Carbonate extension. A versatile procedure for functionalization of acyclic homoallylic alcohols with moderate stereocontrol

Abstract

Iodocyclization of a series of homoallylic tert-butyl carbonates is an efficient and moderately erythro stereoselective method for the functionalization of homoallylic alcohols with 1,3 relative asymmetric induction. Comparison with the anionic carbonate cyclization process of Cardillo et al.1 234 5reveals a similar stereoselectivity for the two methods. Experiments with a number of carbonate derivatives (tert-butyl, benzyl, and 4-methoxy-and 2,4dimethoxybenzyl) show that loss of the alkyl cation from cyclic intermediate 16 is rate determining. Depending on the cleavage conditions employed, the cyclic iodo carbonates (e.g., 9) can be converted with high selectivity to the iodohydrin methyl carbonate 18, epoxy methyl carbonate 19, or epoxy alcohol 20, offering a significant advantage over our previously reported phosphate cyclization method.

Anticancer Agents from the Australian Tropical Rainforest: Spiroacetals EBC‐23, 24, 25, 72, 73, 75 and 76

“…In the first instance the reiterative [16] Bartlett iodo carbonate cyclization [17] approach was applied to the synthesis of the left-hand fragment 29. Reaction of epoxide 24 with vinyl magnesium bromide followed by treatment with di-tert-butyl dicarbonate afforded 26, which on treatment with iodine bromide gave iodo carbonate 27.…”

“…The synthetic approach to the left-hand fragment 16 must contain sufficient stereochemical flexibility in the event that the relative stereochemical assignment of 1 is incorrect, or structure-activity studies (SAR) are required. For this task multiple options are available, for example, via asymmetric aldol chemistry, reiterative [16] Bartlett iodo carbonate cyclization (i.e., 19), [17] or again Tietze [13] -Smith [14] linchpin methodology to access ketone 23 from dithiane 20 and epoxides 21 and 22 (Scheme 1).…”

A simple stereoselective synthesis of (+)-[6]-gingerdiol

“…The later was treated with di (tert-butyl) carbonate in the presence of DMAP to form the homoallylic tert-butyl carbonate, 9. The treatment of compound 9 with I2 in MeCN at -20 O C furnished the iodocarbonate 10 which was subsequently treated with K2CO3 in MeOH to afford the synepoxy alcohol 11 The cleavage of the TBS ether group also took place simultaneously [14,15]. Finally, the reaction of compound 11 with Grignard reagent, n-C4H9MgBr using CuI produced the target molecule, (+)- [6]-gingerdiol (1) [16].…”

A Stereoselective Total Synthesis of Verbalactone

“…The latter was treated with di(tert-butyl) dicarbonate in the presence of DMAP in MeCN forming the homoallylic tert-butyl carbonate 5 in 81% yield [11], which was prepared for the diastereoselective I 2 -induced electrophilic cyclization to introduce the required stereogenic centre. The treatment of 5 with I 2 in MeCN at À 208 formed the iodocarbonate 6 (72%) [12] [13], which was subsequently treated with K 2 CO 3 in MeOH to give the desired syn-epoxy alcohol 7 in 82% yield [12]. The alcohol 7 was protected with t BuMe 2 SiCl (TBS-Cl) to form the TBS-protected epoxide 8, which, on reaction with vinyl magnesium bromide in the presence of CuCN, yielded the corresponding homoallylalcohol 9 in 85% yield [14].…”

“…The residue was purified by CC on SiO 2 (20% AcOEt/hexane) to form acid 11 (0.777 g, 75%) as colorless semisolid. (12). To a ice-cooled soln.…”