Allene annulation

Allene annulation is yet another reaction in which bis(oxazoline) ligands are used for asymmetric induction.One example, shown in Figure 9.60, is the reaction of A-tosyl-2-iodoaniline 207 with 1,2-undecadiene. This reaction proceeds... 

The usefulness of allene derivatives has also been revealed in other examples. Thus, the annulated tetrasubstituted furan illustrated in the following scheme was delivered in a moderate yield using the diazoallene as precursor by a two-step reaction in the presence of Rh-catalyst <06S3605>. 

Some cases are known in which Diels-Alder reactions of electron-deficient allenes and dienes compete with [2 + 2]-cycloadditions (see also Section 7.3.7) [12, 151, 335, 336]. Recently, a phosphane-catalyzed [4 + 2]-annulation starting from allenic ester 337 and N-tosylaldimines 338 was published [337]. However, the formation of the tetrahydropyridines 339 isolated in excellent yields is explained by a multi-step mechanism and only resembles a Diels-Alder reaction. 

The (trimethylsilyl)cyclopentene annulation proceeds most efficiently with the use of 1-substituted (trimethylsilyl)allenes. Even the fully methyl-substituted (tri-methylsilyl)allene reacted with both cyclic and acyclic enones to provide the corresponding cyclopentenes in good yields. 

An allenic ester-tropone annulation is also catalyzed by a phosphine in refluxing benzene, providing a single stereoisomer in good yield [194]. 

Annulations Making Use ofTrialkylsilyl Allenes (Danheiser Reactions) 829... 

The annulation evidently proceeds much more rapidly than conformational interconversion of the intermediate cations. For example, the annulation of ( )-3-methyl-3-penten-2-one 88 with allene 89 leads to acetylcyclopentene 90 as the sole reaction product in 71% yield (Eq. 13.28) [32]. The stereochemical relationship of the two methyls is preserved in the product. When the reaction is repeated with (Z)-3-meth-yl-3-penten-2-one 91 (Eq. 13.29), acetylcyclopentene 92 is isolated as the major product, along with a small amount of 90 [32]. 

Butynone 93 and tetrasubstituted allene 94 combine to form acetyl cyclopenta-diene 95 (Eq. 13.30) [32]. The annulation does not proceed in satisfactory yield in the case of unsubstituted trimethylsilyl allene 96 (Eq. 13.31) [32]. This is presumably due to diminished stabilization of the cationic intermediates in the case of 96, which allows competing reaction pathways to erode the yield. 

In spite of these first successful results, so far Stille cross-couplings have rarely reported employing functionalized stannylated allenes such as easily available donor-substituted allene 80a or allenyl esters such as 81 (Scheme 14.19) [19, 41, 42]. A single palladium-catalyzed annulation reaction with 80b as precursor leading to an a-pyrone derivative was reported [43],... 

Wender et al. s [5 + 2] metal-catalyzed annulation strategy has also been applied to the total synthesis of (+)-aphanamol I (154) [34]. The scope of this method was expanded by using a tetrasubstituted allene that resulted in the stereoselective formation of an angular methyl group. The reaction of allene 149 with 0.5 mol% of rhodium biscarbonyl choride dimer afforded the fused bicyclic product 152 in 93% yield with complete exo/endo and diastereoselectivity (Scheme 19.28). The stereoselectivity of this process was attributed to a preference for formation of the cis-fused metallo-... 

Contrary to the phosphine-catalyzed reaction of the allene buta-2,3-dienoate, which adds to CgQ in a ]3-i-2] cycloaddihon ]354], the allene amide 317 forms the cyclobutane annulated fuUerene derivahve in good yields (Scheme 4.63) [355]. The reaction was also performed with similar allene amides bearing a six- or seven-membered lactam. 

The procedure described here serves to illustrate a general [3+2] annulation method for the synthesis of cyclopentane derivatives. A unique feature of this one-step annulation is its capacity to generate regio-specifically five-raembered rings substituted at each position, functionally equipped for further synthetic elaboration. As formulated in the following equation, the reaction proceeds with remarkably high stereoselectivity via the effective suprafacial addition of the three-carbon allene component to an electron-deficient olefin ("allenophile"). ... 

Some representative examples of the [3+2] annulatlon are listed in Table 1. Both cyclic and acyclic allenophiles participate in the reaction, a-Alkylidene ketones undergo annulation to provide access to spiro-fused systems, and acetylenic allenophiles react to form cyclopentadiene derivatives. The reactions of (E)- and (Z)-3-methy1-3-penten-2-one illustrate the stereochemical course of the annulation, which proceeds with a strong preference for the suprafacial addition of the allene to the two-carbon allenophile. The high stereoselectivity displayed by the reaction permits the stereocontrol led synthesis of a variety of mono- and polycyclic systems. 

A significant part of the examples of transition metal catalyzed formation of five membered heterocycles utilizes a carbon-heteroatom bond forming reaction as the concluding step. The palladium or copper promoted addition of amines or alcohols onto unsaturated bonds (acetylene, olefin, allene or allyl moieties) is a prime example. This chapter summarises all those catalytic transformations, where the five membered ring is formed in the intramolecular connection of a carbon atom and a heteroatom, except for annulation reactions, involving the formation of a carbon-heteroatom bond, which are discussed in Chapter 3.4. 

Based on this precedent, Nelson et al. used an intramolecular reaction in the total synthesis of (-)-rhazinilam. In this context, trisubstituted allenes are excellent precursors for a diastereoselective heterocyclic annulation that highlights the usefulness of this reaction in target-oriented synthesis [49]. In this case, the aforementioned catalyst that yielded the best results was [AuPPh3OTf], affording a higher yield and diastereoselectivity than Pd(II). 

Regioselective [3 + 2] annulation has been reported for the preparation of a wide variety of furans. Reaction of acid chlorides with trialkylsilyl-substituted allenes under the influence of A1C13 (CH2C12, — 20°C) yields the desired compounds (Scheme 52). The intramolecular variant of this method has also been described (89JA4407). 

It is reported that the palladium-catalysed intramolecular aromatization of 1,1 -dichIoro-9//-fluoren-9-yIidcnc (15) may lead to the formation of fidlerene fragments.89 The annulation reaction, under palladium catalysis, between iodoanilines and ketones may yield indole derivatives.90 There have also been studies of the palladium-catalysed carbonylation of o-iodophenols with allenes which may lead to l-benzopyran-4-one derivatives,91 of the intramolecular coupling of phenols with aryl halides,92 and of the intramolecular Heck arylation of cyclic enamides.93... 

A palladium-catalyzed asymmetric annulation of the allene 1133 with 2-iodobenzoic acids proceeds in the presence of a chiral bisoxazoline ligand to afford 4-methylenedihydroisocoumarins in good yield and enantiomeric excess (Equation 440) <1999JOC7312>. 

Allenylation of N-tosylimines 47 has been shown to effect the Kwon annulation with the allene derivative 48 on catalysis with the axially chiral phosphine 50 (Scheme 7.8), affording the piperidine derivative 49 with good diastereocontrol (9 1) and high enantioselectivity (93% ee) [52, 53]. 

A pyrrole synthesis leading to 20 has been achieved by a CuBr catalyzed cyclization of the intermediate imine 21, which was prepared over several steps from 1,3-hexadiyne (22) in a one-pot operation <02CHE748>. Aminomethyl substituted allenes have also been used for the synthesis of pyrroles by a palladium catalyzed annulation with aryl iodides <02H(57)2261>. 

A strategy for the synthsis of maleimides 141 has been reported that involves the Zn(OTf)2-catalyzed annulations of allenic esters 139 and isonitriles 140 <070L4057>. Subsequent photoinduced ring closure of 141, followed by oxidative aromatization afforded the corresponding carbazole. 

Eq. 6) and allenes to give annulated products [33, 34]. Naphthylmethyl and quinoylmethyl acetates react with malonates (Eq. 7) [35, 36]. The reactions in Eqs. 6 and 7 involve 7r-allylpalladium type intermediates. 

In a detailed study, bis-oxazoline (9) has been employed for the enantiocontrol of a palladium-catalyzed annulation of allenes with aryl and vinylic iodides. This procedure pro-... 

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