epimeric centre of various compounds (see above), a process most likely due to a mechanism analogous to Mechanism 1. The difference in epimerization rate and deuterium incorporation states merely that Mechanism 1 is not primarily responsible for the acid-catalysed epimerization reaction and hence does not completely discredit it. Evidence for all three mechanisms therefore now exists, revealing the complexity of the epimerization process. The results with p-carbolines and the trapping of 3,4-secoreserpine (27) and secolactam 38 provide strong evidence for Mechanism 3. Mechanism 2, which was earlier considered to be responsible for the epimerization reaction, has since been discredited. Nevertheless, the presence of 2,3-secoreserpine (26) in the trapping reaction remains undisputed and indicates that Mechanism 2 is active under the conditions employed. Thus, several mechanisms may be active simultaneously in the epimerization reaction, so further complicating the matter. 

Scheme 32 illustrates an application of a 6-exo-trig radical cyclization in the total synthesis of ( )-mossambine (166) [68-69]. Indoloazepine 160 was obtained from tiyptamine in four steps (30% overall yield). Pyrolysis of 160 in refluxing toluene in the presence of 2-acetoxyacetaldehyde led to transient generation of an enamine acrylate 161, which stereoselectively formed the tetracyclic vinylogous urethane 162. Hydrolysis of the acetate... 

An alternative and successful approach to the Elaeocarpus alkaloids has been based on use of the vinylogous urethane (20). This method has led to the synthesis of ( )-elaeocarpine, ( )-isoelaeocarpine, and the ( )-elaeokanines A, B, and C.8 The vinylogous urethane method has been extended to the synthesis of ipalbidine, which is the aglycon of the alkaloid ipalbine.9... 

The stereoselectivity of the reduction of vinylogous urethane 4, as shown in Scheme 2, may be attributed to steric hindrance, by which the catalytic hydrogenation occurs from the less hindered site (a-face) of 4 to give an all cw-substituted reduction product (Fig 2). 

Finally, the type IV chiral building block 15 was synthesized via the iminium reduction of the corresponding iminiun salt derived from the vinylogous urethane 14 as shown in Scheme 5. With all four stereoisomers of the chiral building blocks (I IV) for synthesis of 3-piperidinol alkaloid in hand, we examined the synthesis of prosafrinine,... 

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