Carbonyl function, blocking

Vicinally donor-acceptor-substituted cyclopropanol carboxylic esters have been proven to be versatile synthetic building blocks in organic synthesis [11]. They readily undergo a retroaldol reaction, thus creating a stable enolate that at the same time can be considered as a homoenolate in relation to the newly formed carbonyl function. Shimada et al. applied this strategy to the preparation of y-substituted lactones starting from cyclopropane 21 (Scheme 3) [12]. 

One of useful building blocks for the synthesis of 2-(l//)-pyrazinones is iV-BOC amino acids, whose carboxylic acid moiety reacts with the amino group of another component having cyano or carbonyl functionality at the a-position, such as a-amino nitriles <2004T835>, a-amino amide (Scheme 46) <2000H(53)1559>, a-amino ketones... 

S,.S)-Bissetone (28), when traced back to building block 27, only lacks the 3-carbon branch, i. e. acetone. Indeed, the lithium enolate of acetone proved to be a suitable three-carbon synthon attacking the carbonyl function with a 4 1 preference from the proaxial side (27 -> 30). The benzoyl group shift directly following the attack elaborates the desired 2-oxopropyl-branehed tetrahydro-pyranone 31, the dibenzoate of bissetone in fact, from which the parent compound is generated simply by de-O-benzoylation (48) ... 

Elaboration of (S -palythazine (29) from the key building block 27 was similarly effected in a high-yielding reaction sequence conversion into oxime 32, liberation of the carbonyl function by debenzoylation (- 33), and controlled catalytic hydrogenation to the aminoketone 34, which dimerizes at pH 9 the concluding step is an air oxidation of the dihydropyrazine initially formed (52). 

The linking of two building blocks to form a double bond under the conditions of the Wittig reaction required that one of the building blocks has phosphorus ylide functionality and that the other has carbonyl functionality. The appropriate C5 building block for vitamin A can thus be either l-triphenyl-2-methyl-4-hydroxy-2-butenylidenephosphorane (26) 9) or P-formylcrotyl alcohol (2-methyl-4-hydroxy-2-butenal) (8 a). 

This conformation has the chlorine atom cis to the C-7 gem-dimethyl group. Since a diene approach from the CSi face is entirely blocked by the C-2 carbonyl function, complete asymmetric induction is observed. 

Carbonyl functions often are protected as thioacetals, because these derivatives are stable to acids and bases. Dithio-acetals and -ketals generally are prepared by reaction of the carbonyl compound with a thiol in the presence of an acid catalyst. This transformation has been used in carbohydrate chemistry for a long time to lock aldoses in their acyclic forms (see equation 26). In recent years, this blocking principle for carbohydrates has been exploited in several chiral pool syntheses. Several other methods for... 

Diketones often are protected as enol ethers or enamines and these selectively functionalized compounds may be subjected to complementary transformations (Scheme 94). Also silylenes can be prepared from diketones and -hydroxycarbonyl compounds by reaction with dimethyldicyanosilane. Naturally, these blocking groups are relatively sensitive to hydrolysis. On the other hand, partial solvolysis can open a route to monoprotected derivatives (e.g. 101), usually blocked at the sterically less demanding carbonyl function as 0-silyl cyanohydrins (see Scheme 95). Deprotection is finally achieved with silver fluoride in THF. 

Hydrolysis of 1 J-dioxolanes and epoxidesA carbonyl function is often protected by conversion into a 1,3-dioxolane (ethyleneacetal or ketal) with ethylene glycol. In case quantitative removal of the blocking group is difficult, due to an unfavorable equilibrium, complete hydrolysis can be accomplished in aqueous dioxane solution by addition of an equivalent amount of periodic acid. This destroys the ethylene glycol formed and drives the equilibrium to completion. A procedure employed in a total synthesis of linoleic acid is as follows. A mixture of 1.6 g. (0.0070 mole) of... 

Bioactive compounds that contain the difluoromethylene group adjacent to the carbonyl functionality have been the subject of increased research efforts in recent yearsf 59). The most widely utilized methods that have been employed to introduce this group into organic molecules have been (a) Reformatsky reaction of halodifluoroacetates (60-66) (b) elaboration of difluoroketene silyl acetals (67-69) (c) metal catalyzed addition of 3-bromo-3,3-difluoropropene to aldehydes and ketones (70) and (d) alkylation of CuCF2COOR(77). The modest yields associated with these methods prompted us to explore alternative methodology for the preparation of this useful building block. 

The above results are consistent with those obtained by van Ryswyk and coworkers. They prepared mixed monolayers of isonicotinate esters and alkane thiols. By varying the relative amount of the alkanethiol and the ester in the deposition solution it is possible to control the surface density of the isonicotinate ester groups. Monolayers of pure ester hydrolyse extremely slowly, probably because of the blocked access to the carbonyl functional group319. 

Dioxolanes are stable to bases. They are hydrolysed by dilute acids even at room temperature in a reversal of their formation. The conversion of aldehydes and ketones into 1,3-dioxolanes is one of the most important methods for the protection of the carbonyl function in multistep syntheses. It is also the standard method for blocking two vicinal cw-positioned hydroxy groups in a carbohydrate, via reaction with acetone, e.g. ... 

BF3 Et20, smoothly passes into (218) it may be noted that isomerization of the oxirane ring to the carbonyl function under the influence of BF3 Et20, the usual reaction, is blocked in the present case as the migration of the eut/o-hydrogen from C-1 to C-6 required by such an isomerization will result in inversion at C-6, which in the present case is sterically prohibitive 139). 

The formation of a dithioacetal as an intermediate in organic synthesis is not new to most chemists. However, in recent years there has been a continuing improvement in the methods of preparation as well as the subsequent reactions. The early use of the dithioacetal group as a means to reduce carbonyl functions with Raney nickel has been expanded to extensive use as a protecting group, methylene blocking group and as an intermediate in the preparation of complex hydrocarbons, olefins, aldehydes and ketones. 

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