Gem-Diacetates

Diabetes mellitus Diabetic retinopathy Diabetic urine Diabmese gem-Diacetates... 

By oxidation of the methyl derivative of an aromatic hydrocarbon with a solution of chromic anhydride in acetic anhydride and acetic acid. The aldehyde formed is immediately converted into the gem-diacetate, which is stable to oxidation. The diacetate is collected and hydrolysed with sulphuric add, for example ... 

If, however, the two carboxyl groups are present on the same carbon e.g., malonic acid series, then also decarboxylation takes place and gem. diacetate (acylals) are produced. 

Yadav JS, Subba Reddy VB, Srihari P (2000) Scandium triflate catalyzed allylation of acetals and gem-diacetates a facile synthesis of homoallyl ethers and acetates. Synlett 673... 

Yadav JS, Reddy BVS, Madhuri C, Sabitha G (2001) Indium(III) chloride catalyzed allylation of gem-diacetates a facile synthesis of homoallyl acetates. Chem Lett 18... 

Compounds containing geminal carboxyl groups (disubstituted malonic acid derivatives) can also be bisdecarboxylated with lead tetraacetate,245 gem-diacetates (acylals) being produced, which are easily hydrolyzable to ketones 246... 

Displacement of allylic gem -diacetates.1 In the presence of Pd(dppe)22 as catalyst and 0,N-bis(trimethylsilyl)acetamide as base, one acetoxy group of an allylic gem-diacetate can be displaced by a stabilized nucleophile. 

Whereas preparation of a-amino acid derivatives by asymmetric allylation of an acyclic iminoglycinate gave a modest enantioselectivity (62% ee) in an early investigation [189], the use of conformationally constrained nucleophiles in an analogous alkylation resulted in high selectivities (Scheme 8E.43) [190], With 2-cyclohexenyl acetate, the alkylation of azlactones occurred with good diastereomeric ratios as well as excellent enantioselectivities. This method provides very facile access to a variety of a-alkylamino acids, which are difficult to synthesize by other methods. When a series of azlactones were alkylated with a prochiral gem-diacetate, excellent enantioselectivities were uniformly obtained for both the major and minor diastereom-ers (Eq. 8E.20 and Table 8E.12). 

Constructing a quaternary center by the alkylation of azlactones has led to development of a new strategy for the synthesis of sphingosine analogs. The azlactone derived from alanine was alkylated with a gem-diacetate to give a 10.5 1 mixture of diastereomers both with 89% ee [191 ]. 

Several procedures for the synthesis of aromatic aldehydes are available which involve the selective oxidation of a methyl group attached to an aromatic ring. A useful general reagent is a solution of chromium trioxide in acetic anhydride and acetic acid. The aldehyde is converted into the gem-diacetate as it is formed and is thus protected from further oxidation. The aldehyde is liberated from the diacetate by hydrolysis under acid conditions the yields, however, are frequently only moderate (e.g. p-nitrobenzaldehyde, Expt 6.117). 

The formation of 1,1-diacetates 5 from aldehydes 4 and Ac20 dates back to early systematic studies by Knoevenagel [9]. A representative example is given with the preparation of compound 5a in Scheme 8.1. Several groups have since then developed improved protocols for acylal formation [10]. It was realized that these gem-diacetates such as compound 5b are perfect substrates for palladium-catalyzed... 

The mechanism of the Perkin condensation involving benzal acetate has been revised.17 It has been demonstrated that the enolate of the gem-diacetate derived from the aromatic aldehyde and acetic anhydride-rather than the enolate of acetic anhydride itself-adds to the aldehyde in the key step. The deprotonation of the diacetate to the enolate appeared to be assisted electrophilically by the neighbouring acetate group. 

This BI3 complex cleaves aryl methyl ethers to phenols at room temperature in good yield. Dialkyl ethers are converted into iodinated products. It also converts terminal gem-diacetates into aldehydes.3... 

Allylic silanes react with gem-diacetates in the presence of InCl3 to give a homo-allylic acetate or with dimethyl acetals and TMSOTf in an ionic liquid to give the homoallylic methyl etherJ Allylic alcohols can be treated with TMS—Cl and Nal,... 

In the case of methylbenzenes, oxidation of the side chain can be interrupted by trapping the aldehyde in the form of a non-oxidizable derivative, the gem-diacetate (Latin Gemini, twins), which is isolated and then hydrolyzed. 

Indium(III) chloride catalyzes the allylation of gem-diacetates with allyltrimethylsi-lane to afford the corresponding homoallylic acetates (Scheme 8.131) [174]. Gly-cals react with silyl nucleophiles, e.g. allyltrimethylsilane, cyanotrirnethylsilane, and azidotrimethylsilane, in the presence of a catalytic amount of InBr, to give the corresponding 2,3-unsaturated allyl-, cyano-, and azidoglycosides, respectively (Scheme 8.132) [175]. 

Acetylation. Alcohols, thiols, and amines are acetylated by a CufOT j-catalyzed reaction with acetic anhydride at room temperature. Various aldehydes (but not ketones) are similarly transformed into gem-diacetates." ... 

Allylic gem.-diaceUUes In the presence of this Pd(0) catalyst, propargyl acetates react with acetic acid to form (E)-allylic gem-diacetates in 55-79% yield (equation I). Mixed gem-dicarboxylates can also be prepared. 

The azalactone 152 has been used as a prochiral nucleophile in a similar process providing the substitution product 153 and 154 upon reaction with either cyclohexenyl acetate 92 or the gem-diacetate... 

Allylation of acetals and gem-diacetates using Sc(OTf)3 as a catalyst was also successful [13]. In addition, synthesis of Cbz-protected homoallyl amines was achieved using allyltrimethylsilane as an allylating reagent in the presence of Sc(OTf)3 [14]. 

---