Bromomethylation Bromomethyl dimethylsilyl ethers

Intramolecular free radical reactions have been also exploited using silicon temporary attachment [97]. Reduction of enone 134, gave the corresponding allylic alcohol, which is transformed into the bromomethyl-(dimethylsilyl) ether 137 (Scheme 47). Radical cy-... 

Highly diastereoselective 7-rro/o-radical cyclization of (bromomethyl)dimethylsilyl ethers 150, derived from ethyl y-hydroxy-a-methylenecarboxylates, bearing a bulky y-substituent such as isopropyl, cyclohexyl, and tert- mty in THF gave cyclic silyl ethers 151 bearing preferentially the ethoxycarbonyl group anti to the y-substituent (Equation 28) <2004TL4329>. 

Scheme 10-41 Synthesis of 1,3- and 1,4-diols from (bromomethyl)dimethylsilyl ethers. Reagents and conditions i) Bu3SnH-, AIBN, PhH, reflux ii) 30% H2O2, DMF, KF, 60 °C iii) 30% H2O2, MeOH, THF, NazCOj, reflux.

Controlled radical cyclization directly onto a ring junction is less easy. Lejeune and Lallemand envisaged that a tethered radical cyclization of a (bromomethyl)dimethylsilyl ether onto an allylic double bond could be used to incorporate a hydroxymethyl functionality into an angular position at the ring junction of a decalin system [53]. This would then provide an interesting entry into a variety of natural products containing this skeletal functionality, such as the insect antifeedant clerodin 132 (Scheme 10-45). 

Use of the (Bromomethyl)dimethylsilyl Ether Group in a Radical Cyclization in the Synthesis of Talaromycin A, 140 [54]... 

The mode of cyclization of a-silyl radicals generated from homoallylic (bromomethyl)dimethylsilyl ethers is highly dependent upon the substitution pattern on the distal alkenic carbon. Thus while those with unsubstituted distal alkene carbons provide seven-membered siloxanes (J-endo) (eq 1) those having substituted carbons undergo a 6-exo-mode of radical cyclization in a highly regio- and stereoselective manner (eq 8). These six-membered siloxanes provide, upon Tamao oxidation, branched chain 1,4-diols (eq 8). ... 

Olefins andAlkynes. The increased scope of the silicon tether in radical chemistry, which is still the most important reactivity allowed by the (bromomethyl)dimethylsilane moiety, has been reviewed. Some authors have again illustrated the synthetic interest of Nishiyama-Stork radical cyclizations of allylic (bromomethyl)dimethylsilyl ethers. Jenkins achieved stereoselective cyclizations on a fused cyclopentanol, while Herdewijn prepared pyranosyl nucleosides. Starting from /-substituted... 

The unusual angular 4,6,5-tricyclic framework of the protoillu-danes was attained by following a similar transannular strategy in which the (bromomethyl)dimethylsilyl ether was switched from one propargylic position to the other on the cycloundecadienyne platform (eq 19). The first total synthesis of epi-illudol proceeds through a biomimetic tandem of transannular A-exo 6-exo cyclizations of the vinyl radical. 

The total synthesis of (—)-Lasonolide A has been envisaged by using the radical cyclization of a (bromomethyl)dimethylsilyl ether precursor. Lee proposed the use of such a step at an early stage of the synthesis (eq 22). Upon treatment with tributyltin... 

The stereoselective branching of L-rhamnal at C-1 and C-2 via a silicon tethered radical cyclization is illustrated in Scheme 7, and allyl alcohol groups which are protected as their (bromomethyl)dimethylsilyl ethers undergo a radical-induced cyclization to give branched-chain sugars as shown in Scheme ZP... 

Bromomethyl)dimethylsilyl chloride is the most widely investigated and important reagent for incorporating a radical precursor into a silyl tether. It is commercially available and readily introduced as a silyl ether under standard conditions. Moreover, the facile cleavage of the silicon tether under a variety of conditions after reaction yet further enhances its synthetic utility. 

The extention of radical cyclization of (bromomethyl)dimethylsilyl allyl ethers to propargyl analogs 17 has been studied by Malacria and coworkers. The intermediate exocyclic vinyl radical 18 can be either trapped by the hydrogen atom to give, after simple chemical transformations, the trisubstituted alkene 19 (equation 25) or can be added intramolecularly to give cyclic products when suitably located double bonds are present (equations 26 and 27). An attempt to apply this methodology to the stereoselective synthesis of angular and linear triquinane has also been performed. When = t rt-butyl,... 

Nitrogen-based Functional Groups. Important efforts have been devoted to (bromomethyl)dimethylsilyl radical reactions featuring nitrogen atoms. Renaud introduced a powerful new terminating step for the Nishiyama-Stork cyclization. After conversion of the silyl ether to the corresponding iodide, cycliza-tion in the presence of phenylsulfonyl azide allowed azidation of the cyclized radical (eq 13). 

Interestingly, placement of the (bromomethyl)dimethyl-silylether to the other propargylic position of the macrocycle (i.e., 121, Scheme 20.32) led to a transannular radical reaction cascade to give a single diastereomeric 4-6-5 tricyclic 126, which was converted to 127 by the Tamao oxidation in 47% yield over two steps. The high chemo-selectivity of the radical reaction of the primary radical 122 toward the 5-exo-dig versus 5-exo-trig cyclization was also notable for the mixed allylic and propargylic (bromo-methyl)dimethylsilyl ether 121 (Scheme 20.32). 

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