Central-to-axial chirality transfer

Chan has discovered a completely atropdiasteroselective synthesis of a biaryl diphosphine by asymmetric intramolecular Ullmann coupling or Fe(m)-promoted oxidative coupling. A chiral atropisomeric biaryl bisphosphine ligand 2 was synthesized through this central-to-axial chirality transfer.38 Recently, a xylyl-biaryl bisphosphine ligand, Xyl-TetraPHEMP, was introduced by Moran, and is found to be effective for the Ru-catalyzed hydrogenation of aryl ketone.39... 

After the prototropic isomerizations, these rearrangements are the second most important synthetic methodology. In the concerted reactions a highly selective central to axial chirality transfer is possible, but this has already been exploited before the timeframe covered by this review and has been summarized [378]. 

The concept of central-to-axial chirality transfer is demonstrated in the benzannulation of carbene complex 18 with 1-pentyne (Scheme 11.9) [30] that affords configurationally stable allocolchicin derivatives like 19 as a single diastereomer bearing a functionalized C ring. Modification of both oxygen functionalities at C-8 and C-11 (see 19) and the choice of the alkyne component used in the benzannulation allow for a flexible substitution pattern at positions C-8 through C-11 of the allocolchicin C ring. 

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]. 

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). 

Intramolecular pinacol coupling of 2,2 -biaryldicarbaldehyde with samarium(ll) iodide shows that axial chirality transfer to central chirality proceeds in a stereospecific manner. ... 

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. 

The stereospecificity of the reaction was already mentioned around 1990 [34, 35]. Since enantiomerically pure allenes are available by a number of methods [36, 37], this clean axial to central chirality transfer is very useful in organic synthesis. Several further examples can be found in the literature [38, 39], one example being the cydi-zation of 74 to 75 (Scheme 15.17) [40]. 

Further applications include the synthesis of ( )-pinidine 132 (Scheme 15.41) [91] and the synthesis of (K)-(-)-coniine via an axial to central chirality transfer in the cydization of enantiomerically pure 133 to 134 [92]. 

In these reactions a clean axial to central chirality transfer can be achieved. The phosphine oxide 232 cleanly delivers 234 as a single diastereomer the relative configuration shown was determined by single-crystal X-ray analysis (Scheme 15.73) [143]. 

For example, the copper catalyzed addition of Grignard compounds to alkynyl substituted /(-lactones 55 delivers /S-allenic acids 56 in high yields [38], During these reactions, the central chirality of one of the stereogenic centers of the /Mactone is transferred to the axial chirality of the allene. 

In 1999, Suzuki completed the synthesis of pradimicinone,63 the aromatic pen-tacyclic aglycone moiety common to both the pradimicin and benanomicin antibiotic classes. The key step in the approach involves a Sml2-mediated pinacol cyclisation of an axially chiral 2,2 -biaryldicarbaldehyde 54 (Scheme 7.24). This cyclisation proceeds to give the trans- 1,2-diol 55 in quantitative yield and with complete transfer of the axial chirality in the starting material to the central chirality of the product, which is obtained in enantiomerically pure form. The selectivity and chiral transfer were attributed to an i e,i e-cyclisation mode, giving the diequatorial product.63... 

Crotonates bearing an atropisomeric 1-naphthamide moiety can be reacted in a Sml2-mediated reductive coupling with a variety of aldehydes to yield enantiomerically enriched 7-butyrolactones. The crotonate derived from 2-hydroxy-8-methoxy-Tnaphthamide reacted with pentanal to afford the highest ee of >99% in a combined yield of 90% with a cisltrans-mt o of 90 10. The chiral crotonate can also be linked to a Rink amide resin with the C-8 oxygen, and in the solid-phase reaction the same level of axial-to-central chirality transfer was obtained (Equation 103) <2006JOC2445>. 

Interaction of a strong base with nitrosoureas 601 led to the formation of di-azocyclopropanes 603, which proved to be less stable and to decompose via a carbene intermediate (622) (for trapping of 603, see Refs 43,101,174, 606), rearranging to allenes (624)39 3-85,88.141,174,606.607 (Scheme 16). Allene rearrangement was also reported for a cyclopropyl-l,2-bisnitrosourea 5. By the sequence 623 -4 624 allenes could be synthesized in good yields. It was shown that optical activity was transferred from the nitrosourea precursor 601 (central chirality) to the allene product 624 (axial chirality) 5o. 6s. ss... 

Optically active allenyltrichlorosilanes can be prepared by the Pd-catalyzed asymmetric hydrosilylation of 1,3-enynes with I ISiCb, (Scheme 10.138) [389]. In this reaction use of bisPPFOMe (125) as the chiral ligand achieves high enantioselectivity. The allenylsilanes smoothly react with PhCHO in DMF to give optically active homopropargyl alcohols, and the axial chirality of allenylsilanes is completely transferred to the central chirality of the products by a syn-SE process. 

The complete transfer of axial chirality to central chirality during the Stevens rearrangement of binaphthyl compounds is demonstrated (eq 41). Treatment with an excess of BuLi results first into the expected Stevens [l,2]-benzyl shift, which... 

Axial-to-central chirality transfer in cyclization processes 13CSR8434. Bifunctional primary amine-thioureas in asymmetric organocatalysis 13OBC7051. 

Meyers AI, Wettlaufer DG (1984) Complete intramolecular transfer of a central chiral element to an axial chiral element. Oxidation of (S)-4-naphthyldihydroquinolines to (S)-4-Naphthylquinolines. J Am Chem Soc 106 1135-1136... 

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