Allenes asymmetric synthesis

Arai Y., Koizumi T. Synthesis and Asymmetric Diels-Alder Reactions of Chiral. Alpha.,.Beta.-Unsaturated Sulfoxides Bearing a 2-Exo-Hydroxy-lO-Bornyl Group As an Efficient Ligand on the Sulfur Center Rev. Heteroat. Chem. 1992 6 202-217 Keywords allenic sulfoxide, a-sulfinylmaleate, a-sulfinylmaleimide, asymmetric synthesis, chiral unsaturated sulfoxides... 

Asymmetric hydrosilylation can be extended to 1,3-diynes for the synthesis of optically active allenes, which are of great importance in organic synthesis, and few synthetic methods are known for their asymmetric synthesis with chiral catalysts. Catalytic asymmetric hydrosilylation of butadiynes provides a possible way to optically allenes, though the selectivity and scope of this reaction are relatively low. A chiral rhodium complex coordinated with (2S,4S)-PPM turned out to be the best catalyst for the asymmetric hydrosilylation of butadiyne to give an allene of 22% ee (Scheme 3-20) [59]. 

An asymmetric synthesis of the spiropentanes 630, albeit with low enantiomeric excess, was achieved by the reaction of allenes 629 with diazomethane in the presence of an optically pure copper (II) chelate complex (R) or (S)-631 (Scheme 94) [170],... 

All of the reactions discussed above are cyclic carbometallation reactions of metallacycles. Very recently, an interesting Cr-catalyzed carboalumination of propargyl derivatives producing allenes via a carbometallation-elimina-tion sequence has been studied. This reaction provides an asymmetric synthesis of chiral allenes (Scheme 57). 

Axial Chirality. For a system with four groups arranged out of the plane in pairs about an axis, the system is asymmetric when the groups on each side of the axis are different. Such a system is referred to as an axial chiral system. This structure can be considered a variant of central chirality. Some axial chiral molecules are allenes, alkylidene cyclohexanes, spiranes, and biaryls (along with their respective isomorphs). For example, compound 7a (binaphthol), which belongs to the class of biaryl-type axial chiral compounds, is extensively used in asymmetric synthesis. Examples of axial chiral compounds are given in Figure 1-5. 

The axially chiral (allenylmethyl) silanes 110 were also prepared in optically active form using chiral Pd catalysts [98]. For the asymmetric synthesis of 110, a Pd/(R)-segphos system was much better in terms of enantioselectivity than the Pd/(R)-binap catalyst. Under the optimized conditions, 110m and llOt were obtained in 79% ee (57% yield) and 87% ee (63% yield), respectively (Scheme 3.56). The enantio-merically enriched (allenylmethyl) silanes 110 served for Lewis acid-promoted SE reaction with tBuCH(OMe)2 to give conjugated dienes 111 with a newly formed chiral carbon center (Scheme 3.56). During the SE reaction, the allenic axial chirality was transferred to the carbon central chirality with up to 88% transfer efficiency. 

In 2001, a palladium-catalyzed asymmetric hydrosilylation of 4-substituted-but-l-en-3-ynes (146) was reported by Hayashi and co-workers [115]. It was found that a monodentate bulky chiral phosphine, (S)-(R)-bisPPFOMe, was effective for the asymmetric synthesis of the axially chiral allenes 147 and up to 90% ee was achieved (Scheme 3.75). The bulky substituent at the 4-position in 146 is essential for the selective formation of the allene 147 the reaction of nC6H13C=CCH=CH2 gave a complex mixture of hydrosilylation products which consisted of <20% of the allenylsilane. 

Scheme 4.7 Asymmetric synthesis of allene via a diastereoselective reduction.

The asymmetric synthesis of allenes via enantioselective hydrogenation of ketones with ruthenium(II) catalyst was reported by Malacria and co-workers (Scheme 4.11) [15, 16]. The ketone 46 was hydrogenated in the presence of iPrOH, KOH and 5 mol% of a chiral ruthenium catalyst, prepared from [(p-cymene) RuC12]2 and (S,S)-TsDPEN (2 equiv./Ru), to afford 47 in 75% yield with 95% ee. The alcohol 47 was converted into the corresponding chiral allene 48 (>95% ee) by the reaction of the corresponding mesylate with MeCu(CN)MgBr. A phosphine oxide derivative of the allenediyne 48 was proved to be a substrate for a cobalt-mediated [2 + 2+ 2] cycloaddition. 

Carreira and co-workers developed a highly efficient enantioselective addition of terminal alkynes to aldehydes giving propargyl alcohols by the mediation of zinc tri-flate and N-methylephedrine [17]. This reaction serves as a convenient and powerful synthetic route to a wide variety of enantioenriched allenes via propargyl alcohols. Dieter and Yu applied this alkynylation to the asymmetric synthesis of allenes (Scheme 4.12) [18]. Reaction of phenylacetylene with isobutyraldehyde afforded the propargyl alcohol in 80% yield with 99% ee, which was mesylated to 49 in quantitative yield. Reaction of 49 with the cyanocuprate 50 afforded the desired allene 51 with 83% ee. 

Scheme 4.12 Asymmetric synthesis of allene 51 via Carreira s alkynylation.

In 1963, an asymmetric synthesis of chloroallenes was reported by the SNi reaction of propargyl alcohols with thionyl chloride [34]. Since then, rearrangement of pro-pargylic precursors has been one of the most useful methodologies for the synthesis of allenes [35]. Treatment of 84, obtained by asymmetric reduction with LiAlH4-Dar-von alcohol complex, with thionyl bromide gave 86 as the major product via 85 (Scheme 4.21) [36],... 

Scheme 4.22 Asymmetric synthesis of allene 89 by the orthoester Claisen rearrangement.

Scheme 4.26 [2,3] Wittig rearrangement for asymmetric synthesis of allenic alcohol 102.

Scheme 4.27 Asymmetric synthesis of allenes by oxidative rearrangement.

Scheme 4.34 Asymmetric synthesis of fluorine-containing allenes.

Scheme 4.48 Asymmetric synthesis of/i-allenic acids 184,186 and (-)-malyngolide 187 via /Mactones.

Scheme 4.49 Asymmetric synthesis of allenic alcohols from cyclic carbonates or sulfites...

Scheme 4.50 Asymmetric synthesis of allenes via stable propargyllithium intermediates...

Scheme 4.52 Asymmetric synthesis of allenes via the allenyl- or propargylsilanes.

Shioiri and co-workers developed a catalytic asymmetric synthesis of allenes by isomerization of the alkyne 240 to allene 242 under the control of a chiral phase-transfer catalyst 241 (Scheme 4.62) [98], Although the enantiomeric excess is not high (35% ee), this is the first example of the asymmetric isomerization of alkynes under phase-transfer catalyzed conditions. 

Direct Asymmetric Synthesis of Allenes Using an External Chiral Catalyst... 

The asymmetric synthesis of allenes by stereoselective manipulations of enantio-merically pure or enriched substrates relies on the availability of such optically active substrates. In contrast, a direct synthesis of allenes by the reaction of prochiral substrates in the presence of an external asymmetric catalyst is an almost ideal process [102]. Most of the catalytic asymmetric syntheses in organic chemistry involve the creation of chiral tetrahedral carbon centers [103], whereas the asymmetric synthesis of allenes requires the construction of an axis of chirality. 

The catalytic asymmetric synthesis of allenes was first achieved by Elsevier and co-workers in 1989 [104]. A palladium-catalyzed cross-coupling reaction of an allenyl-metal compound 250 (M = ZnCl, MgCl or Cu) with iodobenzene in the presence of DIOP 251 gave 252 in 25% ee (Scheme 4.65). The synthesis of 252 by the reaction of 250 (M = Br) with phenylzinc chloride in the presence of a chiral palladium catalyst gave a quantitative conversion but very low enantiomeric excesses (3-9% ee). 

Scheme 4.65 First catalytic asymmetric synthesis of allene 252 with a chiral palladium catalyst.

Scheme 4.67 Asymmetric synthesis of allene 260 by rhodium-catalyzed hydrosilylation of diyne 258.

Scheme 4.71 Camphor-derived auxiliary for the asymmetric synthesis of chiral allene ether 280.

The 36d-LAH complex has been used in the asymmetric synthesis of (3-allenic alcohols by reduction of enynols (41) as shown in eq. [14]. Although similar... 

Allenes are versatile intermediates in organic synthesis and a variety of useful applications has been established [66]. A very interesting feature of allenes is their axial chirality along the cumulated diene system, so that optically active allenes were frequently used in asymmetric synthesis, in most cases being prepared from enantiomerically enriched precursors. 

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