Tetrahedron report number 612 o-Quinone methides: intermediates underdeveloped and underutilized in organic synthesis Ryan W. Van De Water and Thomas R. R. Pettus p Department of Chemistry and Biochemistry, University of California at Santa Barbara, Santa Barbara, CA 93106, USA Received 15 March 2002 Contents 1. Introduction to o-quinone methides 5367 1.1. Scope of this review 5368 1.2. Evidence for the existence of o-QMs 5368 1.3. Theoretical considerations regarding reactivity 5368 1.4. Earlier reviews and discussions 5369 1.5. Past synthetic applications employing o-QMs 5369 1.6. Biochemical rami®cations of o-QMs 5371 2. Synthetic methods used to generate o-QMs 5372 2.1. Initiation by tautomerization 5372 2.2. Oxidative initiation 5372 2.3. Thermal initiation 5373 2.4. Photochemical facilitation 5375 2.5. Acid facilitation and triggers 5376 2.6. Base facilitation and triggers 5377 2.7. Ole®nation of o-quinones 5380 3. Reactions of o-QMs 5381 3.1. [412] Cycloadditions resulting in benzopyrans 5381 3.2. Reduction of o-QMs 5387 3.3. Addition of other nucleophiles 5389 3.4. d-Lactone formation 5395 3.5. g-Lactone and furan formation 5395 3.6. Net [414] reactions 5396 3.7. Rearrangements 5396 3.8. Photochemical reactions 5397 4. Conclusions 5398 4.1. Syntheses of o-alkylated aromatics 5398 4.2. Chroman synthesis 5399 4.3. Synthesis of a-branched phenols 5399 4.4. Future synthetic applications 5400 1. Introduction to o-quinone methides o-Methylene cyclohexadienones such as 1 and their b-substituted counterparts (R 2 or R 3 ±H, Fig. 1), which are collectively referred to as ortho-quinone methides (o-QMs), are highly reactive and ephemeral intermediates that have been extensively harnessed by nature. A variety of plants, animals and insects capitalize upon these species as a means of defense. Moreover, the therapeutic bene®ts of vitamins E and K as well as the anti-cancer properties of natural products such as the anthracycline antibiotics result Tetrahedron 58 (2002) 5367±5405 Pergamon TETRAHEDRON 0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved. PII: S0040-4020(02)00496-9 Keywords: o-quinone methides; organic synthesis; chromans; o-alkylated phenols; benzopyrans. p Corresponding author. Fax: 11-805-893-5690; e-mail: pettus@chem.ucsb.edu