Anti:syn control

Allylic Chromium Reagents 1,2-Asymmetric Induction (Anti/Syn Control)... 

An interesting case of product-controlled simple diastereoselectivity has been reported103. [l-[Methyl(nitrosoamino)]-2-propenyl]lithium adds to benzaldehyde at — 78°C to give the amino alcohol with an anti/syn ratio of 65 35, but equilibration of the reversible reaction at room temperature leads exclusively to the more stable, vv -product. 

Racemic methyl cucurbate and racemic methyl epijasmonate were synthesized via a thermal Alder-ene reaction (Scheme 40).99 The newly formed stereocenters are controlled by the existing protected hydroxyl group of 166 in an anti/syn relationship. 

Addition of the indium reagent derived from the foregoing (P)-allenylstannane to /8-benzyloxy-a-methylpropanal as the aldehyde substrate at low temperature afforded a 70 30 mixture of anti,anti and anti,syn adducts (Eq. 9.141). The improved dia-stereoselectivity in this case can be attributed to substrate control, reflecting the chelating ability of an OBn versus an ODPS group. The lower temperature may also account for the improved diasteroselectivity. 

The use of chiral Br0nsted acids is illustrated in Eq. 93 as a method for catalyst-controlled double diastereoselective additions of pinacol allylic boronates. Aside from circumventing the need for a chiral boronate, these additions can lead to very good amplification of facial stereoselectivity. For example, compared to both non-catalyzed (room temperature, Eq. 90) and SnCU-catalyzed variants, the use of the matched diol-SnCU enantiomer at a low temperature leads to a significant improvement in the proportion of the desired anti-syn diastereomer in the crotylation of aldehyde 117 with pinacolate reagent (Z)-7 (Eq. 93). Moreover, unlike reagent (Z)-ll (Eq. 91) none of the other diastereomers arising from Z- to E-isomerization is observed. 

Additions of the chiral allenylzinc reagents to enantiomeric -methyl-/ -OBn aldehyde substrates proceeded with a high degree of reagent control to afford anti,syn or anti,anti adducts (equations 23 and 24). In these additions, the preferred anti orientation of the allenyl methyl and the aldehyde substituents requires the reaction to proceed by the normally less-favored anti Felkin-Anh pathway (equation 25). 

Under thermodynamic control, the homoallylic alcohol is obtained with an anti/syn selectivity up to 95 531-33. In order to prevent competition between the transmetallation and the complexation of the aldehyde, it is important that the allyltin reagent is added first to the Lewis acid. This is termed a reverse addition . 

The mechanism is complicated by the possibility of anti-syn-isomerization and by n - a-rearrangements (it - r 3-allyl Act - r 1 -allyl). In the case of C2-unsubstituted dienes such as BD the syn-form is thermodynamically favored [646,647] whereas the anti-isomer is kinetically favored [648]. If monomer insertion is faster than the anti-syn-rearrangement the formation of the czs- 1,4-polymer is favored. A higher trans- 1,4-content is obtained if monomer insertion is slow compared to anti-syn-isomerization. Thus, the microstructure of the polymer (czs-1,4- and frazzs-1,4-structures) is a result of the ratio of the relative rates of monomer insertion and anti-syn-isomerization. As a consequence of these considerations an influence of monomer concentration on cis/trans-content of BR can be predicted as demonstrated by Sabirov et al. [649]. A reduction of monomer concentration results in a lower rate of monomer insertion and yields a higher trans-1,4-content. On the other hand the czs-1,4-content increases with increasing monomer concentration. These theoretical considerations were experimentally verified by Dolgoplosk et al. and Iovu et al. [133,650,651]. Furthermore, an increase of the polymerization temperature favors the formation of the kinetically controlled product and results in a higher cis- 1,4-content [486]. l,2-poly(butadiene) can be formed from the anti- as well as from the syn-isomer. In both cases 2,1-insertion occurs [486]. By the addition of electron donors the number of vacant coordination sites at the metal center is reduced. The reduction of coordination sites for BD results in the formation of the 1,2-polymer. In summary, the microstructure of poly(diene) depends on steric factors on the metal site, monomer concentration and temperature. 

Additions of the presumed /3-oxygenated allylic trichlorostannane to a-methyl, a-benzyloxy and /3-benzyloxy aldehydes are characterized by high reagent-controlled diastereoselectivity (Eq. 48) [70]. In the several examples examined aldehyde facial attack is little influenced by the resident chirality of the aldehyde. The result is particularly striking with the a-methyl aldehyde where the syn, syn adduct is the product of Felkin-Ahn addition and the anti, syn adduct is the anh-Felkin-Ahn or chelation-controlled adduct. 

Further evidence for the racemization premise was obtained from experiments employing (R)-a-methyl-/3-ODPS propanal (Eq, 85) [93]. Addition of the allenylin-dium chloride derived from an enantioenriched (P)-allenyl stannane yielded a 60 40 mixture of anti, anti and anti, syn adducts, not unlike that obtained when racemic alle-nylstannane was used to generate the transient allenylindium chloride. When the (5) aldehyde was employed for this addition a 40 60 mixture of anti, anti and anti, syn adducts was formed. Thus it can be concluded that substrate control (Felkin-Ahn or chelation) is, at best, only modest in these reactions, and that the rate of racemization is only slightly less than the rate of addition. The use of -benzyloxy-a-methyl propa-... 

The scope of the reaction is further demonstrated by the reaction of matched and mismatched reagent pairs with aldehyde (5)-106 (Scheme 10-109).The anti,anti adduct 313 is obtained in 87% yield from (R)-312 and the anti,syn adduct 314 is formed in 88% yield from (5)-312. Only a trace of the diastereomeric product was detected by H-NMR analysis. These reactions indicate that the addition is strongly reagent controlled. 

Keck further demonstrated that the anti,syn- ddact 114 can be formed with high selectivity from the chelate-controlled reaction of aldehyde 97a with the (y-silyloxyallyl)tri-n-butylstannane 113, presumably through transition state 115 (Eq.(11.3)) [90]. 

Reactions of enantiomeric allenylstannanes (P)-286 and (M)-286 with (5)-2-benzyloxypropion-aldehyde, in the presence of MgBr2 OEt2, are highly substrate-controlled processes, giving the syn,syn-297 and anti,syn-298 diastereomers, respectively (Scheme 5.2.65). 

Now, whether this local syn arrangement is anti or syn to the more remote chiral centre in the enol borinate (1,3-control) can be controlled by the use of one enantiomer or other of a chiral boron reagent. The cis enol borinate with achiral boron reagent does not have much will of its own and leads to a 1 1.2 ratio of syn, syn anti, syn. 

Both 2,3-e iio,eM(io-dimethylnorboman-7-one 23 and 2,3-enc o,e iio-diethylnor boman-7-one 24 are anti-selective. However, the anti-selectivity of the diethyl derivative is significantly superior to that of the dimethyl derivative. For instance, on reduction with LiAlH4, the anti syn selectivity is 79 21 for 24 and only 55 45 for 23. If cjvicinai —> a interaction, as advocated by Cieplak, is indeed the control element, both molecules will be predicted to exhibit syn selectivity because (a) crc H is more electron-donating than cjc c and (b) the anti side has two endo Cc-h bonds in lieu of the two endo cjc c bonds on the syn side. Consequently, the Cci ce and CJC4-C5 bonds, both on the anti side, must be more electron-rich than the tfci-C2... 

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