[reaction: see text] The marine sponge derived beta2-adrenoceptor agonist S1319 has been synthesized following a six-step linear sequence. Central to the approach employed is the formation of a 7-lithiated-2,4-dialkoxybenzothiazole intermediate obtained via a directed-lithiation/benzyne-mediated cyclization reaction. The incorporation of a tert-butyl ether residue into the cyclization precursor for the pivotal ring-closing step has been shown to significantly increase the efficiency of the reaction by the suppression of a competing directed ortho-lithiation reaction.

Dedicated to Professor Dieter Seebach on the occasion of his 65th birthday 1,1-Disilyl alcohols like 6 give the silyl ethers like 9 on treatment with base and alkyl halides, in a reaction which may be formulated as the alkylation of the Brook-rearranged carbanion 8. The products can be oxidised to give ketones like 10, showing that this Brook-rearranging system supplies a controlled d 1 synthon of the acyl anion class. The alcohols can be prepared from the acid chloride 12 and dimethyl(phenyl)silyllithium, but the intermediate anion 21 need not be worked up; it can be used directly in the alkylation step.Introduction. ± The 1,2-Brook rearrangement is usually formulated as an equilibrium between an oxy anion having an a-silyl substituent, such as 1, and a carbanion having an a-silyloxy substituent, such as 2, with the former normally in high concentration and the latter in low concentration [1]. Whether or not this is an accurate description of the species present 3 ), it often reacts with electrophiles as a carbon nucleophile, and as such it can be classified as a d 1 synthon [3].For example, if benzaldehyde (PhCHO) is treated with dimethyl(phenyl)silyllithium (Me 2 PhSiLi) the products are the a-silylbenzyl alcohol 3 and, after workup, the pinacol 4 (Scheme 1) [4]. The latter is the product from the reaction of an anion 2 with another molecule of PhCHO, but it is not possible to use this nucleophile with a range of electrophiles. Although homocoupling is relatively easy, as here, it is limited to aromatic aldehydes and ketones [5], because easy Brook rearrangement 1 3 2 needs the stabilisation of the carbanion provided by the aromatic ring. We have found, as Kuwajima and co-workers have also [6], that it can also be made to give a cross-coupled pinacol 5, but only when the electrophilic component is a nonenolisable aldehyde [7]. The yield was low, there were several other products, and it was clear that this was not a general or reliable way of gaining access to a reliable d 1 synthon.The Brook rearrangement can be set up in several ways: most commonly when an a-silylcarbinol is treated with base [8], when an aldehyde or ketone is treated with a silyllithium reagent [9], or when an acylsilane is treated with a nucleophile [10]. There are a few reactions in which a Brook rearrangement, set up in one of these ways, is the

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

No abstract

Organo-silicon compoundsOrgano-silicon compounds S 0060 1,1-Disilyl Alcohols as d 1 Synthons: Harnessing the 1,2-Brook Rearrangement.-In the presence of base, 1,1-disilyl alcohols such as (III) undergo 1,2-Brook rearrangement. Carbanions are formed which can be trapped with alkyl halides to afford silyl ethers of type (V) and (IX). The latter smoothly undergo oxidation to ketones revealing the full capacity of the rearrangement system as an acyl anion equivalent. Double 1,2-Brook rearrangement-alkylation is also possible as is shown by formation of the silyl ether (XII). -(FLEMING*, I.; LAWRENCE, A. J.; RICHARDSON, R. D.; SURRY, D. S.; WEST, M. C.; Helv. Chim. Acta 85 (2002) 10, 3349-3365; Dep. Chem., Univ. Cambridge, Cambridge CB2 1EW, UK; Eng.) -Jannicke 11-173 2003 Organo-silicon compounds