Enynes cyclic

The cyclic 2,4-dienoate 184, formed by the Pd-catalyzed cyclization of the 1,6-enyne 183, reacted with 154 to form the azulene derivative 185[118], The 3-methylenepyrrolidine 188 is formed by the reaction of the Zn reagent 186 with the chiral imine 187 with high diastereomeric excess. The structure of the allylic ethers is important for obtaining high diastereoselectivity[l 19],... 

Another interesting transformation is the intramolecular metathesis reaction of 1,6-enynes. Depending on the substrates and catalytic species, very different products are formed by the intramolecular enyne metathesis reaction of l,6-enynes[41]. The cyclic 1,3-diene 71 is formed from a linear 1,6-enyne. The bridged tricyclic compound 73 with a bridgehead alkene can be prepared by the enyne metathesis of the cyclic enyne 72. The first step of... 

Clark s group also reported on ring-closing enyne metathesis for the preparation of six- and seven-membered cyclic enol ethers 428 n= 1,2) as potential building blocks for the synthesis of marine polyether natural compounds such as brevetoxins and ciguatoxins. Metathesis products 428 were obtained from ene-ynes 427 in 72-98% yield when the NHC-bearing catalyst C was used (Scheme 84) [179]. 

Scheme 84 Synthesis of cyclic enol ethers 428 by enyne RCM [179]...

In a reaction similar to the (>-alkoxide elimination reactions seen with zir-conocenes, catalytic Rh(OH)(cod)2 and 2 eq. of arylboronic acids gave cyclic products 165 from enynes 166 (Scheme 35) [100]. In this reaction, transmet-allation of Rh - OR with B - Ph gave Rh - Ph species 167, which inserted into the alkyne, cyclized to 168, and finally underwent [>-alkoxidc elimination to provide Rh-OCH3. This reaction is limited to the formation of five-membered rings, but it can also undergo cascade type reactions of enediynes to give multicyclic products [100]. 

A wide variety of organoalkynyl derivatives of cotarnine hydrochloride, a cyclic iminium salt with rich biological activity, were prepared from the direct alkynylation of cotarnine hydrochloride using silver(l) alkynyls.180 Substituted enynes were prepared from the coupling reactions of silver alkynyls with the palladium allyl intermediates, which was... 

It should also be mentioned that very recently, a new cycloisomerization of enynes has been shown to proceed via a rhodium-vinylidene complex,187 which, after [2 + 2]-cycloaddition and ring opening of a rhodacyclobutane, furnishes versatile cyclic dienes (Scheme 47).188 Not only does this constitute a fifth mechanistic pathway, but it also opens new opportunites for C-C bond constructions. 

Few other examples of such reaction sequences have been described to date. Oh has reported the palladium-catalyzed reductive cyclizations of 1,6-enynes in the presence of formic acid or triethylsilane via an alkylpalladium intermediate and its application to organic synthesis. Palladium complexes also catalyze the conversion of a range of enynes to cyclic 6,7-unsaturated carboxylic acids in the presence of CO.260... 

To probe the reaction mechanism of the silane-mediated reaction, EtjSiD was substituted for PMHS in the cyclization of 1,6-enyne 34a.5 The mono-deuterated reductive cyclization product 34b was obtained as a single diastereomer. This result is consistent with entry of palladium into the catalytic cycle as the hydride derived from its reaction with acetic acid. Alkyne hydrometallation provides intermediate A-7, which upon cw-carbopalladation gives rise to cyclic intermediate B-6. Delivery of deuterium to the palladium center provides C-2, which upon reductive elimination provides the mono-deuterated product 34b, along with palladium(O) to close the catalytic cycle. The relative stereochemistry of 34b was not determined but was inferred on the basis of the aforementioned mechanism (Scheme 24). 

Undheim [24] described the stereoselective synthesis of cyclic 1-amino-l-carboxylic acid using ruthenium-catalyzed enyne metathesis. His plan is shown... 

Stoichiometric bicydization of enynes, diynes, and dienes by cyclic carbozirconation... 

The sequential double migratory insertion of CO into acydic and cydic diorganozircono-cene complexes through acylzirconocene and ketone—zirconocene species provides a convenient procedure for preparing acyclic and cyclic ketones (Scheme 5.6) [8], Thus, the bi-cydic enones from enynes can be obtained through CO insertion into zirconacyclopen-tenes followed by a subsequent rearrangement (Scheme 5.7). The scope and limitations of this procedure have been described in detail elsewhere [8d]. This procedure provides a complementary version of the well-known Pauson Khand reaction [9]. 

Twenty chapters cover such new and exciting developments as metal-catalyzed synthesis of allenes, strained cyclic allenes, the numerous applications of different metallated allenes in organic synthesis, as well as the many addition and rearrangement reactions of allenes and allene units in natural products like the remarkable enyne-allenes. 

A similar process involving an all-carbon cyclic system has also been investigated [59]. Other examples involving the prototropic rearrangement of enediynes having an imino or a keto substituent at the propargylic position to form the corresponding enyne-allenes have also been observed [60, 61]. 

The propargylic alcohol 102, prepared by condensation between 100 and the lithium acetylide 101, was efficiently reduced to the hydrocarbon 103, which on treatment with potassium tert-butoxide was isomerized to the benzannulated enyne-allene 104 (Scheme 20.22) [62], At room temperature, the formation of 104 was detected. In refluxing toluene, the Schmittel cyclization occurs readily to generate the biradical 105, which then undergoes intramolecular radical-radical coupling to give 106 and, after a prototropic rearrangement, the llJ-f-benzo[fo]fluorene 107. Several other HJ-f-benzo[fo]fluorenes were likewise synthesized from cyclic aromatic ketones. 

Scheme 20.40 Cyclic enyne-allene via conjugate addition.

Analogously to the carbocycle and oxycycle synthesis, cyclic amines can be obtained by the hydrosilylation of a suitable enyne, such as 46 (Reaction 7.54), which gave the six-membered ring via a 6-endo cyclization of the vinyl radical onto the C=N bond [63]. In another example, the isothiocyanide functionality of compounds 47 or 48 reacts with silane under radical conditions... 

Cycloisomerization represents another approach for the construction of cyclic compounds from acyclic substrates, with iridium complexes functioning as efficient catalysts. The reaction of enynes has been widely studied for example, Chatani et al. reported the transformation of 1,6-enynes into 1-vinylcyclopentenes using [lrCl(CO)3]n (Scheme 11.26) [39]. In contrast, when 1,6-enynes were submitted in the presence of [lrCl(cod)]2 and AcOH, cyclopentanes with two exo-olefin moieties were obtained (Scheme 11.27) [39]. Interestingly, however, when the Ir-DPPF complex was used, the geometry of olefinic moiety in the product was opposite (Scheme 11.28) [17]. The Ir-catalyzed cycloisomerization was efficiently utilized in a tandem reaction along with a Cu(l)-catalyzed three-component coupling, Diels-Alder reaction, and dehydrogenation for the synthesis of polycyclic pyrroles [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]. 

A new cyclization strategy via PET-generated electrophilic selenium species starting from diphenyldiselenide was introduced by Pandey et al. They succeeded in the cyclization of enyne compounds in good yields in the range 50-60% as well as in synthesizing a,a -trans dialkyl cyclic ethers via diastereoselective oxyselenation of l,n-diolefins (Scheme 31) [42,43],... 

When enyne 144 is treated with ruthenium carbene complex in the presence of methyl acrylate, RCM-CM occurs to afford cyclic compound 145 in good yield ... 

So-called domino or cascade reactions have become more and more important for the efficient synthesis of complex organic molecules [1211. In this respect methyl 2-chloro-2-cyclopropylideneacetate (1-Me) has been used as a dieno-phile to trap cyclic dienes which were produced by intramolecular Heck reactions in Diels-Alder cycloadditions. Thus, the spirocyclopropanated functionalized bicyclo[4.3.0lnonenes 248,250 (Fig. 11) were obtained from the bromo-diene 247 or enynes 249 in 56-83% yield (Scheme 71) [122,1231. 

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