Allenes axial chirality

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. 

Many syntheses of chiral allenes of high enantiomeric purity start from chiral precursors, notably propynyl compounds, with the central chirality being converted into allene axial chirality by a mechanism-controlled reaction. 

The chirality at sulfur in the sulfinylallenes 1 is lost on prolonged standing. The racemization of the sulfur center must be due to an equilibration between the propynylsulfenate and the sulfinylallene, which racemizes the sulfur center but does not affect the stereochemical integrity of the allene axial chirality. 

The catalytic reaction giving allenes by the addition of a hydrosilane twice to 1,3-diynes65 has been applied to the asymmetric synthesis of axially chiral allenylsilanes although the selectivity and scope of this reaction are relatively low. A chiral rhodium complex coordinated with (23, 43 )-PPM is the best catalyst for the addition of phenyldimethyl-silane to diyne 52 giving allene 53 with 22% ee (Scheme 14).66 663... 

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. 

INAS reactions of carbonates of 3,5-dienyl alcohols (i. e., involving a conjugated diene moiety) [72] and 3,4-dienyl alcohols (i. e., having an allene moiety) [73] also proceed smoothly to furnish the corresponding (3,y-unsaturated esters. The reaction of 4-silyl- or 4-stannyl-3,4-dienyl carbonate having axial chirality proceeds with excellent chirality transfer, as exemplified in Eq. 9.39, thereby affording a novel access to optically active a-substituted p.y-unsaturated esters [73],... 

In this context, albeit not real isomerizations, the [2,3]-Wittig rearrangements induced by a tin-lithium exchange must also be mentioned. Starting from enantio-merically pure propargylic alcohols, high ee values for the axial chiral allenes could be observed as shown for 153 (Scheme 1.69) [505, 506],... 

The Diels-Alder reaction outlined above is a typical example of the utilization of axially chiral allenes, accessible through 1,6-addition or other methods, to generate selectively new stereogenic centers. This transfer of chirality is also possible via in-termolecular Diels-Alder reactions of vinylallenes [57], aldol reactions of allenyl eno-lates [19f] and Ireland-Claisen rearrangements of silyl allenylketene acetals [58]. Furthermore, it has been utilized recently in the diastereoselective oxidation of titanium allenyl enolates (formed by deprotonation of /3-allenecarboxylates of type 65 and transmetalation with titanocene dichloride) with dimethyl dioxirane (DMDO) [25, 59] and in subsequent acid- or gold-catalyzed cycloisomerization reactions of a-hydroxyallenes into 2,5-dihydrofurans (cf. Chapter 15) [25, 59, 60],... 

A propargyl substrate having a substituent at the propargyl position is centrally chiral and an allenic product from the SN2 substitution reaction will be axially chiral. Chirality transfer in the SN2 reaction, accordingly, may be achieved starting from an enantiomerically enriched propargyl electrophile [29]. The reactions in Scheme 3.11 are some recent examples of the center to axis chirality transfer by Pd-catalyzed SN2 reactions [41, 42]. 

Efficient chirality transfer was reported for the reactions of enantiomerically enriched 75 with Grignard reagents [85], Using 10mol% of CuBr or CuCN-2LiBr, the axially chiral allenes 76 are obtained from the centrally chiral 75 with nearly complete chirality transfer (Scheme 3.39). 

An example of an iron-catalyzed C-C bond formation reaction was reported in 2001 [89]. Treatment of propargyl sulfides 87 with trimethylsilyldiazomethane in the presence of 5 mol% FeCl2(dppb) gave substituted homoallenylsilanes 88 in good to moderate yields (Scheme 3.43). The silanes 88d and 88e, which bear two centers of chirality, were obtained as 1 1 mixtures of diastereomers. Slight diastereoselectivity (2 1) was seen for the formation 88f, which is an axially chiral allene with a sterogenic center. 

The palladium-catalyzed allene preparation method was extended to an asymmetric counterpart using a Pd/(R)-binap species as a chiral catalyst and axially chiral allenes 103 were obtained with good eantioselectivity [96]. It was found that the pres-... 

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. 

This chapter has discussed the transition metal-catalyzed synthesis of allenes. Because allenes have attracted considerable attention as useful synthons for synthetic organic chemistry, effective synthetic methods for their preparation are desirable. Some recent reports have demonstrated the potential usefulness of optically active axially chiral allenes as chiral synthons however, methods for supplying the enantiomerically enriched allenes are still limited. Apparently, transition metal-catalyzed reactions can provide solutions to these problems. From the economics point of view, the enantioselective synthesis of axially chiral allenes from achiral precursors using catalytic amounts of chiral transition metal catalysts is especially attractive. Considering these facts, further novel metal-catalyzed reactions for the preparation of allenes will certainly be developed in the future. 

The stereoselective elimination reaction of suitably substituted allylic compounds is a reasonable approach to the construction of the propadiene framework. Central chirality at the allylic position is transferred to axial chirality of the allene by stereoselective /3-elimination (Scheme 4.53). 

A variety of optically active 4,4-disubstituted allenecarboxylates 245 were provided by HWE reaction of intermediate disubstituted ketene acetates 244 with homochiral HWE reagents 246 developed by Tanaka and co-workers (Scheme 4.63) [99]. a,a-Di-substituted phenyl or 2,6-di-tert-butyl-4-methylphenyl (BHT) acetates 243 were used for the formation of 245 [100]. Addition of ZnCl2 to a solution of the lithiated phos-phonate may cause binding of the rigidly chelated phosphonate anion by Zn2+, where the axially chiral binaphthyl group dictates the orientation of the approach to the electrophile from the less hindered si phase of the reagent. Similarly, the aryl phosphorus methylphosphonium salt 248 was converted to a titanium ylide, which was condensed with aromatic aldehydes to provide allenes 249 with poor ee (Scheme 4.64) [101]. 

So far, axially chiral donor-substituted allenes have rarely been used although they should be capable of transferring their stereochemical information to a new center of chirality. This lack may be due to the difficulties of generating axially chiral donor-substituted allenes with high enantiomeric purity. We expect that this gap will be filled in near future. 

The origin of this preference is illustrated by Eq. 13.3. When the allene is terminally substituted, as it is in 6, it is axially chiral. Consequently, there are two reaction pathways that the allenyl vinyl ketone (10 in Eq. 13.3) can follow. The major reaction pathway for 10 involves counterclockwise conrotation, leading to 11, whereas the... 

Application of silver-catalyzed cydization is a key step in the synthesis of clavepic-tines A and B, a synthesis which also established the absolute configuration for these compounds. With regard to the allene unit and the heterocycle, enantiomeri-cally pure precursor 129 was prepared and then cyclized to the quinolizidine 130 with AgN03 in a diastereoselective manner (Scheme 15.40) [89, 90]. The synthesis was conducted with an inseparable 1 1 mixture of diastereomers at C-14 from the diastereomerically pure allene with regard to the axial chirality of the allene a 7 1 mixture of diastereomers (at C-10) was formed. 

Early attempts atintrodncing axial chirality to allenes (viacarbenerearrangement) or to biaryls [throngh (—)-sparteine-mediated deprotonation of 2,2, 6,6 -tetramethylbiphenyl] proved less snccessfnl. 

The sulfenate-sulfoxide and sulfinate-sulfone rearrangements are very reliable and proceed with complete syn stereoselectivity17, ls. The allenic sulfoxides can be used for the synthesis of chiral alkylallenes with retention of configuration (see Section 1.1.3.). The relative configuration at sulfur in the allenic sulfoxides is not important for further synthetic purposes and racemization at sulfur is often observed without affecting the allenic axial dissymmetry. 

While the even-numbered cumulene gives (Z)-111 of C2y symmetry and ( )-112 of C2h symmetry, the odd-numbered cumulene gives two enantiomers 113 and 114 both of C2 symmetry. Bridging these two substituents A and A in 113 or 114 by a chain gives rise to a single-bridged allene of C2 symmetry whose chirality can be specified following the axial chirality rule 11 ... 

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