Rhodium-catalyzed cycloisomerization

The Rh-BINAP-catalyzed intramolecular Alder-ene cycloisomerization is very rapid and, therefore, sequentially Rh-catalyzed sequences for the efficient enantioselective generation of five-membered carbo- and heterocycles were envisioned. Korber et al. [21] reported the enantioselective rhodium-catalyzed cycloisomerization of alkyl and (hetero)aryl alkynyl allyl alcohols for the generation of aldehyde-bearing chiral 4-alkyl 3-alkylidene THFs and tetrahydro-furanones, which were converted into a,P-unsaturated carbonyl side chains in a one-pot manner via a concluding Wittig olefination in good yields. 

VCP-substituted propargylic ester 65 rearranged to the seven-membered product 66 in the presence of [RhCl(CO)2]2 (Scheme 2.53) [74]. 1,3-Acyloxy migration generated VCP-substituted allene, which acts as a seven-carbon component in rhodium-catalyzed cycloisomerization. The subsequent ring opening produced methylenecycloheptadiene. 

Mukai et al. have found scission of a cyclopentane ring of allenyne 34 in the rhodium-catalyzed cycloisomerization (Scheme 7.11) [14]. When 34 was treated with a rhodium catalyst, the bicyclo [7.4.0]tridecatriene 37 was formed. Mechanistically, initial coordination of 34 to rhodium(I) would occur between an allenic distal double bond and an alkyne to form the intermediary ir-coordinating complex, which undergoes oxidative cyclization to form the rhodabicyclo[4.3.0]nonadiene intermediate 35. Subsequent P-carbon elimination, presumably assisted by release of the ring strain of the cyclopentane (6.3 kcal mol ), results in the formation of the 10-membered rhodacycle 36. Reductive elimination ensues to give the final product 37. 

A rhodium-catalyzed cycloisomerization reaction of triyne 137 to 141 involves cleavage of the C=C triple bond (Scheme 7.49) [68]. The following reaction pathway is proposed initially, oxidative cyclization produces the rhodacycle 138, which then undergoes reductive elimination. The rhodium cyclobutadiene complex 139 is thus generated, and then undergoes oxidative addition to produce the rhodacycle 140. This isomerization from 138 to 140 would reduce the steric congestion of the heUcal structure. Subsequently, a cycloaddition reaction between the rhodacycle and the pendant alkyne moiety takes place to afford 141. 

SCHEME 7.38 Seminal publication on rhodium-catalyzed cycloisomerization of 1,6-dienes. 

SCHEME 7.39 Selectivity of rhodium-catalyzed cycloisomerization of dienes. 

SCHEME 7.40 Postulated mechanism for rhodium-catalyzed cycloisomerizations. 

Trost BM, McClory A (2007) Rhodium-catalyzed cycloisomerization formation of indoles benzofurans and enol lactones. Angew Chem Int Ed Engl 46 2074-2077... 

Zhang54 published the first and only account of a non-asymmetric rhodium-catalyzed Alder-ene cycloisomerization of 1,6-enynes.55 The conditions developed by Zhang and co-workers are advantageous in that, similar to the ruthenium conditions developed by Trost, selectivity for 1,4-diene products is exhibited. The rhodium conditions are dissimilar from many other transition metal conditions in that only (Z)-olefins give cycloisomerization products. 

Brummond and Shibata independently reported the Rh(i)-catalyzed cycloisomerization of allenynes to cross-conjugated trienes. The rhodium conditions were shown to have broad functional group tolerance. Brummond et al 9 observed rate and selectivity enhancements when they switched to an iridium catalyst (Equation (77)). The rate acceleration observed in the Alder-ene cyclization of aminoester containing allenyne 121 (Equation (78)) was attributed to the Thorpe-Ingold effect.80... 

For rhodium-catalyzed enantioselective enyne cycloisomerization and hydrosily-lation-cyclization, see (a) C. Ping,... 

When (R,R)-Me-Duphos, (R,R,R,R)-BICPO [9] or BINAP [10] is used, the rhodium-catalyzed asymmetric cycloisomerization of 3 affords 4 with up to >99.5% enantiomeric excess (Scheme 7 2). This methodology was applied to the synthesis of functionalized a-methylene-y-butyrolactone derivatives 6 such as (-i-)-pilocarpine 7 (Scheme 7.3) [11]. 

Tab. 8.1 summarizes the various substrates that were subjected to the rhodium-catalyzed reaction using a Rh-dppb catalyst system. Only ds-alkenes were cycloisomerized under these conditions, because the trans-alkenes simply did not react. Moreover, the formation of the y-butyrolactone (Tab. 8.1, entry 8) is significant, because the corresponding palladium-, ruthenium-, and titanium-catalyzed Alder-ene versions of this reaction have not been reported. In each of the precursors shown in Tab. 8.1 (excluding entry 7), a methyl group is attached to the alkene. This leads to cycloisomerization products possessing a terminal alkene, thus avoiding any stereochemical issues. Also,... 

The rhodium catalyzed Alder-ene reaction represents just one exciting cycloisomerization process that is still in its infancy. The synthetic potential of this reaction is currently being investigated, and new findings will undoubtedly be made. 

Scheme 5. The first rhodium-catalyzed enantioselective enyne cycloisomerization.

As variations of Rh-catalyzed cycloisomerization Widenhoefer and coworkers have developed asymmetric 1,6-enyne cyclization/hydrosilylation reactions by using the Rh(I)/biphemp system excellent de and ee were obtained [42]. Brum-mond et al. also discovered a rhodium(I)-catalyzed allenic Alder-ene reaction that... 

The ether-tethered allenyne 248 undergoes a rhodium(l)-catalyzed intramolecular allenic Alder ene reaction to afford the ( )-3,6-dihydropyran 249 as the major product (Equation 111) <2002JA15186>. Likewise, ether tethered enynes can undergo rhodium(i)-catalyzed cycloisomerizations to afford 3,6-dihydropyrans <2005JA10180>. 

An intramolecular rhodium-catalyzed [2+2+2] cycloaddition of diynenitriles <07OL1295> diyne esters <07T12853> and alkynevinyl oximes <07TL6852> also afforded pyridine versions of dihydrobenzo[c]furans. Trost prepared these pyridine derivatives employing a similar ruthenium-catalyzed cycloisomerization-6 cyclization route as depicted in the following scheme <07OL1473>. 

Analogously, intramolecular hydrosilation reactions have been carried out with alkenes cyclization of alkenyloxy-silanes catalyzed by thiols <1998J(P1)467> and by Pt <1996TL827> has been described. In addition, intramolecular temporary silicon-tethered rhodium-catalyzed [4- -2- -2]-cycloisomerization reactions have been carried out by Evans and Bawn (Equation 50) <2004JA11150>. 

The Rh-catalyzed cycloisomerization of 1,6-enynes that occurs via rhodium vinylidene-mediated intermediates was first described in 1988 by Grigg et al. (471). Cyclization of 1,6-enynes (I, Scheme 57) with [RhCl(cod)]2/P(p-FC6H4)3, where cod=l,5-lyclooctadiene as the catalyst generates a metal-vinylidene that undergoes [2 + 2] cycloaddition and... 

Tokunaga and Wakatsuki reported a one-pot indole synthesis from anilines and propargyl alcohols using Rn3(CO)j2 [5], and Nicholas and colleagues reported a Ru-catalyzed indole synthesis via the reductive annulation of nitros-oarenes with alkynes (equation 3) [6, 7]. Saa and coworkers described the Ru-catalyzed cycloisomerization of o-alkynylanihnes (equation 4) [8, 9]. Nissen and Detert reported a total synthesis of lavendamycin that featnred a Ru-catalyzed [2-f2-f2] cycloaddition of an o-alkynyl-ynamide, a method that was superior to rhodium catalysis both in terms of efficiency and regiochemistiy [10]. 

An example of a rhodium(I)-catalyzed cycloisomerization of nitrogen-tethered indole-alkylidenecyclopropanes 13 was reported allowing for ready access to azepinoindole derivatives 14, which are tetrahydro-P-carboline homologs (13CEJ13668). 

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