Non-basic conditions

Torgov introduced an important variation of the Michael addition allylic alcohols are used as vinylogous a -synthons and 1,3-dioxo compounds as d -reagents (S.N. Ananchenko, 1962, 1963 H. Smith, 1964 C. Rufer) 1967). Mild reaction conditions have been successful in the addition of ],3-dioxo compounds to vinyl ketones. Potassium fluoride can act as weakly basic, non-nudeophilic catalyst in such Michael additions under essentially non-acidic and non-basic conditions (Y. Kitabara, 1964). 

The isolation of flavonoids from the methanol extract of G. uralensis was carried out under non-basic conditions, because some flavonoids isomerize under basic conditions, e.g. racemization of flavanones and isoflavanones, ring-open reaction of flavanones etc. Bioactive fractions were separated by some chromatographic methods and each step was monitored with anti-H. pylori activity with the paper disk method. Eighteen compounds were isolated from these bioactive fractions and... 

Tertiary alkyl halides are essentially unreactive to strong nucleophiles in polar, aprotic solvents, i.e. the conditions for the Sn2 reaction. Tertiary alkyl halides can undergo E2 reactions when treated with a strong base in protic solvent and will do so in good yield since the SN2 reaction is so highly disfavoured. Under non-basic conditions in a protic solvent, El elimination and SN1 substitution both occur. 

Because disconnection of a-alkoxy-y-amino acid 28 calls for (3-alkoxyhydra-zone 30, the potential for (3-elimination of the alkoxy group from the hydrazone precursor 30 (Scheme 7) makes non-basic conditions critical. In fact, treatment of 30 with TBAF in THF led to just such a (3-elimination (Marie, University of Iowa, unpublished). However, the manganese-mediated radical addition of isopropyl iodide proceeded in 77% yield, without any evidence of (3-elimination, to afford 31 as a single diastereomer. Reductive removal of the chiral auxiliary and oxidation to the carboxylic acid gave 28 in good overall yield [103]. 

The classical permanent protecting group of carbohydrate hydroxyl functions is probably the benzyl ether. It is very stable and can be readily removed under essentially neutral conditions. For this reason, numerous benzylation and 0-debenzylation procedures have been described. Benzyl ether formation is usually achieved by the reaction of alcohols and benzyl halides in the presence of a base such as sodium hydride in anhydrous DMF (O Scheme 2) [11], or a mild base (Ag20) in THF using a phase-transfer catalyst [12]. Benzylation can also be accomplished by the use of an acidic catalyst with benzyltrichloroacetimidate as the reagent [13]. A method using the reductive etherification of TMS ethers under non-basic conditions has also been reported [14]. 

Apart from the theoretical significance, these carbene precursors constitute convenient sources of singlet carbenes which can be generated under non-basic conditions that are particularly suitable for small-scale preparations and C labeling experiments. Nevertheless, attempts at generating dialkylcarbenes from precursors of type 14 failed. ... 

It was reported that TMSOTf selectively activated acetals rather than aldehydes in the aldol-type reaction of silyl enolates (a) Noyori R,Murata S, Suzuki M (1981) Tetrahedron 37 3899 (b) Mukai C, Hashizume S, Nagami K, Hanaoka M (1990) Chem Pharm Bull 38 1509. (c) Murata S, Suzuki M, Noyori R (1980) J Am Chem Soc 102 3248. Selective activation of acetals or aldehydes under certain non-basic conditions are now under investigation in our group cf. (d) Mukaiyama T, Ohno T, Han JS, Kobayashi S (1991) Chem Lett 949... 

A-Benzyl PRT groups. An obvious solution to the conformation problem discussed above is the use of or/Z/u-halobenzyl PRT groups instead of the benzoyl derivatives [117]. Ito [121] and Undheim [122] have demonstrated the synthetic potential of this approach. Under classical tin hydride conditions, excellent yields for the alkylation of amines have been obtained as shown in Scheme 33 (Eq. 33.1) [122]. Starting from a chiral 1,3-oxazolidine, a novel approach for the functionalization of aminoalcohols has been reported [123]. When samarium iodide was used for such reactions, the formation of an organosamarium intermediate at the a-N position was achieved. This corresponds to the metallation of an amine under non-basic conditions. Subsequent reaction of the organosamarium species with electrophiles such as ketones [121, 124, 125[ (Eq. 33.2) and isocyanides [121, 124[ has been reported. 

Another method for producing DCC from dicyclohexylurea is a two-step process using phosphoryl chloride in dichloromethane at 40 °C for 4 h under non-basic conditions followed by removal of acidic components with aq. sodium hydroxide. This method, which gives an 89% yield of DCC, has been presented in a patent application [1256] (see Section 4.5.3.5, Table 4.48). 

Trimethylsilyl)ethyl vinyl ether was developed as a reagent for protecting alcohols under non-basic conditions. The reagent was prepared by treatment of a solution 2-(trimethylsilyl)ethanol in ethyl vinyl ether with a catalytic amount of mercuric trifluo-roacetate and triethylamine (eq 24). ... 

Other Alkyl and Aryl Ethers. - The reagent system of allyl ethyl carbonate and a Pd(0) catalyst, applied to carbohydrate alcohols, has been utilised for making allyl ethers under neutral conditions. The synthesis of benzyl ethers from the parent alcohols under non-basic conditions has been achieved using phenyldiazomethane and HBF4. Dibutylstannylene compounds derived from benzyl -D-lactoside and its derivatives have been regioselectively benzylated. ° Similarly, 2,2 -di-0-alkyl-4,6 4 6 -di-0-benzylidene-Qt,a-trehaloses have been prepared by regioselective alkylation of a dibutylstannylene derivative. Phase transfer catalysed benzylation... 

Figure 7 The single-crystal X-ray structure of the diphenylboronic acid - fructose complex obtained by Fallon and co-workers from a 2 to 1 ratio ofphenylboronic acid and d-fructose under non-basic conditions and in the absence of Lewis basic components. Atoms marked in red represent oxygen, pink boron and grey carbon. For clarity hydrogen atoms are not displayed. From the structure it can be observed that the O-B-0 bond angles are reduced, in this instance, to 113° from 120°, while the...

The established rhodium-catalyzed methylenation condition was successfully applied [24] to several optically pure trifluoromethyl ketones 35 containing a-chiral centers, which are potentially racemizable under basic conditions (Scheme 16). Due to the mild and non-basic conditions employed in Rh-catalyzed olefination... 

Alkylations at Carbon. In an important recent development, primary a-alkylation of carbonyl compounds under non-basic conditions has been achieved (eq 5) by alkylation of silyl enol ethers with MeOTf and other primary alkyl triflates, catalyzed by MethylaUinunum Bis(4-bromo-2,6-di-t-butylphenoxide) (MABR). ... 

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