Starting from optically active 3,3-difluorolactaldehyde, an alkenyl or aryl boronic acid, and an amine, a one-step three-component methodology was developed for the stereoselective preparation of anti-alpha-(difluoromethyl)-beta-amino alcohols. beta-Furyl-substituted anti-alpha-(difluoromethyl)-beta-amino alcohol was further elaborated to form (2S,3R)-difluorothreonine in high yield and ee.

A short stereocontrolled preparation of anti-alpha-(trifluoromethyl)-beta-amino alcohols is described, involving an initial CF(3) transfer to cinnamaldehyde and a one-step, three-component condensation of 3,3,3-trifluorolactic aldehyde, an alkenyl (aryl) boronic acid, and an amine. Applying this methodology to chiral 3,3,3-trifluorolactic aldehyde allowed us to generate an amino alcohol enantioselectively in 92% ee.

Remarkable increases of molecular complexity in a single procedural step are achieved with the title reaction. Only a slight modification in the substitution pattern on the acyclic precursor 2 can change the mode of tetracyclization to either yield skeletons of type 1 or 3 exclusively.

The outcomes and the mechanistic pathways of the palladium-catalyzed Heck-type cascade oligocyclizations of various 2-bromoalkenediynes were explored with respect to the lengths of the tethers between the multiple bonds and the nature of the substituent at the acetylenic terminus. Just like substrates containing two three-atom tethers, 2-bromotridec-1-ene-6,13-diynes 10a,b with one three-and one four-atom tether undergo two consecutive intramolecular 5-and 6-exodig carbopalladations with subsequent 6π-electrocyclization and β-hydride elimination to form tricycles 35a,b with a central benzene ring in 67 and 61 % yield, respectively, independent of the fact that 10a contains an electron donor and 10b an electron acceptor at the acetylene terminus. However, when 2-bromotetradec-1-ene-7,13-diynes 22, 29 on one side and 16, 27, 31 on the other are subjected to Heck reaction conditions, tricycles with a central benzene ring are formed only, when the substituent at the acetylene terminus is not a

2-Bromotetradec-1-ene-7,13-diynes 1, 5, 12 with different substituents at the acetylenic terminus under palladium catalysis have been found to either yield an angularly bisannelated benzene derivative 3 (79%), or fulvene derivatives of type 5 (52-74%) as well as monoannelated fulvenes 13b-e (32-48%). The mechanisms for all three reaction modes most probably involve intramolecular 5-exo-trig carbopalladations of an intermediate 1,3,5-hexatrienyl-6-palladium bromide intermediate. Transition-metal-catalyzed C-C-bond forming reactions have been widely explored in the past 15 years. Among them, palladium-catalyzed cross-couplings have attracted considerable attention in both academic and industrial research laboratories.1 Towards the construction of complex organic molecules from relatively simple open chain precursors, the Heck reaction is particularly attractive, as it is compatible with a variety of functional groups and can be incorporated more than once in multistep sequential processes 2 following a number of distinctly different reaction pathways.1,3 Thus, single operation tricyclizations of 2-bromoalk-1-enediynes have been used to prepare carbocyclic as well as heterocyclic angularly bisannelated benzene derivatives in moderate to good yields. 4 All previously reported examples, however, contained either two five-or one five-and one six-membered ring attached to the aromatic central ring. In order to test the accessibility of the octahydrophenanthrene skeleton by this route, we have prepared several 2-bromotetradec-1-ene-7,13-diynes and subjected them to typical Heck cross-coupling conditions. 5Upon treatment of dimethyl 2-bromo-14-(tert-butyldimethylsilyl)-tetradec-1-ene-7,13-diyne-4,4-dicarboxylate (1) with palladium acetate in the presence of triphenylphosphine and potassium carbonate in acetonitrile at 60°C for 20 h, it was smoothly converted into dimethyl (9-tert-butyldimethylsilyl)-1,2,3,4,5,6,7,8-octahydrophenanthrene-2,2-dicarboxylate (3).6 This transformation appears to have proceeded via a 6-endo-trig cyclization or a 6p-electrocyclization of the alkenylpalladium intermediate 2, (Scheme 1), followed by a,b-dehydropalladation. In contrast, dimethyl 2-bromotetradec-1-ene-7,13-diyne-4,4-dicarboxylate (4a) which was obtained from 1 by hydrodesilylation at the acetylenic terminus, under identical conditions did not yield the unsilylated octahydrophenanthrene, but the bisannelated fulvene derivative 5a within 1 h in 74% yield (Scheme 2).7 The 9-methoxy-substituted analog 4b and the heteroanalogous bromoenediyne 4c, under slightly modified conditions, reacted in the same way to give the fulvenes 5b in 65% yield within 45 min, and 5c in 52% yield within 1.5 h, respectively. The structure of the fulvene 5b was rigorously proved by an X-ray crystal structure analysis of the Diels-Alder adduct that was readily formed upon treatment of 5b with dimethyl acetylenedicarboxylate (Figure). 8 The formation of fulvenes 5 may be rationalized in terms of a 5-exo-trig-carbopalladation instead of the 6-endotr...