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A simple procedure for the conversion of tertiary lactams to 2-monoalkylated cyclic amines is described. The reaction sequence involves conversion of a lactam to a thioiminium ion followed by reaction with an organocopper (RCu) reagent and final reduction with triacetoxyborohydride. The reaction is high yielding and shows an excellent functional group tolerance. Its utility is demonstrated by a rapid synthesis of indolizidine 167B. The excellent chemoselectivity of the process, where only monoalkylation products are formed, is rationalized by a mechanism involving the formation of a transient enamine.

A systematic study of the diastereoselectivity of the radical carboazidation of methylenecyclohexane derivatives is presented. Several substitution patterns leading to a high level of stereocontrol have been identified. Axial attack is the preferred reaction pathway for cyclohexyl radicals, and excellent stereoselectivities can be obtained by introducing an axial substitutent at position 2. In this case, a second equatorial substituent at position 2 may be tolerated without a large detrimental effect on the diastereoselectivity. Finally, a high level of equatorial attack is observed with a very bulky substituent at position 2.

Azabicyclo[4.3.0]nonanes were assembled, from chiral allylsilanes possessing an oxime moiety, using a stereocontrolled formal [2 + 2 + 2] radical-ionic process. The cascade involves the addition of an alpha-iodoester to the less substituted end of the enoxime which is then followed by a 5-exo-trig cyclization onto the aldoxime function, producing an alkoxyaminyl radical species which finally lactamizes to afford the titled piperidinone. High levels of stereoinduction were observed, demonstrating the ability of a silicon group located at the allylic position to efficiently control the stereochemistry of the two newly created stereogenic centers. When the radical cascade was extended to ketoximes, the resulting sterically hindered alkoxyaminyl radical did not react further with the initiator Et3B to produce the expected nucleophilic amidoborane complex. In sharp contrast, this long-lived radical recombined with the initial alpha-stabilized ester radical to produce a cyclopentane incorporating two ester fragments.

Regioselectivity of the sulfonyl radical mediated 5-exo-trig cyclization of 3-silylheptadienyl systems 3a-d has been studied. At low temperature, the reaction of the sulfonyl radical occurs regioselectively at the allylsilane terminus, while a reversal of regioselectivity is observed at 80 degrees C. This general trend has been rationalized on the basis of polar effects and radical stabilization. Thiyl-mediated radical cyclization of dienes 3a, 3c-d, 7 with subsequent sulfur atom transfer was also studied, providing thiabicyclo[3.3.0] skeleton in one step with excellent stereocontrol.

[Chemical reaction: See text] Free-radical-mediated 5-exo-trig cyclization of hepta-1,6-dienes 6a-c incorporating an allylsilane moiety was shown to provide at low temperature exclusively the trans-cis cyclopentanes 7a-c in good yield. In contrast, the same reaction with the alkyl analogue 9a led to the formation of all four possible stereoisomers. Interestingly, extension of this sequence of radical processes to alkoxy analogues 12-14 provided the complementary cis-cis stereoisomers with modest to excellent stereoselectivity. It is noteworthy that under such conditions allylsilanes were found to be much more reactive than their alkyl and alkoxy analogues. Beckwith-Houk-type models were proposed that rationalize the stereochemical course of these 5-exo-trig cyclizations. Finally, an illustration of the value of this methodology was proposed with the synthesis of the A-B-C tricyclic unit of polyketide hexacyclinic acid 3a.

C2-Substituted silacyclopent-3-enes have been prepared in good yields in two steps starting from commercially available diallylsilane 9. Coupling between carbanion of 9 and aldehydes or epoxides followed by ring-closing metathesis of the corresponding substituted diallylsilanes led to various silacyclopent-3-enes having a beta- or a gamma-hydroxysilane moiety. Dihydroxylation and epoxidation of the sila-cycle then led stereoselectively to polyhydroxylated silacyclopentanes. These processes were shown to occur with opposite topicity, offering a complementary and stereocontrolled access to diastereomeric polyols having up to five contiguous stereogenic centers.

Condensation of 2,3,4,6-tetra-O-benzyl-beta-D-glucopyranosylcarbaldehyde with isolevoglucosenone induced by Et(2)AlI, followed by epoxidation, gave an aldol that was fluorinated into a monofluoromethylene C-glucopyranoside that was converted into the title C-disaccharide 1. Its conformational behavior in water has been studied by using a combination of NMR spectroscopy (J and NOE data) and molecular mechanics calculations.

At low temperature 1-alkoxy-1,3-dienes add to sulfur dioxide activated by a Lewis or Brønstedt acid and generate zwitterionic intermediates that can be quenched by enoxysilanes. The resulting beta,gamma-unsaturated silyl sulfinates can be desilylated and reacted with methyl iodide to provide polyfunctional sulfones. Exploratory studies of this four-component synthesis of sulfones are reported. Enantiomerically pure derivatives containing up to three new stereogenic centers can be obtained using enantiomerically pure (E,E)-1-alkoxy-2-methylpenta-1,3-dienes derived from alpha-methyl benzyl alcohols, including the Greene's chiral auxiliary. The stereochemistry of the reactions is consistent with a mechanism involving the suprafacial hetero-Diels-Alder addition of sulfur dioxide to the 1-alkoxy-1,3-dienes that are rapidly ionized into zwitterionic intermediates.