Alkenes from silyl-alcohols

A simple example involves the reaction of the silyl ether 213, made from the corresponding 4-hydroxy-alkene by treatment with (bromomethyl)chloro-dimethylsilane, with tributyltin hydride and a radical initiator. Bromine abstraction and intramolecular cyclization with the double bond leads to the bicyclic 214, which upon oxidation with hydrogen peroxide gives the branched-chain 215 in an overall yield of 73% from the alcohol precursor of 213 (Scheme 21). When the sequence is conducted with the C-4 epimeric starting alcohol, the final product again has the hydroxymethyl group cis-related to the hydroxy group.217... 

Nucleophilic attack on ( -alkene)Fp+ cations may be effected by heteroatom nucleophiles including amines, azide ion, cyanate ion (through N), alcohols, and thiols (Scheme 39). Carbon-based nucleophiles, such as the anions of active methylene compounds (malonic esters, /3-keto esters, cyanoac-etate), enamines, cyanide, cuprates, Grignard reagents, and ( l -allyl)Fe(Cp)(CO)2 complexes react similarly. In addition, several hydride sources, most notably NaBHsCN, deliver hydride ion to Fp(jj -alkene)+ complexes. Subjecting complexes of type (79) to Nal or NaBr in acetone, however, does not give nncleophilic attack, but instead results rehably in the displacement of the alkene from the iron residue. Cyclohexanone enolates or silyl enol ethers also may be added, and the iron alkyl complexes thus produced can give Robinson annulation-type products (Scheme 40). Vinyl ether-cationic Fp complexes as the electrophiles are nseful as vinyl cation equivalents. ... 

Asymmetric Intramolecular Hydrosilation. Intramolecular hydrosilation of allylic alcohols followed by oxidation is a convenient method for the stereoselective preparation of 1,3-diols. An enantioselective version is achieved by use of diene-free BINAP-Rh+ (eq 6). Both silyl ethers derived from cinnamyl alcohol and its cis isomer give (iJ)-l-phenylpropane-l,3-diol in high ee regardless of alkene geometry. 

Synthesis of alkenes from a-silyl carbanions and carbonyl compounds. In cases where separation of p—silyl alcohol diastereomers (e.g. 6) can be achieved, pure Z or E olefins can be isolated (see 1st edition). 

Epoxide opening. A stereoselective alkene synthesis starts from reaction of triethylsilyloxirane with an organocuprate reagent, and it is concluded by oxidation of the j8-silyl alcohol to the aldehyde, Grignard reaction and elimination of [Et Si/OH]. The elimination leads to either the ( )- or the (Z)-alkene by using different reagents. 

Related to the alkene-to-allylic alcohol conversion is the oxiran to allylic alcohol isomerization. Two recent reports describe the use of trimethylsilyl iodide, either ready-made or prepared in situ from hexamethyldisilane and iodine, with DBU (Scheme 12) the initially formed 2-iodo-alkoxysilane (31) eliminates HI to give an allylic silyl ether that is cleaved during hydrolytic work-up. An alternative procedure (also Scheme 12) employs t-butyldimethyl-silyl iodide, generated in situ according to equation (14), and DBN. In this... 

Thioethers. Bridgehead positions in hydrocarbons are functionalized as butyl-thioethers by reaction with lead tetra-acetate and butanethiol (c/. ref. 1). Reductive sulphidation of aldehydes is accomplished by conversion to a silyl monothio-acetal and cleavage of the C-O bond as outlined in Scheme 38. Reaction of primary alcohols with aryl isothiocyanates and triphenyl phosphine produces arylalkylthioethers, presumably via the sequence of Scheme 39. In secondary and tertiary cases elimination (to ArSH and alkene) from (76) is a competing process. 

Recently, Szabo and co-workers synthesized allyl silanes either from alkenes by C-H silylation or from allylic alcohols. ... 

In a formal synthesis of fasicularin, the critical spirocyclic ketone intermediate 183 was obtained by use of the rearrangement reaction of the silyloxy epoxide 182, derived from the unsaturated alcohol 180. Alkene 180 was epoxidized with DMDO to produce epoxy alcohol 181 as a single diastereoisomer, which was transformed into the trimethyl silyl ether derivative 182. Treatment of 182 with HCU resulted in smooth ring-expansion to produce spiro compound 183, which was subsequently elaborated to the desired natural product (Scheme 8.46) [88]. 

The ruthenium carbene catalysts 1 developed by Grubbs are distinguished by an exceptional tolerance towards polar functional groups [3]. Although generalizations are difficult and further experimental data are necessary in order to obtain a fully comprehensive picture, some trends may be deduced from the literature reports. Thus, many examples indicate that ethers, silyl ethers, acetals, esters, amides, carbamates, sulfonamides, silanes and various heterocyclic entities do not disturb. Moreover, ketones and even aldehyde functions are compatible, in contrast to reactions catalyzed by the molybdenum alkylidene complex 24 which is known to react with these groups under certain conditions [26]. Even unprotected alcohols and free carboxylic acids seem to be tolerated by 1. It should also be emphasized that the sensitivity of 1 toward the substitution pattern of alkenes outlined above usually leaves pre-existing di-, tri- and tetrasubstituted double bonds in the substrates unaffected. A nice example that illustrates many of these features is the clean dimerization of FK-506 45 to compound 46 reported by Schreiber et al. (Scheme 12) [27]. 

In recent years, dioxiranes have become workhorses for a variety of selective transformations in organic synthesis, from epoxidation of alkenes to the conversion of alcohols into fee corresponding ketones <99CJC308>. Dioxirane-mediated epoxidation continues to be the method of choice for complex substrates wife acid-sensitive functionality. Thus, fee dimethyl-dioxirane (DMD)-mediated epoxidation of the silylated stilbene lactam 159 has been reported as a key step in fee synthesis of protoberberines <99JOC877>. 

Two recently developed coupling reactions of an alkene (R1CH2CH=CH2), an aldehyde (R2CHO), and a silyl triflate (R33SiOTf) yield an allylic (66) or homoallylic (67) alcohol (in protected form).188 Employing nickel-phosphine catalysts, either product can be selected by small changes in the phosphine component. A mechanism distinct from that of Lewis acid-catalysed carbonyl-ene reactions is proposed and discussed. 

Polystyrene-bound silanes are usually prepared by reaction of organolithium compounds with resin-bound silyl chlorides [12, 13]. The C-Si bonds of aryl-, heteroaryl-, vinyl-, and allylsilanes are stable towards alcoholates or weak reducing agents, but can be cleaved under mild conditions by treatment with acids or fluoride to yield a hydrocarbon and a silyl ester or silyl fluoride. Several linkers of this type have been tested and have proven useful for the preparation of unfunctionalized arenes and alkenes upon cleavage from insoluble supports. 

Another synthetic application of Roush s crotylboration methodology using a (Z)-crotylboronate can be found in the formal synthesis of (+)-discodermolide (75)29 (Scheme 3.1z). The aldehyde (S)-67, which was prepared from the Roche ester, reacted with (Z)-crotylboronate (S,S)-43Z to give the syn-homoallylic alcohol 76. Silylation of alcohol and oxidative cleavage of the alkene 77 provided the aldehyde 78, from which the final product (75) can be synthesized according to a known procedure.30... 

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