Diels Alder-type cyclization reactions

Owing to the high Lewis acidity the group 14 organometallic cations are polymerization catalysts par excellence. so Silanorbonyl cations and triethylsilyl arenium have been shown to be efficient catalysts for metal-free hydrosilylation reactions. Chiral silyl cation complexes with acetonitrile have been applied as cata -lysts in Diels Alder-type cyclization reactions °792 intramolecularly stabilized tetracoordinated silyl cations have been successfully used as efficient catalysts in Mukaiyama-type aldol reactions. 

If the C-15, C-16 bond is oxidatively cleaved, the secodine skeleton results (the proposed progenitor of the Aspidosperma and the iboga systems) through alternative Diels-Alder type cyclizations to afford tabersonine and catharanthine. The bisindole alkaloids of Catharanthus roseus reflect the union of vindoline and catharanthine to afford anhydrovinblastine modification affords the clinically significant alkaloids, vinblastine (VLB) and vincristine (VCR Fig. 39). The alkaloids, particularly VCR, are important as anticancer agents and have led to the development of the semisynthetic derivatives vindesine and vinorelbine (Fig. 40). Synthetic approaches are available to join the monomeric precursors. The enzymatically controlled sequence of reactions from tabersonine to vindoline has been elucidated. 

Hetero substituted 2-cyclopropylideneacetates are ring-strain activated acrylates, highly reactive dienophiles in Diels-Alder reactions, but also powerful Michael acceptors. The reactivity of these compounds is enhanced by the same strain release in the Diels-Alder cycloadditions as well as in the 1,4-additions, and indeed the borderline between tandem Michael-cyclization and Diels-Alder-type cycloaddition is not well defined in many cases. 

Estrones An A —> BCD approach to estrones involves a cobalt-catalyzed intramolecular [2 + 2 + 2] cycloaddition of the enediyne 1 to form the B, C, and D rings in one step. The high stereoselectivity suggests that the cyclization involves a Diels-Alder-type reaction of the vinyl group with a cobaltacyclopentadiene formed by coupling of the two alkyne units. The homoannular diene obtained on demetalation is isomerized easily to the diene 3. 

Keck also investigated asymmetric catalysis with a BINOL-derived titanium complex [102,103] for the Mukaiyama aldol reaction. The reaction of a-benzyloxyalde-hyde with Danishefsky s dienes as functionalized silyl enol ethers gave aldol products instead of hetero Diels-Alder cycloadducts (Sch. 40) [103], The aldol product can be transformed into hetero Diels-Alder type adducts by acid-catalyzed cyclization. The catalyst was prepared from BINOL and Ti(OPr )4, in 1 1 or 2 1 stoichiometry, and oven-dried MS 4A, in ether under reflux. They reported the catalyst to be of BINOL-Ti(OPr% structure. 

The cobalt-catalyzed co-cyclization of alkynes with heterofunctional substrates is not limited to nitriles. / -Cp-cobalt half-sandwich complexes are capable of co-oligomerizing alkynes with a number of C=C, C=N, C=0, or C=S bonds in a Diels-Alder-type reaction. Chen has observed that these cycloadditions are best performed in the presence of a small amount of ketones or esters [48]. This modified cycloaddition may be used for the formation of dihydroindole systems at the 7 -Cp-cobalt catalyst (eq. (17)). 

MO calculations have been carried out for the [4-f2] Diels-Alder-like cyclization of aminoboranes R2B = NR 2 with substituted m-1,3-butadienes <2003OM3748>, and for the [4-1-2] ene-type reactions between iminoboranes... 

In addition to the preceding processes that involve cycloadditions in direct analogy to Diels-Alder-type processes, several formal [4+2] cycloaddition processes have been described that proceed via completely different substrate classes and reaction pathways. In one example, a novel two-carbon ring expansion process was reported by Murakami, wherein the addition of cyclobutanones with alkynes provides cyclohexenones by two-carbon ring expansion of the starting material (Scheme 3-23). The mechanism of this process likely involves oxidative cyclization of die ketone and alkyne with Ni(0) to provide a five-membered metallacycle, followed by a ringexpanding p-carbon elimination as key steps of the process. 

Metallacyclopentadiene is a common intermediate in the [2 -b 2 -b 2] cycloaddition of alkynes. The oxidative cyclization of alkynes to a metal center gives metaUacyclopen-tadiene. Various metallacyclopentadiene complexes are formed by this reaction. It is generally accepted that there are two mechanisms for the reaction of metallacyclopentadiene with alkynes to give benzenes a Diels-Alder type of mechanism to give l-metallabicyclo[2.2.0]hepta-3,6-diene intermediate and an insertion mechanism to give metallacycloheptatriene (Scheme 5.23). 

Yamamoto et al reported nitroso Diels-Alder type reaction of diene with nitrosobenzene by a binaphthol derivative (39). Bicyclo ketones were obtained with excellent diastereo- and enantioselectivity (Scheme 2.82) [151]. The cyclization reaction involved the sequential N-nitroso aldol reaction followed by the Michael reaction. Optically active l-amino-3,4-diols are synthesized. 

An unexpected result from the same series of work as above by Perumal et al was obtained when cycloalkenones were used as dienophiles [187]. Instead of the imino Diels-Alder product, azabicyclic ketones were obtained (Figure 8.79). The authors proposed a novel Diels-Alder reaction between In-dienolate ions as dienes, and the imines as dienophiles. Another possibility brought up by the authors was that the products were the result of a tandem aldol reaction on the imine, followed by a Michael-type cyclization reaction. 

In addition to Diels-Alder type annulations, also enantioselective intramolecular [2 -I- 2 -I- 2] cyclization reactions have been carried out on dien-yne... 

Scheme 4 Access to various a,/ -unsaturated carbene complexes from alkynylcarbene complexes 23. A 1,3-Dipolar cycloaddition. B Diels-Alder reaction. C Ene reaction. D [2+2] Cycloaddition. E Michael-type addition followed by cyclization. F Michael-type additions...

The chemistry and utility of zinc-based Lewis acids are similar to those of their magnesium analogs. Their mild Lewis acidity promotes several synthetic reactions, such as Diels-Alder reactions, hetero Diels-Alder reactions,229 radical-mediated reactions,230 ene-type cyclization, and Simmons-Smith reactions. 

The retrosynthetic concept of the Nicolaou group is shown in Scheme 22. The target molecule 36 is disconnected via an IMDA cyclization of the diene quinone precursor 138, which would be generated from the tetraline derivative 139 using Wittig chemistry followed by aromatic oxidation. A Claisen-type rearrangement would provide access to 139 whereby the side chain required for the rearrangement of 140 would be introduced by 0-acylation. The core of 141 would be formed via an intermolecular Diels-Alder reaction between diene 142 andp-benzoquinone 130 [42]. 

An exo-type cyclization, proceeding through a cycloalkylidene carbene (49 n = 1, 3, 4), was proposed to explain the formation of enynes (50) and (52) from alkynyl lithium species (48). The proposed carbene (49) could be trapped by addition to cyclohexene and the cycloalkyne intermediate (51) was trapped by Diels-Alder reaction with 1,3-diphenylisobenzofiiran. 

A previous review has highlighted the following methods of ring synthesis intramolecular cyclization of oximes, nitro alkenes, and nitrones, and [4+2] cycloaddition reactions <1996CHEC-II(6)279>. In addition to that, this review includes the intramolecular cyclization of hydroxylamines, hydroxamates, hetero-Diels-Alder [4+2], 1,3-dipolar cycloaddition of nitrile oxides to alkenes, and [3+3] cycloaddition reactions. This review does not cover cycloaddition reactions of the [4+2] [3+2] and [4+2] [3+2] [3+2] types which primarily led to heterocycle-fused oxazine ring systems. 

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