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Aliphatic Substitution, Nucleophilic and Organometallic
The Sommelet–Hauser rearrangement competes when Z is an aryl group (see Reaction
13-31). Hofmann elimination competes when one of the R groups contains a b hydrogen
atom (Reaction 17-7 and 17-8).
Sulfur ylids containing a Z group give an analogous rearrangement (see the reaction),
sometimes referred to as a Stevens rearrangement.426 In this case too, there is much evidence
(including CIDNP) that a radical-pair cage mechanism is operating,427 except that when the
migrating group is allylic, the mechanism may be different (see Reaction 18-35).
Another reaction with a similar mechanism428 is the Meisenheimer rearrangement,429
in which certain tertiary amine oxides rearrange on heating to give substituted hydroxylamines (see reaction).430 The migrating group R1 is almost always allylic or benzilic.431
Both R2 and R3 may be alkyl or aryl, but if one of the R groups contains a b hydrogen, Cope
elimination (Reaction 17-9) often competes. In a related reaction, when 2-methylpyridine
N-oxides are treated with trifluoroacetic anhydride, the Boekelheide reaction occurs to
Certain tertiary benzylic amines, when treated with BuLi, undergo a rearrangement
analogous to the Wittig rearrangement (Reaction 18-22, e.g., PhCH2NPh2 !
Ph2CHNHPh).433 Only aryl groups migrate in this reaction.
Isocyanides, when heated in the gas phase or in nonpolar solvents, undergo a 1,2intramolecular rearrangement to nitriles (RNC ! RCN).434 In polar solvents, the mechanism is different.435
18-22 The Wittig Rearrangement436
Olsen, R.K.; Currie, Jr., J.O. in Patai, S. The Chemistry of The Thiol Group, pt. 2, Wiley, NY, 1974,
pp. 561–566. See Okazaki, Y.; Asai, T.; Ando, F.; Koketsu, J. Chem. Lett. 2006, 35, 98.
See Iwamura, H.I.; Iwamura, M.; Nishida, T.; Yoshida, M.; Nakayama, T. Tetrahedron Lett. 1971, 63.
See Ostermann, G.; Sch€ollkopf, U. Liebigs Ann. Chem. 1970, 737, 170; Lorand, J.P.; Grant, R.W.; Samuel,
P.A.; O’Connell, E.; Zaro, J. Tetrahedron Lett. 1969, 4087.
Johnstone, R.A.W. Mech. Mol. Migr. 1969, 2, 249. See Buston, J.E.H.; Coldham, I.; Mulholland, K.R. J.
Chem. Soc., Perkin Trans. 1 1999, 2327.
See Buston, J.E.H.; Coldham, I.; Mulholland, K.R. Tetrahedron Asymmetry, 1998, 9, 1995.
See Khuthier, A.; Al-Mallah, K.Y.; Hanna, S.Y.; Abdulla, N.I. J. Org. Chem. 1987, 52, 1710, and references
Fontenas, C.; Bejan, E.; Haddon, H.A.; Balavoine, G.G.A. Synth. Commun. 1995, 25, 629.
Eisch, J.J.; Kovacs, C.A.; Chobe, P. J. Org. Chem. 1989, 54, 1275.
See Pakusch, J.; R€uchardt, C. Chem. Ber. 1991, 124, 971 and references cited therein.
Meier, M.; R€
uchardt, C. Chimia 1986, 40, 238.
See Hiersemann, M.; Abraham, L.; Pollex, A. Synlett 2003, 1088.
The rearrangement of ethers upon treatment with alkyllithium reagents is called the
Wittig rearrangement (not to be confused with the Wittig Reaction, 16-44) and is similar to
18-21.411 However, a stronger base is required (e.g., phenyllithium or sodium amide). The
R and R0 groups may be alkyl,437 aryl, or vinylic.438 Also, one of the hydrogen atoms may
be replaced by an alkyl or aryl group, in which case the product is the salt of a tertiary
alcohol. Migratory aptitudes here are allylic, benzylic > ethyl > methyl > phenyl.439 The
stereospecificity of the 1,2-Wittig rearrangement has been discussed.440 The following
radical-pair mechanism441 (similar to mechanism a of Reaction 18-21) is likely, after
removal of the proton by the base. One of the
the radical pair is a ketyl. Evidence for this mechanism includes (1) the rearrangement is
largely intramolecular; (2) migratory aptitudes are in the order of free-radical stabilities,
not of carbanion stabilities442 (which rules out an ion-pair mechanism similar to mechanism b of Reaction 18-21); (3) aldehydes are obtained as side products443; (4) partial
racemization of R0 has been observed444 (the remainder of the product retained its
configuration); (5) cross-over products have been detected445; and (6) when ketyl radicals
and R radicals from different precursors were brought together, similar products
resulted.446 However, there is evidence that at least in some cases the radical-pair
mechanism accounts for only a portion of the product, and some kind of concerted
mechanism can also take place.447 Most of the above investigations were carried out with
systems where R0 is alkyl, but a radical-pair mechanism has also been suggested for the
case where R0 is aryl.448 When R0 is allylic a concerted mechanism can operate
When R is vinylic it is possible, by using a combination of an alkyllithium and t-BuOK,
to get migration to the g carbon (as well as to the a carbon), producing an enolate that, on
hydrolysis, gives an aldehyde449:
R0 CH2 ÀÀCHÀ
R0 CH2 CH2 CHO
See Bailey, W.F.; England, M.D.; Mealy, M.J.; Thongsornkleeb, C.; Teng, L. Org. Lett. 2000, 2, 489.
For migration of vinyl, see Rautenstrauch, V.; B€uchi, G.; W€uest, H. J. Am. Chem. Soc. 1974, 96, 2576. For
rearrangment of an a-trimethylsilyl allyl ether see Maleczka, Jr., R.E.; Geng, F. Org. Lett. 1999, 1, 1115.
Wittig, G. Angew. Chem. 1954, 66, 10; Solov’yanov, A.A.; Ahmed, E.A.A.; Beletskaya, I.P.; Reutov, O.A. J.
Chem. Soc., Chem. Commun. 1987, 23, 1232.
Maleczka Jr., R.E.; Geng, F. J. Am. Chem. Soc. 1998, 120, 8551.
See Sch€ollkopf, U. Angew. Chem. Int. Ed. 1970, 9, 763.
See Sch€afer, H.; Sch€ollkopf, U.; Walter, D. Tetrahedron Lett. 1968, 2809.
See Cast, J.; Stevens, T.S.; Holmes, J. J. Chem. Soc. 1960, 3521.
Hebert, E.; Welvart, Z. J. Chem. Soc., Chem. Commun. 1980, 1035; Nouv. J. Chim. 1981, 5, 327.
Lansbury, P.T.; Pattison, V.A. J. Org. Chem. 1962, 27, 1933; J. Am. Chem. Soc. 1962, 84, 4295.
Garst, J.F.; Smith, C.D. J. Am. Chem. Soc. 1973, 95, 6870.
Garst, J.F.; Smith, C.D. J. Am. Chem. Soc. 1976, 98, 1526. For evidence against this, see Hebert, E.; Welvart,
Z.; Ghelfenstein, M.; Szwarc, H. Tetrahedron Lett. 1983, 24, 1381.
Eisch, J.J.; Kovacs, C.A.; Rhee, S. J. Organomet. Chem. 1974, 65, 289.
Schlosser, M.; Strunk, S. Tetrahedron 1989, 45, 2649.
An aza-Wittig rearrangement is also known.450 Other [2,3]-rearrangements are discussed
in Reaction 18-35.
There are no OS references, but see OS VIII, 501, for a related reaction.
F. Boron-to-Carbon Migrations451
For another reaction involving boron-to-carbon migration, see 10-73.
18-23 Conversion of Boranes to Alcohols
R-OH ỵ BOHị3
Oxidation of trialkylboranes (see Reaction 15-16) uses NaOH and H2O2, which
react to give the hydroperoxide anion, (HOOÀ). Reaction of the organoborane with
basic H2O2 (via HOOÀ) leads to an ate-complex, and subsequent B ! O rearrangement
of an alkyl group on boron to a peroxy oxygen, with expulsion of hydroxide, leads to a
borate, and then an alcohol after hydrolysis. The proposed mechanism452 is shown in
which a trialkylborane is converted to 3 molar equivalents of the alcohol, along with
R3B + HOO–
R B O O
B OR + – OH
B OH + 3 ROH
Using the hydroboration reaction in 15-16, this procedure converts alkenes to an antiMarkovnikov borane, and oxidation leads to the anti-Markovnikov alcohol. An example is
the conversion of methylcyclopentene to trans-2-methylcyclopentanol.453 Formation
of the organoborane proceeds via a cis-addition of BÀÀH, placing the boron trans to
the methyl group, and stereoselective oxidation and B ! O rearrangement leads
to retention of configuration in the alcohol, as shown.
BH3 , heat
Anderson, J.C.; Siddons, D.C.; Smith, S.C.; Swarbrick, M.E. J. Chem. Soc., Chem. Commun. 1995, 1835;
Ahman, J.; Somfai, P. J. Am. Chem. Soc. 1994, 116, 9781.
Matteson, D.S. in Hartley, F.R. The Chemistry of the Metal–Carbon Bond, Vol. 4, Wiley, NY, 1984, pp. 307–
409, pp. 346–387; Pelter, A.; Smith, K.; Brown, H.C. Borane Reagents, Academic Press, NY, 1988, pp. 256–301;
Negishi, E.; Idacavage, M.J. Org. React. 1985, 33, 1; Suzuki, A. Top. Curr. Chem. 1983, 112, 67; Pelter, A. Chem.
Soc. Rev. 1982, 11, 191; Cragg, G.M.L.; Koch, K.R. Chem. Soc. Rev. 1977, 6, 393; Weill-Raynal, J. Synthesis
1976, 633; Cragg, G.M.L. Organoboranes in Organic Synthesis, Marcel Dekker, NY, 1973, pp. 249–300;
Paetzold, P.I.; Grundke, H. Synthesis 1973, 635.
Brown, H.C. Hydroboration, W.A. Benjamin, New York, 1962. See Kuivila, H.G. J. Am. Chem. Soc. 1954, 76,
870; 1955, 77, 4014; Kuivila, H.G.; Wiles, R.A. J. Am. Chem. Soc. 1955, 77, 4830; Kuivila, H.G.; Armour, A.G. J.
Am. Chem. Soc. 1957, 79, 5659; Wechter, W.J. Chem. & Ind. (London) 1959, 294.
Zweifel, G.; Brown, H.C. Org. React. 1964, 13, 1.
Trialkylboranes can be prepared from alkenes by Reaction 15-16, and they react
with carbon monoxide454 at 100–125 C in the presence of ethylene glycol to give the
2-bora-1,3-dioxolanes (96), which are easily oxidized (Reaction 12-27) to tertiary alcohols.455 The R groups may be primary, secondary, or tertiary, and may be the same or
different.456 Yields are high and the reaction is quite useful, especially for the preparation
of sterically hindered alcohols (e.g., tricyclohexylcarbinol, 97 and tri-2-norbornylcarbinol,
98), which are difficult to prepare by Reaction 16-24. Heterocycles in which boron is a ring
atom react similarly (except that high CO pressures are required), and cyclic alcohols can
be obtained from these substrates.457 The preparation of such heterocyclic boranes was
discussed at Reaction 15-16. The overall conversion of a diene or triene to a cyclic alcohol
has been described by H.C. Brown as “stitching” with boron and “riveting” with carbon.
R3B + CO
The mechanism has been shown to be intramolecular by the failure to find cross-over
products when mixtures of boranes are used.458 The following scheme, involving three
boron-to-carbon migrations, to 99 and then to 100 has been suggested.
R B C O
R C B O
The purpose of the ethylene glycol is to intercept the boronic anhydride (100), which
otherwise forms polymers that are difficult to oxidize. As will be seen in Reaction 18-23
and 18-24, it is possible to stop the reaction after only one or two migrations have taken
R3 B ỵ CN
R3 B ỵ CHCl2 OMe
1: LiOCEt3 ÀTHF
2: H2 O2 ÀNaOH
1: excess ðCF3 COÞ2 O
2: NaOHÀH2 O2
There are two other methods for achieving the conversion R3B ! R3COH, which often
give better results: (1) treatment with a,a-dichloromethyl methyl ether and the base
lithium triethylcarboxide459 (2) treatment with a suspension of sodium cyanide in THF
See Negishi, E. Intra-Sci. Chem. Rep. 1973, 7(1), 81; Brown, H.C. Boranes in Organic Chemistry, Cornell
University Press, Ithica, NY, 1972, pp. 343–371; Acc. Chem. Res. 1969, 2, 65.
See Brown, H.C.; Cole, T.E.; Srebnik, M.; Kim, K. J. Org. Chem. 1986, 51, 4925.
Negishi, E.; Brown, H.C. Synthesis 1972, 197.
Brown, H.C.; Negishi, E.; Dickason, W.C. J. Org. Chem. 1985, 50, 520, and references cited therein.
Brown, H.C.; Rathke, M.W. J. Am. Chem. Soc. 1967, 89, 4528.
Brown, H.C.; Carlson, B.A. J. Org. Chem. 1973, 38, 2422; Brown, H.C.; Katz, J.; Carlson, B.A. J. Org. Chem.
1973, 38, 3968.
followed by reaction of the resulting trialkylcyanoborate (101) with an excess (>2 equiv)
of trifluoroacetic anhydride.460 All the above migrations take place with retention of
configuration at the migrating carbon.461
Several other methods for the conversion of boranes to tertiary alcohols are also
If the reaction between trialkylboranes and carbon monoxide (18-23) is carried out in the
presence of water followed by addition of NaOH, the product is a secondary alcohol. If H2O2
is added along with the NaOH, the corresponding ketone is obtained instead.463 Various
functional groups (e.g., OAc, COOR, CN) may be present in R without being affected,464
although if they are in the a or b position relative to the boron atom, difficulties
1: ðCF3 COÞ2 O
2: H2 O2 -OHÀ
may be encountered. The use of an equimolar amount of trifluoroacetic anhydride leads to
the ketone rather than the tertiary alcohol.465 By this procedure thexylboranes (RR0 R2B,
where R2 ¼ thexyl) can be converted to unsymmetrical ketones (RCOR0 ).466 Variations of
this methodology have been used to prepare optically active alcohols.467 For another
conversion of trialkylboranes to ketones see Reaction 18-26.468
OS VII, 427. Also see, OS VI, 137.
18-24 Conversion of Boranes to Primary Alcohols, Aldehydes, or Carboxylic Acids
R3 B þ CO
R3 B þ CO
2: H2 O2 À OH
2: H2 O2 À NaH2 PO4 À Na2 PHO4
When the reaction between a trialkylborane and carbon monoxide (18-23) is carried out
in the presence of a reducing agent (e.g., lithium borohydride or potassium triisopropoxyborohydride), the reduction agent intercepts the intermediate (99), so that only one
boron!carbon migration takes place, and the product is hydrolyzed to a primary alcohol or
oxidized to an aldehyde.469 This procedure wastes two of the three R groups, but this
problem can be avoided by the use of B-alkyl-9-BBN derivatives (see Reaction 15-16).
Pelter, A.; Hutchings, M.G.; Smith, K.; Williams, D.J. J. Chem. Soc. Perkin Trans. 1 1975, 145, and references
See, however, Pelter, A.; Maddocks, P.J.; Smith, K. J. Chem. Soc., Chem. Commun. 1978, 805.
See Pelter, A.; Rao, J.M. J. Organomet. Chem. 1985, 285, 65; Junchai, B.; Hongxun, D. J. Chem. Soc., Chem.
Commun. 1990, 323.
Brown, H.C.; Rathke, M.W. J. Am. Chem. Soc. 1967, 89, 2738.
Brown, H.C.; Kabalka, G.W.; Rathke, M.W. J. Am. Chem. Soc. 1967, 89, 4530.
Pelter, A.; Smith, K.; Hutchings, M.G.; Rowe, K. J. Chem. Soc. Perkin Trans. 1 1975, 129; See also, Mallison,
P.R.; White, D.N.J.; Pelter, A.; Rowe, K.; Smith, K. J. Chem. Res. (S), 1978, 234. See also, Ref. 460.
See Brown, H.C.; Bakshi, R.K.; Singaram, B. J. Am. Chem. Soc. 1988, 110, 1529.
See Matteson, D.S. Mol. Struct. Energ. 1988, 5, 343; Acc. Chem. Res. 1988, 21, 294; Synthesis 1986, 973,
See Pelter, A.; Rao, J.M. J. Organomet. Chem. 1985, 285, 65; Brown. H.C.; Bhat, N.G.; Basavaiah, D.
Synthesis 1983, 885; Narayana, C.; Periasamy, M. Tetrahedron Lett. 1985, 26, 6361.
Brown, H.C.; Hubbard, J.L.; Smith, K. Synthesis 1979, 701, and references cited therein. See Hubbard, J.L.;
Smith, K. J. Organomet. Chem. 1984, 276, C41.
Since only the 9-alkyl group migrates, this method permits the conversion in high yield of
an alkene to a primary alcohol or aldehyde containing one more carbon.470 When B-alkyl9-BBN derivatives are treated with CO and lithium tri-tert-butoxyaluminum hydride,471
other functional groups (e.g., CN and ester) can be present in the alkyl group without being
reduced.472 Boranes can be directly converted to carboxylic acids by reaction with the
dianion of phenoxyacetic acid.473
R B R
R B R
Boronic esters [RB(OR0 )2] react with methoxy(phenylthio)methyllithium
[LiCH(OMe)SPh] to give salts, which, after treatment with HgCl2, and then H2O2, yield
aldehydes.474 This synthesis has been made enantioselective, with high ee values (>99%),
by the use of an optically pure boronic ester,475 for example:
(R) or (S)
18-25 Conversion of Vinylic Boranes to Alkenes
The reaction between trialkylboranes and iodine to give alkyl iodides was mentioned at
12-31. When the substrate contains a vinylic group, the reaction takes a different course,476
with one of the R0 groups migrating to the carbon, to give alkenes.477 The reaction is
stereospecific in two senses: (1) if the groups R and R00 are cis in the starting compound,
they will be trans in the product; (2) there is retention of configuration within the migrating
group R0 .478 Since vinylic boranes can be prepared from alkynes (Reaction 15-16), this is a
method for the addition of R0 and H to a triple bond. If R2 ¼ H, the product is a (Z)-alkene.
The mechanism is believed to involve an iodonium intermediate, (e.g., 102) and attack by
iodide on boron. When R0 is vinylic, the product is a conjugated diene.479
Brown, H.C.; Knights, E.F.; Coleman, R.A. J. Am. Chem. Soc. 1969, 91, 2144.
Brown, H.C.; Coleman, R.A. J. Am. Chem. Soc. 1969, 91, 4606.
See Negishi, E.; Yoshida, T.; Silveira, Jr., A.; Chiou, B.L. J. Org. Chem. 1975, 40, 814.
Hara, S.; Kishimura, K.; Suzuki, A.; Dhillon, R.S. J. Org. Chem. 1990, 55, 6356. See also, Brown, H.C.; Imai,
T. J. Org. Chem. 1984, 49, 892.
Brown, H.C.; Imai, T. J. Am. Chem. Soc. 1983, 105, 6285. For a related method that produces primary
alcohols, see Brown, H.C.; Imai, T.; Perumal, P.T.; Singaram, B. J. Org. Chem. 1985, 50, 4032.
Brown, H.C.; Imai, T.; Desai, M.C.; Singaram, B. J. Am. Chem. Soc. 1985, 107, 4980.
Basavaiah, D.; Kulkarni, S.U.; Bhat, N.G.; Vara Prasad, J.V.N. J. Org. Chem. 1988, 53, 239.
For a list of methods of preparing alkenes using boron reagents, with references, see Larock, R.C.
Comprehensive Organic Transformations; 2nd ed., Wiley–VCH, NY, 1999, pp. 421–427.
Zweifel, G.; Fisher, R.P.; Snow, J.T.; Whitney, C.C. J. Am. Chem. Soc. 1971, 93, 6309.
Hyuga, S.; Takinami, S.; Hara, S.; Suzuki, A. Tetrahedron Lett. 1986, 27, 977.
In another procedure, the addition of a dialkylborane to a 1-haloalkyne produces an
a-halo vinylic borane (103).480 Treatment of 103 with NaOMe gives the rearrangement
shown, and protonolysis of the product produces the (E)-alkene.478 If R is a vinylic group,
the product is a 1,3-diene.481 If one of the groups is thexyl, the other migrates.482 A
combination of both of the procedures described above results in the preparation of
R2BH-H + Br C C R1
18-26 Formation of Alkynes, Alkenes, and Ketones from Boranes and Acetylides
R3 B þ RCÀ
3 0 Liþ
A hydrogen directly attached to a triple-bond carbon can be replaced in high yield by an
alkyl or an aryl group, by treatment of the lithium acetylide with a trialkyl- or triarylborane,
followed by reaction of the lithium alkynyltrialkylborate (104) with iodine.484 The R0
group may be primary or secondary alkyl as well as aryl, so the reaction has a broader scope
than the older Reaction 10-74.485 The R group may be alkyl, aryl, or hydrogen, although in
the last-mentioned case satisfactory yields are obtained only if lithium acetylideethylenediamine is used as the starting compound.486 Optically active alkynes can be
prepared by using optically active thexylborinates (RR2BOR0 , R2 ¼ thexyl, where R is
chiral) and LiCÀ
ÀCSiMe3.487 The reaction can be adapted to the preparation of alkenes488
by treatment of 104 with an electrophile (e.g., propanoic acid489 or tributyltin chloride).490
The reaction with Bu3SnCl produces the (Z)-alkene stereoselectively.
For improvements in this method, see Brown, H.C.; Basavaiah, D.; Kulkarni, S.U.; Lee, H.D.; Negishi, E.;
Katz, J. J. Org. Chem. 1986, 51, 5270.
Negishi, E.; Yoshida, T. J. Chem. Soc. Chem.Commun. 1973, 606; See also, Negishi, E.; Yoshida, T.;
Abramovitch, A.; Lew, G.; Williams, R.H. Tetrahedron 1991, 47, 343.
Corey, E.J.; Ravindranathan, T. J. Am. Chem. Soc. 1972, 94, 4013; Negishi, E.; Katz, J.; Brown, H.C. Synthesis
Zweifel, G.; Fisher, R.P. Synthesis 1972, 557.
Suzuki, A.; Miyaura, N.; Abiko, S.; Itoh, M.; Brown, H.C.; Sinclair, J.A.; Midland, M.M. J. Org. Chem. 1986,
51, 4507; Sikorski, J.A.; Bhat, N.G.; Cole, T.E.; Wang, K.K.; Brown, H.C. J. Org. Chem. 1986, 51, 4521. For a
review of reactions of organoborates, see Suzuki, A. Acc. Chem. Res. 1982, 15, 178.
For a study of the relative migratory aptitudes of R’, see Slayden, S.W. J. Org. Chem. 1981, 46, 2311.
Midland, M.M.; Sinclair, J.A.; Brown, H.C. J. Org. Chem. 1974, 39, 731.
Brown, H.C.; Mahindroo, V.K.; Bhat, N.G.; Singaram, B. J. Org. Chem. 1991, 56, 1500.
See Larock, R.C. Comprehensive Organic Transformations; 2nd ed., Wiley–VCH, NY, 1999, pp. 218–222.
Pelter, A.; Gould, K.J.; Harrison, C.R. Tetrahedron Lett. 1975, 3327.
Wang, K.K.; Chu, K. J. Org. Chem. 1984, 49, 5175.
Treatment of 104 with electrophiles (e.g., methyl sulfate, allyl bromide, or triethyloxonium borofluoride), followed by oxidation of the resulting vinylic borane, gives a
ketone (illustrated for methyl sulfate)491:
Me O OMe
R C C B R' Li+
Note that there are reactions that involve N ! O rearrangements, including those
mediated by silicon.492
18.F.ii. Non-1,2 Rearrangements
A. Electrocyclic Rearrangements
18-27 Electrocyclic Rearrangements of Cyclobutenes and 1,3-Cyclohexadienes
(4) seco-1/4/Detachment; (4) cyclo-1/4/Attachment
(6) seco-1,6/Detachment; (6) cyclo-1/6/Attachment
Cyclobutenes and 1,3-dienes can be interconverted by treatment with UV light or with
heat.493 These are 4p-electrocyclizations. The thermal reaction is generally not reversible
(although exceptions494 are known), and many cyclobutenes have been converted to 1,3dienes by heating at temperatures between 100 and 200 C.495 Benzocyclobutenes also
undergo electrocyclic ring opening,496 as do benzocyclobutanones.497 The photochemical
conversion can in principle be carried out in either direction, but most often 1,3-dienes are
converted to cyclobutenes rather than the reverse, because the dienes are stronger absorbers
of light at the wavelengths used.498 In a similar reaction, 1,3-cyclohexadienes interconvert
with 1,3,5-trienes, but in this case the ring-closing process is generally favored thermally
and the ring-opening process photochemically, but exceptions are known in both
Pelter, A.; Drake, R.A. Tetrahedron Lett. 1988, 29, 4181.
Talami, S.; Stirling, C.J.M. Can. J. Chem. 1999, 77, 1105.
See Dolbier, Jr., W.R.; Koroniak, H.; Houk, K.N.; Sheu, C. Acc. Chem. Res. 1996, 29, 471; Niwayama, S.;
Kallel, E.A.; Spellmeyer, D.C.; Sheu, C.; Houk, K.N. J. Org. Chem. 1996, 61, 2813. The effect of pressure on this
reaction has been discussed, see Jenner, G. Tetrahedron 1998, 54, 2771.
See Steiner, R.P.; Michl, J. J. Am. Chem. Soc. 1978, 100, 6413 and references cited therein.
See Um, J.M.; Xu, H.; Houk, K.N.; Tang, W. J. Am. Chem. Soc. 2009, 131, 6664.
Matsuya, Y.; Ohsawa, N.; Nemoto, H. J. Am. Chem. Soc. 2006, 128, 412.
Matsuya, Y.; Ohsawa, N.; Nemoto, H. J. Am. Chem. Soc. 2006, 128, 13072.
See Dauben, W.G.; Haubrich, J.E. J. Org. Chem. 1988, 53, 600.
directions.499 Substituent effects can lead to acceleration of the electrocyclization process.500 Torquoselectivity in cyclobutene ring-opening reaction has been examined.501
Examples of these types of reactions include:
An interesting example of 1,3-cyclohexadiene!1,3,5-triene interconversion is the
reaction of norcaradienes to give cycloheptatrienes.503 This is a 6p-electrocyclization,
and it has been catalyzed by Lewis acids.504 Norcaradienes give this reaction so readily
(because they are cis-1,2-divinylcyclopropanes, see Reaction 18-32) that they cannot
generally be isolated, though some exceptions are known505 (see also, 15-64).
These reactions, called electrocyclic rearrangements,506 take place by pericyclic mechanisms. The evidence comes from stereochemical studies, which show a remarkable stereospecificity whose direction depends on whether the reaction is induced by heat or light.
For example, it was found for the thermal reaction that cis-3,4-dimethylcyclobutene gave
only cis,trans-2,4-hexadiene, while the trans isomer gave only the trans–trans-diene507:
See Dauben, W.G.; McInnis, E.L.; Michno, D.M. in de Mayo, P. Rearrangements in Ground and Excited
States, Vol. 3, Academic Press, NY, 1980, pp. 91–129. For an ab initio study see Rodrıguez-Otero, J. J. Org. Chem.
1999, 64, 6842.
Tanaka, K.; Mori, H.; Yamamoto, M.; Katsumura, S. J. Org. Chem. 2001, 66, 3099. See Beaudry, C.M.;
Malerich, J.P.; Trauner, D. Chem. Rev. 2005, 105, 4757.
Yasui, M.; Naruse, Y.; Inagaki, S. J. Org. Chem. 2004, 69, 7246.
Chapman, O.L.; Pasto, D.J.; Borden, G.W.; Griswold, A.A. J. Am. Chem. Soc. 1962, 84, 1220.
See Maier, G. Angew. Chem. Int. Ed. 1967, 6, 402; Vogel, E. Pure Appl. Chem. 1969, 20, 237.
Bishop, L.M.; Barbarow, J.E.; Bergman, R.G.; Trauner, D. Angew. Chem. Int. Ed. 2008, 47, 8100.
See Ciganek, E. J. Am. Chem. Soc. 1967, 89, 1454.; Iyoda, M.; Oda, M. Angew. Chem. Int. Ed. 1987, 26, 559.
See Gajewski, J.J. Hydrocarbon Thermal Isomerizations, Academic Press, NY, 1981; Marvell, E.N. Thermal
Electrocyclic Reactions, Academic Press, NY, 1980; Laarhoven, W.H. Org. Photochem. 1987, 9, 129; George, M.
V.; Mitra, A.; Sukumaran, K.B. Angew. Chem. Int. Ed. 1980, 19, 973; Jutz, J.C. Top. Curr. Chem. 1978, 73, 125;
Gilchrist, T.L.; Storr, R.C. Organic Reactions and Orbital Symmetry, Cambridge University Press, Cambridge,
1972, pp. 48–72; Criegee, R. Angew. Chem. Int. Ed. 1968, 7, 559. See Schultz, A.G.; Motyka, L. Org. Photochem.
1983, 6, 1.
Winter, R.E.K. Tetrahedron Lett. 1965, 1207; Criegee, R.; Noll, K. Liebigs Ann. Chem. 1959, 627, 1.
This is evidence for a four-membered cyclic transition state and arises from conrotatory
motion about the C-3–C-4 bond.508 It is called conrotatory because both movements are
clockwise (or both counterclockwise). Because both rotate in the same direction, the cis
isomer gives the cis–trans-diene.509 The other possibility (disrotatory motion) would have
one moving clockwise while the other moves counterclockwise; the cis isomer would have
given the cis–cis-diene (shown) or the trans–trans-diene. If the motion had been
disrotatory, this would still have been evidence for a cyclic mechanism. If the mechanism
were a diradical or some other kind of noncyclic process, it is likely that no stereospecificity of either kind would have been observed. The reverse
reaction is also conrotatory. In contrast, the photochemical cyclobutene: 1,3-diene interconversion is disrotatory in either direction.510 On the other hand, the cyclohexadiene: 1,3,5triene interconversion shows precisely the opposite behavior. The thermal process is disrotatory, while the photochemical process is conrotatory (in either direction). These startling
results are a consequence of the symmetry rules mentioned in Section 15-60, the FOM.511 As in
the case of cycloaddition reactions, we will use the FOM and M€obius–H€uckel approaches.512
The Frontier Orbital Method (FOM)513
As applied to these reactions, the FOM may be expressed: A s bond will open in such a
way that the resulting p orbitals will have the symmetry of the highest occupied p orbital
of the product. In the case of cyclobutenes, the HOMO of the product in the thermal
reaction is the x2 orbital (Fig. 18.1). Therefore, in a thermal process, the cyclobutene must
open so that on one side the positive lobe lies above the plane, and on the other side below
it. Thus the substituents are forced into conrotatory motion (Fig. 18.2). On the other hand,
in the photochemical process, the HOMO of the product is now the x3 orbital (Fig. 18.1),
and in order for the p orbitals to achieve this symmetry (the two plus lobes on the same side
of the plane), the substituents are forced into disrotatory motion.
This reaction may be considered from the opposite direction (ring closing). For this
direction, the rule is that those lobes of orbitals that overlap (in the HOMO) must be of
the same sign. For thermal cyclization of butadienes, this requires conrotatory motion
Baldwin, J.E.; Gallagher, S.S.; Leber, P.A.; Raghavan, A.S.; Shukla, R. J. Org. Chem. 2004, 69, 7212.
See Woodward, R.B.; Hoffmann, R. J. Am. Chem. Soc. 1965, 87, 395.
See Leigh, W.J.; Zheng, K. J. Am. Chem. Soc. 1991, 113, 4019; Leigh, W.J.; Zheng, K.; Nguyen, N.; Werstiuk,
N.H.; Ma, J. J. Am. Chem. Soc. 1991, 113, 4993, and references cited therein.
Woodward, R.B.; Hoffmann, R. J. Am. Chem. Soc. 1965, 87, 395. Also see, Longuet-Higgins, H.C.;
Abrahamson, E.W. J. Am. Chem. Soc. 1965, 87, 2045; Fukui, K. Tetrahedron Lett. 1965, 2009.
See Jones, R.A.Y. Physical and Mechanistic Organic Chemistry, 2nd ed., Cambridge University Press,
Cambridge, 1984, pp. 352–359; Yates, K. H€uckel Molecular Orbital Theory, Academic Press, NY, 1978, pp. 250–
263. Also see, Zimmerman, H.E. in Marchand, A.P.; Lehr, R.E. Pericyclic Reactions, Vol. 2, Academic Press, NY,
1977, pp. 53–107; Acc. Chem. Res. 1971, 4, 272; Dewar, M.J.S. Angew. Chem. Int. Ed. 1971, 10, 761; Jefford, C.
W.; Burger, U. Chimia 1971, 25, 297; Herndon, W.C. J. Chem. Educ. 1981, 58, 371.
Fukui, K. Fortschr. Acc. Chem. Res. 1971, 4, 57; Houk, K.N. Acc. Chem. Res. 1975, 8, 361. See also, Chu, S.
Tetrahedron 1978, 34, 645; Fleming, I. Pericyclic Reactions, Oxford Univ. Press, Oxford, 1999; Fukui, K. Angew.
Chem. Int. Ed. 1982, 21, 801; Houk, K.N., in Marchand, A.P.; Lehr, R.E. Pericyclic Reactions, Vol. 2, Academic
Press, NY, 1977, pp. 181–271.
FIG. 18.1. Symmetries of the X2 and X3Ã orbitals of a conjugated diene
H – Me Me +
FIG. 18.2. Thermal opening of 1,2-diethylcyclobutene. The two hydrogens and two methyls are forced
into conrotatory motion so that the resulting p-orbitals have the symmetry of the HOMO of the diene.
(Fig. 18.3). In the photochemical process, the HOMO is the x3 orbital, so that disrotatory
motion is required for lobes of the same sign to overlap.
As seen in Reaction 15-60, the M€
uckel Method, a basis set of p orbitals is chosen
and inspected for sign inversions in the transition state. Figure 18.4 shows a basis set for a 1,3diene. It is seen that disrotatory ring closing (Fig. 18.4a) results in overlap of plus lobes only,
while in conrotatory closing (Fig. 18.4b) there is one overlap of a plus with a minus lobe.
In the first case, there are zero sign inversions, while in the second there is one sign inversion.
With zero (or an even number of) sign inversions, the disrotatory transition state is a
uckel system, and so is allowed thermally only if the total number of electrons is 4n ỵ 2
(Sec. 15-60, the M€
uckel Method). Since the total here is 4, the disrotatory process is
not allowed. On the other hand, the conrotatory process, with one sign inversion, is a M€obius
FIG. 18.3. Thermal ring closing of a 1,3-diene. Conrotatory motion is required for two ỵ lobes to