C3 -> C4 ring enlargements

Peterson olefination of the aldehyde 171b with l-trimethylsilylprop-3-ynyl lithium 137), furnished a (Z, E) mixture of enynes 225 in 85 % yield. Desilylation with KF in DMF l38), metalation with n-butyllithium, condensation with hexanal and lithium aluminum hydride reduction gave the conjugated dienol 226 in 72% overall yield from 171b. Treatment of 226 with 10 mol. % of PPTS 1011 in ethanol at 55 °C led directly, within 30 min, as monitored by t.l.c. to (E, E)-2-( 1,3-nonadienyl)-cyclo-butanone 227 (Eq. (70))96). This C3 -> C4 ring enlargement occurred under rather mildly acidic conditions since the pH of a 1 M aqueous solution of PPTS is 3.0 101 K... 

Cyclopropanes adjacent to an electron-deficient centre X (carbon or heteroatom) undergo C3 - C4 ring enlargement into four-membered ring derivatives via routes involving cations, radicals or car bene intermediates. Furthermore, when the cyclopropanes also bear on the same carbon an electron-donor substituent Y they undergo a specific C3 - C4 ring expansion, important from the synthetic point of view, into cyclobutanone (or related) derivatives (equation 67). 

Cyclobutyl compounds are significant products of the C3 - C4 ring enlargement of cyclopropylmethyl derivatives thus, deamination of cyclopropylmethylamine, hydro-lyis of the j -naphthalenesulphonate of cyclopropylmethanoF or treatment of cyclop-ropylmethanol itself with aqueous hydrochloric acid lead to cyclobutanol in 40,42 and... 

In the same way, the cyclopropylidenemethyl cations produced on solvolysis of cyclopropylidenemethyl bromides (103) undergo C3 - C4 ring enlargement into cyclobu-tanones depending upon the ability of the electron-releasing substituents in the a-position to stabilize the intermediate vinyl cations (equation 73). ... 

Solvolysis of (l-methyl-2-methylenecyclopropyl)methylcarbinyl-3,5-dinitrobenzoates (105) in aqueous acetone in the presence of 2,6-lutidine led to C3 - C4 ring enlargement products (equation 75). ... 

Attempts to prepare 1-hydroxycyclopropanecarboxaldehyde (132) have failed it undergoes spontaneous C3 - C4 ring enlargement into 1-hydroxycyclobutanone (133) (equation 99). ... 

The rearrangement which involves the intermediacy of the same cyclopropylcarbinyl cation (138) is completed in few minutes as monitored by t.l.c. Upon treatment with 10 mol % of pyridinium p-toluenesulphonate (PPTS) in ethanol at 55°C in order to cleave the protective group, some tetrahydropyranyl ethers of conjugated dienols (140) or enones (141) have undergone total C3 - C4 ring enlargement (equation 102) ... 

In conclusion, the C3 - C4 ring enlargement of 1-hydroxycyclopropanecarboxaldehyde derivatives involve much milder conditions than those required with the 1-sulphide, 1-selenide or 1-methoxycyclopropane derivatives, reported in Section IILD. 

Jones and Price"" therefore concluded that diazomethane ring enlargement of 17j5-hydroxy-5a-androstan-3-one (Ic) proceeds with predominately C3—C4. migration, in contrast to the 5a-cholestane series which differs from (Ic) only in the 17-substituent. 

The rearrangements reported herein concern only the 2-vinylcyclobutanone derivatives which have also been obtained from the cycloaddition of vinylketenes to simple olefins 142,143). For such a stepwise C3 - C4 - C5 ring enlargement, not involving a 2-vinylcyclobutanone, see for instance Scheme 3 (Sect. 5.1.3). 

---