Triphenylphosphine Reformatsky reactions

G.R. Pettit and co-workers used a novel fefraA/s(triphenylphosphine)cobalt(0)-promoted Reformatsky reaction for the synthesis of a dolastatin 10 unit, dolaproine in a Boc-protected form. ... 

The starting material 6-methylhept-5-en-2-one (170) was converted, with methanol, into the methoxy compound 171 which was condensed with ethyl bromoacetate (172) in a Reformatsky reaction to give the ester 173. Reaction of 173 with NBS and then dehydrobromination led to the ester 174 which was reduced with LiAIH4 and transformed with triphenylphosphine hydrobromide to the Cio-phosphonium salt 175 and then coupled with crocetindialdehyde (27) in the presence of sodium methoxide as base in a Wittig reaction to give spirilloxanthin (169) in an overall yield of 2% referred to 170 [87] (Scheme 40). 

As the dosage of air is hardly controlled in these protocols and oxygen causes undesired side reactions, Cozzi and coworkers elaborated a procedure that used t-butyl hydroperoxide as an oxidative additive. In addition, the readily available amino alcohol 323 was used as the chiral ligand. Again, the presence of triphenylphosphine oxide was required as shown in the Reformatsky reaction with aldehydes (Scheme 5.88) [166]. The long reaction times over more than 100 h required at -25 °C indicates a rather sluggish conversion. It may be abbreviated by running the reaction at 25 °C, however, at the expense of reduced enantiomeric excess of P-hydroxy esters 316. Enantioselectivity varied considerably, was fair for most aromatic aldehydes, but was low for aliphatic aldehydes, except for pivalalde-hyde that provided 93% ee. The procedure was also applied to prochiral ketones. 

Raney nickel, 135, 312,411 Ratcliffe reagent, 37, 70 Redudion decyanization, 324-325 Reductive dimerization, 369 Reformatsky-type reactions, 151-152 Resolution, 79,113 Resorcinol dibenzoate, 57 Retinal, 372 Retroaldol reaction, 303 RhodiumGl) acetate, 76, 313 Rhodium(II) n-butanoate, 313 Rhodium(II) carboxylates, 313 Rhodium(III) chloride, 313-314 Rhodium(III) chloride-Triphenylphosphine, 314... 

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