Dienamine

The following compounds have been obtained from thiete 1,1-dioxide Substituted cycloheptatrienes, benzyl o-toluenethiosulfinate, pyrazoles, - naphthothiete 1,1-dioxides, and 3-subst1tuted thietane 1,1-dioxides.It is a dienophile in Diels-Alder reactions and undergoes cycloadditions with enamines, dienamines, and ynamines. Thiete 1,1-dioxide is a source of the novel intermediate, vinylsulfene (CH2=CHCH=SQ2). which undergoes cyclo-additions to strained olefinic double bonds, reacts with phenol to give allyl sulfonate derivatives or cyclizes unimolecularly to give an unsaturated sultene. - Platinum and iron complexes of thiete 1,1-dioxide have been reported. 

Androst-4-ene-3,l 1,17-trionehas been converted into several 3,17-dienamine derivatives which, on reduction with LiAlH4 followed by removal of the protecting groups, give 11 jS-hydroxyandrost-4-ene-3,17-dione. An unsaturated 3-ketone has also been protected as an enamine in the LiAlH4 reduction of a 21-ester group a further example is the conversion of 7-methylene-5a-an-drostane-3,17-dione into the 3-pyrrolidine enamine followed by reduction of the 17-ketone by Li[OC(CH3)3]3 AlH. ... 

Less reactive reagents may act more selectively. Thus androst-4-ene-3,11,17-trione (7) is converted into the 3-monoenamine (8) with morpholine and into the 3,17-dienamine (9) with pyrrolidine.The greater reactivity of pyrrolidine as compared to piperidine and morpholine has been attributed to the greater stability associated with a double bond exocyclic to a 5-mem-bered ring which facilitates the dehydration step. ... 

Steroidal A -dienamines are formed with a high degree of selectivity in the presence of 17- or 20-ketones. Preparation of morpholine and pyrrolidine enamines is achieved by azeotropic removal of water with or without a catalyst. Pyrrolidine enamines are also formed efficiently by addition of the base to the hot solution of the ketone in methanol followed by immediate cooling. ... 

Steroidal a,j8-unsaturated ketones such as /l -3-ketones undergo a facile reaction with pyrrolidine to give the corresponding, d - -dienamines (111) (40,53). The reaction is much slower with morpholine and piperidine, which is undoubtedly due to the generation of the double bond exocyclic to the six-membered hetero rings in the step involving the dehydration of the intermediate carbinolamine (112) to the corresponding iminium ion (113). 

By analogy with the kinetic protonation of steroidal zl -enolate anions with weak acids such as acetic acid, which proceeds at the C-4 atom, since the maximum negative charge resides at this position (54,55), the kinetic protonation of the -dienamines with weak acids also occurs at this... 

Madsen and Lavvesson (6/), however, have reported recently that the treatment of /7-alkyl methyl ketones with morpholine in the presence of p-toluenesulfonic acid for a short period of time resulted in the formation of a mixture of condensation product of the ketone (122) and the corresponding dienamine (123). 

Similar results were encountered by Bianchetti et al. (i52), who found that e ketal derivatives of //-alkyl methyl ketones with morpholine led to the enamines of the condensation products of these ketones. The authors have Suggested the following probable mechanism for the dienamine formation. 

In the case of dienamines an additional site becomes available for protonation and three conjugate acids 9,10, and 11 are possible. Evidence available suggests that although protonation with mineral acids gives the protonated form (10) as the final product, the latter is the result of rearrangement of an... 

The alkylation of dienamines has not been studied extensively. Thus the dienamine (44) is reported (43,44) to alkylate at Cj with methyl iodide to give the iminium salt (45), which on hydrolysis gives the alkylated a,)3-unsatur-ated ketone (46). Similar dienamines prepared from A -2-oko steroids. On the other hand, are reported to undergo only N alkylation (45). 

The reaction of enamines with perfluoro olefins has also been reported (62). Dienamines have been reported to react with ethyl acrylate at C2 to give the alkylated a,j8-unsaturated ketone derivative. Thus the dienamine (44) gave 71 in 50 % yield on reaction with ethyl acrylate in dioxane for 40 hr (63). 

The acylation of dienamines has not been extensively investigated. The dienamine (127) prepared by Birch reduction of N,N-dimethyl-p-toluidine has been shown to react with diketene (90) to give the chromone (128), showing that attack occurs at the /9-carbon of the dienamine system. 

The dienamine (148) can react in two ways with methane sulfonyl chloride. In one a 1,4 Diels-Alder-type addition gives 149 in the other way the initially formed product reacts further to give the bis-cyclic sulfone (150) (102,103). 

If the cisoid structure of the dienamine is fixed only the Diels-Alder-type addition occurs (100). 

Hydrazoic acid has been shown to add to dienamines to give a complex mixture of 1 -azido- and 1,3-diazido-amines 135). 

The reaction has been applied to more complex enamines 13) and to dienamines 19). The reduction may be rationalized by initial protonation at the enamine carbon and subsequent decarboxylation of formate ion and addition of the hydride ion to the iminium cation. This mechanism has been given support by the reaction of the enamine (205) with deuterated formic acid 143) to give the corresponding amines. The formation of 206 on reaction with DCOOH clearly indicates that protonation at the enamine carbon is the initial step. 

A similar sequence of reactions has been shown to take place with the dienamine derived from isophorone and morpholine (77). Reaction of this enamine with trichloroacetic acid gave a trichloromethyl derivative which was not isolated but which undergoes rearrangement and hydrolysis with base to give the diene acid (210). 

Dienamines, for example, 61, have been reported 89) to be reduced by formic acid to give a mixture of products 62 and 63 in 21 % yield. 

Enamines have been observed to act both as dienophiles (46-48) and dienes (47,49) (dienamines in this case) in one-step, Diels-Alder type of 1,4 cycloadditions with acrylate esters and their vinylogs. This is illustrated by the reaction between l-(N-pyrrolidino)cyclohexene (34) and methyl t/-a i-2,4-pentadienoate (35), where the enamine acts as the dienophile to give the adduct 36 (47). In a competitive type of reaction, however, the... 

The addition of p-quinone to enamines normally produces furan derivatives, especially when the enamine possesses a 3 hydrogen (see Section III. A). 1,2 Cycloaddition is claimed to take place to give a cyclobutane derivative when p-quinone and an enamine with no jS hydrogens are allowed to react at low temperatures (51). However, little evidence is reported to verify this structural assignment, and the actual structure probably is a benzofuranol (52). Reaction of a dienamine (formed in situ) with p-quinone in the presence... 

Dienamine 56a has been reported to undergo a 1,4 cycloaddition with acrylonitrile to form bicycloaminonitrile 57 in a 74% yield (61). A recent report has indicated that both possible 1,4-cycloaddition adducts are obtained from the reaction of acrylonitrile with a 1 1 equilibrium mixture of the linear- and cross-conjugated isomers of dienamine 56b (61a). 

Similar adducts are formed when the dienamine is allowed to react with methyl vinyl ketone and with methyl acrylate. 

The reaction of methyl propiolate (82) with acyclic enamines produces acyclic dienamines (100), as was the case with dimethyl acetylenedicarboxylate, and the treatment of the pyrrolidine enamines of cycloheptanone, cyclooctanone, cycloundecanone, and cyclododecanone with methyl propiolate results in ring enlargement products (100,101). When the enamines of cyclohexanone are allowed to react with methyl propiolate, rather anomalous products are formed (100). The pyrrolidine enamine of cyclopentanone forms stable 1,2-cycloaddition adduct 83 with methyl propiolate (82). Adduct 83 rearranges to the simple alkylation product 84 upon standing at room temperature, and heating 83 to about 90° causes ring expansion to 85 (97,100). 

Irradiation of dienamine 94 for 3 days results in the formation of 95 through a 1,4 cycloaddition (J20). 

Dienamines undergo 1,4 cycloaddition with sulfenes as well as 1,2 cycloaddition. For example, l-(N,N-diethylamino)butadiene (111), when treated with sulfene (generated from methanesulfonyl chloride and triethyl-amine), produces 1,4 cycloadduct 116 in an 18 % yield and di-1,2-cycloadduct 117 in a 60 % yield (160). Cycloadduct 116 was shown not to be the precursor for 117 by treating 116 with excess sulfene and recovering the starting material unchanged (160). This reaction probably takes place by way of zwitterion 115, which can close in either a 1,4 or 3,4 manner to form cycloadducts 116 and 118, respectively. The 3,4 cycloaddition would then be followed by a 1,2 cycloaddition of a second mole of sulfene to form 117. Cycloadduct 117 must form in the 3,4 cycloaddition followed by a 1,2-cycloaddition sequence rather than the reverse sequence since sulfenes undergo cycloaddition only in the presence of an electron-rich olefinic center (159). Such a center is present as an enamine in 118, but it is not present in 119. 

Vinylogous forma mides have been obtained by double Vilsmeier reactions of methyl ketones (53,54), 4-methylpyridine (53,54), and olefinic (55) compounds. The dienamine intermediates were demonstrated in the latter cases. 

Similarly, the addition of organometallic reagents to pyridines leads to dienamine intermediates, which can be demonstrated (167-170). 

The stereospecific generation of enamines by -elimination reactions (187) and a vinylogous elimination, which leads to a dienamine (188), have been reported. The loss of an a substituent from a tertiary amine is seen in the generation of enamines by elimination of hydrogen cyanide from benzylic a-aminonitriles (189,190). 

In the generation of 3,5-dibenzylpyridine from piperidine and benzalde-hyde, the formation of enamine and dienamine intermediates must also be involved (191-193). 

Alkylation of dienamines with alkyl halides has been found to take place at the oc carbon (288-290). The reaction was used in the synthesis of steroid analogs (291). 

Positively activated olefins have also been condensed with dienamines derived from aldehydes 321,330,347,348) and ketones. Of special interest is the formation of bridged systems from homoannular dienes (229-231) which has been applied to the isoquinuclidine system of the iboga alkaloids (137-140,349). 

Conjugated dienamines were found to give predominantly double four-membered-ring adducts as well as a small amount of the six-membered-ring adduct (466,468). This important result indicates preferred attack at the terminal carbon of the dienamine system (in contrast to alkylation, for instance) in the generation of an initial zwitterionic intermediate. Addition of sulfonyl chloride and triethylamine to a homocyclic dienamine gave only the bridged product (446). 

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