Tetrasubstituted allenes

Dienes such as 90 can be accessed by a multi-component reaction under ruthenium catalysis involving an allene 88 and an enone (methyl vinyl ketone in this case), with cerium(m) chloride as an additive in DMF (Scheme 26).95,96 With an allene concentration of 0.25 M, yields are moderate to good. Different ruthenium catalysts and additives were tested in order to optimize this reaction. CpRu(COD)Cl 89 and CpRu(MeCN)3PF6 appeared to be more versatile ones. The mono-, di-, tri-, and tetrasubstituted allenes have been investigated with methyl vinyl... 

Trost et alJ2 also explored the compatibility of di-, tri-, and tetrasubstituted allenes with their intermolecular Alder-ene protocol. Multiple substituents present the opportunity for a mixture of products to arise from differing regio- and chemoselectivity. 1,1-Disubstituted allenes were coupled to methyl vinyl ketone with excellent chemo-selectivity only when one set of /3-hydrogens was activated by an cy-ester or amide (Equation (69)). If the /3-hydrogens were of similar acidity, a mixture of products was obtained, as in the coupling of allenol 103 with methyl vinyl ketone dienes 104 and 105 are produced in a 1.3 1 mixture (Equation (70)). 

PtCl2 was shown to catalyze a similar Alder-ene transformation, as in the cycloisomerization of allenyne 117 to triene 118 (Equation (76)).78 In the same study, it was noticed that tetrasubstituted allenes cyclized to bicyclic compounds, such as 120 (Scheme 23), under identical PtCl2 conditions, presumably due to A(1,3) strain in intermediate 119. 

Substituted propargylic carbonates react with terminal acetylenes in the presence of a catalytic amount of Pd(PPh3)4 and Cul to produce Sonogashira-type cross-coupling products (Eq. 9.114) [84]. Presumably, the reaction proceeds through an allenylpalladium complex. Addition of a salt, such as KBr, increased the yield of the coupling product. Only tetrasubstituted allenes could be obtained by this procedure. 

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. 

Treatment of bromoallene 27a and phenylethynyltrimethylsilane (35) with a reagent cocktail as given in Eq. 14.3 afforded yne-allene 36 in moderate yield [19]. The key intermediate in the formation of the tetrasubstituted allene 36 is phenylace-tylene, which is generated in situ by spontaneous desilylation of 35 by potassium hydroxide. 

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-... 

Similar differences may be observed in hydrobromination of tetrasubstituted allenes. Ring size and reaction conditions determine the outcome of hydrobromination of cyclic allenes.92... 

It should be pointed out that while the dihalocyclopropane-allene conversion discussed here represents the best general synthesis of allenes, occasional problems due to the formation of side products have been reported. An example is the formation of the bicyclobutane (16) along with the expected allene (equation 53).166 The method is especially unsuitable for the synthesis of tetrasubstituted allenes. Steri-cally demanding substituents on the dihalocyclopropanes are believed to be responsible for the change of course of the reaction. 

Both mono- and diadducts are formed on reaction of dichlorocarbene with tetrasubstituted allenes, e.g. formation of 32 and 33. ... 

Tetrasubstituted allene can also give the diadduct, e.g. formation of monoadduct 4 and diadduct 5.51... 

The lithiocarbon C3Li4 reacts with organic and organometallic substrates to give a variety of highly unsaturated derivatives (Scheme 1). With organometallic halides such as trialkylchlorosilanes, the usual products are tetrasubstituted allenes (2). Alkyl halides often give explosions, but the alkyl sulfates produce mixtures of tetraalkyl derivatives of propyne and propadiene (3). 

Degenerate orbitals are also found in tetrasubstituted allenes, that is, allenes of symmetry Dm (cf. Fig. 9). However, the (e) degeneracy of these last molecules is due to symmetry. 

Among chiral allenes, tetrasubstituted ones are not readily accessible by existing catalytic asymmetric reactions. We therefore examined the possibility of developing the asymmetric alkylation of trisubstituted allenes by a chiral PTC, and found that optically enriched tetrasubstituted allenes could be synthesised through the regio- and stereoselective alleviation of in situ generated cumulenoates with a newly elaborated binaphthyl-based PTC (S)-20 (Scheme 17.26). ... 

Scheme 17.26 Synthesis of tetrasubstituted allenes by asymmetric alkylation of...

Miller extended the scope of the aza-Morita-Baylis-Hillman reaction by employing highly functionalised allenoate 26 as a,p-unsaturated carbonyl component. Catalyst 24 effectively converted racemic trisubstituted allene 26 to tetrasubstituted allene 27 in up to 42 1 diastereomeric ratio and 88% enantiomeric excess (Scheme 22.5). 

Scheme 22.5 As5tmmetric synthesis of tetrasubstituted allenes by aza-Morita-Baylis-Hillman reaction.

Zhang and Widenhoefer have reported a highly regio- anddiastereo-selective method for the intermolecular hydroalkoxylation of aUenes with alcohols [108]. As an example, reaction of 1-phenyl-l,2-butadiene with 2-phenyl-l-ethanol catalyzed by a 1.1 mixture of (IPr)AuCl [IPr = l,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene] and AgOTf in toluene at room temperature led to isolation of ( )-(3-phenethoxy-l-butenyl)benzene in 96% yield as a single regio- and stereo-isomer (Eq. (12.38)). The protocol was effective for primary and secondary alcohols and for monosubstituted, 1,1- and 1,3-disubstituted, trisubstituted, and tetrasubstituted allenes. Transfer of moiety to the newly formed tetrahedral stereocenter in the y o oxy ation of axially chiral 1,3-disubstituted allenes ranged from 0 to 81%, epen ing on the nature of the allene and the concentration of the alcohol. 

While the focus of this chapter is on hydroamination with amines, impressive recent advances in the hydroamidation and hydrocarbamation of allenes have been disclosed. Espinet showed that acyclic carbenes can be used as ligands for Au(I) to realize intramolecular hydrocarbamation [240], while Widenhoefer has used the commercially available l,3-bis[(2,6-diisopropylphenyl)imidazole-2-ylidine] (IPr) NHC in combination with cationic Au(I) to realize regioselective intermolecular hydroamination of 1,1-disubstituted allenes with benzyl carbamate to access allylamines with quaternary centers adjacent to N. This same catalyst can also accommodate 1,3-disubstituted allenes and even tetrasubstituted allenes (Table 15.19) [241]. Interestingly, these products are in contrast to the preferred products accessed with related Au(I)-phosphine complexes in combination with aniline substrates (Table 15.18) [239]. Hydroureation has been achieved intramolecularly [242, 243] and will be later discussed (Section 15.3.6). 

Table 6.1 Dimerization of some tetrasubstituted allenes with polar substituents...

Sometimes, different cyclodimers are formed in the dimerization of tetrasubstituted allenes. For example, from the allene 72 cyclodimers are formed by a 1,4-dipolar addition of the mesomeric form of the allene to the ketenacetal-like double bond in the second molecule, followed by an electrocyclic reaction to give the cyclodimers 73 . 

Tetrasubstituted allenes with cyclopropane substituents, such as 198, react with CF2=CCl2 across the three-membered ring-substituted double bond to give the cycloadduct... 

The allenic dianion (219) is obtained from the acetylene (220) by treatment with two moles of butyl-lithium. Alkylation can be carried out successively using two different reagents to yield the tetrasubstituted allenes (221) hydrolysis of the monoalkylated products yields a -unsaturated aldehydes (222),... 

Alienation Another olefin metathesis-carbonyl olefination sequence utilizing titanacyclobutanes 11 is employed for the preparation of tri- or tetrasubstituted allenes [56]. Titanocene-methylidene 4 generated from 11 reacts with 1,1-disubsti-tuted allenes to produce the a-alkylidenetitanacyclobutanes 25 with the hberation of an olefin. Simple treatment of 25 with ketones and aldehydes at room temperature affords substituted allenes. The vinylidene complexes 26 are formed as the active species in these transformations (Scheme 4.20). 

Finally, it is worthy mentioning other families of diols that are less known but have also been selectively desymmetrized using lipase acylation protocols. Hammel and Deska reported the acetylation of prochiral tetrasubstituted allenic diols, )deld-ing highly enantioenriched axially chiral allenyl monoesters (68-99% ee) with good yields (59-90%), after their reaction with five equivalents of vinyl butanoate in 1,4-diox-ane at 40 °C using PPL as biocatalyst [158]. Other prochiral diols bearing a heteroatom such as boron [159] or sulfur [160], have also been studied, leading usually to modest yields or selectivities. 

Tetrasubstituted allene 2,4-diethyl-2,3-pentadiene was also reacted with H-phosphonate, but the addition reaction was accompanied with double bond isomerization leading to a mixture of allyl- and vinylphosphonates. 

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