Rh2 OAc 4 Catalyst

We began our search by looking for silanes and catalysts that would allow a single addition of an alcohol to a dihydridosilane under mild conditions. The silanes that were studied are diethylsilane, diphenyl silane and diisopropylsilane. These silanes were treated with (+)-ethyl lactate in the presence of a variety of transition metal catalysts. The silanes were 

Following our results with diethylsilane and diphenylsilane, we consider the evaluation of diisopropylsilane or di-tert-butylsilane. Diisopropylsilane and di-tert-butylsilane may both be bulky enough that they would allow only one addition however diisopropylsilane (bp 96 °C) has a lower boiling point than di-tert-butylsilane (bp 128 °C) and would be easier to be removed at the end of the reaction by simple evaporation on a rotary evaporation apparatus. Unlike the two previous silanes, diethylsilane and diphenylsilane, diisopropylsilane was not commercially 

Following our success in finding a suitable silane and catalyst for the first step in the synthesis of unsymmetrical bis-alkoxy si lanes, we set out to evaluate catalysts to achieve the second alcoholysis. We were aware from prior reports in the literature that there were a variety of catalysts capable of performing alcoholysis of silanes.10 17 From prior evaluation of catalysts in the first step, we knew that 10 % Pd/C, Rh2(pfb)4, and CuH all catalyze the reaction of the second step with diethylsilane and Rh2(pfb)4 catalyzes the reaction of the second step (10 %) with diphenylsilane (Table 4). Rli2(OAc)4 was ruled out by our discovery that only one addition of alcohol occurred with diisopropylsilane. 

The mono-alkoxy products from the first addition of both diisopropylsilane and diphenylsilane with (+)-ethyl lactate was evaluated with [PPhjCuHje, Rh2(pfb)4 and 10 % Pd/C. When [PPh3CuH]6 was used as catalyst with the mono-alkoxy product from (+)-ethyl lactate and diisopropylsilane (le), a 30 % yield (isolated by flash chromatography) of the desired silyl ketal product was obtained. The yields rose to up to 70 % for the reaction of the mono-alkoxy diisopropylsilane using [Rh2(pfb)4] after 14 h at room temperature. 

Our optimized method was applied to form several unsymmetrical bis-alkoxysilanes in very good yields over two steps (Table 6). Tertiary alcohols, which can be difficult to protect, readily react under the conditions to give good yields of the unsymmetrical bis-alkoxysilane product.21 

---

Interestingly, while the chiral Rh2(4S-MACIM)4 catalyst gave the desired isomer from the C-H insertion reaction, the achiral Rh2(OAc)4 catalyst afforded the opposite diastereoisomer in low yield. The enantioselective preparation of / -lactams by C-H insertion has also been examined, and some like 34 and 35 are formed with high enan-tiocontrol [68], but the generality of this process has not yet been established. 

The 1,3-dipolar cycloaddition of a-keto carbenoids to the polar double bond of heterocumulenes provides a direct access to five-membered heterocycles. The reaction of a-diazo ketones 132 with phenyl isocyanate in the presence of a Rh2(OAc)4 catalyst affords the 1,3-cycloadduct, 3-phenyl-2(3//)-oxazolones 133 (Fig. 5.32). ... 

Activation by silicon of a P-C-H bond to an intramolecular carbene insertion reaction is exemplified by the silicon-directed Bamford-Stevens reaction.68 For example, thermal decomposition of P-trimethylsilyl /V-aziridinyl imines 72 in toluene (Scheme 8) [with or without Rh2(OAc)4 catalyst] results in the formation of allylic silanes 73 as major or exclusive products by the preferential insertion of the carbene intermediate into the C-H bond P to the silicon substituent. 

After obtaining this encouraging result, the Rh2(OAc)4 catalyst was evaluated with several other alcohols using diisopropylsilane (Scheme 24). The reaction works with primary, secondary and tertiary alcohols (Table 5). Alcohols with aryl halide functionality also work, however the reaction failed with alcohols containing double and triple bonds because hydrosilylation and/or hydrogenation of double and triple bonds is believed to be a major side reaction as judged by NMR analysis of crude mixture. 

The specific size of the stirring bar Is not Important, but the stirring rate should be adjusted so that the Rh2(OAc)4 catalyst remains suspended in solution. It should not be resting on the bottom of the round-bottomed flask, nor should it be splashed onto the sides of the flask. 

In the presence of Rh2(OAc)4 catalyst, the S atom as well as SO transfer to another alkene at room temperature are possible <1998SL391, 2000J(P1)153>. 

Decomposition of IV-furfuryl-N-methyl diazoacetamide over a Rh2(OAc)4 catalyst gives 3-(l-methyl-5-oxo-l,5-dihydropyrrol-3-yl) acrolein (14%), which appears to result from a consecutive carbenoid addition onto the C=C bond of a fur an ring and subsequent rearrangement (87HCA1429). 

Muller chose to examine cyclohexene and 1,4-cyclohexadiene (ten equivalents relative to diazo compound) as model systems, and screened a variety of carbenoid precursors and catalysts (Scheme 24, left). All reactions were conducted in DCM at 25 °C. The results with 1,4-cyclohexadiene were quite clear-cut. With acceptor-substituted carbenes, selectivity was >95 5 in favor of cyclopropanation 108 for Cu° or Rh2(OAc)4 catalysts. For acceptor/acceptor carbenoid precursors, CuCl still favored cyclopropanation >95 5, but with Rh2(OAc)4 insertion 109 now became... 

The reaction in Equation (a) is controlled mainly by the catalyst substrate control by the menthyl group plays only a minor role. This is evident from the fact that with the achiral [Rh2(OAc)4] catalyst only 9% ee can be achieved for the cis product and 13 % ee for the trans product. Catalysis with [Rh2(55-mepy)4] was extended from styrene to other prochiral olefins for which similar results were obtained. [16]... 

The search for the racemic form of 15, prepared by allylic cyclopropanation of farnesyl diazoacetate 14, prompted the use of Rh2(OAc)4 for this process. But, instead of 15, addition occurred to the terminal double bond exclusively and in high yield (Eq. 6) [65]. This example initiated studies that have demonstrated the generality of the process [66-68] and its suitability for asymmetric cyclopropanation [69]. Since carbon-hydrogen insertion is in competition with addition, only the most reactive carboxamidate-ligated catalysts effect macrocyclic cyclopropanation [70] (Eq. 7), and CuPF6/bis-oxazoline 28 generally produces the highest level of enantiocontrol. 

The premier example of this process in an ylide transformation designed for [2,3]-sigmatropic rearrangement is reported in Eq. 15 [107]. The threo product 47 is dominant with the use of the chiral Rh2(MEOX)4 catalysts but is the minor product with Rh2(OAc)4. That this process occurs through the metal-stabilized ylide rather than a chiral free ylide was shown from asymmetric induction using allyl iodide and ethyl diazoacetate [107]. Somewhat lower enantioselectivities have been observed in other systems [108]. 

Williams employed complexes of Al, Rh, or Ir in combination with Pseudomonas Jluorescens lipase (PFL) for the DKR of 1-phenylethanol. The best results were obtained using Rh2(OAc)4 as the catalyst for the racemization, and 60% conversion of the alcohol to give 1-phenylethyl acetate in 98% ee was obtained (Figure 4.6) [19]. At higher conversion, the enantiomeric excess dropped and 76% conversion gave 80% ee. 

As for cyclopropanation of alkenes with aryldiazomethanes, there seems to be only one report of a successful reaction with a group 9 transition metal catalyst Rh2(OAc)4 promotes phenylcyclopropane formation with phenyldiazomethane, but satisfactory yields are obtained only with vinyl ethers 4S) (Scheme 2). Cis- and trans-stilbene as well as benzalazine represent by-products of these reactions, and Rh2(OAc)4 has to be used in an unusually high concentration because the azine inhibits its catalytic activity. With most monosubstituted alkenes of Scheme 2, a preference for the Z-cyclopropane is observed similarly, -selectivity in cyclopropanation of cyclopentene is found. These selectivities are the exact opposite to those obtained in reactions of ethyl diazoacetate with the same olefins 45). Furthermore, they are temperature-dependent for example, the cisjtrcms ratio for l-ethoxy-2-phenylcyclopropane increases with decreasing temperature. 

Only one report mentions the cyclopropanation with diazodiphenylmethane in the presence of a group VIII metal catalyst. Remarkably enough, the selectivity of the reaction with 5-methylene-bicyclo[2.2.1]hept-2-ene (8) can be reversed completely. With Rh2(OAc)4 as catalyst, the exocyclie double bond is cyclopropanated exclusively (>100 1), whereas in the presence of bis(benzonitrile) palladium(II) chloride the endocyclic C=C bond is attacked with very high selectivity (>50 1)47). 

Rh2(OAc)4 is the most effective and versatile of the three catalysts used. Terminal and non-terminal olefins, strained olefins (norbomene, norbomadiene) and conjugated olefins (styrene) all react in good yield. 

Cu(OTf)2 generally gives yields intermediate between those of the other two catalysts, but with a closer resemblance to rhodium. In competition experiments, the better coordinating norbomene is preferred over styrene, just as in the case with Pd(OAc)2. Cu(acac)2, however, parallels Rh2(OAc)4 in its preference for styrene. These findings illustrate the variability of copper-promoted cyclopropanations, and it was suggested that in the Cu(OTf)2-catalyzed reactions of diazoesters, basic by-products, which are formed as the reaction proceeds, may gradually suppress... 

It is not known whether or not this transformation is catalyzed by the transition metal. However, the metal-catalyzed ring-opening reaction of (3-alkoxycyclopropane carboxylates yielding vinyl ethers (e.g. 50 -> 51 and 52 - 53) is well documented 97 120 . Several catalysts are suited [PtCl2 2 PhCN, Rh2(OAc)4, [Rh(CO)2Cl]2, [Ru(CO)3Cl2]2, Cu bronze, CuCl], but with all of them, reaction temperatures higher than those needed for the carbenoid cyclopropanation reaction are required. 

Furthermore, Rhg(CO)16, which can be used advantageously for cyclopropanation of more electron-rich alkenes, furnished only insignificant amounts of cyclopropane from acrylonitrile or ethyl acrylate and ethyl diazoacetate from methacrylonitrile and ethyl diazoacetate, equally low yields of vinyloxazole, cyclopropane and carbene dimers resulted (Scheme 20)145). The use of Rh2(OAc)4 or [Rh(CO)2Cl]2 as catalysts did not change this situation. 

Allyl halides153). The competition between insertion product 123 and cyclopropane 124 depends on the halogen atom and on the catalyst. In the presence of Rh2(OAc)4, no cyclopropane 124 at all is obtained from allyl iodide, but mainly cyclopropane... 

In addition to cyclopropane 145 and the expected [2,3] rearrangement product 143 of an intermediary oxonium ylide, a formal [1,2] rearrangement product 144 and small amounts of ethyl alkoxyacetate 146 are obtained in certain cases. Comparable results were obtained when starting with dimethyl diazomalonate. Rh2(CF3COO)4 displayed an efficiency similar to Rh2(OAc)4, whereas reduced yields did not recommend the use of Rh6(CO)16 and several copper catalysts. Raising the reaction temperature had a deleterious effect on total product yield, as had... 

The distinction between Pd and Rh catalysts was also verified for diazoketone 190. In this case, the carbonyl ylide was trapped by intramolecular [3+2] cycloaddition to the C=C bond195. Decomposition of bis-diazoketone 191 in the presence of CuCl P(OEt)3 or Rh2(OAc)4 led to the pentacyclic ketone 192 most remarkably, one diazoketone unit reacted by cyclopropanation, the second one by carbonyl ylide formation 194). With [(r 3-C3H5)PdCl]2, a non-separable mixture containing mostly polymers was obtained, although bis-diazoketones with one or two allyl side chains instead of the butenyl groups underwent successful twofold cyclopropanation 196). 

Transition-metal catalyzed decomposition of alkyl diazoacetates in the presence of acetylenes offers direct access to cyclopropene carboxylates 224 in some cases, the bicyclobutane derivatives 225 were isolated as minor by-products. It seems justified to state that the traditional copper catalysts have been superseded meanwhile by Rh2(OAc)4, because of higher yields and milder reaction conditions217,218) (Table 17). [(n3-C3H5)PdCl]2 has been shown to promote cyclopropenation of 2-butyne with ethyl diazoacetate under very mild conditions, too 2l9), but obviously, this variant did not achieve general usage. Moreover, Rh2(OAc)4 proved to be the much more efficient catalyst in this special case (see Table 17). 

Rhodium(II) acetate was found to be much more superior to copper catalysts in catalyzing reactions between thiophenes and diazoesters or diazoketones 246 K The outcome of the reaction depends on the particular diazo compound 246> With /-butyl diazoacetate, high-yield cydopropanation takes place, yielding 6-eco-substituted thiabicyclohexene 262. Dimethyl or diethyl diazomalonate, upon Rh2(OAc)4-catalysis at room temperature, furnish stable thiophenium bis(alkoxycarbonyl)methanides 263, but exclusively the corresponding carbene dimer upon heating. In contrast, only 2-thienylmalonate (36 %) and carbene dimer were obtained upon heating the reactants for 8 days in the presence of Cul P(OEt)3. The Rh(II)-promoted ylide formation... 

The view has been expressed that a primarily formed ylide may be responsible for both the insertion and the cyclopropanation products 230 246,249). In fact, ylide 263 rearranges intramolecularly to the 2-thienylmalonate at the temperature applied for the Cul P(OEt)3 catalyzed reaction between thiophene and the diazomalonic ester 250) this readily accounts for the different outcome of the latter reaction and the Rh2(OAc)4-catalyzed reaction at room temperature. Alternatively, it was found that 2,5-dichlorothiophenium bis(methoxycarbonyl)methanide, in the presence of copper or rhodium catalysts, undergoes typical carben(oid) reactions intermole-cularly 251,252) whether this has any bearing on the formation of 262 or 265, is not known, however. 

Furans and some of its derivatives have been cyclopropanated with the ketocarbenoids derived from ethyl diazoacetate and copper catalysts. The 2-oxabicyclo[3.1.0]hex-3-enes thus formed are easily ring-opened to 1,4-diacylbutadienes thermally, thermo-catalytically or by proton catalysis 14,136). The method has been put to good use by Rh2(OAc)4-catalyzed cyclopropanation of furan with diazoketones 275 to bicyclic products 276. Even at room temperature, they undergo electrocyclic ring-opening and cis, trans-dienes 277a are obtained with fair selectivity 257,258). These compounds served as starting materials in the total syntheses 257 259) of some HETE s (mono-... 

Rh2(OAc)4 has become the catalyst of choice for insertion of carbene moieties into the N—H bond of (3-lactams. Two cases of intermolecular reaction have been reported. The carbene unit derived from alkyl aryldiazoacetates 322 seems to be inserted only into the ring N—H bond of 323 246). Similarly, N-malonyl- 3-lactams 327 are available from diazomalonic esters 325 and (3-lactams 326 297). If, however, the acetate function in 326 is replaced by an alkylthio or arylthio group, C/S insertion rather than N/H insertion takes place (see Sect. 7.2). Reaction of ethyl diazoacetoacetate 57b with 328 also yields an N/H insertion product (329) 298>, rather than ethyl l-aza-4-oxa-3-methyl-7-oxabicyclo[3.2.0]hex-2-ene-2-earboxylate, as had been claimed before 299). 

For intramolecular N/H insertion involving a (3-lactam, Rh2(OAc)4 was found to be superior to other catalysts and to the photochemical route 300). Therefore, this procedure has been appraised to be the most efficient one for constructing a bicyclic P-lactam and, consequently, has become a standard method for synthesizing... 

---