Bingel Macrocyclization Synthesis of cis-2 Bis-adduct 42 Starting from Benzene-1,2-dimethanol Scheme

Ethyl 3-chloro-3-oxopropanoate (ethyl malonyl chloride, 2.3 mL, 18.09 mmol) was added to a stirred solution of benzene-1,2-dimethanol (1.00 g, 7.24 mmol) and pyridine (1.5 mL, 18.09 mmol) in CH2CI2 (100 mL) at 0°C. The solution was allowed to slowly 

We thank the Swiss National Science foundation for continuing generous support of fullerene research and Prof. Jules Rebek, Jr., at the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, for hosting F.D. for his sabbatical, during which this article was written. 

An attractive and powerful feature of free-radical addition sequences is their ability to create multiple carbon-carbon bonds in a single reaction [5], In order for this methodology to be successful in the synthesis of repetitive molecular fragments such as those noted above, two general considerations must be addressed (1) control of stereochemistry, and (2) control of the number of iterative units which become incorporated. 

There has been intense interest in the control of stereochemistry of free-radical addition reactions by use of chiral auxiliaries [6] and, even more recently, using enantioselec-tive catalysis [7-12]. As a result, the current understanding of stereochemical control has clearly progressed to the point where this obstacle can be overcome. There have also been reports of strategies that simplify telomer distribution in free-radical oligomeriza- 

Exposure of 14 (m = 3, R = rcrf-Bu) to cyclohexyl iodide, allyltributylstannane, and AIBN leads to a macrocycle 15 with two new stereogenic centers. The allyl group provides additional functionality for further transformations and also creates a new stereocenter in the process. In order to effect the desired macrocyclization, addition of the first-formed radical to the proximal acrylamide moiety must be faster than addition to the chain transfer agent allyltributylstannane, a requirement that can be fulfilled under appropriate reaction conditions. Premature chain transfer in this particular system, under conditions that discourage bimolecular reaction between two templates, leads to two simple n = 1 products (vide infra). 

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Bingel Macrocyclization Synthesis of cis-2 Bis-adduct 42 Starting from Benzene-1,2-dimethanol (Scheme 7-8) [25]... 

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