Acylsilanes cyclization

Addition of acyl anions generated from acylsilanes to a,(3-unsaturated ketones using N-heterocyclic carbenes (NHCs) derived from thiazolium salts as catalyst produced 1,4-diketones, which cyclized to form the corresponding furans in good yields under an acidic condition <06JOC5715>. 

The biomimetic cationic domino cyclization of an acyclic unsaturated substrate to give the tetracyclic scaffold of triterpenes and steroids is intensively described in the literature.1121 The concept has recently been used by Corey et al. to prepare enanti-opure (+)-dammarenediol II 18 in an exceptional short way.1131 The synthesis demonstrates the power of the combination of cation-olefin polyannulation with the aldol cyclization for tetraannulation (scheme 4). Successive treatment of the acylsilane 13 with 2-propenyllithium 14 and the iodoalkane 15 efficiently yidds the epoxytriene 16. The Lewis acid... 

Because of the readiness with which cyclopropanes are formed from 3-halopropyl ketones, cyclization of the latter to dihydrofurans is difficult, and few examples of such cyclizations have been reported (Scheme9.18). Acylsilanes, on the other hand, are more nucleophilic at oxygen than ketones, and readily undergo intramolecular O-alkylations [73-75],... 

Tsai, M.-Y. Chemg, C.-D. Nieh, H.-C. Sieh, J.-A. The formation of oxygen-containing heterocycles via intramolecular cyclizations of halo-substituted acylsilanes and unsaturated acylsilanes. Tetrahedron 1999, 55, 14587-14598. 

Acylsilanes of type 152 with radicalphiles attached to the silicon atom underwent tandem radical cyclization to give 7,7,10-trimethyl-6-oxa-7-silaspiro[4.6]undecane (153 n = 1) and 8,8,ll-trimethyl-7-oxo-8-sila-spiro[5.6]dodecane (153 n = 2) (Equation 29) <2005T2037>. 

Acylsilanes bearing an acrylate Michael acceptor are smoofhly cyclized by treatment... 

Intramolecular competition experiments using a radical clock have revealed that the 5- and 6-exo cyclizations of primary alkyl radicals bearing an acylsilane moiety are slightly faster than those of the 5- and 6-alkenyl radicals [600]. The rate of cyclization depends on the substituents on silicon - the presence of a phenyl group on silicon increases the rate, probably because of its electron-withdrawing nature. 

Radical cyclization using acylsilanes is apphcable to the synthesis of cychc silyl enolates by yS-elimination of the a-siloxyalkyl radical intermediate (Scheme 10.234) [603]. 5-Bromo-5-stannyl- and 5-bromo-2-sulfonyl-alkanoylsilanes are cychzed to cyclopentanone silyl enolates with ehmination of the stannyl and sulfonyl groups. 

Radical cyclization reactions have proven to be a very efficient approach for polycyclic natural product synthesis. In many cases, the last step involves a reduction of a cyclic radical with formation of a new stereogenic center. Very good stereochemical control has been achieved with such polycyclic radicals. For example, Beckwith has reported a highly stereoselective formation of a quinolizidine ring (Scheme 19, Eq. 19.1) [41b]. This process is the key reaction in a four-step synthesis of epilupinine and the stereochemical outcome results from a stereoselective axial reduction by tin hydride of a bicyclic radical. In a related process, Tsai has prepared silylated hydroxyquinolizidine by radical cyclization to an acylsilane followed by a radical-Brook rearrangement (Scheme 19, Eq. 19.2) [42]. 

In addition to a,y -unsaturated ketones, a,yff-unsaturated esters also undergo cyclization, albeit at much slower rates than the corresponding a -unsaturated ketones. Treatment of methyl acrylate (49) with silylallene 34 at 25 °C (rather than the standard -78 °C) in the presence of TiCU furnished the expected cyclopentene 50 in 49% yield. To access carboxylate derivatives, Danheiser has reported the use of a, -unsaturated acylsilanes as the electrophilic component in the annulation process producing the corresponding acylsilane substituted cyclopentenes. " The acylsilane can then... 

Likewise, 2-silyldihydropyrans and furans can be prepared by heating the corresponding bromo- or cbloroacylsilanes in Al-methyl-2-pyrrolidinone (NMP) in tbe presence of potassium iodide as shown in eqs 25 and 26, respectively. Treatment of unsaturated acylsilanes with either iodine or phenylselenenyl bromide generates the cyclized iodides or selenides (eqs 27 and 28). ... 

Intramolecular radical cyclizations of acylsilanes containing the methyldiphenylsilyl moiety were investigated by the Tsai group (eq 29). As indicated in eq 29 products of radical addition to the carbonyl group involve silyl migration, whereas attack at the alkene center gives simple adducts. 

Formation of Bi (acyl ilane ). 2-TMS-l,3-dithiane has also been used in the generation of acylsilanes. Recently 1,4-, 1,5-, 1,6-and l,7-bis(acylsilanes) have been reported and used to produce silyl-substituted heterocycles. For example. Bouillon and Portella reported, in 1997, the formation of 1,5- and l,6-bis(acylsilanes) employing 2-lithio-2-TMS-l,3-dithiane and epichlorohydrin and diepoxide, respectively, as electrophiles (eqs 30 and 31). In the latter case the acylsilane was not isolated, as upon treatment with CaCOs and I2 the resulting acylsilane underwent cyclization to furnish the 2,5-bis-trimethylsilylfuran. 

Portella also reported the formation of non-hydroxy-containing 1,4- and l,5-bis(acylsilanes). For example, treatment of 2-TMS-1,3-dithiane with n-butyllithium followed by exposure to a variety of l,2-bis(triflates) provided symmetric and unsymmet-ric 1,4-bisdithianes in modest to good yield. Treatment with mercury salts or Mel revealed the bis(acylsilane), which upon exposure to PTSA cyclized to afford the corresponding 2,5-bis-trimethylsilylfuran (eq 32). 

Two alternative routes to (+)-swainsonine (ent-37S) developed by Chen and Tsai, Hke that used in their synthesis of lentiginosine (c Scheme 47 Section 3.3.2), created the bond to C-8a by means of free radical cycUzations onto an acylsilane. The first approach entailed the creation of the C-l/C-8a bond (Scheme 86). Amide formation between the amine 638 and the acid chloride prepared in situ from the chiral lactone-acid 639 yielded (—)-640, which was cyclized with base to the imide (—)-641 in 91% yield. Chemoselective reduction of the C-2 carbonyl group, acid-catalyzed reaction with thiophenol, and protection of the hydroxyl substituent as the benzoate gave 642 as a mixture of isomers. After hydrolysis of the dithiane to the acylsilane 643 with iodobenzene bis(trifluoroacetate), treatment with tri-butyltin hydride and l,lCazobis(cyclohexane-l-carbonitrile) (ACCN) as radical initiator produced the indohzidin-5-one 644 in 86% yield as a... 

Radical cyclization of an acylsilane was the featured reaction in a formal synthesis of (—)-epiquinamide (e <-2104) by Chen and Tsai (Scheme 278). Acylation of the same dithiane-protected amine 647 that they used in their synthesis of (+)-swainsonine (cf Scheme 87 Section... 

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