Reduction palladium-catalyzed

A synthesis of (-)-4a,5-dihydrostreptazolin was accomplished in a similar manner only a reductive palladium-catalyzed cyclization was utilized.104 The hydride source was polymethylhydroxysilane (PMHS), and the unprotected hydroxyl group of 174 (Equation (89)) had an accelerating effect, since the reaction was completed in minutes instead of hours, as in the example above. 

Epoxides are normally hydrogenated in preference to saturated ketones but double bonds are usually reduced under these conditions. It is possible in some cases to selectively cleave an epoxide without saturating double bonds by the use of the deactivated catalysts recommended for the partial reduction of acetylenes (see section IV) or by the addition of silver nitrate to the palladium-catalyzed reaction mixture. " ... 

The parent system 4 has also been jnepared employing a double reductive ring closure of a dinitrodiphenylbenzene derivative (Scheme 25). The required starting material, 195, was prepared using a palladium-catalyzed coupling of 1,4-dibromo-2,5-dinittobenzene with phenylboronic acid and after reaction with tri-ethylphosphite in hot tert-butylbenzene, 4 could be isolated in a moderate yield (92JHC1237). 

An unusual by-product was obtained in small yield in palladium-catalyzed reduction of 2-amino-4,5-dimethoxyindanone hydrochloride, The reduction was done in two stages first, a rapid absorption of 1 mol of hydrogen at 38 C to give the amino alcohol, and then a much slower reduction in the presence of HCIO4 at 70 "C. The rearranged by-product was shown to arise from attack of acid on the amino alcohol (50), Resistance to hydrogenolysis is characteristic of / -amino aromatic alcohols (56), a fact that makes reduction of aromatic oximino ketones to amino benzyl alcohols a useful synthetic reaction. 

Examples of palladium-catalyzed reduction are 4-chloro-2,6-di-r-butyl-phenol to 2,6-di-t-butylcyclohexanone (750 psig, 25 C) with loss of halogen 24), 1,8-dihydroxynaphthalene to 8-hydroxy-1-tetralone 30), and 2,4-dimethylphenol to 2,4-dimethylcyclohexanone (27). 

The key step in a short and efficient synthesis of pleraplysillin-1 (127) is the palladium-catalyzed cross-coupling of vinylstannane 125 with vinyl triflate 126 (see Scheme 33). This synthesis is noteworthy in two respects. First, vinyl triflate 126 is generated regio-specifically from the kinetic enolate arising from a conjugate reduction of enone 124 the conjugate reduction of an enone is, in fact, a... 

In 1995, palladium-catalyzed reduction of vinylaziridines with formic acid was reported [42]. As shown in Scheme 2.26, 1,2-reduction products 95 and 1,4-products 96 were obtained in ratios depending on the reaction conditions, such as the additive, solvent, and catalyst employed. Both the E/Z selectivity of 95 and the... 

The N-substituted aminoacids required could be prepared by microwave-assisted reductive amination of aminoacid methyl esters with aldehydes, and although in the Westman report soluble NaBH(OAc)3 was used to perform this step, other reports have shown how this transformation can be performed in using polymer-supported borohydrides (such as polymer-supported cyanoborohydride) under microwave irradiation [90]. An additional point of diversity could be inserted by use of a palladium-catalyzed reaction if suitably substituted aldehydes had been used. Again, these transformations might eventually be accomplished using supported palladium catalysts under microwave irradiation, as reported by several groups [91-93]. 

The dechlorination of the C-3 and C-5 position of the pyrazinone system was described to be fast under microwave irradiation [29]. Contrary to the reported de-chlorination [26] via palladium-catalyzed reaction with sodium formate 100 °C for 2-4 h and at the C-5 position in 2-3 days, a dramatic rate enhancement was observed under microwave irradiation (Scheme 12). The mono-reduction at C-3 was performed at 190 °C in DMF in merely 5 min, and the reduction of C-5, starting from the mono-reduction product, was performed in n-butanol in 55 min to afford the fois-reduction product in good overall yield. 

In another reductive coupling, substituted alkenes (CH2=CH Y Y = R, COOMe, OAc, CN, etc.) can be dimerized to substituted alkanes (CH3CHYCHYCH3) by photolysis in an H2 atmosphere, using Hg as a photosensitizer. Still another procedure involves palladium-catalyzed addition of vinylic halides to triple bonds to give 1,3-dienes. ... 

This reaction typifies the two possibilities of reaction routes for M-catalyzed addition of an S-X (or Se-X) bond to alkyne (a) oxidative addition of the S-X bond to M(0) to form 94, (b) insertion of alkyne into either the M-S or M-X bond to provide 95 or 96 (c) C-X or C-S bond-forming reductive elimination to give 97 (Scheme 7-21). Comparable reaction sequences are also discussed when the Chalk-Harrod mechanism is compared with the modified Chalk-Harrod mechanism in hydrosily-lations [1,3]. The palladium-catalyzed thioboratiori, that is, addition of an S-B bond to an alkyne was reported by Miyaura and Suzuki et al. to furnish the cis-adducts 98 with the sulfur bound to the internal carbon and the boron center to the terminal carbon (Eq. 7.61) [62]. 

In conclusion, N,N-dialkylglucamines are prepared in high yield and purity by palladium-catalyzed reductive alkylation of an N-alkylglucamine with an aldehyde or ketone. A wide variety of 1 with moderate to very high hydro-phobicity are readily accessible. 

In conclusion, N,N -dialkyl-N,N -di(l-deoxyglucityl)alkylenediamines (2) are prepared in good yield and purity by palladium-catalyzed reductive coupling of straight chain N-alkyl-(l-deoxyglucityl)amines with glyoxal. A wide variety of 2 with moderate to high hydrophobicity is readily accessible. 

The palladium-catalyzed reductive coupling reactions were used in the synthesis of several natural products, including laurene [75], ceratopicanol [80], and dihydrostreptazolin 141 [81]. The cyclization leading to dihydrostrepta-zolin shown in Eq. 26 highlights the diastereoselectivity and functional group compatibility seen with this catalytic system. 

The palladium-catalyzed cyclization reaction was used in the syntheses of several natural products such as siccanin [86], streptazolin [87], and ceratopi-canol (through a diyne, diene cascade) [80]. The production of the streptazolin precursor 149 through reductive cyclization of 150 is illustrative of the complexity that the reaction can provide (Eq. 29) [87]. 

A wide variety of heterocycles can be readily prepared by the heteroannulation of alkynes. For example, the palladium-catalyzed annulation of internal alkynes by 2-iodoanilines provides easy access to 2,3-disubstituted indoles by a process that involves initial reduction of Pd(OAc)2 to Pd(0), oxidative addition of the aryl halide to Pd(0), c/s-addition of the arylpalladium... 

To investigate the feasibility of employing 3-oxidopyridinium betaines as stabilized 1,3-dipoles in an intramolecular dipolar cycloaddition to construct the hetisine alkaloid core (Scheme 1.8, 77 78), a series of model cycloaddition substrates were prepared. In the first (Scheme 1.9a), an ene-nitrile substrate (i.e., 83) was selected as an activated dipolarophile functionality. Nitrile 66 was subjected to reduction with DIBAL-H, affording aldehyde 79 in 79 % yield. This was followed by reductive amination of aldehyde x with furfurylamine (80) to afford the furan amine 81 in 80 % yield. The ene-nitrile was then readily accessed via palladium-catalyzed cyanation of the enol triflate with KCN, 18-crown-6, and Pd(PPh3)4 in refluxing benzene to provide ene-nitrile 82 in 75 % yield. Finally, bromine-mediated aza-Achmatowicz reaction [44] of 82 then delivered oxidopyridinium betaine 83 in 65 % yield. 

Ene-nitrile oxidoisoquinolinium betaine 131 was readily prepared from vinyl triflate aldehyde 79 (Scheme 1.14). Palladium-catalyzed cyanation of vinyl triflate 79 with Zn(CN)2 in DMF at 60 °C produced ene-nitrile aldehyde 129 in 85 % yield [54]. Using the previously developed Staudinger-aza-Wittig reduction sequence, aldehyde 129 was coupled with cyclic ketal azide 121 to afford a 79 % yield of amine 130. The cyclic ketal amine 130 was then treated with 9 1 mixture of CH2CI2/TFA to provide ene-nitrile oxidoisoquinolinium betaine 131 in 93 % yield. 

Intramolecular arylation of G-H bonds gives cyclic aromatic compounds. In this intramolecular arylation, the carbon-palladium cr-bond is first formed by the oxidative addition of Pd(0) species and then the resulting electrophilic Pd(n) species undergoes the intramolecular G-H bond activation leading to the formation of the palladacycle, which finally affords the cyclic aromatic compounds via reductive elimination.87 For example, the fluoroanthene derivative is formed by the palladium-catalyzed reaction of the binaphthyl triflate, as shown in Scheme 8.88 This type of intramolecular arylation is applied to the construction of five- and six-membered carbocyclic and heterocyclic systems.89 89 89 ... 

Few other examples of such reaction sequences have been described to date. Oh has reported the palladium-catalyzed reductive cyclizations of 1,6-enynes in the presence of formic acid or triethylsilane via an alkylpalladium intermediate and its application to organic synthesis. Palladium complexes also catalyze the conversion of a range of enynes to cyclic 6,7-unsaturated carboxylic acids in the presence of CO.260... 

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