Zinc/Silver Couple

In the course of a synthesis of /V-acetylneuraminic acid55, the [2-(Av7-butoxycarbonyl)-2-propenyl]zinc bromide reagent, preformed from a zinc/silver couple on graphite36, gave the best result. Several other methods of generation resulted either in lower yields or stereoselectivities 55. 

The cyclopropanation of 1-trimethylsilyloxycyclohexene in the present procedure is accomplished by reaction with diiodomethane and diethylzinc in ethyl ether." This modification of the usual Simmons-Smith reaction in which diiodomethane and activated zinc are used has the advantage of being homogeneous and is often more effective for the cyclopropanation of olefins such as enol ethers which polymerize readily. However, in the case of trimethylsilyl enol ethers, the heterogeneous procedures with either zinc-copper couple or zinc-silver couple are also successful. Attempts by the checkers to carry out Part B in benzene or toluene at reflux instead of ethyl ether afforded the trimethylsilyl ether of 2-methylenecyclohexanol, evidently owing to zinc iodide-catalyzed isomerization of the initially formed cyclopropyl ether. The preparation of l-trimethylsilyloxybicyclo[4.1.0]heptane by cyclopropanation with diethylzinc and chloroiodomethane in the presence of oxygen has been reported. "... 

The direct reaction of zinc metal with organic iodides dates back to the work of Frankland(67). Several modifications have been suggested since that time to increase the reactivity of the metal. The majority of these modifications have employed zinc-copper couples(68-72), sodium-zinc alloys(73), or zinc-silver couples(77). Some recent work has indicated that certain zinc-copper couples will react with alkyl bromides to give modest yields of dialkylzinc compounds(74,73). However, all attempts to react zinc with aryl iodides or bromides have met with failure. The primary use of zinc couples has been in the Simmons-Smith reaction. This reaction has been primarily used with diiodomethane as 1,1-dibromides or longer chain diiodides have proven to be too unneactive even with the most reactive zinc couples. 

Improvement to the Reformatsky reactions was achieved (53) by the use of a highly activated zinc - silver couple dispersed on the surface of graphite. T reatment of protected aldono-1,4-lactones 10b or 25b and 1,5-lactones 51a or 51b with a Reformatsky reagent prepared from a-haloesters or alkyl 2-(bromomethyl)acrylates resulted in the formation of the corresponding 3-or 4-glyculofuranos (or pyranos)onates 49a,b-50a,b, or 52a,b, respectively, under mild conditions (— 40 ° to 00) and in very good yields. Ethyl 2-deoxy-2-fluoro (and 2-bromo)-a-D-wa o-3,6-furanos-3-octulosonate derivatives were also obtained. 

U.yUNSATURATED KETONES Bis-(l,5-cyclooctadiene)nickel(0). Dimethyl-(phenylthio)aluminum. a-Phenylglycine methyl ester. Phcnylselcnoacetaldchydc. Zinc-Silver couple. 

Heterocyclic derivatives of a range of metals other than lithium have received considerable attention, especially as precursors for coupling reactions. These derivatives can be prepared either directly from halo compounds or from the lithio compounds. Thus, direct formation of the pyrrolylzinc compounds can be effected under very mild conditions by treatment of an iodide with a zinc-silver couple... 

Fluorine is simultaneously eliminated with other halogens if it is the only halogen vicinal to iodine, bromine or chlorine. The elimination tendency decreases in the series IF > BrF > C1F. The group CF2CHFX is relatively stable towards elimination and requires stronger reaction conditions. The dehalogenation of saturated fluorohalo compounds with zinc dust or zinc/ copper and zinc/silver couples is one of the most useful methods for the preparation of fluoroalkenes (see Table 8). Zinc/zinc(II) chloride has also been used instead of zinc alone. 

Conia and his co-workers144 modified the Simmons-Smith reaction145,146 by using enol ether plus predominantly diiodomethane/zinc-silver couple instead of the common known diiodomethane/zinc-copper couple147. This method is an excellent access to cyclopropanols and related compounds148 149 (Scheme 29). Furthermore,... 

In diethyl ether, the yields of the zinc-mediated Barbier condensation are medium or poor,1 and THF should be preferred for most of the synthetic uses. Sonication is frequently used, e.g. in the reaction of methallyl bromide and salicylaldehyde which provide the expected alcohol27 The condensation of 4-bromo-2-sulfolene with a series of aldehydes and ketones was effected with the zinc-silver couple and ultrasound.28 The reaction occurs without transposition, which is not the case in the presence of magnesium. In refluxing... 

In a flame dried round-bottom flask, place 4-bromo-2-sulfolene (98.5 mg, 0.5 mmol), acetone (41 mg, 0.7 mmol), and THF (3.5 mL), then add the zinc-silver couple (38 mg, 0.6 mmol). Flush with dry nitrogen then stopper the flask with a rubber septum. 

Compounds with carbon-nitrogen multiple bonds were also successfully used in the Barbier procedure. Allylic groups add to imines in high yields (> 77% in the examples published), even enolizable substrates, possibly due to the low basicity of the medium.37 Additions to nitriles occur in THF in the presence of the zinc-silver couple.38 Terpenic ketones were prepared by this method. 

In a flame dried round-bottom flask fitted with magnetic bar and dropping funnel, place zinc-silver couple (3.27 g, 52 mmol) and dimethylacrylonitrile (3.30 g, 37.5 mmol) in anhydrous THF (10 mL). 

The selective cyclopropanation of the a-enone silyl enol ether 75, by methylene iodide and the zinc-silver couple 2), is remarkable. Only the double bond bearing the tri-methylsiloxy group reacted to yield the 1-trimethylsiloxy vinylcyclopropane 76 when not more than 1.1 equivalent of the Simmons-Smith reagent was used, but the bis-cyclopropanation product 77 was obtained in good yield with an excess (3 equivalents) of the cyclopropanating reagent, Eq. (24) 42). 

The Simmons-Smith reaction often starts very slowly and proceeds quite slowly at room temperature. The method of the preparation of active zinc-copper couple has been improved 93, 196, 298, 376, 443, 466). The use of zinc dust/cuprous chloride instead of zinc-copper couple gives higher yields in the Simmons-Smith reaction 407). The reaction with homoallylic alcohols of low reactivity was facilitated by use of excess Simmons-Smith reagent and distillation of ether to a halfvolume followed by heating in a stainless steel tube 182). The Simmons-Smith reaction was successfully applied to vinyl trimethylsilyl ethers to prepare, after methanolysis, cyclopropyl alcohols unobtainable by other methods 109). Here, the zinc-silver couple was used instead of the zinc-copper couple, and the quenching of the reaction mixture of the Simmons-Smith reaction was improved by using pyridine under nonaqueous conditions. 

QUiNODiMETHANES Ccsium fluoride. Chro-mium(II) chloride. Zinc-Silver couple. 

Recently, the occasionally capricious reduction of a,a -dibromo-o-xylenes (550) has been improved by the use of Zn/ultrasound, zinc/silver couple, reactive nickel (0) or CrCb, as assayed by in situ trapping of (551) with typical dienophiles (Scheme 128, Table 33). ... 

Improved reaction. Conia et al. have reported two modifications of the Simmons-Smith reaction which ave improved yields. One is the use of a zinc-silver couple in place of the zinc copper couple. This couple is prepared by adding granular zinc to a stirred hot solution of silver acetate in acetic acid. The mixture is stirred for 30 sec. and the zinc-silver couple formed is isolated by decantation and washed with acetic acid and ether. It is then stabilized by addition of a small amount of silver wool. The second improvement is that the reaction mixture is not subjected to acid hydrolysis. Instead an amine, for example pyridine, is added. This forms the insoluble complexes Znlj-C HsN and ICH jZnl -(C, 115N)j the cyclopropane products are then isolated from the filtrate. 

DIBAL-H/n-butyllithium, in cyclic and acyclic systems with iron pentacarbonyl, in cyclodecanes with lithium dihydrodimethoxyaluminate(III)/copper(I) iodide, and in cyclohexane and cyclopentane systems with NaH/sodium r-butylpentyl/Ni(OAc)2. ° The monoreduction of 1,3-diketones can be carried out under similar conditions, as illustrated by the reaction of a substituted cyclohexane-1,3-dione with oxalyl chloride to give the corresponding 1-chlorocyclohexenone, which was subsequently reduced to the enone with zinc-silver couple (Scheme 45). Kropp et al. have reported the photolytic reduction of vinyl iodides in acyclic systems however, when an a-hydrogen is present, formation of the diene product is a limiting side reaction (Scheme 46). For a more extensive discussion of vinyl halide reductions, see the preceding chapter in this volume. 

One synthesis of cyclopentenone [80], requiring a resolution, involved initial ring contraction of phenol when treated with alkaline hypochlorite (49). Resolution of the resulting cis acid [85] was effected with brucine. The desired enantiomer [86] formed the more soluble brucine salt and was thus obtained from the mother liquors of the initial resolution. Oxidative decarboxylation with lead tetracetate, partial dechlorination with chro-mous chloride, and alcohol protection gave chloro enone [87]. Zinc-silver couple (50) dechlorinated [87] to the desired cyclopentenone [80]. 

As mentioned in Section 4.2, zinc couples such as zinc-copper and zinc-silver couples have frequently been used in organic synthesis due to their increased reactivity. Their use in the preparation of dialkyl zinc compounds has already been pointed out. To try to summarize all the reactions in which the use of zinc couples has been reported, even for just the past few years, would be much to ambitious for this review. Therefore, we shall just present some representative examples and key papers reporting the latest advances in new types of couples. 

Table 7. Examples of improved Simmons-Smith reactions using zinc-silver couple and pyridine work-up... 

Clark and Heathcock59 have reported a recent modification of Conia s method and have found their zinc-silver couple to be very useful for the reduction of /3-chloro-a, 3-unsaturated ketones to a, /3-unsaturated ketones. 

A suspension of anhydrous silver acetate in boiling acetic acid is then added. After the mixture is stirred for 1 minute, the supernatant is again decanted and the black zinc-silver couple is washed with acetic acid, ether and finally methanol. Some of the results they obtained are shown in Table 8. 

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