Cyclohexane-1,2-diacetal protection

Two new methods have been discovered for the selective protection of mmr-diequatorial vicinal diols [44,45]. One of them uses 3,3, 4,4 -tettahydro-6,6 -bi-2W-pyran (bis-DHP) 40 to transform diols into dispiroacetals and the second uses 1,1,2,2-tetrahydromethoxycyclo-hexane 41 to obtain cyclohexane-1,2-diacetal-protected sugars. These two methods have been compared [44,45] and we give here, as representative examples, one procedure for each strategy. 

S. V. Ley and H. W. M. Priepke, Cyclohexane 1,2-diacetals in synthesis. A facile one-pot synthesis of a trisaccharide unit from the common polysaccharide antigen of group B Streptococci using cyclohexane-1,2-diacetal protected rhamnosides, Angew. Chem. Int. Ed 33 (1994) 2290-2292. 

Until recently, the protection of the trans-hydroxyl groups of sugars has been an inefficient process.2 This protection has now been simplified by the introduction of the dispiroketal protecting group,3 and the cyclohexane diacetal (CDA) protecting group.4... 

Further research within in our laboratory has illustrated that certain substrates bearing trans-hydroxyl groups can be directly protected using cyclic and acyclic diones, thus alleviating the requirement for prior formation of the tetramethoxydiacetals.6 For example, butane-2,3-dione has proved particularly useful for the preparation of butane diacetal (BDA) derivatives, which serve as useful alternatives to cyclohexane diacetal (CDA) derivatives. 

Only short comments will be given for other acetal dnivatives fiiat are less pq ular. Chart 1 presents a list of formulae of cyclic acetals, mainly, those wifii five- and six-member rings (1,3-dioxolanes and 1,3-dioxanes). Seven-membered ring acetals are omitted because they are scarcely represented in carbohydrate chmnistry. The special case of spiroacetals and cyclohexane-l,2-diacetal-protecting groups, which have been reported recently, will be presented in Part n. 

Benzylidene and isopropylidene acetals are often used for the selective protection 1,2-cis or 1,3-cisjtrans diols of sugar derivatives. They are stable to strong basic conditions but quite fragile towards acid. Recently, dispirodiketal and cyclohexane-1,2-diacetal groups have been introduced to protect selectively 1,2-trans diols of carbohydrates. 

Benzylidene and isopropylidene acetals of irons-1,2-diols are very labile as a result of ring strain and are not often used for synthetic applications. Fortunately, the protection of these diols can be accomplished with the recently developed dispiroketal (dispoke)35 and cyclohexane-1,2-diacetal (CDA) groups.36... 

Isopropylidene (acetonides) and benzylidene derivatives are the most commonly used acetals for the simultaneous protection of 1,2- and 1,3-diols in carbohydrate and nucleoside chemistry [123]. Cyclohexylidene acetals are occasionally used, most often as an alternative to benzylidene acetals. Protection using cyclohexane- 1,2-diacetals or the related butane-2,3-diacetals represents a new approach which has proved its value in complex oligosaccharide synthesis [124]. 

Douglas et al. [19]. discovered that the cyclohexane-1,2-diacetal (CDA) protection group (e.g., 48) (Fig. 5.13) as weU as the octahydro-2,2 -bi-2H-pyran-2,2 -diyl (dispoke) group (e.g., 47) had a reactivity tuning effect between that of the fully... 

Cyclohexane-1,2-diacetal (CDA) and dispiroketal (dispoke) protocols provide bulkier groups for rran -I,2-diol protection [86]. 

To overcome these problems, 1,1,2,2-tetramethoxycyclohexane (TMC) 2 was developed as an alternative to bis-DHP for carbohydrate protection (Scheme 2) [28]. Initially, TMC 2 was easily prepared from inexpensive cyclohexane-1,2-dione although it is currently commercially available. TMC 2 allows the use of more polar solvents, such as methanol, and cyclohexane-1,2-diacetals (CDA) are obtained in higher yields than the corresponding dispiroketals. 

There are some other remote protecting groups which are not the usual electron-withdrawing groups, but they still deactivate glycosyl donors 4,6-benzyUdene acetal, 3,4-cyclohexylidene diacetal (cyclohexane-1,2-diacetal CD A), dispiroketal (dispoke), and butane diacetal (BDA) (Fig. 2). 

Cyclohexane-l,2-diaceta] protection, a new protecting teduiique for vicinal diols, is illustrated in Scheme 5. It is selective for Crons-disposed hydroxyl grotqis giving mainly the 2,3-acetal of metl a-D-galactopyranoside, the 3,4-acetals of methyl a-D-maimo- and a-L-thamno- and a-D-lyxo-pyranoside, and 2,3/3,4-mixtures in the g/uco-seriesThe 3,4-0-( ohexane-l,2-diacetal) derivatives of methyl a-L-ihamnoside and ethyl l-thio-oi-L-rhamnoside were used successfully in a trisaccharide thesis (see Ch o 4), ... 

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