Cyclohexylidene protecting group

The cyclohexylidene protecting group has been employed in several syntheses. A preparation of 2,3-0-cyclohexylidene-4-deoxy-L-threose (445) fi om L-( + )-diethyltartrate (lb) in seven steps illustrates one synthetic application (Scheme 99). Conversion of the monobenzyl protected alcohol 443 to its tosylate followed by reduction with sodium borohydride provides the deoxy intermediate 444, which is reductively deprotected and Swem oxidized to 445 in good overall yield. Treatment with benzylamine provides an imine that undergoes a stereoselective carbon-carbon bond forming reaction with a-lithio-A, A -dimethylacetamide in the presence of the Lewis acid zinc bromide to furnish, after Cbz-amine protection, the j9-aminoamide 446. This is converted in four steps to A -acetyl-L-daunosamine (447), a sugar moiety particularly important as the carbohydrate constituent of the anthracycline antibiotics [149]. 

The two pairs of fran -diols (0-370-4 and 0-5/0-6) on neamine can be selectively protected by protecting groups, such as cyclohexylidene (Scheme 4.4). The 0-3 /0-4 diol is less hindered than the O-5/0-6 diol. Therefore, the... 

A cyclohexylidene acetal can be cleaved with Py(HF), (CHCI3, 0°C, to rt, 89% yield) in the presence of the fluoride labile TIPS protective group. 

An improved synthesis of paromamine was effected with a Schiff base and a more protected 2-deoxystreptamine. The cyclohexylidene derivative of l,3-di-2V-(ethoxycarbonyl)-2-deoxystreptamine (79, race-mate) was condensed with 3,4,6-tri-0-acetyl-2-deoxy-2-(p-methoxy-benzylideneamino)-a-D-glucopyranosyl bromide (see Refs. 174 and 175 on p. 153) to give two products (80 and 81), which, after removal of the protecting groups, furnished paromamine (78) and an isomer, 6-0-(2-amino-2-deoxy-o-D-glucopyranosyl)-2-deoxystreptamine (82). The latter was devoid of antibacterial activity. 

This methodology was optimised further by protecting the C-4 and C-6 hydroxyl groups with a cyclohexylidene acetal [66]. It was envisaged that the rigid chair conformation of the cyclohexylidene protected thiomethyl mannoside donor 83 would favour an Sn2 type pathway during the lAD reaction. This in turn would suppress any side reactions occurring from the formation of an anomeric carbonium ion. 

Notes and discussion. The PMB-assisted lAD reaction between the cyclohexylidene protected thiomethyl mannoside donor 83 and the very unreactive glucosamine derived acceptor 84 affords exclusive entry to the p-(l,4)-mannoside 85 in an excellent yield of 83%. Advantages of this methodology include (i) the possibility of using various methods for the introduction of the 0-p-methoxybenzyl group (ii) the use of mild and near neutral conditions for the formation of the mixed acetal. 

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). 

The 3,4-cyclohexylidene diacetal, which was introduced for the selective protection of trans diequatorial vicinal diols [33], is resistant to the flattening of carbohydrate ring required for the generation of an oxocarbonium ion intermediate and thus a torsionally disarming protecting group [15]. Similarly, the dispiroketal [15, 34]... 

Perhaps classical for the protection of 1,2- and 1,3-cis-diols is the isopropyl-idene (acetonide) function. This acid labile ketal may be formed by reaction of a ribonucleoside with acetone in the presence of an acid (HCl, p-toluene-sulfonic, H2SO4) and water scavenger (2,2-dimethoxypropane, ethyl orthoformate). Other similar protecting groups include the benzylidene and cyclohexylidene functions. 

Cyclohexylidene is the only ketal system besides isopropylidene which has been used to any extent as a protecting group [126-128]. Cyclohexylidene derivatives have been prepared by allowing the glycol to react with cyclohexanone in the presence... 

It has recently been reported that the choice of protection groups also plays an important role. Thus using a 4,6-O-cyclohexylidene-protected mannose derivative as glycosyl donor gave the desired P-mannopyranosides in high yields [13]. 

The electrophilicity of the carbonyl group of the ester functionality is a dominant feature of its chemistry and shields carbonyls from nucleophilic attack. However, its electrophilic properties must be considered as a major obstacle in any synthetic approach of stereoselective functionalization. This difficult task of protecting the carbonyl group can be achieved by highly stereoselective functionalization with very strong nucleophiles. This selective protection by functionalization with various blocking groups such as benzylidene, isopropylidene, and cyclohexylidene acetals is reported [27]. 

Vicinal hydroxyl groups can be protected advantageously by conversion into cyclohexylidene derivatives according to Bissett. This reaction has been used by Umezawa for the differentiation of the hydroxyl groups in neaniine and for the synthesis of 3 ,4 - and 5,6-modified neamine derivatives ... 

Penta- -(ethoxycarbonyl)kanamycin B was converted into the di-O-isopropylidene derivative (188). (Alternatively, the hydroxyl groups could be protected with cyclohexylidene groups.) The remaining hydroxyl... 

---