Type 2 Ene Reactions

Reactions of the allylic position of alkenes with carbonyl or imine electrophiles are known as Prins reactions and have been discussed in previous sections (3.2.9). More examples of similar Alder-ene-type reactions (the Prins reaction) will be discussed in Chapter 8. 

Silenes derived from aromatic di- or polysilanes have been characterized in particular by the ene-type reactions they undergo when treated with isobutene or acetone. Recently, Leigh80 observed the first reported case of one of these silenes undergoing [2+2] cycloaddition (21% yield) with acetone. The ene product, the only product previously detected from the reaction of such silenes, was formed in 41% yield, as shown in Eq. (33). 

Malacria and coworkers [274] used an intermolecular trimerization of alkynes to gain efficient access to the skeleton of the phyllocladane family. Thus, the Co-cata-lyzed reaction of the polyunsaturated precursor 6/4-4 gave 6/4-5 in 42% yield. Here, six new carbon-carbon bonds and four stereogenic centers are formed. The first step is formation of the cyclopentane derivative 6/4-6 by a Co-catalyzed Conia-ene-type reaction [275] which, on addition o f his( Iri me ill y I si ly 1) e thy ne (btmse), led to the benzocyclobutenes 6/4-7 (Scheme 6/4.2). The reaction is terminated by the addition of dppe and heating to reflux in decane to give the desired products 6/4-5 by an electrocyclic ring opening, followed by [4+2] cycloaddition. 

The utility of this metallo-ene-type reaction has also been demonstrated by the reaction of 1,6- or 1,7-enynes bearing a chiral 1,2-diphenylethylene acetal moiety as the leaving group. The reaction was found to proceed with excellent chiral induction to give optically active cyclopentane and cydohexane derivatives, respectively, which was followed by reaction of the resulting vinyl titaniums with electrophiles, as exemplified in Eq. 9.60, s.p. 348 [108]. 

A similar ene-type reaction was also observed with 1,2-allenyl sulfides to afford 2-methylene-3-thio methylalk-3-enylamines [40]. 

In the presence of [lrCl(cod)]2, heteroatom-tethered enynes with ( )-olefinic moieties were transformed into cyclic 1,4-dienes. The ene-type reaction was achieved previously with a Rh catalyst, but only enynes with (Z)-olefinic moieties were used. It is worthy of note here that the cycloisomerization showed a clear acceleration when an ionic liquid was used as the solvent (Scheme 11.29) [41]. 

Scheme 27 Vinylogous Mannich reaction of silyl dienolates 2.3.5 Aza-Ene-Type Reaction...

Two years later, Terada and coworkers described an asymmetric organocatalytic aza-ene-type reaction (Scheme 28) [50], BINOL phosphate (7 )-3m (0.1 mol%, R = 9-anthryl) bearing 9-anthryl substituents mediated the reaction of A-benzoylated aldimines 32 with enecarbamate 76 derived from acetophenone. Subsequent hydrolysis led to the formation of P-amino ketones 77 in good yields (53-97%) and excellent enantioselectivities (92-98% ee). A substrate/catalyst ratio of 1,000 1 has rarely been achieved in asymmetric Brpnsted acid catalysis before. 

In 2007, Terada et al. extended their previously described chiral phosphoric acid-catalyzed aza-ene-type reaction of M-acyl aldimines with disubstituted enecarbamates (Scheme 28) to a tandem aza-ene-type reaction/cyclization cascade as a one-pot entry to enantioenriched piperidines 121 (Scheme 48). The sequential process was rendered possible by using monosubstituted 122 instead of a disubstituted enecarbamate 76 to produce a reactive aldimine intermediate 123, which is prone to undergo a further aza-ene-type reaction with a second enecarbamate equivalent. Subsequent intramolecular cychzation of intermediate 124 terminates the sequence. The optimal chiral BINOL phosphate (R)-3h (2-5 mol%, R = 4-Ph-C H ) provided the 2,4,6-sub-stituted M-Boc-protected piperidines 121 in good to exceUent yields (68 to > 99%) and accomplished the formation of three stereogenic centers with high diastereo- and exceUent enantiocontrol (7.3 1 to 19 1 transicis, 97 to > 99% ee(trans)) [72]. 

Scheme 48 Tandem aza-ene-type reaction/cyclization cascade scope and reaction intermediates...

Scheme 55 Aza-ene-type reaction between ethyl glyoxylate and various enecarbamates...

Rhodium(I) complexes have also been shown to promote metallo-ene type reactions efficiently (Scheme 7.14) [26]. Typically, the reaction of 2,7-octadienyl-l-carbonate 27 is carried out using the RhH(PPh3)4-tris(2,4,6-trimethoxyphenyl)phosphine system as the catalyst in acetic acid at 80 °C for 1-1.5 h, to give the corresponding l-exo-methylene-2-ethenylcyclopentane 28 in high yield. 

In related studies, Terada described the synthesis of optically pure piperidines via a tandem aza-ene-type reaction/cyclization sequence (Scheme 5.18) [32]. The reaction of a monosubstituted enecarbamate and an N-acyl aldimine affords aza-ene-type intermediate 5, which reacts with a second equivalent of enecarbamate to give aldimine 6. Subsequent intramolecular cyclization terminates the aze-ene-type reaction sequence to furnish trans-piperidine 7 in high enantio- and diasterio-selectivities. 

The general problem of simple diastereoselection (see Section A. 1.), as outlined below refers to the combination of two enantiofaces, which is possible in 4 different orientations (1, 3, 5 and 7). 1/7 and 3/5 are enantiomorphous and lead to enantiomeric pairs (2/8 and 4/6, respectively). In reactions with closed transition states , this means that the two olefins are in a syn orientation. Generally, this orientation is enforced by the transfer of a metal cation or a proton from D to A [ene-type reaction]8. D is a donor and A an acceptor group. 

Primary allylmagnesium halides64-65 and allylzinc66 reagents react similarly, presumably by an ene-type reaction, to give selectively the cyclopropyl derivative in which the more substituted allylic carbon is attached to the ring (equation 24). Allylzinc compounds have been employed in the same manner in carbozincation of cyclopropenone acetals67. 

See also the direct reaction of aldehydes and ketones with allylic halides and other allylic substrates plus metals earlier in this section, as well as page 236, Sections 7 and 8, far ene-type reactions. 

Scheme 8C.24. Asymmetric aldol (prototropic ene-type) reaction.

Carreira et al. used a chiral BlNOL-derived Schiff base-titanium complex as the catalyst for the aldol reactions of acetate-derived ketene silyl acetals (Scheme 8C.29) [64a]. The catalyst was prepared in toluene in the presence of salicylic acid, which was reported to be crucial to attain a high enantioselectivity. A similar Schiff base-titanium complex is also applicable to the carbonyl-ene type reaction with 2-methoxypropene [64b], Although the reaction, when con-... 

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