Gary E. Keck

One electron C-C bond forming reactions VIA allylstannanes: Scope and limitations

Abstract Free radical (or “one-electron”) methodology for carbon-carbon bond forming reactions using allylstannanes is described in detail. Such reactions have the advantages of tolerating quite complex functionality in the substrate and of being nearly stoichiometric in reagents, and not requiring extensive experimentation for application to new substrates.

Stereochemical consequences for the Lewis acid mediated additions of allyl and crotyltri-n-butylstannane to chiral β-hydroxyaldehyde derivatives

Abstract Proper choice of Lewis acid and hydroxyl protecting group allows for selective addition of crotyltri- n -butylstannane to either face of the aldehyde carbonyl in derivatives of 2-methyl-3-hydroxypropanal with preservation of erythro selectivity for the bond construction; allyl additions are limited to diastereofacial selectivity consistent with “chelation control”.

Stereocontrolled additions of allyltri-n-butyl-stannane to α-hydroxyaldehyde derivatives. A useful route to monoprotected erythro or threo diols.

Abstract By proper choice of Lewis acid and protecting group, the Lewis acid mediated addition of allyltri- n -butylstannane to the α-hydroxyaldehyde derivatives 1b and 1c can be controlled to give excellent (95:5 to > 250:1) stereoselectivity for the formation of either erythro or threo products.

Catalytic asymmetric allylation (CAA) reactions. II: A new enantioselective allylation procedure

A simplified and highly efficient new protocol is described for asymmetric allylation of aldehydes using allyltri-n-butylstannane and a chiral Lewis acid.

Observations on the choice of Lewis acid and mode of addition for the Lewis acid mediated reaction of crotyltri-n-butylstannane with aldehydes: convenient and highly selective access to both erythro and threo products

Abstract For additions crotyltri- n -butylstannane to simple aldehydes mediated by BF3·Et2O, erythro selectivity may be increased considerably (25:1 vs. 9:1, for example) by simply using 2 eq. of stannane, TiCl4 mediated additions give high erythro or threo selectivity depending simply on the order in which reactants are mixed; and other Lewis acids are also evaluated in such reactions.

Reductive cleavage of NO bonds in hydroxylamine and hydroxamic acid derivatives using SmI2/THF

Abstract The title reaction affords a general method for the reductive cleavage of NO bonds, and is successful in some cases where established methods fail.

A versatile method for carbon-nitrogen bond formation via ene reactions of acylnitroso compounds

Abstract The use of acylnitroso compounds of the general formula RCONO as enophiles in the formation of carbon-nitrogen bonds is described. Both inter- and intramolecular ene reactions have been studied. For the intermolecular examples, nitrosocarbonylmethane, thermally liberated from its Diels-Alder adduct with 9,10-dimethylanthracene, is reacted with various olefins giving the corresponding N-alkylhydroxamic acids in moderate to high yields, providing an efficient method for allylic amidation. The regiochemistry of the intermolecular reaction is observed to be the result of kinetic control, and the direction of addition is consistent with attack by the olefin on electron-deficient nitrogen. Several examples of intramolecular ene cyclization are demonstrated, providing efficient entry into both spiro and fused bicyclic nitrogen containing systems which can be viewed as derived from annulation of 5- and 6- membered nitrogen containing rings onto 5- and 6-membered carbocycles, respectively. Various examples of this hetero-annulation scheme are described. Experimental details are also privided describing typical reaction procedures.

Reductive cleavage of NO bonds in hydroxylamines and hydroxamic acid derivatives using samarium diiodide

Abstract An efficient process for the reductive cleavage of NO bonds using samarium diiodide is detailed for a variety of structural types to define the scope and limitations of the method. The reduction is shown to be compatible with base sensitive substrates such as trifluoroacetamide derivatives, which cannot be reduced satisfactorily using aluminum amalgam or sodium amalgam. Direct quenching of the reduction mixture with acylating agents is demonstrated to provide high yields of protected amines in a one-pot process from the NO derivatives.

Convergent assembly of highly potent analogues of bryostatin 1 via pyran annulation: bryostatin look-alikes that mimic phorbol ester function.

Highly potent bryostatin analogues which contain the complete bryostatin core structure have been synthesized using a pyran annulation approach as a key strategic element. The A ring pyran was assembled using a pyran annulation reaction between a C1-C8 hydroxy allylsilane and an aldehyde comprising C9-C13. This pyran was transformed to a new hydroxy allylsilane and then coupled with a preformed C ring aldehyde subunit in a second pyran annulation, with concomitant formation of the B ring. This tricyclic intermediate was elaborated to bryostatin analogues which displayed nanomolar to subnanomolar affinity for PKC, but displayed properties indistinguishable from a phorbol ester in a proliferation/attachment assay.

New allylstannanes for the connective construction of monoprotected vicinal diols

Abstract The preparation of allylstannanes 1a–c , all of which bear an oxygen substituent at the allylic terminus, is described. These reagents react with alpha- and beta-alkoxyaldehydes in the presence of MgBr2 as Lewis acid to give SE′, products with diastereofacial selectivity consistent with “chelation control”; a syn disposition of substituents about the newly formed bond is highly favored in all cases.