Phosphonates, allylic, coupling

Cleavage of the phosphonate allyl esters from Abu[PO(OAl)2]-peptide-resins is accomplished by treatment with Pd(PPh3)4 (50 °C, 5 h)[103l followed by acidolytic deprotection of the Abu[PO(OH)2]-peptide from the resin support. The viability of employing allyl phosphonate protection for phosphopeptide synthesis has been demonstrated by the Fmoc solid-phase synthesis (DIC/HOBt couplings) of several 6-9-mer Abu[PO(OH)2]-containing peptides and has been extended to the synthesis of a 19-mer caldneurin-related Abu[PO(OH)2]-peptide.[104 ... 

An alternative allylic coupling has been reported (J. Am. Chem. Soc. 2004,126, 10676 and 11130) by Amir Hoveda of Boston College. Coupling of the allylic phosphonate 8 with diethyl zinc in the presence of an enantiomerically-pure Cu catalyst gives the branched product 9 in 95% . It is striking that the reaction works almost as well with the allylic phosphonate 10. Reaction with diethyl zinc in the presence of the enantiomerically-pure Cu catalyst forms the quaternary center ofl 1 in 91 % . 

Starting from L-ascorbic acid, a chiral building block from nature, 2,3-isopro-pylidene-L-glyceraldehide 21 was obtained and subjected to an il-selective Homer-Wadsworth-Emmons-type reaction [38] with phosphonate 22 to give -alkene 23. Two-step manipulation of the diol unit in 23 afforded 24 which underwent y-allylic coupling to (R)-25 with 97% e.e. and 77% yield. In the last three steps, cyclic ketone (45)-4 was obtained, with approximately 65% yield. This can be converted to sertraline by one of the routes described above. 

Miscellaneous. Allylic phosphates have found applications in T7-allyl palladium chemistry. It has been demonstrated that allylic phosphates undergo oxidative addition more readily than the corresponding acetate, such that chemoselectivity could be achieved when these functionalities were present in the same molecule (eq 17).2 Finally, p-keto phosphonates were coupled with epoxides to provide useful yields of spirocyclopropanes (eql8).2 ... 

Phosphonic esters, ROPO(OR)2, react with allylic Grignard reagents to give the coupling product/ ... 

AUcynylstannanes can cross-couple with a variety of other functional groups employing the Stille protocol. Couphng to acyl chlorides is a well-known procedure that affords aUcynylketones in respectable yields. Other reports include alkynyltin cross-couplings with a-haloethers and a-halocarbonyls, enol phosphinates and phosphonates, alkenyl(phenyl)iodonium salts, alkynyl halides, and allyl hahdes (Table 9.18). Alkynylstannanes have also been shown to cross-couple with iron halides under the Stille conditions to effectively form iron-carbon bonds. 

Kazmaier and Jena have presented syntheses of stannylated, allyl (86) and vinylphosphonates (87) by molybdenum-catalyzed hydrostannation of the corresponding propargyl- (84) and alkynylphosphonate (85) derivatives (Scheme 27). " The stannylated phosphonates, obtained with high regios-electivities, were applied as building blocks in further modifications, such as Pd-catalyzed cross coupling reactions or iodination. 

A straightforward synthetic approach for a series of novel phosphorus containing heterocycles (410) and (411) has been developed by applying the sequential aromatic Claisen rearrangement, coupling of allyl or vinyl phosphonates (408) or (409), respectively, and a ring closing methathesis protocol (Scheme 124). ... 

Scheme 3-61. Copper/chiral carbene-catalyzed cross-coupling of y-silyl-substituted allyl phosphonates with organozinc reagents.

The synthesis of j3-elemene outlined below6 is also based on the coupling of 1,10-dibromo-2,8-decadienes under influence of nickel carbonyl. The key allylic dibromide (B) has been built up from the unsaturated ester (A) utilizing a Claisen rearrangement and two successive phosphonate Wittig reactions. ... 

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