Oxa-Pictet-Spengler reaction

The oxa-Pictet-Spengler reaction has been used with success to prepare dihydrofurano[2,3-c]pyrans and isochromans from l-(3-furyl)alkan-2-ols and 2-(3 ,4 -dihydroxy)phenylethanol, respectively. Furanyl alcohol 32 reacted with isobutyraldehyde 33 in the presence of p-toluenesulfonic acid to give the corresponding CI5-5,7-diisopropyl 4,5-dihydro-7H-furano[2,3-c]pyran 34 in good yield. ... 

Excellent yields of isochromans are obtained when 2-phenylethanol derivatives react with aldehydes and, with lower yields, ketones in the presence of the zeolite Ersorb-4a. This variation of the oxa-Pictet-Spengler reaction is simple, cheap and environmentally-ffiendly <060BC1220>. 

The oxa-Pictet-Spengler reaction, an intramolecular cyclization, is an important method for the synthesis of phthalans. It requires strong Brpnsted acid and the... 

For that reason an intramolecular benzannulation was developed, which incorporates all components for the intramolecular alkoxycarbonylation into the naphthoquinone 105 [65]. Based on that strategy a short and convergent pathway for the synthesis of racemic deoxyfrenolicin 108 was accomplished. Xu et al. replaced the allylacetylene 100 in the reaction sequence for nanaomycin A by alkynoate 106. The benzannulation product 107 was an appropriate precursor for a subsequent tandem oxa-Pictet-Spengler cyclisation/DDQ-induced coupling reaction [66]. Following this strategy the total synthesis of enan-tiomerically pure deoxyfrenolicin could be accomplished (Scheme 48). 

Heating a well-mixed mixture of l-(2-hydroxyethyl)-2-ethoxycarbo-nyl-6,7-dimethoxy-l,2,3,4-tetrahydroisoquinoline and solid NaOMe at 130 °C for 45 min followed by extraction of the reaction mixture with EtOAc provided 9,10-dimethoxy-1,6,7,11 b-tetrahydro-2H,4H-[l, 3]oxa-zino[4,3- ]isoquinolin-4-one in 52% yield (09T8021). 1,3,4,6,7,11b-Hexahydro-2H-pyrimido[6,l-fl]isoquinolin-4-one 53 was obtained from pyrimidinone 91 by a Pictet-Spengler reaction in CH2C12 in the action of TFA at ambient temperature (09OL1559). 

Considerably more important are reactions involving an endocyclic attack of C-nucleophiles. Besides rarer reactions with aromatic nucleophiles (the oxa analog of the Pictet-Spengler reaction) the use of vinylic nucleophiles especially provides an efficient route to critical , medium-sized oxygen-containing heterocycles. Thus, even nonactivated alkenes like (104) readily undergo acid-catalyzed cyclization in remarkable yields (Scheme 51). ... 

An asymmetric carbon-transfer reaction was also performed by using 2-(/>-tolyl)sulfmylmethyltetrahydro-l,3-oxa-zine 143 as the chiral aldehyde equivalent in the Pictet-Spengler ring closure with tryptamine, but only moderate diastereoselectivity ( 40% de) was observed in favor of the (l/ )-tetrahydro-/3-carboline 165, and the enantiopure main product could be isolated only in low yield (Scbeme 26) <2001H(55)1937, 2004T9171>. 

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