Benzylidene intermediates

Under the conditions used in the current experiment, dehydration-elimination rapidly follows the initial nucleophilic addition with formation of the benzylidene intermediate. The mechanism is shown here ... 

Hurd et al. elegantly elaborated this methodology in the key step of total synthesis of PNU-286607 (Scheme 4) [88]. The benzylidene intermediate 5 was prepared in situ and [1,5]-hydride migration readily proceeded under thermal conditions to give zwitterionic intermediate 6. Via trans-cis isomerization of methyl group, the zwitterion 6 was converted to thermodynamically more favorable zwitterion 7, and a subsequent intramolecular equatorial attack of the enolate on the iminium subunit furnished cis (-)-PNU-286607 in 74 % yield and >99 1 er. 

Matyus et al. described a cascade Knovenagel/1,5-hydride transfer/cyclization reactions of 4-aryl-2-phenyl-1,4-benzoxazepine derivatives 19, which furnished fused 0,A -heterocycles 20 containing tetrahydro-l,4-benzoxazepine and tetrahydroquinoline moieties with high yields and diastereoselectivity (Scheme 9) [92]. Basically, under thermal conditions, the benzylidene intermediate I generated in situ... 

It has recently been demonstrated that treatment of disaccharide 31 with NIS produces the debenzylated compound 32, probably via a benzylidene intermediate and without participation of silicon [24],... 

There are many synthetic routes to alloxan. Probably the best is direct oxidation of barbituric acid (1004 R = H) with chromium trioxide (5208(32)6) but it may be made from barbituric acid via its benzylidene derivative by direct or indirect oxidation of uric acid from 5-chlorobarbituric acid (1004 R = C1) by nitration or from 5-nitrobarbituric acid (1004 R = N02) by chlorination, both via the intermediate (1005) (64M1057) or by permanganate oxidation of uracil (1006) under carefully controlled conditions (73BSF1167). 

Alkylation of enamines with epoxides or acetoxybromoalkanes provided intermediates for cyclic enol ethers (668) and branched chain sugars were obtained by enamine alkylation (669). Sodium enolates of vinylogous amides underwent carbon and nitrogen methylation (570), while vicinal endiamines formed bis-quaternary amonium salts (647). Reactions of enamines with a cyclopropenyl cation gave alkylated imonium products (57/), and 2-benzylidene-3-methylbenzothiazoline was shown to undergo enamine alkylation and acylation (572). A cyclic enamine was alkylated with methylbromoacetate and the product reduced with sodium borohydride to the key intermediate in a synthesis of the quebrachamine skeleton (57i). 

The presence of hydroxyl groups in the benzylidene sugars does not interfere with the reaction and by-products are usually minor. Suitable solvents other than carbon tetrachloride, include benzene and tetra-chloroethane. Epoxide, amide, and other commonly encountered functionalities in sugar derivatives are unaffected under the reaction conditions. The corresponding 6-bromo-4-benzoates are valuable intermediates... 

Treatment of methyl 2-azido-4,6-0-benzylidene-2-deoxy-a-D-altro-pyranoside (128) (42) with 121 followed by refluxing and processing afforded a chloro derivative as a sirup in 70% yield (46, 49). Reduction of this product with an excess of Raney-nickel in methanol containing acetic anhydride afforded a crystalline product, m.p. 179°C., which is formulated as the d-manno analog 131. The actual product is most likely methyl azido-4,6-0-benzylidene-3-chloro-2,3-dideodxy - a - d - mannopyran-oside (130) resulting from attack of chloride ion at C-3 with inversion of configuration in the intermediate 129. Had the chlorination proceeded... 

The synthesis of the right-wing sector, compound 4, commences with the prochiral diol 26 (see Scheme 4). The latter substance is known and can be conveniently prepared in two steps from diethyl malonate via C-allylation, followed by reduction of the two ethoxy-carbonyl functions. Exposure of 26 to benzaldehyde and a catalytic amount of camphorsulfonic acid (CSA) under dehydrating conditions accomplishes the simultaneous protection of both hydroxyl groups in the form of a benzylidene acetal (see intermediate 32, Scheme 4). Interestingly, when benzylidene acetal 32 is treated with lithium aluminum hydride and aluminum trichloride (1 4) in ether at 25 °C, a Lewis acid induced reduction takes place to give... 

With ring G in place, the construction of key intermediate 105 requires only a few functional group manipulations. To this end, benzylation of the free secondary hydroxyl group in 136, followed sequentially by hydroboration/oxidation and benzylation reactions, affords compound 137 in 75% overall yield. Acid-induced solvolysis of the benzylidene acetal in 137 in methanol furnishes a diol (138) the hydroxy groups of which can be easily differentiated. Although the action of 2.5 equivalents of tert-butyldimethylsilyl chloride on compound 138 produces a bis(silyl ether), it was found that the primary TBS ether can be cleaved selectively on treatment with a catalytic amount of CSA in MeOH at 0 °C. Finally, oxidation of the resulting primary alcohol using the Swem procedure furnishes key intermediate 105 (81 % yield from 138). 

The ds-selechvity of the Diels-Alder reachon using aromahc aldehydes is demonstrated in the reachon of aldehydes such as 2-746, which contain a dienophile moiety. Treatment with N, N-dimethylbarbituric acid (2-747) in the presence of ethylene diammonium diacetate at 20 °C led to the ris-fused product 2-749 exclusively in 95% yield (Scheme 2.164) [377]. As an intermediate, the benzylidene-1,3-dicarbonyl compound ( )-2-748 is formed, which can be identified using online NMR-... 

Crowe proposed that benzylidene 6 would be stabilised, relative to alkylidene 8, by conjugation of the a-aryl substituent with the electron-rich metal-carbon bond. Formation of metallacyclobutane 10, rather than 9, should then be favoured by the smaller size and greater nucleophilicity of an incoming alkyl-substituted alkene. Electron-deficient alkyl-substituents would stabilise the competing alkylidene 8, leading to increased production of the self-metathesis product. The high trans selectivity observed was attributed to the greater stability of a fra s- ,p-disubstituted metallacyclobutane intermediate. 

A fused OZT was obtained in the course of the reduction of vicinal azido-thiocarbonates via formation of the intermediate amine, which attacks the thiocarbonyl group (Scheme 37). The condensation reaction proved faster than the deoxygenation process for the synthesis of 2 -amino-2, 3 -dideoxyuridine50 or methyl 3-amino-4,6-0-benzylidene-3-deoxy-2-0-phenoxythiocarbonyl-a-L-talopyranoside.51... 

The borohydride reduction-periodate cleavage applied to 2,3-O-isopro-pylidene-D-ribono- 1,4-lactone (16a) led to L-erythrose (30). The method was also employed (31) for the synthesis of D-erythrose, starting from an Obenzylidene-D-ribonolactone. However, in this case, the structural assignments for the intermediate compounds must be revised, as the starting material formulated as 3,5-O-benzylidene-D-ribono-1,4-lactone (2) was, as discussed previously in this section, the 3,4-0-benzylidene-D-ribono-1,5-lactone (3a). Therefore, the correct structure for the product described as 3,5-O-benzylidene-D-ribitol (20, not isolated) would be 3,4-O-benzylidene-... 

A-Benzylimines have also been reported to react with acrylonitriles under solidrliquid conditions in which the initial anionic intermediate undeigoes an intramolecular nucleophilic ring closure to produce a diastereoisomeric mixture of the pyrrolidine (Scheme 6.23) [30-32], Similar cyclized products have been reported for the reaction of benzylidene-protected a-amino esters and vinyl ketones [33, 34],... 

Calculations on two Wittig reactants, alkylidenetriphenylphosphorane (a non-stabilized ylid) and its benzylidene analogue (a semi-stabilized one), have been used to identify the origin of the product selectivities for the two classes. A planar transition state gives a trani-oxaphosphetane intermediate, while a puckered one leads to cis-. These two transition states were favoured by the semi- and un-stabilized reactants, respectively. 

Working on modifications of trehalose, Richardson (with P.A. Monroe and Les Hough) demonstrated the selective tosylation at 0-2 of 4.6.4. 6 -di-(9-benzylidene-a,a-trehalose to afford a symmetrical 2,2 -ditosylate, which could be converted into the bis-manno-epoxide by the action of base (Scheme 24). The latter underwent trans-diaxial ring-opening with nucleophiles at C-3 and C-3, and many synthetic applications of this intermediate have now been recorded. One of these is shown in Scheme 24, from the Richardson-Hough laboratory, performed by postdoctoral fellow, Edward Tarelli, who contributed voluminously with Richardson to the exploration and development of trehalose chemistry. 

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