Carbon chain inversion

D-glucose and of the fact that 9 and 25 differ only in the oxidation state at C-l and C-6 [the relationship between 9 and 25 was originally recognized by Fischer and Piloty8, and it subsequently played a major role1 in the development of practical syntheses of L-ascorbic acid (6) from D-glucose (25) by carbon-chain inversion that is, reduction at C- ... 

No Carbon-Chain Inversion. This section will discuss the methods by which D-glucose has been converted to L-ascorbic acid without carbon-chain inversion. These syntheses of L-ascorbic acid from D-glucose without carbon-chain inversion involve the oxidation of D-glucose at Cl and C2, and the inversion of chirality at C5. 

Figure 4.3 t-Ascorbic acid from D-glucose with carbon-chain inversion... 

A careful consideration of the Reichstein synthe.sis shows that C-1 of the D-glucose precursor molecule becomes C-6 in the L-ascorbic acid product. This is known as carbon-chain inversion and a number of further synthetic procedures have been reported in recent years involving similar glucose C-1/C-6 inversion. The path of the glucose C-1 carbon is asterisked in Figure 4.3. 

R,8S)-(+)-Disparlure (12) is the female sex pheromone of the gypsy moth (Lymantria dispar). Advent of Sharpless asymmetric dihydroxylation (AD) allowed several new syntheses of 12 possible. Sharpless synthesized 12 as shown in Scheme 17 [27]. Scheme 18 summarizes Ko s synthesis of 12 employing AD-mix-a [28]. He extended the carbon chain of A by Payne rearrangement followed by alkylation of an alkynide anion with the resulting epoxide to give B. Keinan developed another AD-based synthesis of 12 as shown in Scheme 19 [29]. Mit-sunobu inversion of A to give B was the key step, and the diol C could be purified by recrystallization. 

The bond polarization due to electronegative substituents should propagate along the carbon chain and decrease with the inverse cube of the distance. Much smaller inductive effects are thus expected in /I and y position. Table 3.2 shows, however, that the observed ft and y effects do not correlate at all with substituent electronegativities and that the influence of other effects must therefore be involved. 

As stated above, intermolecular coupling reactions between carbon atoms are of limited use. In the classical Wurtz reaction two identical primary alkyl iodide molecules are reduced by sodium. n-Hectane (C100H202), for example, has been made by this method in 60% yield (G. Stallberg, 1956). The unsymmetrical coupling of two alkyl halides can be achieved via dialkylcuprates. The first halide, which may have a branched carbon chain, is lithiated and allowed to react with copper(I) salts. The resulting dialkylcuprate can then be coupled with alkyl or aryl iodides or bromides. Although the reaction probably involves radicals it is quite stereoselective and leads to inversion of chiral halides. For example, lithium diphenyl-cuprate reacts with (R)-2-bromobutane with 90% stereoselectivity to form (S)-2-phenylbutane (G.M. Whitesides, 1969). 

All synthetic routes that have been described, up to this point, have involved, in various sequences, reduction of D-glucose (8) at C-l, and oxidation at C-5 and C-6, resulting in inversion of the carbon chain. In the next two Sections will be described syntheses of 1 in which the carbon chain of D-glucose is not inverted, and C-l in 8 becomes C-I in L-ascorbic acid (1). 

Unnatural d-DET was needed to get the right absolute stereochemistry and 37 was not isolated but protected as a benzyl ether 39 before reaction with allylamine gave the carbon chain of 35. Conversion of OH into NH2 now required inversion. 

A recent study (Tl) showed that in Penicillium notatum, n-glucose-was converted to n-araboascorbic acid with 80 % of the activity in carbon 1, showing the possibility of formation of D-araboascorbic acid from D-glucose without rupture and inversion of the carbon chain. 

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