Diels-Alder reactions propyne

In the course of investigation of reactivity of the mesoionic compound 44 (Scheme 2) the question arose if this bicyclic system participates in Diels-Alder reactions as an electron-rich or an electron-poor component <1999T13703>. The energy level of the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) orbitals were calculated by PM3 method. Comparison of these values with those of two different dienophiles (dimethyl acetylenedicarboxylate (DMAD) and 1,1-diethylamino-l-propyne) suggested that a faster cycloaddition can be expected with the electron-rich ynamine, that is, the Diels-Alder reaction of inverse electron demand is preferred. The experimental results seemed to support this assumption. 

The a-pyrone (635) undergoes an exothermic Diels-Alder reaction with 1-diethylamino-1-propyne to afford the cycloadduct (636) (77JOC2930). Only a single regioisomer is produced, which is in line with the expected polarization of these reagents (Scheme 144). A Diels-Alder reaction of the same a-pyrone with 1-dibenzylamino-l-propyne affords an aniline derivative which has been employed in a chiral synthesis of the aromatic portion of the ionophore antibiotic lasalocid (80JA6178). 

The four possible transition-state structures for the Lewis acid-promoted Diels-Alder reaction of cyclopentadiene with propynal are depicted in Fig. 7. In the chiral Lewis acid-promoted reaction, the enantiomeric excess of an adduct originates in the enantiofacial selectivity of cyclopentadiene, which has prochiral reactive centers. The enantioselective pathway presupposes three characteristics (i) the chiral Lewis acid must sterically shield one enantioface of the coordinated propynal because the open acetylenic jr-face in the chiral catalyst-dienophile complex approaches one face of... 

Figure 7. Four possible transition structures in the Diels-Alder reaction of propynal and cyclopentadiene promoted by Lewis acid. ML = Lewis acid.

Although exo-endo selectivity in the Diels-Alder reaction of olefinic dienophiles has been extensively studied both experimentally and theoretically [31], exo-endo selectivity of the transition structure in the reaction of acetylenic dienophiles has not previously been investigated, because the adducts produced via exo- or endo-transi-tion-state assembly are identical diastereomerically. We used ab initio molecular orbital calculations at the RHF/6-31G level [32] to identify the transition struetures of simple processes of this type, i.e. acid-free and BFs-promoted reactions of cyclopenta-diene and propynal (Fig. 9). As expected, our calculations showed that the exo transition structures are more stable than the endo structures by 0.8 kcal mol" for the former reaction and by 2.0 and 2.4 kcal moF for anti and syn pairs, respectively, for the latter. These calculations strongly suggest the predominance of an exo transition structure and its enhancement by coordination of the Lewis acid. 

Five months later, Corey and Lee reported the enantioselective Diels-Alder reaction between cyclopentadiene and a,/ -acetylenic aldehydes catalyzed by a chiral cationic oxazaborinane catalyst [33]. Although initial studies of the Diels-Alder reaction between cyclopentadiene and 2-butyn-l-al or 2-octyn-l-al with 20 mol % catalyst at -94 °C to -78 °C revealed only 3-5 % conversion to product over a 24-h period, replacement of the /3-alkyl substituent on the aldehyde component by RsSi or RsSn groups resulted in much faster Diels-Alder addition (Eq. 33). The greater yield with 3-tributylstannyl-2-propyn-l-al, compared with the 3-silyl analogs, results from the rate of reaction with the former. In each instance, good enantioselectivity (80-87 % ee) was obtained. 

The strategic level step of the synthesis was next achieved via an asymmetric Diels—Alder reaction between vinylindole 133 and propynal (134) employing imidazolidinone catalyst 135 and tribromoacetic acid. The... 

Trimethylsilyl)vinylketen (20), prepared in four steps from l-(trimethyl-silyl)propyne in 40—60% yield, participates in Diels-Alder reactions as a reactive diene, generating a-(trimethylsilyl)cyclohexenones directly from olefinic dienophiles (Scheme 18). °... 

Another feature of 2-pyrone 87 is its ability to undergo Diels-Alder reactions with acetylenes. The cycloadducts decarboxylate spontaneously to form benzene rings bearing the CF3 group. The substitution pattern is determined by the regioselectivity of the [4-1-2] cycloaddition step. Thus, the reaction of 87 with l-(NJ -diethylamind)-l-propyne takes place at 0 °C to produce 92 as a single isomer. Less electron rich acetylenes require heating at 140-200 C. Treatment of 87 with acetylene at 200 C leads to 93, while with dimethyl acetylenedicarboxylate triester 94 is formed [37] (Scheme 28). 

Bis(trifluoromethyl)-i,2,4,5-tetrazme, which is synthesized from 2,5-bis(trifluoromethyl)-l,3,4-oxadiazole by addition of hydrazine followed by mild oxidation [720] (equation 100), is a reactive and very interesting Diels-Alder diene [727] Its normal reaction is to add the dienophile and then to extrude N2 to form a diazene, as exemplified by its reaction with propyne [720] (equation 101)... 

Employing the high potential of iminium ion activation, MacMillan and coworkers were able to directly access the key intermediate 320 in a single operation cascade reaction between the tryptamine-derived indole derivate 321 and propynal (226) in the presence of their trademark catalyst 227. As illustrated in Scheme 74, the reaction is assumed to proceed via two iminium catalysis cycles (Diels-Alder cyclization first, followed by conjugate addition). It is worth noting that the authors considered either the possibility of intermediate 322 to directly enter the second... 

The Diels-Alder cycloaddition reaction occurs most rapidly if the alkene component, or dienophile ( diene lover ), has an electron-withdrawing substituent group. Thus, ethylene itself reacts sluggishly, but propenal, ethyl propenoate, maleic anhydride, benzoquinone, propenenitrile, and similar compounds are highly reactive. Note also that alkynes, such as methyl propyn-oate, can act as Diels-Alder dienophiles. 

Minfiensine, a secoiridoid indole alkaloid, was isolated from the African plant Strychnos minfiensis by Massiot and co-workers in 1989. The unique structure feature of the 1,2,3,4-tetrahydro-9a,4a-(iminoethano)-9//-carbazole has received much attention for the synthetic efforts and has culminated in several elegant total syntheses. For example. Overman et al. reported on the first and second total synthesis of (-l-)-minfiensine. " In addition, Qin et al. revealed a synthesis of ( )-minfiensine in 2008. Recently, MacMillan and co-workers reported on a nine-step enantiose-lective total synthesis of (-l-)-minfiensine via the key step reaction of organocatalytic Diels-Alder cyclization and amine heterocyclization cascade (Scheme 21.32). For the key step reaction in their approach, reaction of 2-vinylindole 139 and 3 equivalents of propynal in the presence of secondary amine catalyst 140 followed by the addition of NaBH4, stereoselective afforded the tricyclic alcohol 142 via a iminium activated endo-selectiye Diels-Alder cycloaddition and a 5-exo amine heterocy cliz ation. 

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