Regioselective bis-functionalization

Figure 9 Regioselective bis-functionalization of C60 using a saccharide as an imprinting template.

Nishimura and co-workers used bis(o-quinodimethanes) connected by a.n+dioxa-methylene tethers for the regioselective bis-functionalization by double Diels-Alder addition (Scheme 7-14) [93]. The tethered bis(o-quinodimethanes) were intermediately formed by heating the bis(bromomethyl) derivatives 72a-d together with C, in toluene in the presence of KI and [18]crown-6 [90]. With an 0-(CH2)2-0 tether (72a), the cis-2 and cw-3 bis-adducts 73a and ( )-74a were isolated in 10% and 8% yield, respec-... 

Scheme 7-14 Regioselective bis-functionalizations by double Diels-Alder addition of tethered bis(o-quinodimethanes) to Cgo [93, 94].

Scheme 7-15 Regioselective bis-functionalization of Cgo using a saccharide as imprinting template [95, 96],...

Scheme 7-16 Regioselective bis-functionalization by double [3 + 2] cycloaddition of tethered vinylcarbenes to Cgo [98, 99].

While this is certainly a success story the chemistry of phthalocyanines suffers from two main drawbacks (i) the strong tendeney of phthalocyanines to form aggregates hinders the isolation and purification of samples by absorption chromatography, and (ii) while 8 identical substituents or a statistical distribution of different substituents can readily be introduced, phthalocyanines with reduced symmetry and regioselective mono- or bis-functionalization require extremely tedious procedures. 

Porco s route to (—)-kinamycin C (3) began with 2,5-dihydroxybenzaldehyde (38), which was elaborated to the enone 35 by the sequence shown in Scheme 3.6. Regioselective bromination [25] followed by methylation and reduction of the aldehyde function afforded the primary alcohol 39. The alcohol 39 was dearomatized by treatment with bis(acetoxy)iodobenzene, to afford the quinone monoketal 41. Transketalization with 1,3-propanediol followed by silylation of the primary alcohol generated the silyl ether 42 in 72 % yield over three steps. 

Carbonylations involving catalytic amounts of Pd(n) and substoichiometric Cu(n) have been developed for the synthesis of lactams. This Wacker-type process is assumed to proceed via C-H functionalization involving a palladacycle intermediate such a hypothesis is backed by the high degree of regioselectivity attained, when using a bis-chelating substrate (Equation (114)).104... 

Regioselective protection of the pentaol 230 with bis-trichloromethyl carbonate and subsequent acetic anhydride treatment affords the C-10 acetoxy C-l, C-2 carbonate compound 231 in good yield. Deprotection of the acetonide function and regioselective silylation of the C-7 hydroxyl group, followed by... 

As expected, additions to alkynes are also subject to control by polar functions nearby. Thus, nucleophilic attack on trifluoromethylacetylene [116], cyanoacetylene [137], and ethylthioacetylene [138] occurs at the terminal jp-hybridized carbon atom, the substituent at the other end of the triple being an acceptor in all cases. This behavior is to be contrasted with the mode of addition on ethoxyacetylene [3 39], aminoacetylenes [120], The vinylogue, 4-dimethyl-aminobut-3-en-l-yne [121], reacts with aniline at the internal position of the akyne linkage. However, a 2 1 regiose-lectivity, favoring the methanol adduct predicted by the polarity alternation rule, has been observed for the addition of jV,jV-bis(trifluoromethyl)ethynylamine [122], It is not known whether steric factors play a role in the decreased regioselectivity. 

The application of the tether-directed remote functionalization allowed the preparation of stereo-isomeric C70 bis-adducts ( )-55a and ( )-55b with complete regioselectivity, featuring the kinetically disfavored five o clock addition pattern [63], see Figure 18. 

The scope of the tether-directed remote functionalization has been expanded from Cgo to the higher fullerene C70, and the described reactions are completely regioselective, featuring, in the case of C70, the kinetically disfavored addition pattern. The crown ether is a real template, since it can be readily removed by transesterification, giving a much-improved access to certain bis-adducts that are not accessible by the direct route. Cation-binding studies by CV reveal that cyclophane-type crown ethers derived from C60 and C70 form stable complexes with metal cations, and a perturbation of the fullerene reduction potentials occurs because the cation is tightly held close to the fullerene surface. This conclusion is of great importance for future developments of fullerene-based electrochemical ion sensors. 

The diphosphine of choice for obtaining good regioselectivity is the bis(diphe-nylphosphino)butane (Scheme 4). It enables addition of a variety of carboxylic acids to phenylacetylene and hexyne. The reaction temperature, which enables complete conversion can be reduced from 80 to 0 °C when the acidity of the carboxylic acid increases in the pK, range from 5 to 1.5. The milder temperature conditions always lead to higher regioselectivity of the addition. The preparation of functionalized (Z)-cnol esters can be conducted in apolar solvents such as toluene or pentane dienyl esters are selectively produced from conjugated enynes [9]. 

The azide function can enter electron-rich aromatic rings for such reactions another more potent system is suitable, i.e. [bis(trifluoroacetoxy)iodo]benzene (BTI) in hexafluoro-2-propanol. Most substrates had at least one methoxy group and the azide group was attached regioselectively to its ort/jo-position, e.g. [101] ... 

---