Silyl bromides, hydrolysis

A number of approaches have been tried for modified halo-de-diazoniations using l-aryl-3,3-dialkyltriazenes, which form diazonium ions in an acid-catalyzed hydrolysis (see Sec. 13.4). Treatment of such triazenes with trimethylsilyl halides in acetonitrile at 60 °C resulted in the rapid evolution of nitrogen and in the formation of aryl halides (Ku and Barrio, 1981) without an electron transfer reagent or another catalyst. Yields with silyl bromide and with silyl iodide were 60-95%. The authors explain the reaction as shown in (Scheme 10-30). The formation of the intermediate is indicated by higher yields if electron-withdrawing substituents (X = CN, COCH3) are present. In the opinion of the present author, it is likely that the dissociation of this intermediate is not a concerted reaction, but that the dissociation of the A-aryl bond to form an aryl cation is followed by the addition of the halide. The reaction is therefore mechanistically not related to the homolytic halo-de-diazoniations. 

The oxidation of higher alkenes in organic solvents proceeds under almost neutral conditions, and hence many functional groups such as ester or lac-tone[26,56-59], sulfonate[60], aldehyde[61-63], acetal[60], MOM ether[64], car-bobenzoxy[65], /-allylic alcohol[66], bromide[67,68], tertiary amine[69], and phenylselenide[70] can be tolerated. Partial hydrolysis of THP ether[71] and silyl ethers under certain conditions was reported. Alcohols are oxidized with Pd(II)[72-74] but the oxidation is slower than the oxidation of terminal alkenes and gives no problem when alcohols are used as solvents[75,76]. 

R)- and (,S )-1.1,2-Triphenyl-l,2-ethancdiol which are reliable and useful chiral auxiliary groups (see Section 1.3.4.2.2.3.) also perform ami-sclcctive aldol additions with remarkable induced stereoselectivity72. The (/7)-diastercomer, readily available from (7 )-methyl mandelate (2-hy-droxy-2-phcnylaeetate) and phenylmagnesium bromide in a 71 % yield, is esterified to give the chiral propanoate which is converted into the O-silyl protected ester by deprotonation, silylation, and subsequent hydrolysis. When the protected ester is deprotonated with lithium cyclohexyliso-propylamide, transmetalated by the addition of dichloro(dicyclopentadienyl)zirconium, and finally reacted with aldehydes, predominantly twm -diastereomers 15 result. For different aldehydes, the ratio of 15 to the total amount of the syn-diastereomers is between 88 12 and 98 2 while the chemical yields are 71 -90%. Furthermore, high induced stereoselectivity is obtained the diastereomeric ratios of ami-15/anti-16 arc between 95 5 and >98 2. 

The selective hthiation of 2-hexanone phenylaziridinyl-lEl-hydrazone 127 with LDA and subsequent alkylation with 8-(tert-butyldimethylsilyloxy)octyl bromide gave (Z)-hydrazone 128 in 65% yield. Its LDA-catalyzed selective decomposition followed by hydrolysis of the silyl ether yielded (Z)-9-tetradecen-l-ol, which was acetylated to afford the target compound 129 in 80% yield with a complete regioselectivity and a cisitrans ratio of 99.6/0.4. 

Miki and Hachiken reported a total synthesis of murrayaquinone A (107) using 4-benzyl-l-ferf-butyldimethylsiloxy-4fT-furo[3,4-f>]indole (854) as an indolo-2,3-quinodimethane equivalent for the Diels-Alder reaction with methyl acrylate (624). 4-Benzyl-3,4-dihydro-lfT-furo[3,4-f>]indol-l-one (853), the precursor for the 4H-furo[3,4-f>]indole (854), was prepared in five steps and 30% overall yield starting from dimethyl indole-2,3-dicarboxylate (851). Alkaline hydrolysis of 851 followed by N-benzylation of the dicarboxylic acid with benzyl bromide and sodium hydride in DMF, and treatment of the corresponding l-benzylindole-2,3-dicarboxylic acid with trifluoroacetic anhydride (TFAA) gave the anhydride 852. Reduction of 852 with sodium borohydride, followed by lactonization of the intermediate 2-hydroxy-methylindole-3-carboxylic acid with l-methyl-2-chloropyridinium iodide, led to the lactone 853. The lactone 853 was transformed to 4-benzyl-l-ferf-butyldimethylsiloxy-4H-furo[3,4- 7]indole 854 by a base-induced silylation. Without isolation, the... 

The presence of heteroatoms, not only for the regio- and stereoselective functionalization of the allylic 1,1-diorganometallic species, and/or silyl substituents was found to exert a dramatic influence on the course of the allylzincation of allenyllithium reagents. Indeed, when 1,2-decadiene (285) was metaflated and treated with allylzinc bromide, the reaction followed a different course and led after hydrolysis to the bistoo-methylenejcyclohexane... 

Chlorophenyl)glutarate monoethyl ester 87 was reduced to hydroxy acid and subsequently cyclized to afford lactone 88. This was further submitted to reduction with diisobutylaluminium hydride to provide lactol followed by Homer-Emmons reaction, which resulted in the formation of hydroxy ester product 89 in good yield. The alcohol was protected as silyl ether and the double bond in 89 was reduced with magnesium powder in methanol to provide methyl ester 90. The hydrolysis to the acid and condensation of the acid chloride with Evans s chiral auxiliary provided product 91, which was further converted to titanium enolate on reaction with TiCI. This was submitted to enolate-imine condensation in the presence of amine to afford 92. The silylation of the 92 with N, O-bis(trimethylsilyl) acetamide followed by treatment with tetrabutylammonium fluoride resulted in cyclization to form the azetidin-2-one ring and subsequently hydrolysis provided 93. This product was converted to bromide analog, which on treatment with LDA underwent intramolecular cyclization to afford the cholesterol absorption inhibitor spiro-(3-lactam (+)-SCH 54016 94. 

Compound 1 has also been prepared by the following methods. Addition of ethylmagnesium bromide to the protected cyanohydrin of acetone, followed by hydrolysis and silylation provides 1 1n 40t yield (eq 2).2 Metallation of 1-methoxypropene by butyllithium in pentane gives 1-lithio-l-methoxypropene, which reacts with acetone to give, after hydrolysis and silylation, ketone 1... 

On the other hand, the cyclization reaction of a vinyllithium onto an acetylenic unit provides an efficient route to five- and six-membered bis-exocyclic 1,3-dienes, which react stereoselectively with a wide range of dienophiles157. The 5-exo carbolithiation reaction of vinyllithiums 369, derived from the corresponding vinyl bromides, is syw-stereospecific giving, after hydrolysis, the /(-isomer of five-membered outer-ring dienes 370 and tolerates aryl-, silyl- or alkyl-substituents at the distal acetylenic carbon (Scheme 97). However, the alkyl-substituted alkynes are far more resistant to rearrangement than the aryl- or silyl-substrates and the addition of TMEDA and longer reaction times are needed for the latter... 

Block has described a further use for a-haloalkanesulfonyl bromides radical addition to silyl enol ethers followed by simple Ramberg-BScklund rearrangement yields a,p-unsaturated ketones (Scheme 31) 94,98 Ethylene oxide, an acid scavenger, is used as solvent for the radical addition to prevent hydrolysis of the silyl enol ether. 

However, hydrolysis, or condensation with allyl bromide, of these anions led to products of low optical purity. Since the cleavage reaction of the Si-Co bond (eq. [9]) may not be stereospecific, it is difficult to know whether some racemi-zation of the silyl anion occurs. 

Reactions of methyllithium or methyl Grignard reagents resulted in the formation of optically active silyl anions which were characterized after hydrolysis and reaction with allyl bromide (243). The observed overall predominant retention of configuration provides evidence for the optical stability of silyl anions. Their first preparation was reported by Sommer and Mason (245) and they appeared configurationally less stable than the chiral germyl anions (31). 

Compound 47 from the former scheme was also used for the synthesis of the narciclasine alkaloids (Scheme 5). Its treatment with excess ethanethiol and magnesium bromide afforded the dithioacetal 54 in 86% yield. Protection of the hydroxyl groups in 54 followed by hydrolysis of the dithioacetal afforded the corresponding aldehyde, which was treated with nitromethane to give a mixture of diastereomers 55 (1.8 1 ratio) in 80% yield. Treatment of the mixture with excess TBSOTf resulted in the silylation of the hydroxyl group. Subsequent selective deprotection of the phenolic TBS group afforded 56. Oxidation of the mixture of diastereomers 56 with silver(I) oxide afforded 57, whose treatment with DMAP afforded 60 and 61 in 29 and 57% yield, respectively. The minor product 60 possesses five of the six stereogenic centers of pancratistatin (3). 

Hydrolysis or condensation with allyl bromide showed retention of configuration to occur at silicon. However, products of low optical purity were obtained. It is difficult to know whether some racemisation had occurred in the silicon-cobalt bond cleavage or whether it is due to a low configurational stability of the silyl Grignard reagent. 

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