Chroman 2-alken

There has been a number of developments in the use of salicylaldehydes as precursors of both chromenes and chromans. Alkenes activated by acyl, formyl, nitrile and phenylsulfonyl groups react with 2-hydroxybenzaldehydes and 2-hydroxy-1-naphthaldehyde under Bayliss-Hillman conditions to yield 3-substituted chromenes via the in situ dehydration of the initially formed chroman-4-ol <02JCS(P1)1318>. In like manner, P-nitrostyrenes yield 2- and 2,2-substituted derivatives of 3-nitrochromenes <02H(57)1033>. A simple route to 2-phenyl-2H-chromenes starting from salicylaldehyde and utilising a Pd(0)-catalysed cyclisation of an allylic acetate has been described <02SC3667>. 

In this chapter, we have described some useful properties of coordinated QM complexes. For instance, remarkably stable T 2-o-QM complexes of Os can release the QM moiety upon oxidation, followed by controlled reaction with suitable dienophiles to form the chroman ring system.15 16 ri2-Coordinatedp-QM complexes can be easily released upon exposure to an electron-deficient alkene and trapped as the 1,6-Michael addition product.18 19... 

Tethered alkenes feature in the synthesis of benzofuran-fused chromans 48 <00JCS(P1)1387> through intramolecular cycloadditions. 

The condensation of salicylaldehyde derivatives with alkenes in the presence of boron trifluoride yields 4-substituted chromans (64CB682). The use of the acetal (276 R = OEt) leads to 4-ethoxychromans (277 R = OEt), but of more interest is the formation of chroman-4-carbamates (277 R = NHC02Et) from the biscarbamic ester (276 R = NHC02Et Scheme 70). 

In a similar manner, o-quinone methides and their benzologues react with alkenes to give chromans (63CR(256)3323). With styrene, flavans are formed from o-quinone methides (64CR(258)1526). Yields are better with 2,3-naphthoquinone 2-methide than with the ben-zoquinone analogue. 

Pyrolysis of o-hydroxybenzyl alcohol at 550 °C resulted in the formation of simple o-quinone methide, which was directly observed using low-temperature IR spectroscopy.122 Pyrolysis of chroman (Scheme 33) at 400-600 °C gives the simple o-quinone methide and ethene along with o-cresol, benzofuran, and styrene.123,124 The o-quinone methide was trapped with alkenes to form Diels Adler adducts, with hydrogen gas or hydrogen atom to form o-cresol, or underwent a further pyrolysis to CO and fulvene. 

The intramolecular nucleophilic addition of the formyl group to the electron deficient alkene unit in the propenoate (10) affords a benzofuranone when catalysed by a thiazolium salt. However, when NaCN is used as the catalyst, an initial Michael addition to the acrylate function is followed by an intramolecular aldol condensation and the chroman (11) is formed. The corresponding butanoates afford chroman-4-ones under the influence of thiazolium cations, but give benzoxepins in the presence of a basic catalyst (95S1311). 

Exposure of the diastereomeric mixture of alcohols 497 to TFA leads to the construction two nonaromatic rings via a cation-alkene cyclization process. The chroman 498 is isolated as a 1 1 mixture of epimeric alcohols and is a key intermediate during cannabinoid synthesis (Equation 203) <2000JOC6576>. 

Triflates of transition metals catalyse the reaction between alkenes, salicylaldehydes and trimethyl orthoformate (TMOF) that is particularly useful for the synthesis of fused chromans. Generation of an o-quinone methide and its capture by the alkene is the key feature. The examples in Scheme 4 are illustrative. Tran.v-fused pyrano[3,2-c]benzopyrans... 

The one-pot reaction of 0-BOC protected salicylaldehydes and salicyl alcohols with electron-rich alkenes and a Grignard reagent involves a diastereoselective cycloaddition to an o-quinone methide and offers access to a wide range of 4-substituted chromans <02JOC6911>. 

A three-component Pd-catalysed reaction involving a 3-iodophenyl ether, an alkyl halide and an electron-deficient alkene proceeds with the creation of three new C-C bonds resulting in the formation of chromans (Scheme 14). When applied to benzylic ethers, isochromans are formed <03OL4827>. 

Cyclopropanation of the alkene unit by the alkyne moiety in the enynes 28 yields the cycloprop[c]pyrans 29 which on treatment with acid afford chromans. This new benzannulation presumably proceeds by a retro DA opening of the pyran ring followed by cyclisation and dehydration <04OL3191>. 

A radical cation is involved in the direct synthesis of chromans by an intramolecular oxidative cyclisation of 3-arylpropanols 32 brought about by a hypervalent iodine(III) reagent <04TL2293> and iodonium species catalyse the intramolecular arylation of alkenes which yields iodo-substituted chromans 33 <04JA3416>. 3-Allenylchroman-4-ols result from a one-pot reaction between salicylaldehydes and 1,4-dibromobut-2-yne in which the intramolecular cyclisation of the intermediate ether is mediated by In metal <04SL45>... 

A 2,2-disubstituted chromane system was asymmetrically constructed by application of intramolecular oxa-Michael addition reaction through 6-exo-trig mode cyclization [57]. Good asymmetric induction at the quaternary carbon was observed when Z-alkene was treated with the same guanidine 17 used in asymmetric carba-Michael reaction in Table 4.5 (Scheme 4.18). 

Propargyl alcohols (17) are efficiently converted to the tranj-3,4-disubstituted chroman (18) via complexation with Co2(CO)8. The key feature of this one-pot procedure is the cyclisation of a cobalt carbonyl stabilised cation by a trisubstituted alkene <97TL685>. 

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